2006; 8(1) : 1

INDIAN JOURNAL OF
IJPP
PRACTICAL PEDIATRICS
IJPP is a quarterly subscription journal of the Indian Academy of Pediatrics
committed to presenting practical pediatric issues and management updates in a
simple and clear manner
Indexed in Excerpta Medica from January 2003

Vol.8 No.1 JAN-MAR 2006

Dr. A. Balachandran Dr. K.Nedunchelian
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 3

TOPIC OF INTEREST - EMERGENCY MEDICINE

Setting up a pediatric emergency room 6
- Bhavneet Bharti, Sunit Singhi
Basics in Cardio Pulmonary Resuscitation in hospital 16
- Lalitha AV, Subba Rao SD
Acute stridor 27
- Rashmi Kapoor
Status epilepticus 35
- Santosh T Soans, Arun MK
Resuscitation in trauma 43
- Ramakrishnan TV
Dengue hemorrhagic fever and shock syndromes 51
- Suchitra Ranjit, Shrishu R Kamath
Cardiogenic shock in children 61
- Renu P Kurup, Krishna Kumar R
Journal Office: Indian Journal of Practical Pediatrics, IAP-TNSC Flat, F Block, Ground Floor, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
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Address for registered/insured/speed post/courier letters/parcels and communication by various authors:
Dr. A. Balachandran, Editor-in-chief, Indian Journal of Practical Pediatrics, F Block, No. 177, Plot No. 235,
4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
Indian Journal of Practical Pediatrics 2006; 8(1) : 2

Critical care transport 74

- Fazal Nabi, Deepali Mankad
PRACTITIONERS COLUMN
Cholelithiasis in children 79
- Ganesh R, Shivbalan So, Bhaskar Raju B, Malathi S
RADIOLOGIST TALKS TO YOU
Acute abdomen in the child - II 85
- Vijayalakshmi G, Natarajan B, Ramalingam A
CASE STUDY
Klippel - Trenaunay syndrome 87
- Dinesh Kumar J, Anuradha D, Meena Jayashankar, Chandralekha K
Mixed connective tissue disease in childhood 92
- Ganesh R, Sathyaprakash M, Deenadayalan M, Lalitha Janakiraman
GLOBAL CONCERN
The threat of avian influenza (Bird flu) 95
- Editorial Board IJPP
PICTURE QUIZ 99
- Pramod Sharma, Chhangani NP, Randeep Singh, Ashok Pareek
QUESTIONS AND ANSWERS 101
NEWS AND NOTES 15, 26, 34, 42, 50, 60, 73, 78, 84, 86, 94

FOR YOUR KIND ATTENTION

* The views expressed by the authors do not necessarily reflect those of the sponsor or
publisher. Although every care has been taken to ensure technical accuracy, no responsibility is
accepted for errors or omissions.
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responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.

- Editorial Board

Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road, Egmore,
Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works, 9, Iyyah Street,
Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.

2

EDITORS DESK
Greetings from the Journal Committee of IJPP.
In this issue we have highlighted the topics on
Emergency Medicine. This issue is compiled and
edited by Dr.P.Ramachandran, Dr.S.Thangavelu and
Dr.S.Shanthi. In consultation with Journal Committee
they have carefully chosen the topics, which are
relevant to the practising pediatricians and the young
pediatricians who are interested in the pediatric
emergency care.
Setting up a pediatric emergency room is no
longer a requirement for only a big institution. In his
article, Dr.Sunit Singhi, et al have given valid points
and ideas with a floor map for a Pediatric Emergency
care. This will be immensely useful for those who
are planning to establish a pediatric emergency room
in their institution. He has stressed the need for all
pediatricians to organize and develop emergency room
in their respective area.
In a hospital setting, the need for cardio-
pulmonary resuscitation (CPR) should be anticipated
both in the emergency as well as in the wards and
trained personnel and equipments should be available
for resuscitation round the clock. The Basics in CPR
in hospital is well narrated by Dr.Subba Rao, et al
wherein he has mentioned the steps in resuscitation
based on Pediatric Advanced Life Support (PALS)
guidelines. Besides CPR, he has also detailed neonatal
resuscitation in delivery room in a stepwise fashion.
Though stridor may result from relatively benign
conditions yet it may be the first sign of serious life
threatening event in a child in the emergency room.
In her article on Acute stridor Dr.Rashmi Kapoor
has mentioned that stridor demands immediate
attention and thorough evaluation to identify
significant problem and also allay the anxiety of
parents. She has reviewed the etiology and approach
to the management of acute stridor by a flow chart.
We are aware that status epilepticus is still a life
threatening medical emergency in an emergency
room. The article on Status epilepticus by
Dr. Santosh T Soans, et al deals with the classification,
etiology and management including recent trends. He
has also given a practical protocol for management
of status epilepticus.
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2006; 8(1) : 3
Till date, trauma continues to be the most
common cause for deaths and disability in childhood.
The need for cardiopulmonary assessment and prompt
establishment of effective ventilation, oxygenation
and perfusion are the keys to successful treatment of
children with any life threatening injury. This is dealt
in detail by Dr.TV Ramakrishnan in his article on
Resuscitation in trauma. He has also stated that
motor vehicle associated injuries are the most common
cause of deaths in children of all ages, whether the
child is an occupant, a pedestrian or a cyclist, followed
by drowning, housefires, etc.
Among the emerging infections, dengue fever
and dengue hemorrhagic fever pose serious public
health problem and of course it is one of the leading
causes of mortality in children if the condition is not
recognized early. Dr.Suchitra Ranjit, in her article
on Dengue hemorrhagic fever and shock syndromes
has elaborated on case definition, current concepts,
various clinical syndromes and management
protocols. This article also will be of immense use
for all practising pediatricians.
Cardiogenic shock is a life-threatening
complication encountered in an emergency set up. In
his review Dr.Krishna Kumar, et al have focused on
the etiology, pathophysiology and management of
Cardiogenic shock in children
In their article on Critical care transport
Dr.Fazal Nabi, et al have stressed the need for safe
mode of transport for a child with critical illness or
injury to reach the pediatric intensive care unit (PICU)
which requires initial stabilization and admission in
the nearest hospital. They have also given clear cut
guidelines on methods for transport of critically ill
children to the PICU.
In Radiologist talks to you column,
Dr.G. Vijayalakshmi, et al have discussed the
sono-graphic imaging in acute abdomen with
illustrations.
The Journal Committee sincerely thanks all the
authors who have contributed articles for Practitioners
column and case study. The next issue will also focus
on some more topics in emergency medicine.
Indian Journal of Practical Pediatrics 2006; 8(1) : 4

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5
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
SETTING UP A PEDIATRIC
EMERGENCY ROOM
* Bhavneet Bharti
* Sunit Singhi
Abstract: The emergency departments (ED)
dedicated exclusively to children are needed for
meeting emergency care needs of children.
Spectrum of the diseases and their seasonal and
temporal variations, sociocultural factors,
customs and local beliefs of the population should
be given due consideration while planning the
emergency services. ED should be located on the
ground floor, with direct access from the main
road and be easily accessible from the intensive
care unit (ICU), blood bank, laboratory,
operation theatre (OT) and have X-ray units. The
clinical facilities should allow at least 225sq.ft.
per patient and include distinct areas for initial
triage and resuscitation and for monitoring and
treatment. A team of trained pediatricians and
nurses should be present 24 hours a day.
Keywords: Pediatric Emergency Department
(ED), Emergency set up, Emergency services
Emergency is defined by WHO as a
condition determined clinically or considered
(perceived) by the patient or his caretakers as
requiring urgent medical services, failing which
it could result in loss of limb or life. However,
studies have shown that 20-60 % of all patients
presenting to the emergency departments have
* Department of Pediatrics,
Advanced Pediatric Centre, Postgraduate
Institute of Medical Education and Research,
Chandigarh (INDIA)
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2006; 8(1) : 6
urgent yet simple and uncomplicated problems
that can be cared for quickly and efficiently1. The
role of an emergency room in the management
of pediatric emergencies is to distinguish the child
in need of emergency or urgent care from the
large numbers of less serious presentations and
to provide an area where they can receive
effective care. Smaller family norms and rise in
literacy are responsible for the increasing use of
the Emergency department (ED). However,
Pediatric Emergency as a separate specialty was
first formulated and developed in United States
in 19702. The access to emergency services in
India is far from satisfactory and the development
of emergency medicine is in its inceptional
stage3,4. All pediatricians have a role to play in
the development of emergency room in their
respective area. In the public sector often due to
limited resources there is a common emergency
service for adults and children. As the emergency
care needs of children differ from those of adults,
a unit dedicated exclusively to children would
be ideal.
Essential inputs in planning
The services to be provided depend on the
catchment area, which decides the needs of the
population. Poor, socioeconomically deprived
areas place a higher demand on all services than
do more affluent areas. One of the debates of
recent times is upto what age children should be
treated in pediatric facilities 14,16 or 18 years.
Local policies and practice will determine these
needs. It is important for these issues to be
addressed and decisions made in the beginning.
The needs of the adolescent population are
different from those of the infants and toddlers.

Sociocultural factors, customs and local beliefs
of the population should be given due
consideration while planning the emergency
services. Knowledge of the spectrum of the
diseases along with seasonal and temporal
variations is an essential input in planning the
services5. Failure to address these issues will lead
to inefficient use of beds, uneven staffing and
frustration.
Location of the Pediatric Emergency
The emergency department (ED) should be
located on the ground floor, with direct access
from the main road with ample space for
ambulance and parking. A covered porch with
enough space for the vehicle and the patients to
alight at the entrance is important. Proper sign
postings should be there and it should be easily
located. Though the ED should be physically
separate from other areas in the hospital, the
following areas should be easily accessible;
intensive care unit (ICU), blood bank, laboratory
and operation theatre (OT). Having ICU and OT
adjacent to the emergency room will have a
benefit in allowing rapid transfer of critically ill
children to a place of definitive care. Proximity
also allows more frequent meeting and informal
collaboration, which can help to build teamwork.
A standard X-ray unit should be sited or planned
close to the emergency room. Computerized
tomography, ultrasound or magnetic resonance
imaging may be necessary for evaluation of sick
children and these facilities should be accessible
from the emergency. The ED should be close to
admission, medical records and cashiers booth.
Within the treatment setting, distraction therapy
can be employed. Familiar cartoon characters on
the walls, toys and a friendly relaxed atmosphere
can help in diagnosis and treatment5.
Space requirements
It is a frequent misconception among lay
planners to think that pediatric facilities need to
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2006; 8(1) : 7
be smaller than adult facilities because children
are smaller than adults. What is forgotten is that
the parents / family members who accompany
the child, the personnel working in the ED and
the equipments used increase the space
requirements of the Pediatric ED. Total space
requirement depends upon the number of patients
attending in a day, the size and the type of hospital
and the type of diagnostic and therapeutic
facilities available. Simply stated, a daily census
of 50 children requires 500 square meters area.
To this another 50% should be added to prevent
overcrowding. As patient loads generally show
an upward trend in this department, it is better to
plan for over usage than under usage. Besides,
the emergency departments should always have
a provision to cater to a major disaster involving
many children6,7.
Architectural design
It is important to remember the principle
design follows function in planning the ED.
Basically, there are only a few type of designs in
the construction of an emergency department: the
core type, the arena type and the corridor type.
The core design is one in which the treatment
spaces are situated around a central point in which
emergency department personnel work. Ideally
there is a corridor outside the treatment areas from
which the patients enter the cubicles. Visitors,
ancillary personnel use the corridor outside the
core and the support rooms are along the
periphery of corridor. This plan or its
modifications leaves the greatest freedom for
emergency personnel. The arena type is
essentially a core plan without the periphery
corridor and is good for smaller emergency
departments. Many steps are saved since the work
centre is almost in the middle.
Corridor plan is desirable if there is
separation of various services. In general
Accident and Emergency units prefer this plan
Indian Journal of Practical Pediatrics 2006; 8(1) : 8

Fig 1. Pediatric emergency layout (PGI, Chandigarh)

8

as each specialty can be provided separate space.
The design should be such that there is minimum
criss- crossing of patient traffic and privacy is
maintained while treating. The rooms should be
spacious and the joining corridors at least 3
meters in width. Doorways should be so designed
so as to follow unhindered passage of trolleys.
Floor should be nonslippery and wall colors of
light shade. We in our ED follow the modified
core design with many smaller areas, cubicles
and rooms along the corridor (Fig 1).
Physical facilities and layout
Facilities in the emergency are broadly
classified under two categories: administrative
and public facilities, and the clinical facilities.
Administrative and public areas include
reception-control, public waiting area, space /
room for the staff, ambulance driver and
attendant. Reception control is required for the
observation and control of access to the treatment
area and preferably registration. It should be well
equipped with communication including inter
communication system. There should be some
space earmarked for the stretchers and wheel
chairs adjacent to the entrance. Public waiting
area should have toilet facilities, water cooler,
public telephones, facility for charging the mobile
phones, snack bar and a vending machine.
Separate waiting area for the relaxation of the
mothers and other attendants should be available.
A cloak room can ensure safe custody of the
attendants luggage. There should be separate
rooms for the various staff working in the
emergency including the doctors, nurses and the
paramedical staff6.
Clinical facilities should include two distinct
areas after the initial triage and resuscitation:
Monitoring and treatment area for the critically
ill children and observation area where sick
children are observed for short duration. The
monitoring area requires intensive monitoring
facilities with individual patient rooms allowing
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2006; 8(1) : 9
at least 225 ft2 per patient. Electrical power,
oxygen, medical compressed air and vacuum
outlets should be sufficient in number to supply
to all necessary equipments. In most cases, 12 or
more electrical outlets and a minimum of 2
compressed air outlets, 2 oxygen outlets, and 2
vacuum outlets will be necessary per bed space.
Reserve emergency power and gas supply
(oxygen, compressed air) are essential. Screens
or curtains must be provided to ensure patient
privacy. Procedure/treatment area for both minor
and major procedures should be separately
earmarked We in our emergency have two
monitoring beds and separate areas for the
neonates and for children with diarrhea, as they
constitute nearly 16% and 23% of our patients
respectively5. There is a separate isolation room
for children with communicable diseases.
Personnel
Staffing an Emergency has always been a
challenge to the hospital administrators.
Fluctuating patient volumes and acuity prohibit
the accurate assignment of the staff to the
workload. Ideally a team of pediatricians with
skills, knowledge and commitment to care for
critically ill children should be present 24 hours
per day, 7days per week. However in small
emergency rooms providing a basic facility, a
trained assistant or a resident can supplement the
work of a pediatrician who is promptly available
(on call) for supervision and provide directions
to the staff.
Nurses are the most important personnel in
an ED. To help determine the nurse staffing,
workforce measures such as hours per patient
visit and nurse to patient ratios have generated
considerable debate. The hours per patient visit
method for calculating staffing is based on the
historic benchmark data. The limitation of this
method is that it considers patient volume and
available nursing hours without consideration of
factors such as patient acuity, length of stay and
Indian Journal of Practical Pediatrics
the nursing interventions and activities. There are
others who propose using nurse to patient specific
ratios such as in ICUs. A critical limitation in
use of ratios is that ratios do not account the
variability found in institutions, available internal
and external resources (e.g. inpatient beds,
equipment, other staff), individual and aggregate
patient needs (e.g. volume, intensity,
demographics, length of stay) and the nursing
expertise required by the patient population. The
use of ratios have been challenged because the
mandated staffing may be interpreted by the
institutions as the maximum required staffing,
when in fact it is the minimum mandated staffing
standard. Further, ratios may lead to minimum
safe staffing and patient care instead of best
practice staffing and care8.
To identify safe, effective and realistic best
practice staffing in emergency, six key factors
have been identified in the projection of staffing
requirements which include patient census,
patient acuity, patient length of stay, nursing time
for nursing interventions, skill mix for providing
patient care based on nursing intervention that
can be delegated to an attendant and an
adjustment factor for the non patient care time.
Continued research is needed to determine
patient, and organizational outcome in relation
to predicted staffing.
We have an exclusive pediatric ED which
is a part of 180 bedded Advanced Pediatric Centre
providing training to residents in pediatrics and
its subspecialties. The centre is a part of 1500
bedded multispecialty and postgraduate teaching
and research institute. It has a patient load of
nearly 10000 per year and is manned round the
clock by four residents (trainees in Pediatrics), a
senior resident (a trained pediatrician with
postgraduate qualification) and 4-6 nurses and
paramedical and support staff. A consultant
supervises patient care round the clock and a
senior consultant supervises the overall
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2006; 8(1) : 10
functioning of the Pediatric ED. The distribution
of pediatric patients attending the ED of PGIMER
with respect the major diagnoses are depicted in
Table 1.
The activities improving the initial
emergency management of severely ill children
has received substantial attention and resources
in developed countries; many nurses and doctors
have received training to deliver rapidly
standardized emergency management by
undertaking courses such as the Advanced
pediatric life support and PALS and several
nursing and paramedic pediatric emergency
curricula. Our endeavor should be to train all
the physicians and nurses involved directly in
care of sick children to be trained in pediatric
advanced life support (PALS) course followed
by recertification at regular intervals. In academic
institutions, new residents, doctors are frequently
replacing the trained residents in order to provide
24-hour facilities. Hence, ongoing training and
teaching should be an inherent part of this
department.
Equipments and supplies
Equipments and supplies in the ED can be divided
into three categories
General medical supplies: These are supplies
that are generally disposable and used as they
come from the manufacturer. These supplies may
be stored in the ED or in the queue (outside the
ED)
Reprocessed items: These items are reused and
must be sent elsewhere in the hospital for
reprocessing. These include linen, cut down sets,
tracheostomy sets, respiratory equipment etc.
Support items: These include operational
supplies such as appropriate forms, papers, clips
etc.
The suggested equipments, instruments and
 2006; 8(1) : 11

Table 1. Distribution of 43,800 supplies are listed in the Table 2. Each of these
patients attending pediatric emer- items should be located in or immediately
gency (PGIMER) between 1995-2000, available in the patient care area. This list does
with respect to major diagnosis not include routine medical /surgical supplies
such as adhesive bandages, gauze pads and suture
Major Illnesses No.of patients
material nor does it include routine office items.
(percentage of
A wall mounted oxygen and suction facility is a
total)
must for the EDs catering to larger workloads.
Gastrointestinal 10173(23.3%)
There should be provision of adequate lighting
Diarrhoea 7724
supplemented by procedure lights especially in
Intestinal obstruction 536
the procedure rooms.
Acute liver failure 496
Others 1387 Maintenance of equipment is a common
Respiratory 10269(23.44%) problem in ED. Common complaints about
Upper respiratory infection 3183 missing and nonfunctional equipment is a
Pneumonia 2695 symptom of fragmented maintenance system and
Asthma 2302 lack of accountability for documenting,
Others 2089 responding to and following up on maintenance
Central Nervous System 7038(16.07%) needs. To circumvent this problem maintenance
Seizures 3096 of equipment in emergency should be inventoried
Meningitis(bacterial,aseptic) 1222 and handled on preventive maintenance basis9.
Encephalitis 669
Others 2051 Drugs
Neonatal illnesses 6830(15.59%) It is essential that the drugs required for
Suspected sepsis 1657 emergency treatment are immediately available
Jaundice 1577 without requiring parental purchase (Table 3).
Birth Asphyxia 951
Others 2645 Triage
Systemic infections 2849(6.73%)
Septicemia 1126 Triage is a brief clinical assessment that
Malaria 822 determines the time and sequence in which
patients should be seen in the ED or, if in the
Enteric Fever 493
field, the speed of transport and choice of hospital
Others 408
destination. These decisions generally are based
Cardiac 2070 (4.9%)
on a short evaluation of the patient and on
Acyanotic heart disease 960
assessment of vital signs. The patients overall
Congenital cyanotic heart
appearance, history of illness and/or injury, and
disease 863
mental status also are important in the triage
Others 247
decision. The assessment is done using the PALS
Hematological 2034(4.8%)
guidelines by a junior resident in our set up.
Renal 1996 (4.3%) Correct triage depends upon the experience of
Poisoning 253 (0.58%) the triage staff and adherence to objective
(Adapted from - Singhi S et al, J Trop Pediatr directions. Triaging gets priority over registration
2003; 49:207-11, reference 5) in Emergency.
11
Indian Journal of Practical Pediatrics 2006; 8(1) : 12

Table 2. Suggested equipment and supplies for EDs

General requirements Airway & Breathing needs
Cardiac monitors with defibrillator Suction devices and catheters 6-14
Temporary external pacemaker Oral, nasal and nasopharyngeal airways
EKG monitor and machine Clear oxygen masks, standard and non rebreathing
Pulse oximeter masks
End tidal CO2 detector Bag-valve- mask respirator (pediatric and infant
Heating source size)
Thermometers Laryngoscopes, straight and curved, and stylets
Weighing machines (adult and infant) Endotracheal tubes, sizes 2.5-8.0
Tape measure, Broselows tape Magill forceps
Sphygmomanometer with BP cuffs of all sizes Tracheostomy kit
Ophthalmoscope/Otoscope Cricothyroidotomy kit
Radiograph view Box Circulation needs
IV Poles IV catheters, sets, tubings, poles
Pediatric restraining devices Butterfly needles
Biohazard disposal receptacles, including for Intraosseous needles
sharps Infusion pumps and tubing
Garbage receptacles for non-contaminated Central venous catheter setups with CVP
materials monitoring equipment
Intradepartmental staff communication system: Pericacrdiocentesis instruments
pagers and mobile phones Special Pediatric trays
Fracture management equipment Lumbar puncture
Spinal immobilization board Venous cut down
Splints Tube thoracostomy with under water seal
Semi rigid neck collars Newborn kit (Umbilical vessel cannulation
supplies)
CPAP set
Urinary catheter (Sizes 5-12)

Children presenting as cardiopulmonary
failure or cardiac arrest need to be seen, assessed
and treated on arrival by the most experienced
staff available. Delay in the treatment should be
minimal in children presenting with shock or
respiratory distress. The children who are stable
at presentation can wait for treatment.
One should remember that triage is a
dynamic process. Once the child is placed in a
particular category, he should be regularly
reassessed to determine if he needs to be moved
up or down a category. Parents are usually
12
concerned for their child when they present in
Emergency and if they see other children being
attended first on the basis of emergency or
priority signs. Communication and explanation
of the triage system are therefore needed. The
initial triage of sick children arriving at hospitals
in developing countries is often deficient, with
severely ill children experiencing delays in the
institution of life saving emergency measures6,10.
Components of model case sheet
Initial cardiopulmonary assessment using
triage form is the first step in the Emergency data
 2006; 8(1) : 13

Table 3: Drugs suggested for the emergency room

Resuscitation Vasoactive drugs
Oxygen Inj. Dopamine
Crystalloids (Normal Saline/Ringer lactate) Inj. Dobutamine
Inj. Epinephrine Inj. Milrinone
Inj. Calcium gluconate & Ca chloride 10% Antiarrhythmics
Inj. NaHCO3 7.5% Inj. Adenosine
Dextrose solution 5, 10, & 25% Inj. Lidocaine
Inj. Atropine Inj. Amiodarone
Anticonvulsants Antibiotics
Inj. Midazolam All in common use
Inj. Diazepam Respiratory
Inj. Phenytoin Beta agonists for inhalation and parenteral use
Inj. Phenobarbital - Salbutamol nebulising solution and injections
Analgesics (Opiod and nonopiods) Steroids for oral, parenteral and inhalation- Inj
Inj. Morphine Hydrocortisone and Dexamethasone,
Paracetamol Syp and suppositories Prednisolone tabs, Budesonide resp soln
Antipyretics Inj. Magnesium sulfate
Paracetamol Syp and suppositories Drugs for Raised ICP
Paralyzing agents Inj. Mannitol
Inj. Pancuronium / vecuronium / Inj Dexamethasone
succinylcholine Diuretics
Antihypertensives Inj. and Tabs Furosemide
Sod Nitroprusside Soln for infusion Sera and Miscellaneous
Inj Labetalol Insulin
Inj. Propranolol Potassium chloride soln for IV and oral use
Antidotes of common poisons Hydrocortisone
Inj Methylene blue, Triclofos oral soln.
Inj Desferrioxamine, Oral Rehydration Salt sachets
Inj. Flumazenil, Anti Snake Venom
Inj Pralidoxime, Anti Diphtheritic Serum
Activated Charcoal Tetanus vaccine
Rabies Hyperimmune Serum and Vaccine

recording followed by noting of the especially because of the increasing malpractice

demographics and the reporting date and time.
In EDs with heavy emergency loads,
comprehensive history and examination may be
almost impossible. Depending upon the time
available, problem is focused, or detailed history
or examination is undertaken. Proper
documentation serves two distinct purposes;
clinical necessity and the legal necessity
13
claims. Medical records of the admitted patients
are preserved for at least two years and longer
for the medico- legal cases such as child abuse.
Physicians and nurses must be conversant with
consumer protection forums and the Consumer
Protection Act, and liability suits arising out of
malpractice or negligence, and aware of ways of
protecting themselves and hospital legally.
Indian Journal of Practical Pediatrics
If the resources permit, computer with
internet facilities and networking can further help
the pediatrician meet the expectation of parents
who are assured that their emergency physician
is providing the best and latest in medical
knowledge.
Admission and transfer criteria
Because hospitals vary significantly in their
resources for providing pediatric care, there is
no single set of criteria for admission and transfer
of pediatric patients that has universal
applicability. Each institution must assess its own
capabilities and limitations in light of its mission
and then formulate guidelines. Once guidelines
for transfer of patients have been established,
those for admission become less difficult to
define. This challenging process requires input
from all members of the health care team,
including hospital administration. The goal is to
ensure that each patient in the facility receives
the optimal care that is most appropriate for his
or her medical and psychosocial needs. We in
our hospital admit all children where the
anticipated duration of the stay is more than six
hours . An attempt is made to transfer all
critically sick children to the PICU soon after
stabilization and other stable children to their
respective units within 24 hours of their arrival.
Protocols
The management of common pediatric
emergencies should follow set practices
determined prior to child attending the ED. These
will give a framework for residents and
inexperienced physicians to practice safe and
immediate care. As a general rule these protocols
should be adhered to in the first instance and only
varied by senior advice. Within this framework
there should be supervision by experienced
physicians to help and advise with difficult cases.
Audit
Practice review is an important part of the
emergency care. The continued questioning of
14
2006; 8(1) : 14
current practice by audit and research is vital to
the development of the specialty; without it we
cannot hope for improvement in the service
provided6.
To end, the primary responsibility of
emergency care team is to provide quality health
care to the communities served within available
means. While attempting to provide the efficient
technology based, cost effective services to
pediatric emergency patients we must not forget
the human touch; lack of compassion is the
most common cause of dissatisfaction among
patients and parents.
Points to remember
Spectrum of the diseases and their seasonal
and temporal variations, sociocultural
factors, customs and local beliefs of the
population should be given due
consideration while planning the
emergency services
ED should be located on the ground floor,
with direct access from the main road, and
be easily accessible from the intensive care
unit (ICU), blood bank, laboratory,
operation theatre (OT) and have standard
X-ray units.
A team of trained pediatricians, and nurses
should be present 24 hours per day.
References
1. Mayer T, Cates R. Customer service-survival
skills. Emergency Physicians of North
Virginia.Ltd: 2002. Available at:wysiwyg:
44http:129.174.192.191/jRing/survival
skills.htm.
2. Pena ME, Synder BL. Pediatric Emergency
medicine. The history of growing discipline.
Emerg Med Clin North Am 1995;13:235-253.
3. Posaw LL, Agarwal P,Bernstein SL.
Emergency medicine in New Delhi area, India.
Ann Emerg Med 1998; 32:609-615.
 2006; 8(1) : 15

4. Alagappan K, Cherukuri K, Narang V, In: Pediatric Emergencies. Mosby Wolfe,

Kwiatkowski T, Rajagopalan A. Early
development of emergency medicine in
Chennai, India. Ann Emerg Med 1998; 32:604-
608.
5. Singhi S, Jain V, Gupta G.Pediatric
Emergencies at Tertiary Care Hospital in India.
J Trop Pediatr 2003; 49:207-211.
6. Kunders GD, Gopinath S, Katakam.
Emergency services. In: Hospitals:
Planning,Design and Management.
Eds Kunders GD, Gopinath S, Katakam. Tata
McGraw-Hill, New Delhi, 1998; pp 140-145.
7. BeattieTF, Hendry GM, Hewson GC. The Child
and the Accident and Emergency Department.
London, 2005; pp 1-10
8. Almeida SL. Nursing perspectives on the
emergency department. Emerg Med Clin North
Am 2004;22:117-129.
9. Williams M. Materials management and
logistics in the emergency department. Emerg
Med Clin North Am 2004; 22: 195-215.
10. Gove S, Tamburlini G, Molyneux E, Whitesell
P, Campbell H. Development and technical
basis of simplified guidelines for emergency
triage assessment and treatment in developing
countries. WHO Integrated Management of
Childhood Illness (IMCI) Referral Care Project.
Arch Dis Child 1999; 81:473-477.

NEWS AND NOTES

LAKESIDE EDUCATION TRUST

24th Annual CME on Sunday 23rd July 2006, At Hotel Atria.
Allergic Disorders In Pediatric Practice

For details contact:

Dr.H.Paramesh,
Chairman, Lakeside Education Trust,
PediatricianInChief & Pediatric Pulmonologist,
C/o. Lakeside Medical Center & Hospital,
33/4, Meanee Avenue Road,
Near Ulsoor Lakeside Medical Center and Hospital,
Bangalore 560042.
Phone: 080-25303677, 25304276, 25566738, 25366723, 25512934.
Fax: 25303677.
Email: dr_paramesh1@yahoo.com

15
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
BASICS IN CARDIOPULMONARY
RESUSCITATION IN HOSPITAL
* Lalitha AV
** Subba Rao SD
Abstract: Cardiopulmonary arrest can occur in
children who are brought to the hospital with
many serious illnesses. In this situation
cardiopulmonary resuscitation (CPR) is intended
to support the ventilation and circulation using
an organized approach of stabilizing airway,
breathing and circulation (ABC). In a hospital
setting, need for CPR should be anticipated and
trained personnel, equipments and resuscitation
drugs should be available round the clock.
Neonatal resuscitation in the delivery room
requires a slightly different approach based on
various aspects of evaluation at birth and during
resuscitation.
Key words; CPR in hospital, ABC, Neonatal
resuscitation
Pediatric advanced life support (PALS)
begins with early identification and treatment of
respiratory failure and shock in children. This will
improve survival from a dismal 10% to an
encouraging 85%1. Cardiopulmonary arrest is
the final common pathway for many life
threatening diseases. Because the adult and
pediatric etiologies of cardiopulmonary arrest
differ, a different approach to assessment and
* Lecturer in Pediatrics
** Professor of Pediatrics,
St.Johns Medical College Hospital,
Bangalore 560034
16
2006; 8(1) : 16
intervention is required in the pediatric
population.
This article deals with basics of
cardiopulmonary resuscitation in a hospital
setting when the child may present to the
emergency room with an impending or actual
respiratory or cardiopulmonary arrest or develop
the same during hospital stay. In this setting,
some skills in recognition of cardiopulmonary
arrest and basic equipments for resuscitation are
likely to be present. Besides CPR, this article
also deals with neonatal resuscitation in delivery
room in a stepwise fashion.
Cardiopulmonary resuscitation
(CPR)
CPR is intended to externally support the
circulation and ventilation in a child with
respiratory or cardiopulmonary arrest. The
objective of CPR is to provide oxygen to vital
organs (the heart and the brain) until normal
circulation is restored. Respiratory failure and
shock may begin as clinically distinct problems
but often progress to a state of cardiopulmonary
failure and arrest.
In PALS programme a rapid and systematic
cardiopulmonary assessment and support is
structured around ABCs (airway, breathing and
circulation). As the CPR is initiated child should
be connected to a cardiac monitor if available.
Anticipation and preparation
In a hospital basic equipments for
resuscitation (Bag-mask of various sizes,
airways, laryngoscope, tracheal tubes, oxygen
 2006; 8(1) : 17

and sealing the mask to the face is called the E-C

clamp technique (Fig 3).
Two person BMV technique may provide
more effective ventilation than one person
ventilation when there is significant airway
obstruction or poor lung compliance. One person
Fig 1. Head tilt Chin lift
uses both hands to open the airway and maintain
a tight mask-to-face seal while the other person
compresses the ventilation bag (Fig 4).
Ventilation is carried out at the
recommended rate (Table 1) so that there is time
for exhalation. Gastric inflation can be prevented
Fig 2. Jaw Thrust (spinal cord injuries) by placing a nasogastric tube. The self inflating
ventilation bags for resuscitation are available in
source, suction devices, defibrillator), monitoring sizes suitable for the entire pediatric age range;
equipments (cardiac monitor, pulse oximeter), Term neonate - Minimum 450 ml; pre term - 250
drugs for resuscitation (epinephrine, sodabicarb, ml; beyond 3months - Pediatric and larger bags
Ringers lactate or normal saline, dextrose) and may be used safely provided just adequate force
skilled personale in management should be is given to make the chest rise.
available all the time especially in emergency
room and intensive care units. With oxygen inflow rate of 10-15 litres/min
and a reservoir, high oxygen concentration (60-
Monitoring the airway 95%) can be consistently delivered. In situations
The first step in CPR is maintaining a clear
airway by positioning (supine) and opening the
airway (Fig 1 and 2) by head tilt-chin lift or by
jaw thrust (in case of trauma). The airway should
be cleared of secretions if necessary.
Assisting the ventilation
A child who has impending or actual
respiratory arrest requires immediate ventilatory
support after opening the airway. In a hospital
setting, bag and mask ventilation (BMV) is the
initial method preferred2.
Bag-mask ventilation: A proper sized mask
should provide an airtight seal around the nose
and mouth extending from the bridge of the nose
to the cleft of the chin and then a tidal volume is
delivered by compressing the bag to make the
chest rise. The technique of opening the airway Fig 3. E-C clamp technique

17
Indian Journal of Practical Pediatrics 2006; 8(1) : 18

Table 1. Resuscitation for all ages (modified from Ref 2)

CPR New born Infant (<1 yr) Child (1-8 yrs) Adult and older
child (> 8 yrs)
Compression Lower half of Lower half of Lower half of Lower half of
landmarks sternum (1 fingers sternum (1 fingers sternum sternum
width below width below
intermammary line) intermammary line)
Compression Two thumb-encircling Two thumb- Heel of one Heel of one
method hands for 2- trained encircling hands for hand hand, other
persons or 2-finger 2- trained persons hand on top
technique or 2-finger technique
Compression Approximately 1/3 Approximately 1/3 to Approximately Approximately
depth depth of chest 1/2 depth of chest 1/3 to 1/2 depth 1 to 2 inches
of chest (4-5 cm)
Compression Approximately 120 At least 100/min Approximately Approximately
rate events/min 100/min 100/min
(90 compressions /
30 breaths)
Compression 3:1 5:1 5:1 15:2
ventilation ratio

where tracheal intubation skill is not available,
BMV is continued during resuscitation and if
necessary during transport to a bigger center.
Tracheal tube ventilation3: Ventilation though a
properly placed tracheal tube is the most effective
Fig 4. Two person BMV
18
and reliable method of assisted ventilation. This
should be done after a few minutes of BMV, by
which time necessary equipments and skilled
person(s) become available. Once the tracheal
intubation is done and tube is fixed, verify the
position of tracheal tube at regular intervals.
Maintaining circulation
Chest compression is started
immediately after initiating BMV, when there is
no central pulse or heart rate or when the heart
rate is less than 60 beats per minute in an infant
or child with signs of poor perfusion. Chest
compressions are serial, rhythmic compressions
of chest that circulate blood to the vital organs
(heart, lungs and brain) until other pharmacologic
support can be provided. Chest compressions
must always be accompanied by ventilation at
the recommended compression-ventilation ratio
(Fig 5 and 6, Table 1)

Fig 5. Chest compression in infant
Vascular access and drugs: Gain rapid access to
the circulation by direct venous access or intra-
osseous (IO) access. If vascular access is
delayed, certain drugs for resuscitation
(Epinephrine, Atropine, Lidocaine and
Naloxone) can be given via tracheal tube4. The
initial resuscitation dose of epinephrine is
administered by the IV or IO route (0.1 ml/kg of
1:10000 solution) or by the tracheal route (0.1
ml/kg of 1:1000 solution). For persistent arrest,
repeat the same dose every 3 to 5 minutes during
CPR. As a next step, consider giving sodium
bicarbonate slowly 1 mEq/kg/dose IV or IO to
correct a severe metabolic acidosis while
maintaining effective ventilatory support.
Defibrillation: In an arrest situation, defibrillation
is carried out for ventricular fibrillation (VF) or
ventricular tachycardia without pulse (Pulseless
VT) with an energy of 2-4 joules per kg body
weight. Anti-arrhythmic medications
19
2006; 8(1) : 19
Fig 6. Chest compression technique for child
(Amiadarone or lidocaine) are considered in
shock resistant or recurrent VF / VT.
Treatment of underlying causes
Whenever cardiac arrest or life threatening
arrhythmia develops, certain reversible causes (4
Hs and 4 Ts) should be identified and treated;
Hypoxia
Hypovolemia
Hypothermia
Hyper/hypokalemia, Hions, Ca/Mg
disturbances
Tension pneumothorax
Tamponade (cardiac)
Toxic / therapeutic disturbances
Thromboembolism
A stepwise CPR approach is given in Fig 7.
Discontinuation of life support5
In the emergency department, the decision
to terminate resuscitation is usually based on the
patients response to advanced life support.
In children, the failure to respond to 2
standard doses of ephinephrine is highly
correlated with death.
In the absence of recurrent or refractory VF
or VT, history of toxic drug exposure or
Indian Journal of Practical Pediatrics 2006; 8(1) : 20

Collapsed child, apnea / gasping

Open airway, BMV

Chest rise with BMV initially or after repositioning No Suspect obstructed airway
(FBAO)
Yes
Continuous BMV with O2 and reservoir Appropriate measures for
Tracheal intubation, ventilation FBAO

Central / pulses? Apex audible?

Infant/child HR <60 with poor perfusion

Cardiac massage

IV / IO access
Epinephrine IV/IO/ th tracheal tube

Arrest continuous ECG

Rpt epinephrine 3-5 min; consider sodabicarb

VF, Pulseless Identify and treat

Pulsesless VT electrical activity 4 Hs and 4 Ts

Cardiovert Epinephrine,
(Lidocaine, amiadarone) CPR

FBAO - Foreign body airway obstruction; VF-Ventricular fibrillation, VT-Ventricular tachycardia

Fig 7. CPR algorithm

hypothermia, resuscitation team should Cold-water drowning is perhaps the most

discontinue resuscitative efforts after common clinical situation in which very long
approximately 30 minutes, especially if there resuscitations have occasionally produced
is no return of spontaneous circulation. viable survivors.
20

Resuscitation is not indicated, either in the
emergency department or in the field for
patients with rigor mortis, dependent lividity
or decapitation.
Terminally ill children may have advance
directives in the form of do-not-resuscitate
(DNR) orders.
Neonatal resuscitation
Neonatal resuscitation can be divided into
4 categories of action 6
Basic steps, including rapid assessment and
initial steps in stabilization
Ventilation, including bag-mask or bag-tube
ventilation
Chest compressions
Administration of medications or fluids
All newly born infants require rapid
assessment, including examination for the
presence of meconium in the amniotic fluid or
on the skin; evaluation of breathing, muscle tone,
and color; and classification of gestational age
as term or preterm. Subsequent evaluation and
intervention are based on a triad of characteristics:
(1) respiration, (2) heart rate, and (3) color.
Anticipation of need for resuscitation
Anticipation, adequate preparation, accurate
evaluation and prompt initiation of support are
the key steps to successful neonatal resuscitation.
Resuscitation must be anticipated at every birth.
Personnel capable of initiating resuscitation
should attend every delivery. At least one such
person should be responsible solely for care of
the infant. A person capable of carrying out a
complete resuscitation should be immediately
available for normal low-risk deliveries and in
attendance for all deliveries considered high risk.
21
2006; 8(1) : 21
More than one experienced person should attend
an anticipated high-risk delivery7.
A stepwise neonatal resuscitation algorithm
in given in Fig 8.
Evaluation
Evaluation of infant for the need for
resuscitation should begin immediately after birth
and proceed throughout the resuscitation process.
Baby is evaluated by inspection to answer the
following questions8.
Is there meconium in the amniotic fluid or
on the skin? Is the baby crying or breathing? Does
the baby have good muscle tone? Is the baby
pink? Is the baby term? When there is no
meconium staining or the answer is yes to the
other questions, these babies can be directly
placed on mothers chest, dried and covered with
dry linen. Warmth is maintained by direct skin-
to-skin contact with the mother. Ongoing
observations of babys breathing, color and
activity are carried out8. If there is meconium
staining or the answer is no to other questions,
basic steps of resuscitation are carried out under
the radiant warmer (Fig 8).
Basic steps6
Prevention of heat loss and providing
warmth
Opening and clearing the airway
Drying and initiating breathing by gentle
stimulation, if required
Evaluation of the infant
Warmth: Placing the infant under a radiant
warmer, rapidly drying the skin, removing wet
linen immediately and wrapping the infant in
prewarmed blankets will reduce heat loss. Avoid
hyperthermia because it is associated with
perinatal respiratory depression7.
Indian Journal of Practical Pediatrics
Fig 8. Stepwise neonatal resuscitation in delivery room9
Positioning: The newly born infant should be
placed supine or lying on its side, with the head
in a neutral or slightly extended position. If
respiratory efforts are present but not producing
effective tidal ventilation, often the airway is
obstructed; immediate efforts must be made to
correct overextension or flexion or to remove
secretions.
Clearing the airway: Positioning of the infant and
22
2006; 8(1) : 22
removal of secretions if needed clear the infants
airway.
Suctioning: Healthy, vigorous, newly born infants
generally do not require suctioning after delivery.
If suctioning is necessary, clear secretions first
from the mouth and then the nose with a bulb
syringe or suction catheter (8F or 10F).
Tactile stimulation: Drying and suctioning
produce enough stimulation to initiate effective
 2006; 8(1) : 23

Meconium present?
Yes
Intrapartum suctioning
Suction mouth, nose and posterior
pharynx after delivery of head

Baby vigorous?*
No
No Yes Suction mouth and trachea

Vigorous Not vigorous

Continue with remainder of initial steps: Neonatal resuscitation

Clear mouth and nose of secretions protocol (Fig 8)
Dry, stimulate and reposition
Give oxygen (as necessary)

* A vigorous baby is defined as baby with strong respiratory efforts, good muscle tone and heart rate
greater than 100 bpm

Fig 9. Management of baby born through meconium-stained amniotic fluid

respirations in most newly born infants. If an
infant fails to establish spontaneous and effective
respirations after drying with a towel or gentle
rubbing of the back, flicking the soles of the feet
may initiate spontaneous respirations. Avoid
more vigorous methods of stimulation.
Triad of evaluation: To determine further
resuscitation, evaluate the infants heart rate,
respiratory effort and colour. Monitor this triad
of evaluation throughout the resuscitation and
post resuscitation periods9.
Meconium stained amniotic fluid (MSAF)
(Fig 9):
Intrapartum suctioning (as soon as head is
delivered) from mouth, pharynx and nose is to
be performed in all deliveries born through
MSAF. Large bore suction 12F or 14F suction
catheter is used with a negative pressure of 100
mmHg. Perform direct laryngoscopy for
23
suctioning of meconium from the hypo pharynx
and intubation/suction of the trachea, if the infant
has depressed or absent respiration, decreased
muscle tone, or heart rate <100 bpm. Tracheal
suctioning of the vigorous infant with MSAF does
not improve outcome and may cause
complications7.
Oxygen administration
Hypoxia is nearly always present in a newly
born infant who requires resuscitation. Therefore,
if cyanosis, bradycardia, or other signs of distress
are noted in breathing newborn during
stabilization, administration of 100% oxygen is
indicated while determining the need for
additional intervention. The oxygen source should
deliver at least 5 L/min, and the oxygen should
be held close to the face to maximize the inhaled
concentration 6. If supplemental oxygen is
unavailable, initiate resuscitation of the newly
born with positive pressure ventilation and room
Indian Journal of Practical Pediatrics
air. Current clinical data do not justify routine
practice of ventilating with room air7.
Bag and mask ventilation
Adequate ventilation is the key to neonatal
resuscitation.
Indications: Apnea or gasping respirations, heart
rate <100 bpm, persistent central cyanosis despite
100% oxygen.
Contraindications to bag and mask ventilation
a) Diaphragmatic hernia: Bag and mask
ventilation leads to further aggravation of cardio-
respiratory compromise as ventilation causes
gastrointestinal distension, b) Infants born
through meconium-stained amniotic fluid with
respiratory depression at birth: Intra tracheal
suctioning is indicated first as described.
If bag and mask is ineffective or attempts at
intubation have failed, laryngeal mask airway
(LMA) may be an effective alternative for
establishing airway.
Chest compressions: Initiated if heart rate is
absent or remains <60 bpm despite adequate
ventilation with 100% oxygen for 30 seconds
(Fig 10)7.
Compression technique: a) Compressions should
be delivered on the lower third of the sternum,
Heart rate
Below 60 60-100 Above 100
Continue Continue Watch for
Ventilation Ventilation spontaneous
Chest respiration
Compression ventilation
Fig 10. Intervention based on heart rate
24
2006; 8(1) : 24
b) Acceptable techniques are; the 2 thumb-
encircling hands technique (preferred method -
Fig 5) and 2 fingers on the sternum method 7.
Endotracheal intubation: Endotracheal
intubation may be indicated at several points
during neonatal resuscitation10.
Ineffective bag and mask ventilation
Need for prolonged positive pressure
ventilation
Tracheal suctioning for meconium in a baby
born through meconium-stained amniotic
fluid and who is not vigorous.
Administration of medications (epinephrine)
Suspected congenital diaphragmatic hernia
Surfactant administration in extremely pre-
term babies
After endotracheal intubation, confirm the
position of the tube by the following6.
Observing symmetrical chest-wall motion
Listening for equal breath sounds, especially
in the axillae and for absence of breath
sounds over the stomach.
Confirming absence of gastric inflation
Noting improvement in heart rate, color, and
activity of the infant
Medications
Role of medications during resuscitation
(Table 2)10.
To provide substrate and stimulation to the
heart so that it can supply oxygen to the body,
primarily to the brain.
Give support to the myocardium by
administration of inotropic and chronotropic
drugs.
 2006; 8(1) : 25

Table 2. Dosage of drugs in neonatal resuscitation10

Medication Indication Dosage/route Rate/precautions
Epinephrine HR Zero or below 60/min 0.1-0.3 ml/kg IV/IO/ET Give rapidly, may dilute
(1:10000) after 30secs of PPV and with normal saline to
chest compression 1-2 ml if giving through
ET
Volume expanders Acute bleeding with 10ml/kg IV/IO Give over 5-10mins by
(NS, RL or whole signs of hypovolemia syringe or IV drip
blood)
Sodium bicarbonate Documented metabolic 2 mEq/kg IV (2ml/kg) Give slowly over at
(7.5% solution) acidosis, Apgar 3 or less Never give least 2 mins. Give only
at 5min endotracheally if infant is being
effectively ventilated
Naloxone Maternal narcotic 0.1-0.2 mg/kg Can be repeated 3 times
(0.4 mg/ml) administration within past (0.25-0.5ml/kg) if there is no response
4 hours with respiratory IV or ET
depression in the baby

Correct acidosis, if it is documented and Routes of medication administration: The

resuscitation is prolonged
Ensure adequacy of blood volume.
Combat depression due to narcotic
administration in the mother
Epinephrine is the first medication to be
administered
tracheal route is generally the most rapidly
accessible route for drug administration during
resuscitation. Attempt to establish intravenous
access in neonates who fail to respond to
tracheally administered epinephrine. The
umbilical vein is the most rapidly accessible
venous route.

Do not give sodium bicarbonate unless the
baby is being adequately ventilated.
Epinephrine is indicated when the heart rate
remains below 60 bpm despite 30 seconds
of assisted ventilation and another 30
seconds of coordinated chest compressions
and ventilation8. High dose epinephrine is
not recommended7.
Indication for naloxone hydrochloride:
Severe respiratory depression and a history
of maternal narcotic administration within
the past 4 hours after 30 seconds of positive
pressure ventilation has restored normal
heart rate and colour7.
25
Post-resuscitation: Apgar scores: continue to
assign Apgar score at 1 and 5 minutes after birth
and then sequentially every 5 minutes until vital
signs have stabilized.
Non-initiation of resuscitation: Non-initiation
of resuscitation in the delivery room is apt for
infants with confirmed gestation age <23 weeks
or birth weight <400 g, anencephaly, or
confirmed trisomy 13 or18. Current data suggest
that resuscitation of this group of infants is not
likely to reduce the resulting mortality and neuro
developmental morbidity.
Discontinuation of resuscitation: Resuscitative
efforts in an infant with cardiopulmonary arrest
Indian Journal of Practical Pediatrics
if spontaneous circulation is not achieved in 15
minutes. Resuscitation after 10 minutes of
asystole is very unlikely to result in survival or
survival without severe disability7.
Points to Remember
In any pediatric emergency, assessment and
management should follow- Airway.
Breathing and Circulation. In neonates, in
addition attention to temperature is
important. Hence in neonates it should be
TABC.
Health professionals must be trained in
Evaluation, Action and Decision making in
recognition of emergencies in children.
Respiratory Failure must be diagnosed
early and should be managed aggressively
to curtail mortality and morbidity.
References
1. Bardella IJ Pediatric Advanced Life Support:
A Review of the AHA Recommendations.
American family Physcians 1999;60: 1743-
1752.
2. PALS Provider Manual. American Academy
of Pediatrics. American heart association.
Editor Hazinski MF 2002; p71.
NEWS AND NOTES
CIPP VII
7 TH
INTERNATIONAL CONGRESS ON PEDIATRIC PULMONOLOGY
Date : 8th to 11th July 2006
Venue : Montreal Congress Center, Montreal, Canada.
Contact :
Anne F. Bidart, MD
CIPP VII Secretariat
27, rue Massena 06000 Nice, France
Email : cipp@cipp-meeting.com
Ph : 33(O) 497038597
Fax : 33 (O) 497038598.
26
2006; 8(1) : 26
3. Pediatric Advanced Life Support Resuscitation
guidelines 2000. Resuscitation council.
www.resus.org.uk/pages/pals.htm
4. PALS Provider Manual. American Academy
of Pediatrics. American heart association.
Editor Hazinski MF 2002; p127-147.
5. Brain AB .Discontinuation of Life Support.
In:Gary RS, William RA, Steven L.Eds.
Pediatric Emergency Medicine.2 nd Edn.
American College of Emergency Physcian
2002; p 49
6. Niermeyer S, Kattwinkel J, Van Rampts P,
Nadkarni V. International Guidelines for
Neonatal Resuscitation: An excerpt from the
Guidelines 2000 for Cardiopulmonary
Resuscitation and Emergency Cardiovascular
Care: International Consensus on Science,
Pediatrics, 2002; 106 , Pe 29.
7. Gupta P, Guidelines 2000 for neonatal
Resuscitation. Indian Pediatr 2000;37: 1229-
1233
8. Deorari AK. Newer guidelines for Neonatal
Resuscitation. How my Practice need to
change? Indian Pediatr 2001;38 :496-499.
9. PALS Provider Manual. American Academy
of Pediatrics. American heart association.Editor
Hazinski MF 2002; pp 337-358.
10. Udani RH, Parikh TB. Algorithm for Neonatal
Resuscitation. Pediatrics Today, 2004: 7: 359-
365.

EMERGENCY MEDICINE
ACUTE STRIDOR
* Rashmi Kapoor
Abstract: Stridor is a harsh vibratory sound of
variable pitch caused by partial obstruction of
the upper airway. Although stridor may result
from relatively benign causes, it may also be the
first sign of a serious and life threatening
disorder. As such, stridor demands immediate
attention and a thorough evaluation. This article
reviews the etiology and approach to
management of acute stridor in children.
Keywords: Acute stridor, Acute
laryngotracheobronchitis, Nebulized
epinephrine, Corticosteroids
Definition
Stridor is an auditory manifestation of
disordered respiratory function due to airflow
changes within the larynx and trachea. It is a sign
of upper airway obstruction and as such merits
investigation in every case. It is most often a
musical or sibilant sound, frequency of which
varies from low pitched and sonorous to high
pitched squeaking or whistling1.
Aerodynamic considerations
Stridor is due to turbulence of air within a
partially obstructed respiratory tract. In a small
child the larynx has a narrow opening and this
narrows down further by a number of factors.
* Pediatric Intensivist
Regency Hospital
Kanpur
27
2006; 8(1) : 27
1) Subglottis, the narrowest part of the larynx
has its mucosa loosely attached, so it can
easily become edematous.
2) Airflow through the flaccid, compressible
airway of a child, results in collapse of the
airway and temporary cessation of airflow.
3) Pascals principle and the resilience of the
cartilaginous support causes the airway to
spring open again and the cycle is repeated.
4) The fluttering vibrations thus created give
rise to audible sounds known as stridor.
Stridor can be categorized in relation to
the phase of the respiratory cycle during which
it occurs.
a) Inspiratory stridor: During inspiration, the
relatively mobile, poorly supported
structures of infantile supraglottis tend to
be drawn into the glottic aperture, and a low
pitched, harsh inspiratory stridor is
produced.
b) Biphasic stridor: The relatively rigid walls
of rima glottis, subglottis and trachea prevent
collapse of airway, but in severe obstruction
biphasic and to and fro stridor may result2.
Etiology of acute stridor in infants
and children
1) Infections
a) Acute laryngotracheobronchitis ALTB
(Classical croup)
b) Acute epiglottitis
c) Diphtheria
d) Bacterial tracheitis
Indian Journal of Practical Pediatrics 2006; 8(1) : 28

e) Retropharyngeal abscess Evaluation of acute stridor

f) Peritonsillar abscess Common conditions causing acute stridor
(ALTB, bacterial tracheitis, acute epiglottitis,
g) Ludwigs angina
diphtheria, FB upper airway and spasmodic
h) Any respiratory infection in a child with croup) and their characteristics are described in
laryngomalacia or congenital anomalies of Table 1.
laryngeal structures
A focussed history and clinical examination
2) Trauma will aid in diagnosis and initiating treatment.
a) Foreign body (FB) in glottis, subglottis Presence or absence of toxic appearance may be
or esophagus helpful (Fig 1). Hyperextention of neck may
indicate extrinsic compression at or above larynx
b) External trauma to neck
such as retropharyngeal abscess3. In common
c) Burns causing edema in upper airway conditions like ALTB the diagnosis is clinical.
d) Post extubation The priority is management of airway. A limited
number of investigations may be required in an
e) Post instrumentation emergency.
3) Others
Investigations in a child with stridor
a) Angioedema
Emergency investigations
b) Spasmodic croup
ALTB, the most common cause for acute
c) Tumors (eg. lymphoma in anterior stridor in children is diagnosed clinically.
mediastinum) Investigations, such as x-ray, bronchoscopy or
d) Hypocalcemic tetany blood counts and culture may be required in some
clinical situations. In acute obstruction airway

Acute stridor

Toxic Non-toxic

Epiglottitis Croup
Tracheitis Spasmodic croup
Severe croup Foreign body
Retropharyngeal abscess Post extubation
Angioneurotic edema
Fig 1. Clinical approach to acute stridor
28
 2006; 8(1) : 29

Table 1. Conditions causing acute stridor and their characteristics

Features ALTB Bacterial Acute Diphtheria FB Spasmodic
tracheitis epiglottitis airway croup
Age 6 mo - 6 yrs 1 mo - 6 yrs 2-6 yrs 1-10 years 1-4 yrs 6 mo - 3 yrs
Etiology Parainfl, infl, S.aureus, H.influenzae C.diphtheriae FB Viral,
adeno, RSV H.influenzae, aspiration allergy
Onset Insiduous, Insiduous, Abrupt Gradual Abrupt, Abrupt
preceding preceding history of
URI URI / ALTB FB
Fever May or may Present, toxic Present, Present, Absent Usually
not be present toxic toxic absent
Cough Barking cough,Brassy cough, Weak cough, Barking cough, Cough Metallic
voice hoarseness, hoarseness muffled voice,nasal twang, may or cough
posture worsening at drooling, pseudomembrane may not mostly at
other night dysphagia, over throat be night,
features leaning over present hoarseness
Stridor High pitched Moderate, Low pitched Can be severe Variable Moderate
severe
Radiology Subglottic Subglottic Enlarged Soft tissue Radio Subglottic
narrowing narrowing epiglottis swelling of opaque narrowing
(steeple sign) (subglottic air (thumb sign) neck FB
column
diffusely hazy
with multiple
soft tissue
irregularities)

should be stabilized before radiological
investigations. The child should always be
accompanied to the x-ray room by a person
competent in managing the airway.
X-rays
AP and lateral x-rays of head, neck and
upper thorax are required to rule out certain
conditions like FB in the airway and
retropharyngeal abscess. The lateral neck
radiograph must be taken with a good neck
extension and during inspiration so that
29
pharyngeal soft tissues are not mistaken for a
retropharyngeal mass. In retropharyngeal
abscess, the retropharyngeal space is increased
(greater than half the width of adjacent vertebral
body). In epiglottitis a rounded thickening of
epiglottis looks like an adult thumb, giving rise
to the so called thumb sign. In ALTB, the
symmetrical narrowing of subglottic air shadow
on anteroposterior view is called steeple sign.
AP and lateral views of thorax are useful in
detection of radio-opaque FB in lower airway,
which can at times move up to upper airway to
Indian Journal of Practical Pediatrics
cause intermittent stridor (migratory foreign
body).
Bronchoscopy
An emergency rigid bronchoscopy is
indicated both for diagnosis and endoscopic
removal when FB airway is suspected.
Blood investigations
A complete blood count may reveal
leucocytosis with shift to left in acute epilgottitis,
bacterial tracheitis and diphtheria. Cultures of
blood, airway secretions and epilgottic suface
(during intubation in epiglottitis) may be helpful
in identifiying the causative organisms.
Management
Management of acute stridor depends upon
the cause. It is a sign of narrowing of the air
passage and is an emergency. A child with stridor
should be immediately evaluated by someone
who is skilled in intubation.
General principles of management
1) Ensure adequacy of the airway. Allow the
child to maintain position of comfort
Maintain calm atmosphere. Administer O2
in a non-threatening manner by a non-
rebreathing mask with the child on mothers
lap.
2) If the airway is maintainable, and one is
suspecting laryngotracheobronchitis,
nebulized epinephrine and budesonide
should be considered. However, an
intubation may be considered any time.
3) A team approach with a pediatrician, an
otolaryngologist and if required, an
anesthesiologist is considered the optimal
approach in severe stridor.
4) An ENT specialist has to be involved in all
cases of suspected foreign body, trauma,
30
2006; 8(1) : 30
vocal cord palsy, tumors, congenital
structural malformations and in all cases
where tracheostomy is indicated.
5) If there is an impending respiratory failure,
oxygenation followed by immediate
nasotracheal intubation should be considered
6) If somehow intubation fails, an emergency
tracheostomy is advised
7) Antibiotics are required only when one
suspects bacterial tracheitis, epiglottitis,
diphtheria or when the cause is not
determined.
Croup (Acute laryngo-tracheobron-
chitis-ALTB)
Croup is one of the commonest respiratory
illnesses seen in acute pediatric setting and
accounts for 90% of stridor with fever. The term
croup refers to a heterogenous group of mainly
acute and infectious processes that are
characterized by a bark like or brassy cough and
may be associated with hoarseness, inspiratory
stridor and respiratory distress4. Viral agents
account for most cases of croup. Parainflenza
virus causes more than one third of cases5.
In approximately 60 to 95% of children, the
symptoms resolve in 2 to 5 days. More severe
cases may have, in addition, tachycardia,
tachypnea, nasal flaring, supraclavicular,
infraclavicular, intercostal, and sternal retraction,
continuous stridor and cyanosis. A number of
rating scales have been devised to assess the
severity of croup, the most popular being the
Westley croup score 6 (Table 2).
Management of ALTB (Fig 2)
General supportive measures
It is important to maintain a calm and
reassuring atmosphere for the parents and child.
Antipyretics should be given if the child is febrile.
Adequate hydration should be maintained.
 2006; 8(1) : 31

Table 2. Westley Croup Scoring The onset of action is 10- 30 minutes and
System the duration of action is approximately 2 hours,
at which point the patient returns to their baseline
Symptoms Score
severity (rebound phenomenon). Nebulized
Level of consciousness
epinephrine should be reserved for children with
Normal (including sleep) 0
moderate to severe croup and should be used with
Disoriented 5
caution in children who have tachycardia or
Cyanosis ventricular outlet obstruction. Patients should be
None 0 observed for at least 2 hours after treatment with
Cyanosis with agitation 4 epinephrine.
Cyanosis at rest 5
Stridor Corticosteroids
None 0 Corticosteroids are the mainstay of therapy
When agitated 1 for croup. Corticosteroids have potent
At rest 2 vasoconstrictive and anti-inflammatory
Air entry properties. They reduce the airway inflammation,
Normal 0 vascular permeability, and mucosal edema.
Decreased 1 Dexamethasone is associated with significant
Markedly decreased 2 clinical improvement at 12 hours and 24 hours.
Retractions A meta-analysis9 has shown that if these children
None 0 received steroids in the emergency room the rates
Mild 1 of endotracheal intubation is reduced and so is
Moderate 2 the hospital stay 10. Both systemic (oral or
Severe 3 intramuscular) dexamethasone and inhaled
budesonide have been found to be equally
< 4 mild, 4-6 moderate, > 6 severe
effective 11 . The traditional dose of
Randomized control trials evaluating mist therapy dexamethasone is 0.6 mg/kg single dose. A
in croup did not demonstrate any benefit in using reduced dose of 0.15 mg/kg is also found to be
a humidified atmosphere when compared with effective. Dose of nebulized budesonide is 2 mg.
room air7. Oxygen is given when required. In Indian market 0.5 mg and 1.0 mg respules of
budesonide are available.
Nebulized epinephrine
Nasotracheal intubation
Nebulized racemic epinephrine is In cases where airway is not maintainable
recommended for immediate treatment in or when there is worsening respiratory distress /
moderate to severe croup. Racemic epinephrine respiratory failure (lethargy, inability to maintain
is a 1:1 mixture of dextrorotatory(D) and respiratory efforts, PaO2 <70 on 100% oxygen
levorotatory (L) isomers of epinephrine. or PaCO2 >60) an urgent intubation is indicated.
Recommended dose is 0.5ml of a 2.25% of But this is an extremely rare situation in ALTB.
racemic epinephrine diluted in 2 to 3 ml of normal
saline solution. L-epinephrine (Adrenaline) The following points should be remembered
which is commonly available in India is equally before intubation.
effective. Recommended dose is 5 ml of 1:1,000 1. Intubation is a life saving procedure in sick
solution, diluted in 2 to 5 ml of saline solution8. children
31
Indian Journal of Practical Pediatrics 2006; 8(1) : 32

Croup (ALTB)
(Clinically diagnosed after excluding foreign body aspiration, epiglottitis, etc)

Allow the child to assume position of comfort

Minimise upsetting examination or procedures
Oxygen as necessary (in a non-threatening manner) to keep SaO2 > 93%

If stridor at rest and respiratory distress

Nebulized epinephrine (adrenaline) 1:1,000 0.5 ml/kg

Corticosteroid along with nebulised epinephrine in all
but the mildest of cases (Croup score > 4 as in table 2)
(Dexamethasone 0.6 mg/kg PO or IM
(or)
Prednisolone 1 mg/kg PO
(or)
Nebulised budesonide 2 mg)

Improvement No improvement

Consider need for intubation

Discharge home if:
No stridor at rest
Vitals are normal
Child has been observed
for 4 hours after adrenaline
(for rebound phenomenon)
Fig 2. Management of croup
Admit to Hospital if:
and arrange admission to ICU
Infant <1 year
if SaO2<93% or if there is
Severe croup on presentation
severe or worsening airway
Persistent stridor at rest
compromise (required in less
Child looks toxic
than 2% of cases)
Uncertain about diagnosis
Unable to satisfy discharge
criteria

2. It should be done by experts in this field, as Epiglottitis

severe hypoxic damage may occur in
inexperienced hands.
3. It helps in tracheobronchial toileting and
maintains a patent airway.
4. Nasotracheal intubation is preferred over
orotracheal as the orotracheal tube might get
displaced in a struggling child.
A smaller size tracheal tube (0.5-1.0 mm less
than what is calculated for age) may be needed.
32
This potentially lethal inflammatory
condition is characterized by an acute fulminating
course of high grade fever, sore throat, dyspnea
and rapidly progressing respiratory obstruction.
This condition is usually not seen in children in
our country, although quite a few adults are seen
with this condition (Fig 3).
Clinical features
The disease is characterized by sudden onset
of high fever, toxicity, agitation, stridor, dyspnea,

Fig 3. Acute epiglottitis
muffled voice, dysphagia and drooling. Neck may
be hyperextended in an attempt to maintain the
airway. The child may assume a tripod position
by sitting and leaning forward, with open mouth
and protruding tongue. A brief period of air
hunger may be followed by rapidly increasing
respiratory embarrassment and cyanosis and
coma may ensue.
Diagnosis
The diagnosis requires visualization of a
large cherry red swollen epiglottis on
laryngoscopy. But laryngoscopy must be done
expeditiously in a controlled environment by
an expert. Classic radiograph of a child shows a
thumb sign on lateral film of neck.
Management
This condition is a true otolaryngology
emergency. Prompt attention is mandatory and
management of airway is paramount because
airway obstruction is rapidly progressive. The
patient should be taken to an operating room or
intensive care unit for examination of the airway.
Airway is secured electively by intubation. Once
airway is secured, blood cultures are sent and the
patient is started on appropriate parenteral
antibiotics (ceftriaxone, cefotaxime or a
combination of ampicillin and sulbactum).
33
2006; 8(1) : 33
Humidified oxygen and aggressive respiratory
support is indicated. Epiglottitis resolves in a few
days with antibiotics and the patient is extubated.
Antibiotics are continued for 7 to 10 days.
Cricothyrotomy is carried out only when it
is not possible to secure the airway by intubation
by an expert.
Role of antibiotics in acute stridor
For laryngotracheobronchitis and viral
croup, no antibiotics are indicated.
For acute epiglottitis, a third generation
cephalosporin or a combination of ampicillin
and sulbactum may be used.
For bacterial tracheitis, a combination of
ampicillin and cloxacillin, and a third
generation cephalosporin may be started and
stepped down when culture reports are
available
For diphtheria, crystalline penicillin is
indicated, along with antidiphtheretic serum.
Foreign body aspiration
The diagnosis of an aspirated foreign object
is usually from the history. However in the case
of infants or the mentally handicapped, this may
not be available. Reliance is placed on clinical
signs, as discussed previously, and investigations
including chest radiology and diagnostic indirect
laryngoscopy or fiberoptic bronchoscopy.
Management
Management in the acute situation with a
choking individual entails the prompt and careful
use of the Heimlich procedure. Otherwise,
retrieval with a rigid bronchoscope is indicated.
Both main bronchi must be examined for multiple
obstructions.
If these measures fail and if there is an
impending complete upper airway obstruction,
laryngotomy (cricothyrotomy) is carried out
emergently.
Indian Journal of Practical Pediatrics
Points to remember
Stridor denotes upper airway obstruction
The commonest cause of acute stridor is
croup (ALTB)
In moderate to severe croup nebulised
epinephrine and corticosteroids are
effective in reducing the need for
hospitalisation and intubation
Aggressive intervention like intubation is
rarely needed in ALTB, but is always
required in conditions such as acute
epiglottitis and bacterial tracheitis
REFERENCES
1. Cinnamond MJ. Stridor. In: Scott-Browns
Otolaryngology. 6 th Edn, Ed, Evans JNG,
Butterworth & Co, Oxford, 1997; pp 6/21/1-
6/21/10.
2. Tunkel DE, Zalzal GH. Stridor in infants and
children: ambulatory evaluation and operative
diagnosis. Clin Pediatr 1992;31:48-55.
3. Handler SD. Stridor. In: Textbook of Pediatric
Emergency Medicine. Eds,Fleisher GR,
Ludwig S, Williams & Wilkins, Baltimore,
1993; pp 474-478.
4. Roosevelt GE. Acute inflammatory upper
airway obstruction. In: Nelson Textbook of
Pediatrics. Eds, Nelson WE, Behrman RE,
NEWS AND NOTES
SATELLITE WORKSHOP ON NEONATAL VENTILATION
Date : 6th to 9th April 2006
Contact :
Dr. Sanwar Agrawal
Ekta Institute of Child Health
Shantinagar, Raipur - 4923 001. Chhattisgarh.
Phone : 0771-2424426, 27.
Email : drsanwar@sancharnet.in and
drsanwar50@gmail.com
34
2006; 8(1) : 34
Kliegman RM, Jenson HB. WB Saunders,
Philadelphia, 2004; pp 1404-1409.
5. Leung AKC, Kellner JD. Viral Croup: a current
perspective. J Pediatr Health Care 2004;
18(6):297-301.
6. Westley CR, Cotton EK, Brooks JG. Nebulized
racemic epinephrine by IPPB for treatment of
croup: A double blind study. Am J Dis Child
1978; 132: 484-487.
7. Bourchier D, Dawson KP, Fergusson DM.
Humidification in viral croup: A controlled
trial. Aust Pediatr J 1984; 20: 289-291.
8. Waisman Y, Klein BL, Boenning DA, Young
GM, Chamberlain JM, ODonnell R.
Prospective randomized double blind study
comparing L-epinephrine and racemic
epinephrine aerosols in the treatment of
laryngotracheitis. Pediatrics 1992; 89: 302-306.
9. Kairys SW, Olmstead EM, OConnor GT.
Steroid treatment of laryngo tracheitis :A meta-
analysis of the evidence from randomized
trials. Pediatrics 1989; 83:683-693.
10. Tibblis J, Shann FA, Landau LI. Placebo
controlled trial of prednisolone in children
intubated for croup. Lancet 1992; 340:745-748.
11. Ausejo M, Saenez A, Pham B, Kellner JD,
Johnson DW. The effectiveness of
glucocorticoids in treating croup: meta-
analysis. Brit Med J 1999;319:585-600.
Venue : Chhattisgarh

EMERGENCY MEDICINE
STATUS EPILEPTICUS
* Santosh T Soans
** Arun MK
Abstract: Status Epilepticus (SE) is a life
threatening medical emergency associated with
substantial acute and chronic morbidity. For
practical purpose there have been proposals to
revise the definition. Any seizure type can present
as SE with generalized convulsive SE being the
most common manifestation. Directed history and
general physical and neurological examination
at presentation are sufficient for initial
management. Cardio-respiratory assessment and
supportive care is first priority. Aim of treatment
is to rapidly terminate seizures and prevent
irreversible neurological damage. A protocol for
immediate management is recommended and
practical aspects and recent advances in
management of SE are reviewed.
Key words: Status epilepticus, Benzodiazepines.
Status epilepticus (SE) is a life threatening
medical emergency. It is associated with
substantial acute and chronic morbidity which
may be prevented by appropriate and timely
therapy.
Traditionally SE is defined as continuous
seizure activity or repeated seizures with no
* Professor and Head,
Dept of Pediatrics,
AJ Institute Of Medical Sciences, Mangalore
** Assistant Professor,
Dept of Pediatrics, Kasturba Medical College,
Mangalore.
35
2006; 8(1) : 35
awakening between seizures lasting for 30
minutes or longer. However there have been
proposals to revise the definition. The 30 minutes
duration is based on animal experiments which
showed neuronal injury after 30 minutes of
seizure activity even while maintaining
respiration and circulation1. Seizure activity for
more than 5 minutes or two or more discrete
seizures with incomplete recovery of
consciousness can be considered as SE2. Some
authors consider 10 minutes seizure activity as
SE and there is no consensus at present.
For practical purpose, SE is a condition
which most likely will not terminate rapidly and
spontaneously and requires prompt intervention.
Any child who continues to convulse when
brought to the emergency should be treated as a
case of SE.
Classification
SE can be classified as generalized (tonic -
clonic, absence) or partial (simple, complex or
with secondary generalization)
Generalized tonic-clonic seizures are most
commonly associated with SE (Generalized
convulsive SE). Non-convulsive SE (NCSE) can
occur in absence or partial seizure disorder, in
comatose or pharmacologically sedated or
paralyzed patients. It can occur after prolonged
convulsive SE3.
Etiology
Falls into approximately four equal groups.
1. Febrile SE: seen particularly in children < 3
years
Indian Journal of Practical Pediatrics
2. Idiopathic SE: Seizures in children with no
CNS lesion. Most commonly it results after
sudden withdrawal of antiepileptic drugs
(AED) or children on irregular treatment. SE
may occur as initial presentation of
idiopathic epilepsy.
3. Remote symptomatic: Seizures occur in
association with long standing neurological
disorders like congenital malformation of
CNS, hypoxic-ischemic damage in newborn
period, post-meningitic sequelae or CNS
tumors.
4. Acute symptomatic: Seizures occurring due
to acute neurological or metabolic
conditions. Eg: meningitis, encephalitis,
head trauma, hypoglycemia
Systemic and metabolic effects of SE
During the initial phase of SE, consumption
of O2, glucose and energy substrates (ATP,
phosphocreatine) is significantly increased during
seizures. Cerebral blood flow increases. Massive
sympathetic discharge results in hyperglycemia,
hyperthermia, tachycardia, hypertension and
hyperkalemia.
During prolonged seizures the
compensatory mechanisms fail and hypoxia,
hypotension, hypoglycemia, hypercarbia and
decreased cerebral blood flow result (exhaustion
phase). This transitional period, beyond which
irreversible neuronal damage can occur varies
between 20 to 60 minutes in animals4. In children
however the precise transitional period is not
known hence the convulsions should be
controlled expeditiously.
The factors contributing to neuronal damage
are mismatch between cerebral blood flow and
metabolism, selfsustaining seizure activity and
calcium mediated excitotoxicity4.
Clinical features
The generalized tonic - clonic type (GCSE)
36
2006; 8(1) : 36
is most common and can be recognized easily.
Any type of seizure may present with SE.Tonic
phase may become less conspicuous as status
continues and evolves into continuous clonic
SE.Motor features often shift from side to
side,wax and wane in intensity, involve different
segments of body at different times .The motor
seizures may become less dramatic after
prolonged seizure and seizure evolves into a
Subtle generalized convulsive SE5.
These children with subtle SE appear
comatose with minor motor activity seen
clinically like unilateral clonus, eye deviation,
nystagmus and eyelid twitching. This may
remain undetected unless one lifts up the eyelids
to look for tonic deviation of eyes or nystagmus.
It is extremely important to be aware of this form
of SE as delay in diagnosis and treatment can
seriously affect the prognosis6.
Management (Fig 1)
At presentation, a directed history and
examination suffice. Confirm the diagnosis by
observing the ictal behavior and document
duration. Note the nature of onset of seizure
activity, history of fever or inter-current illness,
medications and compliance, head injury, drug
ingestion, toxic exposure and past history of
seizures. Perform brief general and neurological
examination, assess oxygenation and ventilation,
note cyanosis, peripheral perfusion, pupil size,
asymmetry on neurological examination,
petechiae, purpura or vesicles, deformity or soft
tissue injury of head.
Establish vascular access, send samples for
laboratory studies, and obtain blood glucose,
electrolytes, calcium and magnesium
(particularly in neonates), anticonvulsant drug
levels and toxicology screen if indicated.
Stabilization of patient
First priority is maintenance of vital
 2006; 8(1) : 37

Table 1. First line drugs for the treatment of status epilepticus

Drug Route Dosage and Time to Duration Adverse effect
administration peak effect of action & comments
Diazepam IV, 0.2- 0.3 mg/kg 1-5 min 20-30 min Respiratory
Rectal 0.5 mg/kg depression, sedation
Lorazepam IV 0.05-0.1 mg/kg 1-5 min 12-24 hrs Respiratory
to be diluted depression,sedation
Midazolam IV/IM 0.1-0.2 mg/kg, 1- 5 min 1- 5 hrs Respiratory
max dose 5 mg depression,sedation
Phenytoin IV 20 mg/kg slow 10-30 min 12-24 hrs Hypotension and
infusion, no faster arrhythmia if infused
than 1mg/kg/min; rapidly. Mix only
max: 50 mg/min with normal saline.
BP and cardiac
monitoring
Phenobarbital IV 20 mg/kg infused 10-20 min 24-72 hrs Cardio respiratory
at a rate of depression if infused
1.5-2.0 mg/kg/min; rapidly, sedation.
max: 100 mg/min Can be mixed in NS
or 5% dextrose
functions by establishment of airway, assessment immediately available intra-osseous access may
and support of ventilation if required, be used safely in children7.
administration of 100% O2 by non-rebreathing
Anticonvulstant drugs are adminitered in a
mask, gentle oral suction, monitoring oxygen
sequential fashion according to a standard
saturation (SpO2) and cardiac monitoring. Most
protocol (Fig 1). The timing, route and adequacy
children with convulsive SE will need active bag-
of dosages of drugs used are important. Sufficient
mask ventilation (BMV) often by two persons.
time must be allowed for the drug to act before
Nasogastric tube is introduced. Infuse dextrose
more of the same medication or another
(2 ml/kg of 25% solution) if hypoglycemia is
medication is used.
present or if dextrostix is not available for
immediate confirmation. Hyperglycemia has no The most commonly used drugs for the
adverse effect on outcome of SE. Once the initial treatment of SE are lorazepam, diazepam,
seizures are controlled with medication and phenytoin and phenobarbital. Other drugs which
breathing is normal, patient is placed in lateral are used to treat SE include midazolam,
position to prevent aspiration. fosphenytoin and valproic acid.
Anticonvulsants Benzodiazepines
The goals of anticonvulsant therapy in SE For immediate control of seizures
are to achieve cessation of clinical and electrical benzodiazepines (lorazepam, diazepam,
seizure activity and prevent its recurrence. Drugs midazolam) are used. Protocol for anticonvulsant
are given by IV route. If IV access is not administration begins with IV lorazepam or
37
Indian Journal of Practical Pediatrics
Table 2 Drugs for the treatment of refractory status epilepticus
Drug Loading dose
Midazolam 0.15 - 0.2 mg/kg
increase every 15min
by 1 mcg upto
20 mcg/kg/min
Thiopentone 2 - 8 mg/kg
diazepam (Fig 1). Their lipophilic property
permits rapid entry into brain and are effective
in most clinical types of SE.
Lorazepam: Lorazepam is less lipid soluble than
diazepam, but is almost as fast as diazepam in
controlling seizures (Table 1). Lorazepam is
equally or more effective than diazepam but
possibly with less respiratory depression8. Unlike
diazepam, lorazepam has a long antiepileptic
effect (12-24 hours), giving it an advantage over
diazepam as initial therapy for SE. If seizures
are controlled with lorazepam, it becomes less
imperative to use additional long-acting drugs
immediately, such as phenytoin or phenobarbital.
The dose of lorazepam is repeated (2nd dose) if
convulsion persists.
Diazepam: Diazepam is highly lipid soluble and
appears in the brain quickly (1 minute) with a
median time to terminate seizure of 2 minutes.
But it is quickly redistributed and anticonvulsant
effect is short-lived (20-30 minutes). Because
of its short antiepileptic effect, a longer-acting
agent such as phenytoin or phenobarbital is
required. If seizures persist, the dose of diazepam
is repeated.
Rectal diazepam has a rapid onset of action
and is valuable in pre-hospital setting or when
IV access cannot be obtained. IV preparation is
administered rectally.
38
2006; 8(1) : 38
Maintenance Comment
1-2 mcg/ kg / min Maintain infusion for
48 hrs before
tapering.
1-10 mg/kg/hr Hypotension frequent,
inotrope support
often needed
Midazolam: Midazolam is a water soluble
benzodiazepine which can be administered by IV,
IM, intranasal, buccal or rectal routes. It is the
only agent which can be safely and effectively
used by IM route9. It is administered IM in SE
when IV/IO access is not available. Midazolam
is extremely potent, rapidly absorbed and non-
irritant following IM injection. Short duration of
action requires that it be given by frequent boluses
or continuous infusion.
Midazolam by buccal and nasal route is safe
and effective. Recent multicentric RCT has
shown buccal midazolam to be more effective
than rectal diazepam and incidence of respiratory
depression was same in both groups9. Other
studies have proved buccal midazolam as
alternative to rectal diazepam. Nasal midazolam
is also useful for home and hospital treatment of
acute seizures in children10.
Adverse effects of benzodiazepines include
respiratory depression, apnea and hypotension.
The pre-hospital use of benzodiazepines should
be taken into account before repeating dose.
Although many guidelines do not consider pre-
hospital dose, frequency of respiratory depression
is more if that dose is not counted.
Phenytoin and fosphenytoin
If SE persists after second dose
benzodiazepine, a long-acting drug is used.
 2006; 8(1) : 39

Airway - Open airway; Head tilt and chin lift

- Jaw thrust and cervical spine stabilization if trauma is suspected
- Oropharyngeal suction; NGTube decompression, Insert airway adjunct
Breathing - Spontaneous breathing: oxygen through NRM 10 litres/min
- Apneic : BVM with 100% O2 10 litres/min
Circulation - IV access; Correct shock, if identified, with 20 ml/kg NS bolus; if no shock,
maintenance fluids
- Correct hypoglycemia with 25% Dextrose 2ml/kg
- If IV access not possible, IO access

0 minute Inj. lorazepam 0.05-0.1 mg/kg IV or IO; * If response (seizures

max.4.0 mg/dose at 2.0 mg/minute controlled at any step) and
(or) ABC stablised
Inj.diazepam 0.2 mg/kg IV or IO; max.10 mg/dose Place child in recovery
at 5 mg/min; rectal 0.5 mg/kg (if no IV/IO access) position
(or) Shift to ward under
Inj. midazolam 0.2 mg/kg IM (if no IV/IO access) supervision
No response * Evaluate cause

10 minutes Repeat Inj. lorazepam or diazepam same dose IV/IO (2nd dose)
No response
20 minutes Inj. phenytoin 20 mg/kg IV loading dose slowly over 20 minutes
(1 mg/kg/minute); mix only with normal saline
(or)
Inj. fosphenytoin 30 mg/kg IV loading dose over 10 minutes
(3 mg/kg/minute); 1.5 mg fosphenytoin = 1 mg phenytoin equivalent
No response
40 minutes Inj. phenytoin 10 mg/kg over 10 minutes (2nd dose)
(or)
Inj. fosphenytoin 15 mg/kg over 5 minutes (2nd dose)
No response

60 minutes Plan intubation

Inj phenobarbitone 20 mg/kg at 2 mg/kg/ min over 10 minutes
in 1-2 ml/kg of NS or 5% GDW
No response
Refractory Transfer to Intensive Care Unit
SE Commence EEG monitoring if available
Midazolam 0.15-0.2 mg/kg bolus followed by
infusion at 1 mcg/kg/min; increase every
15 minutes until response; max 20 mcg/kg/min

Fig 1. Management of convulsive status epilepticus / subtle / non-convulsive status epilepticus

in children. Modified from Pediatric Emergency Course Manual 2006
39
Indian Journal of Practical Pediatrics
Phenytoin (PHT) is an effective long acting agent
and is preferred due to its relative lack of sedative
side effects. It is administered at a rate of
20mg/kg, infused slowly at a rate of 1mg/kg/min
diluted in normal saline only. Side effects are
hypotension and arrhythmias and constant
cardiac monitoring is required during infusion.
Recently fosphenytoin (FPHT) is available
as a treatment option. Major reported advantage
over PHT is a more favorable vehicle that does
not contain propylene glycol and has a pH of
8.6-9 as opposed to pH 11-12 for PHT. Hence
the risk of tissue necrosis with extravasation is
less for FPHT. FPHT can be administered in
dextrose containing IV solutions also, at a more
rapid rate (Infusion rate 3 times that of phenytion)
and can be administered IM also11. Both drugs
are equally effective in stopping SE and selection
between them should be based on ease of
administration, side effects and cost issues. An
additional dose (50% of fist dose) of PHT or
FPHT is repeated if SE persists.
Phenobarbital (PB)
Phenobarbital is a potent long-acting
anticonvulsant. It is a depressant drug and can
lead to sedation and respiratory depression,
especially when administered after a
benzodiazepine. Hence, it is usually considered
second to PHT as a long-acting agent and usually
recommended when benzodiazepine and PHT are
ineffective. During or following a loading dose,
assisted ventilation is usually required due to
respiratory depression. It is the drug of choice
for neonatal seizures.
Refractory status epilepticus (RSE)
If SE persists for longer than 60 minutes
even after administration of a benzodiazepine,
PHT or PB it is called refractory status epilepticus
and it may become life threatening. Options at
this point are continuous infusion with diazepam
40
2006; 8(1) : 40
or midazolam, propofol, thiopentone or
pentobarbital or general anaesthesia with
halothane or isoflurane and neuromuscular
blockade. Comparative study of midazolam
against thiopentone has shown that midazolam
is as effective as thiopentone with fewer
complications12. A meta-analysis showed that
mortality rate was lower in midazolam group than
with barbiturates or isoflurane13 and the need for
invasive monitoring and intubation is less
frequent.
Midazolam infusion
In many centers midazolam bolus followed
by continuous infusion is increasingly used for
treatment of refractory SE (Table 2). The rate of
infusion at which seizure control is achieved is
maintained for 48 hours and subsequently the
infusion rate is gradually decreased by
1 mcg/kg/min every 2 hours.
Thiopentone
This is a short-acting barbiturate with a rapid
onset of action. A bolus of 2-8 mg/kg followed
by an infusion of 1-10 mg/kg/hour is used.
Though it is effective in terminating seizures and
inducing a burst suppression pattern on EEG, it
is a potent respiratory and myocardial depressant.
These children are usually intubated and
mechanically ventilated before starting treatment.
They also need invasive monitoring and inotropic
support.
Increased dose phenobarbital
Repeated bolus doses of PB, 10-20 mg/kg
every 30 minutes (Table 2) was effective in
controlling ongoing seizures (max 120 mg/kg/
day) with less morbidity and need for intubation
in RSE.
Valproic acid
Intravenous preparation of valproic
acid is available. In RSE, a loading dose of

20-40 mg/kg is administered over 1-5 minutes
(diluted 1:1 in NS or 5% GDW) and repeated
after 10-15 mins if necessary. This is followed
by an IV infusion of 5 mg/kg/hour. This is found
to be effective in some studies. Valproic acid
can also be administered rectally in a dose of
20 mg/kg diluted 1:1 with sterile water.
Supportive therapy
During the treatment of SE and RSE periodic
assessment of cardio respiratory functions and
supportive care are extremely important.
Hypotension is treated with bolus IV fluids and
inotropic support if needed. Maintain hydration
and correct dyselectrolytemia.Defer lumbar
puncture in unstable patients, but never delay
antibiotic or antiviral treatment on clinical
suspicion. Hyperpyrexia aggravates mismatch of
cerebral metabolic requirement and substrate
delivery, hence treat aggressively with
antipyretics and external cooling. At every step
consider intubation and ventilatory support, as
children with SE are continuously at risk for
respiratory failure and inadequate ventilation and
many of the drugs used to control seizures are
respiratory depressants. Intubation may be
difficult with active seizures. Hence rapid
sequence intubation should be done using drugs.
Acidosis develops in all children and often
resolves rapidly with termination of SE. Hence
ABG is not routinely indicated. Also metabolic
acidosis does not dictate intubation and does not
require bicarbonate 14. As long as patient is
oxygenated well we can wait for resolution of
acidosis without further ABG.
For further evaluation of the child, CT scan
is required in focal seizures or focal deficits, with
history of trauma / bleeding disorder. Urgent EEG
is recommended if non-convulsive status
epilepticus (NCSE) is suspected.
After termination of SE, neurological signs
like pupillary changes, abnormal tone, positive
41
2006; 8(1) : 41
Babinski reflex, posturing and clonus are
common. Post-ictal confusion usually resolves
over several hours. If child does not begin to
respond to painful stimulus within 20-30 min
after GCSE stops, rule out hypoglycemia, CNS
infection, drug toxicity and non-convulsive SE.
Upto 20% of children with SE have non
convulsive SE after GCSE and it is common in
infants less than 2 months 3. Bed side EEG
monitoring, if available, will confirm NCSE.
After control of seizures and stabilization,
identify precipitating factors, modify drug
treatment and start maintenance therapy.
Prognosis of SE is related to the etiology of SE
and duration of seizures.
Points to remember
1. A directed history, physical examination
and neurological examination are
sufficient in emergency room. Obtain only
relevant investigations.
2. Cardiorespiratory assessment and
supportive care is first priority.
3. Use appropriate drugs with proper dosage
and route according to accepted protocol.
References
1. Nevander G, Ingvar M, Auer R, Siesjo BK.
Status epilepticus in well oxygenated rats
causes neuronal necrosis. Ann Neurol 1985;
18 (3): 281-290.
2. Levenstein DH, Bleck T, Macdonald RL. Its
time to revise the definition of SE. Epilepsia
1999; 40(1): 120-122.
3. Towne AR, Waterhouse EJ, Boggs J G, et al.
Prevalence of non-convulsive SE in comatose
patients. Neurology 2000; 54(2): 340-345.
4. Wasterlain LG, Fujikawa DG, Denixl, et al.
Pathophysiological mechanisms of brain
damage from SE. Epilepsia 1993; 34: (Suppl
1) S37-S53.
Indian Journal of Practical Pediatrics 2006; 8(1) : 42

5. Aicardi J. Status epilepticus. In: Epilepsy in
children. 2nd edn, Ed, Wallace SJ, Raven press,
New York, 1986; pp 240-259.
6. Khurana DS. Treatment of status epilepticus.
Indian J Pediatr 2000; 67: S80-S87.
7. Lathers CM, Jim KF, Spivey WH. A
comparison of Intra osseous and IV routes of
administration of AED. Epilepsia 1989; 30:
472-479.
8. Appleton R, Choonara I, Martland T, Phillips
P, Scott R, Whitehouse W. The status
epilepticus working party. The Treatment of
convulsive status epilepticus in children. Arch
Dis Child 2000; 83: 415-419.
9. McIntyre J, Robertson S, Norris E, et al. Safety
and efficacy of buccal midazolam Vs rectal
diazepam for emergency treatment of seizures
in children. Lancet 2005; 22: 366(948): 205-
210
10. Jeannet PY, Roulet E, Maeder-Ingvar M. Home
and hospital treatment of acute seizures in
children with nasal midazolam. Eur J Pediatr
Neurol 1999; 3(2):73-77.
11. Moron LD. Clinical experience with
Fosphenytoin in children. J Child Neurol 1998;
13: S19-S22.
12. Lohr AJS, Werneck LC. Comparative non-
randomized study with midazolam Vs
thiopental in children with refractory SE.
Arquivos de neuro psiquiatria 2000; 58: 282-
287.
13. Gilbert DL, Gartside PS, Glauser TA. Efficacy
and mortality in treatment of refractory SE
children: A Meta analysis. J Child Neurol 1999;
14: 602-609.
14. Treatment of SE. Recommendations of epilepsy
foundation of Americas working group on SE.
JAMA 1993; 270 (7): 854-859.

NEWS AND NOTES

DERMPED 2006
2 National Congress of Pediatric Dermatology
nd

Date : 10th and 11th June 2006 Venue : Savera Hotel, Chennai
Highlights of the Conference
* Panel discussions
* Interactive sessions
* Symposia
* Free papers
Registration tariff
Category Before 31st March Before 30th April Spot
Delegates Rs. 1,300/- Rs. 1,500/- Rs. 1,800/-
PG Rs. 1,100/- Rs. 1,300/- Rs. 1,800/-
Co-delegates Rs. 1,000/- Rs. 12,50/- Rs. 1,500/-
Demand draft in favour of DERMPED 2006 payable at Chennai.
Dr. Jayakar Thomas Dr. V. Anandan Dr. C. Vijayabhaskar Dr. R. Madhu
Organising Chairman Organising Secretaries Hon. Treasurer
For further details contact : The Organising Secretary, DERMPED 2006, IJPP, Halls Towers,
F Block, Ground Floor, 56, Halls Road, Egmore, Chennai 600 008.
Phone : 044-28190032. Email : dermped2006@yahoo.co.in
42

EMERGENCY MEDICINE
RESUSCITATION IN TRAUMA
* Ramakrishnan TV
Abstract: The major consideration in dealing
with injured children is the effect injury may have
on subsequent growth, development and the
childs quality of life for years to come. Rapid
cardiopulmonary assessment and prompt
establishment of effective ventilation,
oxygenation and perfusion are the keys to
successful treatment of children with any life
threatening injury. The primary survey is
designed to identify and treat life-threatening
injuries. The secondary survey is designed for
detailed head to toe examination and history
along with definitive care. Diagnostic adjuncts
like Focused Assessment Sonography in Trauma
(FAST), Diagnostic Peritoneal Lavage (DPL),CT
scan and X-rays are done. Anatomic and
physiologic variations in children produce
pitfalls in management.
Key words: Pediatric trauma, Triage,
Resuscitation
Trauma continues to be the most common
cause of deaths and disability in childhood.
Motor vehicle associated injuries are the most
common cause of deaths in children of all ages,
whether the child is an occupant, a pedestrian, or
a cyclist. This is followed by drowning,
housefires, homicides and falls. The major
consideration in dealing with injured children is
the effect that injury may have on subsequent
* Professor of Anesthesiology,
Department of Accident & Emergency
Medicine, Sri Ramachandra Medical College
& Research Institute (DU), Chennai.
43
2006; 8(1) : 43
growth, development and the childs quality of
life for years to come.
Initial approach to the pediatric
trauma victim
Triage
Triage is a process of patient assessment,
prioritization of treatment and selection of
appropriate treatment location1,2,3,4.
Rapid cardiopulmonary assessment and
prompt establishment of effective ventilation,
oxygenation and perfusion are the keys to
successful treatment of children with any life
threatening injury. In pediatric trauma victims,
abnormalities of airway and breathing are far
more common than abnormalities of circulation.
Circulatory compromise is more lethal, especially
when brain injury is present.
The primary survey is designed to identify
and treat life-threatening injuries unique to
trauma victims. Rapid cardiopulmonary
assessment and support of cardiopulmonary
function are fundamental aspects of the primary
survey. Simultaneously, a rapid patient
examination to detect life threatening injuries of
chest, abdomen or head that may interfere with
successful resuscitation are identified and treated
immediately.
The secondary survey is designed for
detailed head - to - toe examination and history
along with definitive care.
Primary survey ABCDE approach
Airway and cervical spine stabilization
Breathing / ventilation
Indian Journal of Practical Pediatrics
Circulation and control of hemorrhage
Disability evaluate neurologic condition
Exposure environmental control
Airway and cervical spine stabilization
Airway control involves use of a jaw thrust
with cervical spine stabilization. The head tilt
and chin lift is contraindicated in trauma patients
because it may worsen existing spinal cord
injury1,2,3,5,6. Children may sustain spinal cord
injury without radiographic abnormalities
(SCIWORA). So if spinal cord injury is
suspected based on history or results of the
neurologic examination, normal spine x-ray does
not exclude significant spinal cord injury. The
cervical spine should be manually stabilised and
later immobilised with a semi rigid collar and
head immobilizer which is maintained throughout
the resuscitation.
The prominent occiput of the child
frequently causes slight flexion of the neck when
child is placed on a flat surface. To maintain a
neutral position, place a folded cloth under the
childs torso (to elevate it) or use a back board
that contains a well for the head.
Suctioning with a rigid, large bore device
should be used to clear the blood and mucus,
which are common causes of obstruction of the
childs narrow airway. Large foreign bodies can
be removed with the use of Magills forceps. If
the child is unconscious with an adequate
respiratory effort, an oropharyngeal airway can
be used to maintain airway patency until tracheal
intubation is done. Orotracheal intubation with
simultaneous cervical spine immobilization must
always be done by trained persons.
Nasotracheal intubation should not be
performed in children under 9 years of age.
Nasotracheal intubation requires blind passage
around a relatively acute angle in the nasopharynx
towards the anterosuperiorly located glottis
making intubation dificult. The potential for
44
2006; 8(1) : 44
penetrating the childs cranial vault or damaging
the more prominent nasopharyngeal soft tissue
structures resulting in hemorrhage must be kept
in mind.
Indication for intubation
Child with severe head injury who cannot
maintain the airway
Child with signs of respiratory failure
Child with significant hypovolemia
Rapid sequence intubation (RSI)
The sequence of pediatric RSI is
preparation, preoxygenation, premedication,
sedation and paralysis, placement of tube and
post-intubation management2,3,5,6,7. RSI is done
after pre-oxygenation. Atropine sulfate 0.02mg/
kg with a minimal dose of 0.1mg and maximal
dose of 1mg is given at least 1 to 2 minutes before
intubation to reduce the vagal response to
endotracheal intubation. The child is sedated with
midazolam 0.3mg/kg in normotensive and
etomidate 0.3mg/kg in a hypotensive child or
midazolam 0.1mg/kg. After sedation, cricoid
pressure is applied to prevent regurgitation of the
gastric contents thereby avoiding aspiration. The
child is paralyzed with succinylcholine chloride
2mg/kg. In the event of a failed intubation, the
child must be ventilated with bag-valve-mask
device until a definitive airway is secured. When
airway access and control cannot be
accomplished by bag-valve-mask or orotracheal
intubation, alternative airway techniques like the
laryngeal mask airway are preferred.
Cricothyrotomy is not recommended in children
less than 10 years as the cricothyroid membrane
is not readily palpable.
Breathing / Ventilation
Assess for the adequacy of chest rise and
respiratory rate. Provide bag-mask ventilation if
it is found to be inadequate. Bag-mask ventilation
can lead to gastric distention, which can be
relieved, by nasogastric or orogastric tube after
 2006; 8(1) : 45

Table 1. Classification of hemorrhage and shock in pediatric trauma patients

System Mild hemorrhage, Moderate hemorrhage, Severe hemorrhage,
compensated shock, decompensated shock, cardiopulmonary failure,
simple hypovolemia marked hypovolemia profound hypovolemia
(<30% blood volume (30%-45% blood (>45% blood volume
loss) volume loss) loss)
Cardiovascular Mild tachycardia, weak Moderate tachycardia, Severe tachycardia,
peripheral pulses, strong thready peripheral pulses, Absent peripheral pulses,
central pulses, weak central pulses, thready central pulses,
low-normal blood frank hypotension profound hypotension
pressure (SBP < 70 mm Hg + (SBP < 50 mm Hg)
(SBP >70mm Hg + [2 x age in years])
[2 x age in years])
Mild acidosis Moderate acidosis Severe acidosis
Respiratory Mild tachypnea Moderate tachypnea Severe tachypnea
Neurologic Irritable, confused Agitated, lethargic Obtunded, comatose
Skin Cool extremities, mottling,Cool extremities, pallor Cold extremities, cyanosis,
poor capillary refill delayed capillary refill prolonged capillary refill
(>2 seconds) (>3 seconds) (>5 seconds)
Urine output Mild oliguria, increased Marked oliguria, increased Anuria
specific gravity blood urea nitrogen
SBP - Systolic Blood Pressure

securing the airway. Routine hyperventilation is Circulation and hemorrhage control

not recommended because it may increase
intrathoracic pressure, adversely affecting venous
return and cardiac output. Hyperventilation may
also compromise cerebral perfusion in areas of
the brain that is still responsive to changes in
PCO2. Hyperventilation is useful only when there
is a sign of transtentorial herniation8,9,10. As the
childs chest wall is very compliant, there can be
major internal thoracic injuries without any
external wound or rib fractures11,12. If ventilation
is impaired look for tension pneumothorax, open
pneumothorax, hemothorax or flail chest. Needle
and tube thoracostomy are the treatment options
available. Operative thoracotomy is considered
in hemothorax if the initial drainage is greater
than 15ml/kg or the chest tube output exceeds 4
ml/kg/hr.
45
Circulatory support in the trauma victim
includes rapid and frequent assessment of
systemic perfusion. The increased physiologic
reserve of the child allows maintenance of most
vital signs in the normal range, even in the
presence of shock (Table 1). Tachycardia and
poor skin perfusion is often the only key to early
recognition of hypovolemia. A 30% decrease in
circulating blood volume is required to manifest
a change in the childs vital signs2,3. Other subtle
signs of blood loss in the child include loss of
peripheral pulses,narrowing of the pulse pressure
to less than 20 mm Hg, skin mottling, cool
extremities and a decrease in the level of
consciousness.Urine output should be monitored
closely using a urinary catheter. Hypotension in
the child represents a state of decompensated
Indian Journal of Practical Pediatrics 2006; 8(1) : 46

Table 2. Pediatric vitals (Normal)

Age Group Heart Rate Systolic Blood Respiratory Urine output
(in Years) (beats/min) Pressure Rate (ml/kg/hr)
(mm Hg) (breaths / min)
Infant <1 <160 >60 <60 2.0
Toddler 1-<3 <150 >70 <40 1.5
Preschool 3-5 <140 >75 <35 1.0
School age 6-12 <120 >80 <30 1.0
Adolescent >12 <100 >90 <30 0.5

shock and indicates severe blood loss of greater
than 45% of the circulating blood volume
(Table 2).
Venous access
Securing an intravenous access in a
hypovolemic child younger than 6 years is a
challenge. Make upto two attempts at securing a
peripheral venous access. If unsuccessful prepare
for securing an intraosseous access2,3,6.This route
is safe, efficacious and requires less time than a
venous cut down. The preferred site for
intraosseous route is the proximal tibia 1 cm
below the level of tibial tuberosity in the medial
aspect. The femoral vein is the acceptable site
for central venous cannulation than the other sites
especially in a setting of hypovolemic shock.
Venous cut down is preferably done in saphenous
vein in the ankle.
Fluid resuscitation
The goal in fluid resuscitation in the child is
to rapidly replace the circulating volume. A
childs blood volume can be estimated at 80ml/
kg. When shock is suspected, a fluid bolus of
20ml/kg isotonic crystalloid (eg: Normal saline
or lactated Ringers solution) to a maximum of
60ml/kg can be given. The 3-for-1 rule i.e., (for
1ml loss of blood 3ml of crystalloid is given)
applies to the pediatric patient as well as the adult
patient. After the third bolus of 20ml/kg,
consideration should be given to the use of
46
packed red blood cells 10 ml/kg or whole blood
20 ml/kg every 20 to 30 minutes. Although type
specific cross-matched blood is preferable, type
O blood can be given in urgent circumstances.
O negative blood is reserved for girls to prevent
Rh - iso immunization.
Protocol for intravenous access / emergency
drugs
1. First 1.5min
Peripheral IV catheter, two sites
2. 1.5 5min
a. If emergency drugs are required and
there is no venous access, give drugs via
endotracheal tube if intubated (including
epinephrine, atropine, lidocaine)
b. If not intubated: Intraosseous - one site,
continue attempt at peripheral IV - another
site
3. Longer than 5 min - Venous access in the
order of preference
a. Femoral vein
b. External / internal jugular
c. Subclavian vein
d. Saphenous vein cutdown
Control of external hemorrhage is by direct
manual compression. Open or closed long bone
or pelvic fractures may bleed extensively. The
injured limb must be immobilized using
 2006; 8(1) : 47

Table 3. Glasgow Coma scale in adults, infants and children

Response Adult Child Infant Coded
Value
Eye opening Spontaneous Spontaneous Spontaneous 4
To speech To speech To speech 3
To pain To pain To pain 2
None None None 1
Best verbal Oriented Oriented, appropriate Coos and babbles 5
response Confused Confused Irritable, cries 4
Inappropriate words Inappropriate words Cries in response to pain 3
Incomprehensible Incomprehensible words Moans in response to 2
sounds or nonspecific sounds pain
None None None 1
Best motor Obeys Obeys commands Moves spontaneously 6
response and purposefully
Localizes Localizes painful Withdraws in response 5
stimulus to touch
Withdraws Withdraws in response Withdraws in response 4
to pain to pain
Abnormal flexion Flexion in response to Decorticate posturing 3
pain (abnormal flexion) in
response to pain
Extensor response Extension in response Decerebrate posturing 2
to pain (abnormal extension) in
response to pain
None None None 1

appropriate splints after reduction. If the systemic
perfusion is inadequate in spite of volume
replacement, internal haemorrhage is suspected
and early administration of blood products is
necessary13,14.
Diagnostic adjuncts
- Focused Assessment Sonography in Trauma
(FAST)15,16
- Diagnostic Peritoneal Lavage (DPL) can
detect intrabdominal bleeding in a
hypotensive child.
- X-rays to identify life threatening thoracic,
spinal and pelvic injuries15,17,18.
Disability
Disability involves rapid assessment of
critical neurologic functions. The AVPU
pediatric response scale is less specific but
quick to perform. Glasgow coma scale is a
standard instrument, familiar to health providers
(Table 3).
Exposure

- Computed Tomography (CT) in Exposure involves a head to toe physical

hemodynamically stable patients. examination to evaluate for external signs of
47
Indian Journal of Practical Pediatrics 2006; 8(1) : 48

Table 4. Pediatric Trauma Score (PTS)

Components +2 +1 -1
1. Weight > 20kg 10-20 kg < 10 kg
2. Airway patency Normal Maintainable Unmaintainable
Oropharyngeal airway Intubated
3. Systolic blood pressure > 90 mmHg 50-90 mmHg < 50 mmHg
4. CNS Status Awake Obtunded / loss of Coma/ decerebrate
consciousness
5. Open wound None Minor Major / penetrating
6. Skeletal injury None Closed fracture Open/multiple
fractures
A PTS score of 8 indicates potentially major or severe trauma.
The pediatric trauma score predicts potential for death and severe disability2,3

injury due to blunt or penetrating force. Maintain
the child in a neutral thermal environment to
prevent hypothermia or hyperthermia.
The secondary survey
The secondary survey is designed to assess
the patient and treat additional injury not found
on primary survey and also to obtain a more
complete and detailed history remembered by the
mnemonic AMPLE2,3.
A Allergies
M Medications: long and short term, last dose
and time of recent medications
P Past medical history: significant underlying
problems, past surgeries, immunization
status (tetanus)
L Last meal: time and nature of last drink or
food
E Events leading to current injury, key events,
mechanism of injury, hazards at scene,
treatment to date, estimated time or arrival
A pediatric trauma score is compiled on the
basis of physical findings in primary and
secondary survey (Table 4). On the basis of the
nature of injury and physical findings
management decisions are arrived at (Table 5).

Table 5.Classification and disposition of trauma by severity6

Category History Vital Local Findings Lab Probable
Signs Radiographic Disposition
Studies
Mild Minimal force Normal Superficial only Few Discharge
Moderate Significant force Normal Suspicious for Intermediate Evaluate
internal injury
Severe Critical force Abnormal Indicative of Many Immediate
internal injury therapy; admit

48

Pitfalls in pediatric trauma2,3,6,11
Anatomic and physiologic variations in
children can cause difficulties in
management.
Small size endotracheal tube gets easily
obstructed, dislodged and hence requires
frequent reassessment.
Early phases of blood loss is well
compensated in children.
Anticipation, frequent re-evaluation and
preparation for immediate surgical
interventions are needed especially in
abdominal injuries as the incidence of missed
injuries are more.
Orthopedic injuries in children produce only
subtle symptoms and are difficult to
diagnose.
Points to remember
Anatomic and physiologic variations in
children produce pitfalls in management
Early phases of blood loss is well
compensated in children.The 3-for-1 rule
(for 1ml loss of blood 3ml of crystalloid is
given) applies to the pediatric patients also
Normal spine x-rays do not exclude
significant spinal cord injuries in pediatrics
References
1. Cantor RM. Pediatric trauma. In: Rosens
Emergency Medicine Concepts and Clinical
Practice. 6 th Edn. Ed, Marx JA, Mosby,
Philadelphia, 2006; pp 328-343.
2. Advanced Trauma Life Support for Doctors
2004. American College of Surgeons. 7th Ed,
2004; pp 243-260.
3. Pediatric Advanced Life Support provider
manual 2002 -American Heart Association/
American Academy of Pediatrics 2002; pp 253-
281.
4. Salk ED, Schriger DL, Hubbell KA, et al. Effect
of visual cues, vital signs, and protocols on
49
2006; 8(1) : 49
triage: a prospective randomized crossover trial.
Ann Emerg Med 1998; 32: 655-664.
5. Palchak MJ, Holmes JF, Vance CW, et al. A
decision rule for identifying children at low risk
for brain injuries after blunt head trauma. Ann
Emerg Med 2003; 42: 492-506.
6. Ludwig S. Resuscitation. In: Textbook of
Pediatric Emergency Medicine. 4th Edn. Eds,
Fleisher GR, Ludwig S, Lippincott Williams
& Wilkins, Philadelphia, 2000; pp 15-21.
7. Hauda II WE. Pediatric trauma. In: Emergency
Medicine. 6 th Edn. International edn, Ed
Tintinalli JE, McGraw Hill, USA, 2004; 1542-
1548.
8. Stocchetti N. Hyperventilation in head injury:
a review. Chest 2005; 127(5): 1812-1827.
9. Feldman Z, Kanter MJ, Robertson CS, et al.
Effect of head elevation on intracranial
pressure, cerebral perfusion pressure, and
cerebral blood flow in head injured. J Neuro
Surg 1992; 76: 207.
10. Fortune JB, Feustel PJ, Graca L, et al. Effect
of hyperventilation, mannitol, and
ventriculostomy drainage on cerebral blood
flow after head injury. J Trauma 1995; 39:1091.
11. Sanchez JI , Paidas CN. Childhood trauma:
Now and in the new millennium. Surg Clin
North Am 1999; 79: 1503-1535.
12. Schinco M, Tepas JJ. Beyond the golden hour:
avoiding the pitfalls from resuscitation to
critical care. Surg Clin North Am 2002; 82:
325-332.
13. Adelson PD. Guidelines for the acute medical
management of severe traumatic brain injury
in infants, children, and adolescents. Chapter
3. Prehospital airway management - Pediatr Crit
Care Med 2003; 4(3 Suppl): S9-S11.
14. Warner BW. Whats new in pediatric surgery.
J Am Coll Surg 2004; 199(2): 273-285.
15. Keller MS. The utility of routine trauma
laboratories in pediatric trauma resuscitations.
Am J Surg 2004; 188(6): 671-678.
16. Akgr FM. Prospective study investigating
routine usage of ultrasonography as the initial
diagnostic modality for the evaluation of
Indian Journal of Practical Pediatrics 2006; 8(1) : 50

children sustaining blunt abdominal trauma.
J Trauma 1997; 42(4): 626-628.
17. Rees MJ, Aickin R, Kolbe A, et al, The
screening pelvic radiograph in pediatric trauma.
Pediatr Radiol 2001; 31: 497-500.
18. Gittelman MA,Gonzalez-del-Rey J, Brody AS.
Clinical predictors for the selective use of chest
radiographs in pediatric blunt trauma
evaluations. J Trauma 2003; 55: 670-676.

NEWS AND NOTES

IAP Pediatric Drug Formulary CDRom and Book
Publication of Indian Academy of Pediatrics
Presidential Action Plan 2004
Project of IAP CMEG
The IAP Pediatric Drug Formulary CDRom and Book which was part of IAP Presidential Action Plan 2004 and a
Project of IAP CMEG, was released at the last National Conference at Kolkata. It is already being used by around
2000 pediatricians all over India and has been accepted as an official publication of IAP and finds pride of place on
the cover of Academy Today and the website of IAP www.iapindia.org with link to its own website
www.iapdrugformulary.com. This IAP Drug Formulary 2004 is more that just a formulary. It has IAP recommenda-
tions on every pediatric illness in the book presented system-wise and formulated by respective sub chapters of IAP.
Therefore, this becomes a handy desk-top reference in the clinic, during hospital rounds and for teaching purposes.
The unique feature of the IAP Drug Formulary is that once the user buys a copy of the book and CDRom, he would
be having a life long companion as updates of the IAP recommendations for drug therapy for pediatric illnesses and
monographs of new drugs for use in pediatrics would be available for downloading on to the users hard disc at least
once every year forever from the formulary website!. The first web update IAP Drug Formulary Web Update
2005 is now available. This would possibly be the first pediatric drug formulary in the world that offers such an
unique facility to its users. All users who have registered at the formulary site and provided their e-mail addresses will
promptly receive a message once the update becomes available.
This update has a few other highlights. It is for the first time that IAP and NNF have pitched in together for a
formulary of this kind. The Neonatology chapter has been completely overhauled with contribution from 2 members
from the IAP Neonatology Sub Chapter and 2 NNF members namely its National President and Secretary. An
excellent chapter on Dermatology has been added in this update. Most contentious issues have been addressed and all
comments by users have been considered in detail and changes made wherever appropriate. IAP recommendations
for drug therapy of nearly 200 pediatric illnesses and data on a number of brand names and their presentations had
somehow been omitted from the first CD and these have been added. And since this entails a large volume data
alteration, the user would be completely replacing files of the IAP Drug Formulary 2004 on her/his hard disc with
the IAP Drug Formulary Web Update 2005 download by pressing the Web login and update from the pull down
menu of the Update button on the home screen of the Formulary.
However, the request of many, that users be provided the facility to add generic names of their choice to the program,
could not be complied with. This was due to a technical problem. Being a master driven product, the updates from the
main master would go haywire if users started editing the data, and there would be no single master anymore. Every
user would have his own master. Further, the formulary software is a front end to display the data entered in various
combinations using complex queries and the data has necessarily to be entered using a common data entry package.
I place on record, my sincere thanks to IAP President 2005, Dr Raju C Shah and IAP Hon Gen Secretary Dr Bharat
Agarwal for their support and all the IAP Sub Chapters and the contributors for their expert inputs which has made
this update possible. SIDS and Pixel Studio have continued their good work.
I hope meaningful updates can continue to be made available every year so that this ongoing publication of IAP
meets international standards and continues to be sought after by all those caring for children and adolescents.
Dr Jeeson C Unni, Editor-in-Chief, IAP Pediatric Drug Formulary, Consultant Pediatrician, Dr Kunhalus
Nursing Home, T D Road, Kochi 682011 Kerala, India Email : jeeson@asianetindia.com

50

EMERGENCY MEDICINE
DENGUE HEMORRHAGIC FEVER
AND SHOCK SYNDROMES
* Suchitra Ranjit
** Shrishu R Kamath
Abstract: Dengue fever and dengue hemorrhagic
fever (DHF) have emerged as a serious public
health problem and one of the leading causes of
mortality in children. Recognition of the spectrum
of dengue syndrome, close monitoring and timely
management will reduce the mortality. Serial
estimation of hematocrit, hourly monitoring of
urine output, clinical monitoring of vital signs,
titration of IV fluids and judicious usage of
colloids and blood products are the key factors
in management of DHF and dengue shock
syndrome.
Keywords: Dengue fever, Dengue hemorrhagic
fever, Dengue shock syndrome
Dengue fever, a very old disease, has
reemerged in the past 20 years with an expanded
geographic distribution of both the viruses and
the mosquito vectors, increased epidemic activity,
development of hyper-endemicity (the
co-circulation of multiple serotypes) and
emergence of dengue hemorrhagic fever in new
geographic regions1,2,3. In 1998, this mosquito-
borne disease was recognized as the most
important tropical infectious disease after
malaria, with an estimated 100 million cases of
* Consultant Pediatric Intensivist
** Registrar,
PICU, Apollo Hospitals,
Chennai
51
2006; 8(1) : 51
dengue fever, 500,000 cases of dengue
hemorrhagic fever, and 25,000 deaths annually3.
The reasons for this resurgence and emergence
of dengue hemorrhagic fever are complex and
not fully understood, but demographic, social and
public health infrastructure changes in the past
30 years have contributed greatly3.
Dengue fever and syndromes1,2
Dengue virus is spread by Aedes egyptii
mosquito and has varied manifestations (Fig 1).
Case definition of dengue fever (DF)1,2
Dengue fever is an acute febrile illness with
one or more of the following manifestations:-
Headache, retro-orbital pain, myalgia,
arthralgia, rash, hemorrhagic manifestations and
leukopenia.
Case definition of Dengue Hemorrhagic
fever (DHF)1,2
The following must be present
Fever or history of fever lasting for 2-7 days,
occasionally biphasic
Hemorrhagic tendencies evidenced by at
least one or more of the following:
- A positive tourniquet test.
- Petechiae, ecchymosis or purpura.
- Bleeding from mucosa, GIT, injection
sites or other locations.
- Hematemesis and/or malena.
Indian Journal of Practical Pediatrics
Dengue virus infection
Asymptomatic
Undifferentiated fever Dengue fever syndrome
Without hemorrhage With unusual hemorrhage
Fig 1. Manifestations of dengue infection
Evidence of plasma leakage due to increased
vascular permeability, manifested by at least
one of the following
- A rise in the hematocrit equal to or
greater than 20% above average for the
age, sex and population*.
- A drop in the hematocrit following
volume replacement treatment equal to
or greater than 20% of baseline.
- Signs of plasma leakage such as pleural
effusion, ascites and hypoproteinemia
Thrombocytopenia (1 lakh cells/cumm or
less).
* Indian children with DHF have a lower
hematocrit value during the plasma leakage
period. This has been attributed to the high
prevalence of iron deficiency anemia in the
general population.Normal hematorit in
healthy Indian children is 32 3%. One
proposed recommendation for cutoff for
diagnosis of elevated hematocrit was 36.3%,
which correctly identified more than 80%
of children with DSS in India4 .
Case definition of Dengue Shock Syndrome
(DSS)1,2
All the above for DHF plus evidence of
circulatory failure manifested by
52
2006; 8(1) : 52
Symptomatic
Dengue hemorrhagic fever
No shock With shock
- Rapid, thready pulse
- Narrow pulse pressure (< 20mmHg)
- Hypotension for age
- Cold clammy skin
- Restlessness
WHO guidelines for the diagnosis of various
grades of DHF are given in Table 1 and the
spectrum of DHF is depicted in Fig 2. DHF stage
III and IV constitute dengue shock syndrome
(DSS).
The prognosis depends on early recognition
and treatment of shock. DSS is rapidly reversible
and the incidence of disseminated intravascular
coagulation (DIC) can be minimized by careful
monitoring and prompt intervention with
adequate and appropriate fluids.
The critical period for the onset of shock is
usually around the period of defervescence
typically between the 3rd and the 10th day of
illness. A progressive fall in the platelet count
and a rise in hematocrit are important indicators
of the onset of shock.
Indications for hospitalization1,2
Significant dehydration requiring rapid
volume expansion.
 2006; 8(1) : 53

Table 1. WHO guidelines for the diagnosis of DHF and DSS1,2

DHF Hemorrhage Thrombocytopenia Increased vascular permeability
grade (platelets/mm3)
I Positive tourniquet test only <100,000 Plasma leakage
II Spontaneous bleeding <100,000 Plasma leakage
III Positive tourniquet test <100,000 Plasma leakage and circulatory
and/or spontaneous bleeding failure with pulse pressure
<20 mm Hg or hypotension for age
IV Positive tourniquet test <100,000 Plasma leakage and profound
and/or spontaneous bleeding shock with undetectable pulse and
blood pressure
Plasma leakage: As demonstrated by any of the following: elevation of the admission hematocrit
to >20% above the expected mean for age, sex, and population; reduction of the hematocrit to
>20% of the baseline value after fluid resuscitation; clinical signs of plasma leakage, such as
pleural effusion or ascites.
Spontaneous bleeding: For example, skin petechiae, bruising, or mucosal/gastrointestinal
bleeding.
DHF Grade III and IV = Dengue Shock Syndrome (DSS)

Tachycardia. Warning signs of imminent shock

Increased capillary refill time (>2 sec) Severe abdominal pain (causes include
decreased mesenteric perfusion/ gut edema
Cool mottled or pale skin, diminished or hepatomegaly with stretching of the
peripheral pulses. capsule)
Narrowing of pulse pressure (<20 mmHg). Persistent vomiting
Hypotension (a late finding representing Abrupt decrease in temperature from fever
uncorrected shock) to hypothermia
Reluctance to drink fluids, changes in mental Restlessness, lethargy
status.
DSS is a medical emergency and immediate fluid
Oliguria therapy to expand the vascular volume is
essential. Close observation and monitoring is
Sudden increase in hematocrit or
imperative because children may go in and out
continuously increasing hematocrit despite
of shock during the first 24 hour period.
oral fluid intake
Atypical presentations / unusual manifestations
Bleeding in any form in dengue infection include1,5,6
Acute abdominal pain Acute abdominal pain suggesting a surgical
Evidence of plasma leakage, e.g. pleural emergency, diarrhoea, severe
effusion, ascites gastrointestinal hemorrhage

53
Indian Journal of Practical Pediatrics 2006; 8(1) : 54

Dengue infection

Fever Positive Increased Hepatomegaly Thrombocytopenia Grade I

Tourniquet Capillary
Test Permeability v
v

Other hemorrhagic
manifestations Grade II
Leakage of plasma Coagulopathy

v
Hypovolemia
v

Grade III
Shock DIC v
v
Grade IV
Severe bleeding
v
Risk of Death

Fig 2. Spectrum of dengue hemorrhagic fever

Neurological manifestations: Intense Fulminant hepatic failure, obstructive

headache, convulsions and altered jaundice, raised liver enzymes, Reye
sensorium can result from syndrome
- Shock and cerebral hypoperfusion - Reported causes of liver involvement
- Cerebral edema include ischemic type of necrosis due to
hypoperfusion and direct viral hepatic
- Dengue encephalopathy, encephalitis invasion5,10
(dengue virus has been isolated from
CSF suggesting direct involvement of the Acute renal failure, hemolytic uremic
brain)7-9 syndrome

- Metabolic derangements (glucose, Pulmonary edema, myocardial dysfunction

sodium, calcium) (systolic and diastolic)11-13.

- Intracranial hemorrhage Superimposed infection in endemic areas

(malaria, leptospirosis, enteric fever)
Irregular or inappropriately slow pulse rate
for the degree of shock. Vertical transmission in newborns.

54

Essential laboratory tests
Laboratory monitoring (at presentation and as
needed thereafter)
Hemoglobin, hematocrit .
White cell count and peripheral smear will
confirm leucopenia with atypical
lymphocytes. The peripheral smear will also
show decreased platelets and absent platelet
clumps.
Platelet count, coagulation studies
Serum electrolytes, blood gases.
Liver and renal function tests.
The methods for confirmation of dengue viral
infection include1,2
1. Isolation of the virus: Although this is the
definitive test, the technique requires
specialized equipment which may not be
available in most centres.
2. Serological tests. These are simpler and more
rapid but cross-reaction between dengue and
other flaviviruses may give false positive
results. False negatives may occur if testing
is done too early in the course of illness
(within 5 days of onset of fever).
3. Demonstration of viral specific RNA in
tissue or serum by polymerase chain reaction
(PCR)
Monitoring and treatment
Frequent recording of vital signs and
appropriate laboratory investigations are essential
for evaluating the results of treatment. Children
with shock need continuous monitoring in a high-
dependency or intensive care unit.
Monitoring parameters include:
- Pulse, blood pressure and respiration should
be recorded every 30 minutes (or more often)
until stable.
55
2006; 8(1) : 55
- A fluid balance sheet should be kept,
recording the type, rate and volume of fluid
- Infusion pumps may help in precise
regulation of fluid input.
- An indwelling urinary catheter and hourly
output documentation is mandatory in all
children with shock
- Central venous and arterial catheters may be
desirable in patients with refractory shock.
- Chest X-ray, ultrasound abdomen,
electrolytes and ABG may be done 12-24
hourly or as clinically indicated.
- Daily recording of weight will help in early
identification of fluid overload.
Type of fluid for rapid replacement of
plasma loss/fluid resuscitation1,8-10
Normal saline.
Ringers lactate
In severe/refractory shock, colloids such as
plasma, plasma substitutes (6% hetastarch/
dextran/5% albumin) may be preferred14,15
Fresh whole blood or packed red blood cells
(PRBC) may be needed for persistent shock
despite restoration of fluid volume and a fall
in hematocrit, suggesting the possibility of
occult blood loss.1,2,6
Remember that dextrose containing fluids
such as Isolyte P or 5% dextrose in
normal saline should not be administered for
rapid large volume resuscitation.
Rapidly administered dextrose may result in
hyperglycemia and osmotic diuresis,
delaying correction of hypovolemia.
Secondly, dextrose is rapidly metabolized
resulting in a hypotonic solution that is
inappropriate for shock correction15.
Indian Journal of Practical Pediatrics
Suggested protocols for volume replacement of
DHF and management of DSS are given in Fig 3
and Fig 4 respetively.
Continued replacement of ongoing plasma
loss
A variable degree of plasma loss may
continue for 24-48 hours necessitating
frequent and careful titration of fluid
administration tailored to the clinical status.
The end-points/targets of fluid
administration are
A fall in hematocrit of approximately 20%
of admission values (in the non-bleeding
patient) and a urine output of >1ml/kg /hr
with stable vitals.
A urine output in excess of 2.5-3 ml/kg/hr
(in the absence of glycosuria) may be
indicative of excess circulating volume and
should prompt reduction of intravenous
fluid.
Re-absorption of extravasated fluid may cause
hypervolemia with a fall in hematocrit and can
progress to pulmonary edema.
Correction of electrolyte imbalance and
acidosis
Electrolyte and metabolic disturbances
include metabolic acidosis secondary to
tissue hypoperfusion, hyponatremia, and
hypocalcemia (particularly in cases in which
massive blood products transfusions are
given).
The most important intervention to correct
metabolic acidosis is appropriate and
adequate fluid resuscitation. Acidosis, if
uncorrected, may lead to DIC.
Sedatives
Agitation may be a sign of shock, hepatic
failure, metabolic derangement, encephalopathy
56
2006; 8(1) : 56
or cerebral edema. If the above have been ruled
out, chloral hydrate may be the preferred sedative.
Oxygen therapy
All children in shock should be given
oxygen in the highest concentration in the least
invasive manner possible.
Blood and blood product transfusion
Blood grouping and cross-matching should
be performed at admission.
Transfusion is indicated in patients with
significant clinical bleeding. Occult bleeding
may be difficult to recognize in the presence
of hemoconcentration.
A drop in hematocrit with no clinical
improvement in shock status despite
adequate fluid administration indicates
significant internal bleeding.
Transfusion of cryoprecipate and or fresh
frozen plasma should be considered in cases
of DIC with bleeds.
Children with no evidence of bleeds and only
abnormal laboratory values need not
generally be transfused.
Indications for platelet transfusion1,5
Shock, acidosis with rapidly declining
platelets ( greatest risk of DIC)
Significant mucosal bleeds (harbinger of
intracranial hemorrhage)
Platelet count < 20,000 per mm3 in the acute
phase
Need for invasive procedures such as central
lines
A low platelet count is less significant after
recovery from shock and may not require
transfusion.
 2006; 8(1) : 57

5% fluid deficit

Initiate intravenous therapy (deficit + maintenance)*

6-7 ml/kg/hr.

Improvement No Improvement
Hematocrit falls Hematocrit , PR rises
PR and BP stable Pulse pressure <20mmHg
Urine output rises Insert urinary catheter

Decrease total IVF Vitals/ hematocrit Increase total IVF

to 5ml/kg/hr x 2-3 hrs worsens to 7-10ml/kg/hr x 2-3 hrs
.

Improvement Improvement m No Improvement

Decrease IVF Increase IVF

3ml/kg/hr 10ml-15ml/kg/hr x 2-3 hrs
.

Further Deterioration of
improvement vitals and urine

Stop IVF over 24 hrs see algorithm for DSS

* Note
Ideally, infuse maintenance fluid as 5% glucose in normal saline
Replacement and deficit fluid as normal saline/Ringers Lactate (isotonic, non-dextrose containing fluid).
If infusing total maintenance and deficit as GNS, monitor for hyperglycaemia which may delay
hypovolemia correction by causing osmotic diuresis
Fig 3. Volume replacement flow chart for a patient with DHF and a >20% increase in
hematocrit1

Criteria for discharge 2 days after recovery from shock.

Absence of fever for at least 24 hours. No respiratory distress
Return of appetite. Choice of vasoactive agents/ post
Clinical improvement. resuscitation fluid removal11
Shock with low BP for age: Dopamine
Good urine output.
10 g/kg/min or noradrenaline/adrenaline
Stable hematocrit. 0.1-0.2 g/kg/min
57
Indian Journal of Practical Pediatrics 2006; 8(1) : 58

Oxygen , normal saline OR 6% hetastarch/ gelatin 10-20ml/kg as rapid boluses x 2 .

Monitor hourly vitals, urine output with an indwelling catheter
Obtain baseline hematocrit, correct hypoglycaemia, hypocalcemia,

Improvement No improvement, re-check hematocrit,

Evaluate for source of blood loss

Decrease fluid rate

Colloid or plasma substitutes 10-20ml/kg
Repeat as necessary
(If HCT falls or is normal with signs of shock,
Transfuse PRBC 10ml/kg or whole blood 20ml/kg.)

Further
improvement No improvement

Can discontinue fluids over 24-36 hrs Insert CVP with care

Discharge CVP normal or high with shock

CVP low /HCT fall < 20% of baseline

Inotropes/ vasopressors
Fluids till CVP/HCT target Assess LV systolic & diastolic function by echo,
Assess chamber filling

Respiratory distress

Consider assisted ventilation

Hemodynamics stable Hemodynamics unstable Initiate vasodilators when BP stable
Echo evaluation

Low dose diuretics as bolus Assisted ventilation,

or infusion vaso-active agents

Fig 4.Management of dengue shock syndrome with unstable vital signs1,8, 9

Shock with normal BP for age: Dobutamine infusion 3-5mg/kg/day, titrate to urine output
5-10 g/kg/min of 3-5 ml/kg/hr. Cease furosemide infusion
and infuse fluid if hypoperfusion occurs.
Shock with diastolic dysfunction on echo:
Milrinone 0.25-0.5 g/kg/min (no loading
Pulmonary edema, fluid overload,
hemodynamics unstable: Ventilation is vital
dose)
(high risk of mortality) and can consider
Predominant pulmonary edema with fluid peritoneal dialysis if 24 hour experienced
overload, hemodynamics stable: nursing and medical staff are available in
Nitroglycerine 1-3 g/kg/min, furosemide PICU.
58

Signs of fluid overload without features
of pulmonary edema and shock: Just stop
the IV fluid and start oral feeds. No other
treatment required.
Points to remember
Serial hematocrit measurement (if not
bleeding), and urine output provide the
most objective guides to fluid replacement
and prevention of fluid overload.
Check hourly to 2nd hourly hematocrit for
first 6 hours , decreasing frequency as
patient improves.
Aim for approximately 20% fall in
hematocrit and adjust fluid rate downwards
to avoid overload.
Aim for minimal acceptable urine output
(0.5-1ml/kg/hr) by catheterizing bladder
and charting hourly urine output.
A urine output > 3 ml /kg /hour indicates
hypervolemia (rule out glycosuria) and
should prompt the need to decrease rate of
intravenous fluids.
Remember that the patient can go in and
out of shock during the first 24-48 hrs .
Synthetic colloid (hetastarch/dextran/
gelatin) may be used for severe shock and
may limit the severity of fluid overload.
Total volume of colloid should not exceed
30ml/kg/24hrs (Can worsen coagulopathy,
allergic risks).
Avoid Isolyte P for maintenance fluid, can
use GNS or I/2 GNS with added potassium.
GNS or I/2 GNS should not be used for
fluid resuscitation, resultant hyperglycemia
can cause osmotic diuresis and delay
correction of hypovolemia.
59
2006; 8(1) : 59
All invasive procedures (intubation, central
lines, arterial cannulation) must be
performed by the most experienced person
available. If possible, aim for platelets
> 50,000/cmm prior to central line
insertion.
Profuse bleeds may necessitate transfusion
of platelets and FFP regardless of lab
values: conversely, low platelet counts in
the recovering , stable patient may not be
an indication for transfusions .
References
1. WHO. Dengue Haemorrhagic Fever:
Diagnosis, Treatment, Prevention and Control,
2nd edn. Geneva: WHO, 1997.
2. Prevention and control of Dengue and Dengue
haemorrhagic fever. Comprehensive
guidelines. WHO SEARO, New Delhi WHO.
1999; 23:10-15
3. Gibbons RV. Dengue: an escalating problem.
Brit Med J 2002; 324:1563-1566.
4. Gomber S, Ramachandran VG, Kumar S, et al.
Hematological observations as diagnostic
markers in Dengue hemorrhagic fever a
reappraisal. Indian Pediatr 2001;38(5):477-481.
5. Nimmannitya S, Thisyakorn U, Hemsrichart
V. Dengue hemorrhagic fever with unusual
manifestations. Southeast Asian J Trop Med
Public Health 1987; 18(3): 398-405.
6. Kalayanarooj S, Chansiriwongs V, Nimmanitya
S. Dengue Bulletin 2002; 26:33-43.
7. Cam BV, Fonsmark L, Hue NB, Phuong NT,
Poulsen A, Heegaard ED. Prospective case-
control study of encephalopathy in children
with dengue hemorrhagic fever. Am J Trop
Med Hyg 2001; 65(6): 848-851.
8. Lum LC, Lam SK, Choy YS. Dengue
encephalitis: a true entity? Am J Trop Med Hyg
1996; 54; 256-259.
9. Thisyakorn U, Thisyakorn C, Limpitikul W,
Nisalak A. Dengue infection with central
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nervous system manifestations. Southeast
Asian J Trop Med Public Health 1999; 30(3):
504-506.
10. Mohan B, Patwari AK, Anand VK. Hepatic
dysfunction in childhood dengue infections. J
Trop Pediatr 2000; 46(1):40-43.
11. Ranjit S, Kissoon N, Jayakumar I. Aggressive
management of dengue shock syndrome may
decrease mortality rate: A suggested protocol.
Ped Crit Care Med 2005; 6(4): 412-419.
12. Khongphathanayothin A, Suesaowalak M,
Muangmingsook S, Bhattarakosol P,
Pancharoen C. Hemodynamic profiles of
patients with dengue hemorrhagic fever during
toxic stage: an echocardiographic study.
Intensive Care Med 2003; 29(4): 570-574.
13. Kabra SK, Juneja R, Madhulika, et al.
Myocardial dysfunction in children with
dengue haemorrhagic fever. Natl Med J India
1988; 11(2): 59-61.
14. Wills BA, Dung NM, Loan HT, et al.
Comparison of Three Fluid Solutions for
Resuscitation in Dengue Shock Syndrome. N
Engl J Med 2005; 9(353):877-889.
15. Wills B. Volume replacement in dengue shock
syndrome. Dengue Bulletin 2001;25: 50-55.

NEWS AND NOTES

IX NCPID 2006
IX National Conference of Pediatric Infectious Diseases
Date: 14th and 15th October, 2006
Venue: Hotel Green Park, Vadapalani, Chennai
Registration fee
Category Before IAP Non-IAP Acc. PG student /
Member Member Person Sr.Citizen

Very Early 30th April 2006 1000/- 1200/- 1200/- 800/-

Early 31st July 2006 1200/- 1500/- 1500/- 1000/-
Late 30 September 2006
th
1500/- 1700/- 1700/- 1200/-
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onwards
Registration is compulsory for all categories of delegates.
Only demand draft in favour of IX NCPID 2006 payable at Chennai.
Dr.A.Parthasarathy Dr.Major K Nagaraju
Organising Chairman Organising Secretary
For further details contact: Dr.Major K Nagaraju, Organising Secretary, IX NCPID 2006, Halls
Towers, F Block, Ground Floor, 56, Halls Raod, Egmore, Chennai 600 008. Phone: 044-28190032,
Email: ixncpid2006@yahoo.co.in

60

EMERGENCY MEDICINE
CARDIOGENIC SHOCK IN
CHILDREN
* Renu P Kurup
* Krishna Kumar R
Abstract: The term cardiogenic shock can be
understood as circulatory failure resulting
primarily from impaired cardiac performance.
Cardiogenic shock can occur in children and
should be thought of in the differential diagnosis
of any child with circulatory failure. The causes
include myocardial dysfunction from
myocarditis, anomalous coronary artery from
pulmonary artery, sustained tachyarrhythmias,
severe ventricular outflow obstruction, severe
valvular regurgitation and metabolic conditions.
Resuscitation and work-up should proceed
simultaneously. Prognosis is greatly improved
by aggressive intensive care management
together with etiology-specific therapy.
Key words: Circulatory failure, Ventricular
dysfunction in children
Cardiogenic shock is a major and frequently
fatal complication of a variety of disorders that
impair the ability of the heart to maintain adequate
tissue perfusion. The clinical definition of
cardiogenic shock is decreased cardiac output and
evidence of tissue hypoxia in the presence of
adequate intravascular volume1. Cardiogenic
shock occurs in infants and children as a result
of a variety of specific causes, many of which
are correctable (Table 1). This review focuses
* Department of Pediatric Cardiology
Amrita Institute of Medical Sciences and
Research Centre, Kochi
61
2006; 8(1) : 61
on etiology, pathophysiology and management
of cardiogenic shock in children.
Pathophysiology
Shock is a clinical syndrome that results
from an acute circulatory dysfunction and
consequent failure to deliver sufficient oxygen
and other nutrients to meet the metabolic
demands of the tissue beds. Tissue hypoperfusion
and consequent cellular hypoxia leads to
anaerobic glycolysis, with depletion of ATP and
intracellular energy reserves. Anaerobic
glycolysis also causes accumulation of lactic acid
and intracellular acidosis. Failure of energy
dependent ion transport pumps decreases
transmembrane potential, causing intracellular
accumulation of sodium and calcium, swelling,
rupture of cell membrane and cell death. This is
the basis of multiple organ system failure that
occurs in the setting of shock. This metabolic
disruption may occur from either an absolute
deficiency of oxygen delivery (hypoxic shock)
or deficient substrate (glucose) delivery (ischemic
shock). Most often they develop in combination,
which results clinically in hypoxic-ischemic
injury.
Cardiac output, the most important
determinant of tissue perfusion, is the product of
stroke volume and heart rate. Stroke volume is
dependent upon preload, afterload and
myocardial contractility. A decreased contractile
state results in decreased stroke volume and
cardiac output. Low cardiac output, decreased
blood pressure and poor tissue perfusion produce
a rapid downhill spiral of inadequate oxygen
delivery to tissues and micro circulatory failure2
(Fig.1).
Indian Journal of Practical Pediatrics 2006; 8(1) : 62

Table 1. Causes of cardiogenic shock in children

Myocardial insufficiency
Myocarditis: Acute fulminant myocarditis
Cardiomyopathies: Advanced end-stage dilated cardiomyopathy
Following open heart surgery (effects of cardiopulmonary bypass; myocardial preservation during
aortic cross clamping and administration of cardioplegic solution)
Metabolic or Toxic
Hypothermia
Myocardial depressant effect of hypoglycemia, acidosis, hypoxia, hypophosphatemia,
hypocalcaemia
Toxins (Scorpion sting, spider, sepsis)
Drugs (myocardial depressants, -blockers, and calcium channel blockers)
Poisons: Specific myocardial depressants such as aluminium phosphide
Poor myocardial perfusion
Congenital coronary abnormalities: anomalous coronary artery from pulmonary artery
Kawasaki disease with coronary artery occlusion
Coronary embolism: Air or blood clot
Outflow obstruction
Duct dependent systemic circulation: hypoplastic left heart syndrome, interrupted aortic arch
Critical aortic stenosis, coarctation of aorta
Arrhythmias
Tachyarrhythmia: Atrial and ventricular arrhythmias (tachycardia mediated cardiomyopathy)
Severe bradycardia: Congenital complete heart block, yellow oleander poisoning
Acute valve insufficiency:
Acute mitral valve regurgitation (chordal rupture)
Acute aortic regurgitation
Cardiac tamponade
Pulmonary embolism
Rapidly progressive pulmonary hypertension

Recognition of cardiogenic shock documentation of impaired cardiac performance

Shock is a clinico-physiologic diagnosis. No
differential diagnosis exists although different
etiology for cardiogenic shock exists.
Cardiogenic shock is diagnosed after
62
and exclusion of other causes of hypotension.
Cardiogenic shock is relatively rare in general
pediatric population. However, patients with
cardiogenic shock make a significant portion of

Fig 1. The downward spiral of cardiogenic shock. LVEDP - Left ventricular end diastolic
pressure
patients in shock in tertiary care pediatric ICUs.
Recognition and resuscitation have to proceed
simultaneously.
While stabilizing the child with shock one
needs to look for clues to identify the underlying
cause. Often history can only be obtained in brief
initially. Additional details should be sought after
the patient is stabilised.
The history of patients who present in shock
varies depending upon the etiology. A child with
fluid loss (vomiting/diarrhoea/bleeding) is at risk
63
2006; 8(1) : 63
for hypovolemic shock. Fever may herald an
infection that could result in septic shock. An
antecedent viral syndrome is present in more than
half of the patients with myocarditis3. Neonates
and infants with anomalous coronary artery from
pulmonary artery (ALCAPA) may have history
of episodes of respiratory distress with pallor and
sweating with a general appearance of severe
shock, caused by angina 4,5 . In scorpion
envenomation, there is often a clear history of
scorpion sting.
Indian Journal of Practical Pediatrics
Fig 2. Hypocalcemia in a 2 month old with severe ventricular dysfunction. The ECG is
characterized by prolonged QT interval. The QTc was measured as 550 milliseconds
The clinical manifestations of cardiogenic
shock often cannot be distinguished from other
forms of shock. These findings include:
Ashen color/cyanosis with cool and mottled
extremities, prolonged capillary refill >5
seconds.
Tachycardia with low volume pulse.
Hypotension (< 5th percentile of normal
systolic BP for that age)
Hypotension may not always be present.
Children may have an adequate systolic BP,
but may still be in shock - central perfusion
to brain and heart are still considered
adequate, while other vital organ systems
may be hypoperfused. If not reversed, this
will progress to decompensated shock with
a fall in recorded blood pressure.
Signs of hypoperfusion such as altered
mental status and decreased urine output.
64
2006; 8(1) : 64
Specific clues that suggest a cardiac cause
for the shock syndrome are as follows:-
Physical Examination
Presence of grunting and increased work
of breathing
Liver enlargement suggesting elevated
central venous pressure
Basal rales
Prominent jugular venous pulsations aare
difficult to make out in young children
Extreme tachycardia (> 200 in infants and
>180 in young children) or heart rate
irregularity may point towards an underlying
tachyarrhythmia as a cause of the
cardiogenic shock.
Significant bradycardia
(typically <60/min)
 2006; 8(1) : 65

Pulsus alternans and pulsus paradoxus are
rare but very useful clues if present. Pulsus
paradoxus suggests a cardiac tamponade and
pulsus alternans is a feature of advanced
myocardial dysfunction.
Pulse discrepancy: Feeble femoral
pulsations suggest coarctation. Absence of
other pulses may occur in Takayasus
arteritis.
Abnormal cardiac auscultation: Murmurs
(both systolic and diastolic), third heart
sound.
Electrocardiogram
The ECG provides several very useful clues
to underlying heart disease. A prolonged QT
interval suggests severe hypocalcemia (Fig.2).
The presence of an anomalous coronary artery
from the pulmonary artery (ALCAPA) may be
suspected if prominent q waves are seen in V4-
6, I and aVL (Fig. 3). Often this is associated
with ST segment elevation and T wave inversion
over left ventricular leads. A careful evaluation
of rhythm and P wave morphology is a must in
every patient with heart failure. Any long-
standing tachyarrhythmia can be associated with
ventricular dysfunction (tachycardiomyopathy)6.
Typical examples include ectopic atrial
tachycardia (EAT) and, permanent junctional re-
entrant tachycardia (PJRT). In PJRT the P waves
are typically inverted in leads II, III and aVF
(Fig. 4). The P waves of EAT are different from
those obtained during sinus rhythm. Often this
difference is quite subtle. However, the presence
of very rapid rates and irregularities resulting
from transient AV block provide additional help
in making the diagnosis.

Fig 3. This ECG has been obtained from a 4 month old infant with anomalous origin of left
coronary artery from the pulmonary artery. The deep Q waves (indicated by arrows) in leads
I, aVL, V5 and V6 are typical. Note the ST segment elevation in leads V4-6.
65
Indian Journal of Practical Pediatrics 2006; 8(1) : 66

Chest X-ray echo will help in identifying a cardiac etiology

The chest X-ray typically shows cardiac
enlargement and features of pulmonary venous
congestion. Occasionally, however there is no
cardiac enlargement if the duration of symptoms
is short .
Echocardiogram
This investigation is of immense diagnostic
value and helps in identifying the specific
etiology. Echocardiography is often readily
available in many institutions and should be
performed at a relatively low threshold in children
being resuscitated for shock. Any child with a
shock syndrome who fails to respond to initial
resuscitative measures such as fluid and
dopamine should perhaps undergo an echo. An
early and permit introduction of specific
treatment. Myocarditis and cardiomyopathy are
characterized by ventricular enlargement and
global ventricular dysfunction. Regional wall
motion abnormalities with scarring of the
papillary muscles suggest ALCAPA. The
coronary artery origins and flow patterns can be
clearly seen in these patients by echo. While
coarctation is often suspected clinically,
confirmation requires echocardiography.
Pericardial effusion is readily identified by
echocardiography.
Laboratory tests
Blood Gas: An arterial or venous blood gas
sample should ideally be obtained early during
resuscitation. Apart from gas exchange and acid-

Fig 4. This ECG is from a 2 year old child with severe left ventricular dysfunction who was
thought to be having dilated cardiomyopathy. The clue to the presence of tachycardia related
cardiomyopathy is the presence of inverted P waves in leads II, III and aVF (arrows). This is
an example of permanent junctional re-entrant tachycardia. The ventricular dysfunction
completely improved after successful radiofrequency ablation.
66
 2006; 8(1) : 67

Fig 5. Management algorithm of a child who presents with severe hypotension. CVP:central
venous pressure, MAP: mean arterial pressure, ScvO2: Superior caval vein oxygen saturation

base balance other useful information provided
by most modern ABG machines are the lactate
levels, electrolytes, ionised calcium and
hemoglobin. Identification of hypocalcemia is
important as it is one of the reversible causes.
The oxygen saturation of a sample that is
obtained from the superior venacava
(ScvO2)during insertion of a central venous line
is a very good indicator of cardiac output.
67
Saturations of < 70% indicate a reduction in
cardiac output.
Other tests: A complete blood cell count, CRP
and blood cultures help in evaluation of the
possibility of underlying sepsis. It is important
at some stage to assess end-organ insult through
liver and renal function tests. Significant liver
enzyme elevation may indicate substantial end-
organ insult.
Indian Journal of Practical Pediatrics
Management
Cardiogenic shock is an emergency. The
clinician must initiate therapy before shock
irreversibly damages vital organs. At the same
time he or she must perform the clinical
assessment required to understand the cause of
shock and target therapy to that cause.
Major objectives in the management are
rapid recognition of shock state and resuscitation,
protection, support and maintenance of vital
organ function, etiology specific management,
identification and correction of aggravating
factors and monitoring of cardiovascular and
hemodynamic response.
Initial treatment
Regardless of the etiology, ABCs (airway,
breathing, and circulation) must be evaluated and
stabilized immediately. Patient must be
adequately oxygenated and ventilated. Chest
compressions are indicated for bradycardia (<60
beats/min) with poor perfusion. Stabilizing the
airway and providing mechanical ventilation is
almost invariably required to eliminate work of
breathing, improve oxygenation and facilitate
elimination of carbon dioxide. Comprehensive
monitoring needs to be initiated and this should
include pulse oximeter saturations, central venous
pressure and invasive arterial blood pressure.
Arterial blood gases should be obtained at an
appropriate frequency. All patients with
cardiogenic shock should ideally have arterial
lines and central venous catheters inserted.
The treatment approach to address
hypotension is similar to shock of any etiology
with some modifications and is shown in the
algorithm (Fig. 5). In cardiogenic shock it is
better to go slow on fluids unlike in hypovolemic
or septic shock. Usually a 5-10 ml/kg bolus of
RL is given over 20 minutes and the child is
reassessed. If there are no signs of fluid overload
68
2006; 8(1) : 68
another 10 ml/kg may be tried. No further boluses
are needed. If the child develops increase in liver
span or increasing respiratory distress, stop IV
fluids and start physiologically appropriate
treatment to improve cardiac function such as
inotrope infusions for patients with conditions
such as myocarditis and ventricular dysfunction,
antiarrhythmic medication for tachyarrhythmias,
afterload reduction for acute valve regurgitation
and calcium administration for hypocalcemia.
Pharmacologic Support
Inotropes (Table 2)
Inotropic agents increase myocardial
contractility and have variable effects on
peripheral vascular resistance. Some inotropes
are vasoconstrictors (epinephrine,
norepinephrine); others are vasodilators
(dobutamine). Choice of inotropic agent depends
on etiology of shock and contractile status of
patients cardiovascular system. Vasoconstrictors
may have potentially dangerous consequences in
the presence of severe ventricular dysfunction.
Inotropic agents increase myocardial oxygen
demand, which may be detrimental in a
marginally perfused heart. Vasoconstrictors may
further cause microvascular ischemia, which
worsens perfusion to peripheral end organ tissue
capillary beds, mainly the renal vasculature.
Nevertheless, if the patient has refractory central
hypotension, these agents must be employed.
Phosphodiesterase inhibitors
Amrinone and milrinone are
phosphodiesterase inhibitors that work via a
mechanism other than catecholamines. They
produce an increase in cyclic adenosine
monophosphate (cAMP), which increases
intracellular calcium levels, improving cardiac
inotropy and peripheral vasodilatation. They may
be used together with catecholamines to further
increase myocardial contractility while
 2006; 8(1) : 69

Table 2. Commonly used Inotropes

Drug Mechanism of action Dosage Route
Dopamine Vasodilatory effect on end organ perfusion 2-5mcg/kg/min Central line
1 agonist effect, improving myocardial 5-10 mcg/kg/min
contractility, and enhancing conduction
-agonist effect increases and may 10-20 mcg/kg/min
increase peripheral vasoconstriction and
central pressure
Dobutamine Primarily 1 agonist effects, which increases 5mcg/kg/min IV Central or
contractility, weak 2 mediated peripheral gradually increased peripheral
vasodilatation, reduces systemic vascular to 20mcg/kg/min IV line
resistance (afterload) and improves tissue
perfusion.
Epinephrine Stimulates both alpha and receptors, 0.01mcg/kg/min IV Central line
increases myocardial contractility, peripheral up to 0.2-0.3mcg/kg/min only
vasoconstriction
Nor Stimulates alpha receptor mainly. Dominant 0.01 mcg/kg/min- Central line
epinephrine vasoconstriction 0.04mcg/kg/min only

decreasing systemic vascular resistance and Vasodilators

afterload.
Milrinone is 20 times more potent than
amrinone and has largely replaced amrinone.
Milrinone may be initiated with a loading dose
of 25-50mcg/kg over 1 hour followed by a
continuous infusion of 0.375-0.75mcg kg/min.
Adverse effects include arrhythmias as well as
thrombocytopenia.
Milrinone is specifically useful in the early
post operative state7. The specific advantages
here include the fact that it does not increase
myocardial oxygen demand and seldom increases
heart rate. One of the concerns with milrinone is
the hypotension that occurs at the time of the
loading dose. This often responds to fluid
administration. Milrinone is also very useful in
short term support in acute fulminant viral
myocarditis after the initial hypotension is
addressed.
Vasodilators are useful adjunct therapy for
myocardial dysfunction secondary to dilated
cardiomyopathy, coronary insufficiency or
cardiac surgery, systemic or pulmonary
hypertension and valvular regurgitation leading
to volume overload.
Sodium nitroprusside: By lowering systemic
vascular resistance, sodium nitroprusside
improves cardiac output of children with
myocardial dysfunction secondary to
postoperative heart failure, dilated
cardiomyopathy or mitral or aortic valve
regurgitation. Dose: 0.5-8mcg/kg/min.
Tachyphylaxis is common and limits its efficacy
beyond 48 hours.
Nitroglycerin: This is essentially a veno-dilator
and reduces preload. There is also a reduction in
systemic vascular resistance that helps augment

69
Indian Journal of Practical Pediatrics
cardiac output. However this may be offset by
the preload reduction as well as tachyphylaxis
that is common. The dose is 0.1-1mcg/kg/min.
Support of vital organ function
1. Ventilatory support
Abnormality of respiratory function is
almost always present in shock. The work
of breathing is substantially increased;
respiratory drive and lung mechanics may
be abnormal. Respiratory failure can develop
rapidly and is frequently the cause of death.
Therefore patients in cardiogenic shock
should be intubated and ventilated at a low
threshold. A high PEEP is often needed.
2. Support of renal function
Hypoperfusion often leads to acute renal
failure. Careful monitoring of fluid balance
and minute attention to electrolyte levels is
absolutely essential. Once tissue perfusion
improves, recovery of renal function is often
the rule. However, the period of renal failure
may be prolonged and severe enough to
warrant dialysis. Peritoneal dialysis is
preferred initially because it is less invasive,
and is associated with relatively less rapid
changes in intravascular volume. For older
children (>10-15 Kg) hemodialysis is
sometimes a better option especially if renal
failure is severe.
3. Gastrointestinal and nutritional support
Stress bleeding and paralytic ileus are
common accompaniments. For the initial 24-
48 period of stabilization it may be
appropriate to withhold enteral feeding.
Hypokalemia should be corrected.
Sucralfate, H 2 receptor blockers and
pantoprazole may be used to prevent
bleeding from stress ulcers. Metabolic
derangement in shock is characterized by
excessive catabolism of protein and
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2006; 8(1) : 70
decreased synthesis. Enteral nutrition is more
physiological and preferred over parenteral
nutrition.
4. Management of associated infection:
Empiric antibiotics are often started at the
time of initial presentation. Their choice and
use should be reviewed on a daily basis.
Once blood cultures are obtained the
antibiotics should be changed accordingly
and they should be stopped as soon as it is
evident that there is no sepsis.
Etiology specific management
a. Duct dependent systemic circulation:
Examples of duct dependent lesions include
hypoplastic left heart syndrome, interrupted
aortic arch, critical aortic stenosis and critical
coarctation. In these conditions the systemic
blood flow is maintained through the patent
ductus arteriosus. Postnatally when the
ductus closes the systemic blood flow drops
resulting in shock. Here, patency of the duct
has to be restored and maintained by
initiating prostaglandin E1 infusion at a rate
of 0.01-0.2mcg/kg/min until the definitive
surgical procedure or catheter intervention
is undertaken.
b. Other congenital heart disease: Surgical
or catheter based intervention should be
considered as soon as initial stabilization is
achieved. It may be necessary to wait for
return of end-organ functions towards
normal before open heart surgery is
performed to allow better tolerance to
cardiopulmonary bypass.
c. Arrhythmias: Tachyarrhythmia needs
prompt specific treatment. A combined
strategy that simultaneously addresses both
diagnosis and treatment is appropriate8. The
diagnostic/therapeutic strategy is determined
by the QRS duration on the initial EKG or
the rhythm monitor and the degree of

hemodynamic instability. Based on the QRS
duration tachyarrhythmias can be classified
as narrow and wide. This is a useful practical
classification and serves as an excellent
guide to initial treatment. Bradycardia
resulting in shock requires immediae
treatment with support of airway,
oxygenation and ventilation. If bradycardia
persists, chest compression and then
treatment of the cause (hypoxemia,
hypothermia, heart block, toxins/poisons/
drugs) are carried out.
Unstable narrow QRS tachycardia is quite
uncommon as a cause of cardiogenic shock,
especially so in the absence of structural heart
disease. Low energy (0.5-2 J/kg) synchronized
DC cardioversion should be performed. If and
when possible cardioversion should always be
preceded by administration of a short acting
benzodiazepine such as midazolam (0.1-0.2 mg/
kg/dose).
Wide QRS tachycardia with hemodynamic
instability is a medical emergency. Synchronised
cardioversion (0.5-2J/kg) should be performed
as soon as the diagnosis is made. For pulseless
patients CPR should be initiated and for
ventricular fibrillation and pulseless ventricular
tachycardia defibrillation is done.
Monitoring after initial resuscitation
Repeated and careful examination of the
childs clinical and physiological status should
be done for continuous assessment of recovery
of vital organ function, efficacy of treatment and
early detection of correctable problems.
Frequent estimation of arterial blood gases
and calcium and glucose provide useful
additional clues. Correction of derangements of
pH, calcium and glucose will enhance cardiac
function. Indices of tissue perfusion include
serum lactate levels (often obtained in the ABG
71
2006; 8(1) : 71
report) and mixed venous oxygen saturation. A
urine output of 1-2ml/kg/hr or more indicates a
well perfused kidney. Renal parameters and liver
enzymes should be measured frequently
especially if initially elevated to monitor end-
organ recovery. Complete blood counts should
be obtained on a daily basis because of the
constant risk of development of sepsis and blood
cultures should be obtained if the CBC suggests
sepsis. Once signs of recovery are evident,
invasive monitoring should be replaced by non-
invasive monitoring. It is important to avoid
unnecessary prolongation of intensive monitoring
to minimize risk of nosocomial infection and
other complications as well as to limit costs.
Special Categories
Scorpion sting envenomation: Severe
scorpion envenomation is characterized by
cardiocirculatory failure which may lead to
pulmonary edema. These are the major causes
of death among victims of scorpion stings.
Involvement of the heart has been attributed to
the massive release of catecholamines and/or to
a direct toxic effect of the venom on cardiac
fibers, while pulmonary edema has been
considered to be of cardiogenic or non-
cardiogenic origin9. The clinical course of all
the patients is often charatcterized by recovery
over a period of time provided the initial
critical phase is correctly managed by
supporting the ABCs and early administration
of prazosin. The laboratory, ECG and
echocardiographic changes return to normal,
usually within 1 week of the sting10.
Aluminium phosphide poisoning: Aluminium
phosphide is used to control rodents and pests in
grain storage facilities. It produces phosphine gas,
which is a mitochondrial poison. The most
prominent manifestation of severe aluminium
phosphide poisoning is severe myocardial
depression. There are no known antidotes for
Indian Journal of Practical Pediatrics
this poison 11 . Coconut oil may limit its
absorption 12 . N-acetyl cysteine 13 and
trimetazidine14 have been proposed as possible
agents that can reduce the myocardial damage.
Supportive treatment with inotropes, vasodilators
together with intensive monitoring may allow
recovery in a significant proportion of children.
Mechanical support of myocardium
In children with reversible cardiac or
pulmonary dysfunction, prolonged
extracorporeal support has the potential of
improving survival of otherwise unsalvageable
cases. Methods of mechanical support for the
failing heart includes:
Extracorporeal membrane oxygenation
(ECMO)
Ventricular assist device (VADs)
Intra aortic balloon pump (IABP)
Currently ECMO and VADs have become
the mainstay of mechanical support and on
occasion are used as bridge to cardiac
transplantation in developed nations. Many
children with myocardial dysfunction due to
acute myocarditis have reversible cardiac failure
and can recover if the circulation is supported
during the critical days or weeks of inflammation
and healing.
Mechanical circulatory support is an
effective treatment for post cardiac surgery
ventricular dysfunction in children. If the cardiac
output is not adequate despite the use of multiple
inotropic agents or if the dose of epinephrine
exceeds 0.3mcg/kg/min in conjunction with other
agents, mechanical support should be seriously
considered. However, the cardiac and pulmonary
function should be deemed reversible within
reason before patients are placed on mechanical
support15.
Mechanical support however has major
72
2006; 8(1) : 72
limitations in terms of costs and feasibility in all
but the most advanced centers in the developing
world. The daily costs are prohibitive and
considerable human and material resources are
necessary. As far as possible all support measures
should be used to the fullest extent before
mechanical support is considered. Pediatric
cardiac transplantation is largely unavailable in
India.
Prognosis
In the absence of aggressive and highly
experienced technical care, mortality rate among
patients with cardiogenic shock are exceedingly
high 50-80%. The key to achieving good
outcome is rapid diagnosis, prompt supportive
therapy and addressing the underlying etiology.
Many conditions that present as cardiogenic
shock have the potential for complete recovery
provided the supportive care in the critical period
of severe ventricular dysfunction is adequate.
Acute fulminant myocarditis is an example of
such a condition. Conditions with a correctable
cause for ventricular dysfunction often recover
completely once the etiology is addressed. In
ALCAPA for example, the surgical results of
operations that establish a two coronary artery
circulation have dramatically improved the
outcome in recent years in this otherwise fatal
disease.
Points to Remember
It is important to consider cardiac
conditions in a child presenting with shock.
Aggressive treatment measures should
include a low threshold for mechanical
ventilation and physiologically appropriate
medications.
Many causes of cardiogenic shock in
children can be addressed through specific
treatment measures with the prospect of a
good prognosis.

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Cardiogenic Shock. Ann Intern Med 1999; 131:
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2. Singhi S. Management of Shock. Indian Pediatr
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3. McCarthy RE III, Boehmer JP, Hruban RH, et
al. Long-term outcome of fulminant
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4. Hoffman JIE. Congenital anomalies of the
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NEWS AND NOTES
th
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Date: 23rd April 2006
Contact:
Dr.Gautam Ghosh, Mobile No: 9830161815
Dr.K.K.Ghosh, Mobile No: 9830034876 Email: ghosped@cal3.vsnl.net.in / amanglik@cal2.vsnl.net.in
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literature. Hum Exp Toxicol 2005; 24: 27-33.
12. Shadnia S, Rahimi M, Pajoumand A, Rasouli
MH, Abdollahi M. Successful treatment of
acute aluminium phosphide poisoning: possible
benefit of coconut oil. Hum Exp Toxicol 2005;
24: 215-218.
13. Azad A, Lall SB, Mittra S. Effect of N-
acetylcysteine and L-NAME on aluminium
phosphide induced cardiovascular toxicity in
rats. Acta Pharmacol Sin 2001; 22: 298-304.
14. Duenas A, Perez-Castrillon JL, Cobos MA,
Herreros V. Treatment of the cardiovascular
manifestations of phosphine poisoning with
trimetazidine, a new antiischemic drug. Am J
Emerg Med 1999; 17: 219-220.
15. Reddy M, Hanley FL. Mechanical Support of
the myocardium. In: Pediatric Cardiac Intensive
Care, eds Chang AC, Hanley FL, Wernovsky
G, et al, Williams & Wilkins, Maryland USA,
1998; p345-349.
Dr.Subhasis Roy, Mobile No: 9830036761
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
CRITICAL CARE TRANSPORT
* Fazal Nabi
** Deepali Mankad
Abstract: In an event of critical illness or injury
far from a Pediatric Intensive Care Unit (PICU),
the child needs admission and stabilization in the
nearest hospital. If the childs needs exceed the
capabilities of the local hospital, interhospital
transport must be provided to a PICU to
maximize the likelihood of a good outcome. A
dedicated transport team well versed in transport
medicine and pediatric critical care is required
for transferring a critically ill child. The goal of
the transport team is to function as an extension
of the PICU, delivering the same care during
transfer. When the critically ill child is cared in
a specialized pediatric ICU, it was found that
the morbidity and mortality significantly
decreased.
Keywords: Critical care transport, Trained team,
Equipment, Communication.
The modern era, with advances in science
and technology, provides good care to critically
ill infants and children. Illness and injury can
happen at places remote from the advanced
pediatric care center. Unfortunately, such
advanced units by their nature are located only
in a few centers throughout the country 1.
* Consultant Pediatric Intensivist
** Senior Pediatric Registrar,
Jaslok Hospital and Research Center,
Saifee Hospital Trust,
Breech Candy Hospital, Mumbai .
74
2006; 8(1) : 74
Interhospital transport programme facilitates the
transfer of infants, children and adolescents to
the Pediatric Intensive Care Unit (PICU).
Anticipation of potential difficulties, preparation
to overcome or to prevent them and effective
communication among all involved parties are
essential for a successful transport system.
Appropriate equipment and personnel can assure
patient safety during transport. These guidelines
promote measures for transport of critical
children 2. Every hospital should establish
protocols that outline access to the various
transport systems before a seriously ill or injured
child actually requires transport. A list of names
and telephone numbers of facilities equipped to
care for critically ill and injured children and
transport systems capable of transporting
pediatric patients should be displayed in the
emergency department.
Modes of transport
There are two modes of transport3
1. Transport in an ambulance by road: This is
the most common, convenient and cost
effective mode of transport.
2. Transport by air: This is the quickest mode
of transport but is very expensive.
This article will explore issues in the
management of transfer of a critically ill baby
by road.
Types of inter-hospital transport: Three
options are commonly available for interhospital
transport. The patient may be sent by local
emergency services without medical personnel,
local (referring) emergency medical services i.e.

via ambulance with the referring physician and/
or nurse, or specialized pediatric critical care
transport team.
The first two modes are referred to as one-
way transports and the third as two-way transport.
The only advantage of sending a patient on one-
way transport is time. However two-way
transport has many advantages.
Advantages of two-way interhospital transport
are critical care equipments like ventilators and
monitors, are dedicated for transporting critically
ill patients, equipment and drugs are prepared
beforehand and entire team has transport
experience and is familiar with the equipment.
Composition of transport team: Patients must
be transported by individuals, qualified and
trained, to provide the appropriate treatment to
maintain the patients condition and to treat
reasonably foreseeable complications1.
The smallest team undertaking an
interhospital transport of a critically ill child is
one physician and one nurse, both adequately
experienced. If the child requires only level I care
it is possible that only a nurse may fetch him or
her.
Qualities and tasks of the transport team
personnel:
Transport physician should be a Pediatric
intensivist or registrar who will be available 24
hours/day, able to determine diagnostic and
therapeutic priorities in critically ill children,
preferably an APLS/PALS provider and skilled
in endotracheal intubation, venous and arterial
catheterization and chest drain insertion
Transport nurse must be a Pediatric nurse with
PICU training or PALS training and competent
in managing airway and operating transport
equipment. She should be available 24 hours/day.
75
2006; 8(1) : 75
It will be better, if the driver and ambulance
attendant are also trained in BLS, cervical spine
stablization and transport.
Equipment: Each transport team, when
developing protocols, must devise a list of
equipments, supplies and drugs as well as an
inventory checklist4. Written protocols must be
available delineating management of potential
crises during transport (eg. respiratory failure or
arrest, cardiac arrest and seizures activity). A
list of necessary equipments and drugs should
be prepared in advance.
The British Pediatric Association, the British
Intensive Care Society and the American
Academy of Pediatrics have drawn up guidelines
on transport equipment. When selecting
equipment one should ensure to meet these
guidelines3.
Equipment required during transport of a
critically ill child:
Patient movement restraint:
Trolley
1. Incubator for children < 5 kg
2. Metal pole or shelf system to secure
ventilator, pumps, monitors
3. Adjustable belts (safety belts) to secure
patient during transfer
Equipment bags
Multiple compartments allow access to items
without unpacking all instruments
Drug boxes
Airway management:
Equipment to establish and maintain a secure
airway
Indian Journal of Practical Pediatrics
1. Bag-valve device (e.g. Ambu bag) with
selected mask sizes
2. Endotracheal tubes (all sizes), stylet and
Magil forceps
3. Laryngoscope with assorted size blades
Portable mechanical ventilator capable of
ventilating infants and children of all ages
Small, lightweight with economical gas
usage
Portable Oxygen supply
High-pressure supply with low-pressure
metered flow
Suction - portable, battery powered;
De Lees suction catheter and bulb suckers
can be kept as stand by.
Intravenous infusion
Equipment to establish and maintain venous
and arterial access
Drugs - Resuscitation drugs, sedating and
paralytic agents and inotropic drugs
Infusion pumps - small, lightweight, long
battery life
Monitoring:
Monitor (preferably multichannel including pulse
oximetry, capnography, etc)
Portable, battery powered, clear illuminated
display
Pulse oximetry, capnography, invasive
channels (preferably 2) for CVP and invasive
BP
Alarms must be visible as well as audible
because of extraneous noises
Document folder:
Recording chart, audit form
Infusion charts and crash drug charts
Mobile telephone
76
For further details contact :
2006; 8(1) : 76
Preparation immediately before transport
Written consent to transport should be
obtained from the patients legal guardian. If
airway patency or ventilatory status is
questionable, airway should be secured with a
tracheal tube before transport and taped in place.
Vascular catheters should be properly taped.
Cervical spine and any fracture should be
stabilised before transport. All patient records
and X-rays should be sent along. If indicated,
blood products should be kept ready and sent with
the patient.
Communication
Successful communication between the
receiving and referring hospitals is essential for
successful transport. The initial call to transfer a
patient should be made by one physician to
another. Specific details about the vital signs,
fluids administered, timing of events etc should
be informed. Nurses from both hospitals should
request and provide updates on the patients
status. Communicate clearly and deal sensitively
with family and their care takers
Documentation
A written clinical record is necessary, as
with any patient treatment, but possibly more
important because these are patients who are
generally critically ill but who in addition, for
the duration of the transfer, are not managed in
an optimal environment
Ongoing assessment should occur at regular
intervals throughout the transfer
Vital signs must be regularly recorded on a
flow sheet
Safety
Consider the safety of the patient as well as
the transport team at all times. There is no need
for the ambulance to exceed the speed limits.

Traveling at high speed with a siren blaring and
blue lights ablaze may be dramatic but will save
very little time. It is clearly unnecessary if the
patient has been adequately assessed and properly
stabilized.
Finally, the work of the transport team is
not complete until the patient has been safely
transferred to static equipment of the PICU. A
member of the team should ensure that the
transport equipment is put back on charge and
any faults are notified to the appropriate
department for prompt repair.
Transport Physiology
During transport child can have stresses
which may be dynamic as in acceleration or
deceleration, or static, relating to the problems
of the available environment. This can lead to
unpredictable effect on the blood pressure and
intracranial pressures4.
If patient is lying, as is typical, with the head
towards the front of the ambulance, rapid
acceleration will tend to reduce the venous return,
and hence reduce the filling pressures, leading
to reduced cardiac output. Conversely,
deceleration increases venous return to the heart
and may increase cardiac output, or with failing
heart may cause heart failure and reduced cardiac
output. In general, the patient will tolerate sudden
increase in venous return better than sudden
decrease.
Sudden increase in venous pooling in the
head will lead to increase in intracranial pressure
which may be of significance to the head injured
patient. Also, acute reduction in blood pressure
caused by venous pooling in the legs will reduce
cerebral perfusion.
In air transport with high altitude, child may
develop two problems.
1. Expansion of gas filled spaces eg.
77
2006; 8(1) : 77
Pneumothorax, stomach gas, blood
pressure cuff, ETT cuffs.
2. Reduction in oxygenation
The ambulance environment
The aim of the transport team is to recreate
intensive care for the patient within the
ambulance. The small space available,
unfamiliarity of the environment and the motion
of the ambulance make this difficult.
The ambulance for transport must have a
method of securing the incubator or trolley and
any other instrument and power supply where
required (i.e. for transport incubator).
Access to the patient
The patient is normally placed on one side
of the ambulance, so that access is restricted to
the free side only, with limited access to the head.
The side arrangement of the patient leaves lot of
space for the retrieval team to work as compared
to the central arrangement of the patient.
Seating configurations
One person should be at the head end to
provide constant monitoring and to look after the
airway and others at the side. The nurse should
be in a position to easily reach equipment and to
observe the patient and the monitor.
It is very important to maintain appropriate
ambulance environment for effective and safe
transport.
What when things go wrong?
With adequate preparation and intervention
most retrieval will pass off without any problems.
However sometimes things can go wrong3.
Unsalvageable child
Occasionally, the patient to be transferred
may deteriorate in the interim period. Whether
Indian Journal of Practical Pediatrics 2006; 8(1) : 78

or not to transfer will depend on the referring Conclusion

doctor and familys expectations. The patient
should be transferred in case he needs an
advanced life support. The patient can be
transferred to the transition unit giving the family
time to call more relatives and make
arrangements for religious rituals. If the patient
is not transported then assure a good airway and
inotropic support.
Morbidity in transit
Morbidity on the way is due to equipment
failure or failure to recognize poor oxygenation
and shock. Such incidents are reduced by
appropriate training of the staff, prior planning
and familiarity with retrieval equipment.
Death in transit
Unfortunately, if the child develops cardio
respiratory arrest, CPR should be started but how
long to resuscitate depends on the diagnosis and
prognosis of the patient. Besides, if the base or
any ICU is nearby one should continue
resuscitation.
There are two rules for CPR:
Most retrievals are uneventful with prior
knowledge of the equipment, sound preparation
and good clinical skills. Occasionally difficult
clinical, administrative and ethical problems arise
that would tax the skills of most of the team
members. Discussion among the crew members
can help solve such problems. After transporting
the child, once everything has settled, revisit the
problem and determine how to deal with it next
time2.
References
1. Pon S, Notterman DA. The Organization of a
Pediatric Critical Care Transport Program.
Pediatr Clin North Am 1993; 40:241-262.
2. Warren J, Fromm RE, Orr RA, Rotello LC,
Robert EF, Horst M. Guidelines for the inter
and intrahospital transport of critically ill
patients. Criti Care Med 2004; 32(1): 256-262.
3. Bary P, Hunt C, Merriman M, Luyt D,
Leslie A. Pediatric and Infant Critical Care
Transport Course manual, 3rd Edn, July 2003;
pp 1.5-15.5.

If one is doing CPR make sure it is effective.
If any hospital nearby can be reached fast, it
is better to reach there to continue CPR rather
than of the back of an ambulance
4. Kicullen JK, Kedar SD, Vladimir K. Transport
of a Critically ill patient. In: Textbook of
Intensive Care Medicine. 5th Edn, Eds Irwin RS
& Rippe JM, Lippincott Williams, Philadelphia,
2003; pp 2258-2265.

NEWS AND NOTES

PALS Provider Course, Lucknow

Date: 26th & 27th August 2006
Contact:
Dr.Banani Poddar
Department of Critical Care Medicine,
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow 226 014. Uttar Pradesh.
Tel: 0522-2668700, Ext: 2540, 2549
Fax: 522-2668017, 2668078.
Email: bananip@sgpgi.ac.in / bananip@hotmail.com

78

PRACTITIONERS COLUMN
CHOLELITHIASIS IN CHILDREN
* Ganesh R
** Shivbalan So
***Bhaskar Raju B
*** Malathi Sathiyasekaran
Cholelithiasis is relatively uncommon in
infancy and childhood. Since the advent of
ultrasonography incidental or silent
gallstones are now being detected more often in
children and even in utero.
Epidemiology
The prevalence of gallstones in children is
0.15-0.22% compared to 4-11% in adults1 and is
influenced by age, sex, culture, ethnicity, medical
factors and geography. A higher prevalence of
4.7% is seen in Downs syndrome. Fetal
gallstones are rare and are usually detected in
the last trimester and are more common among
male fetus. The incidence of cholelithiasis is
lower in boys of all ages, whereas girls have a
significant increase during adolescence. In a
review by Friesen et al of 693 cases of childhood
gallstones 10% were less than 6 months, 21%
were 6 months to 10 years and 69% were 10-21
years of age2.
A retrospective analysis of 13675 abdominal
ultrasound studies performed in children
* Resident in Pediatrics
** Assistant professor of Pediatrics, SRMC &RI
(DU)
*** Consultant Pediatric Gastroenterologist,
Kanchi Kamakoti CHILDS Trust Hospital
Chennai -600 034.
79
2006; 8(1) : 79
attending KKCTH Chennai, for varying
indications revealed gallstones in 43 (0.31%), of
which only 2 had symptomatic cholelithiasis
requiring cholecystectomy. The age distribution
was less than 1 year 28%, 1-5 years 23%, 5-10
years 37% and 10-15 years 12%3. A similar
analysis of children with symptomatic
cholelithiasis, who underwent cholecystectomy
in ICH Chennai, during the period 1996 to 2004,
was done and 28(0.009%) children out of a total
of 2,92,000 admissions were identified. Of these
2 had additional choledocholithiasis. There was
no child less than 3 years but 75% were more
than 7 years of age.
Pathophysiology
Bile consists of 5 major components: water,
bilirubin, cholesterol, bile pigments and
phospholipids (lecithin) and 2 minor components:
calcium salts and some proteins. Gallstones occur
owing to the precipitation of the insoluble
constituents namely bile pigments, cholesterol
and calcium salts. The 3 primary conditions that
are necessary for formation of gallstones are
supersaturation of bile with cholesterol or bile
pigments, nucleation to solid crystals and stasis
of bile in the gall bladder. The associated
conditions such as hypersecretion of mucus by
gall bladder and increase in arachidonyl lecithin
could further enhance stone formation1.
Types of Gall stones
The 3 types of gallstones namely cholesterol
stones, pigment stones and mixed stones are also
seen in children, with pigment stones being
predominant below the age of 5 years and
cholesterol stones increasing in incidence after
Indian Journal of Practical Pediatrics
the age of 6 years. However studies in adults have
shown regional variations with pigment stones
being more common in south India compared to
the cholesterol stones seen in the north Similar
studies in Indian children are not are available.
Cholesterol stones: These are yellowish white,
hard, solitary or multiple, radiolucent stones
located in the gallbladder which can migrate to
the biliary passage. Spontaneous dissolution of
stones occurs in 50% of infants. Cholesterol
stones are associated with hyperlipidemia,
obesity, cystic fibrosis and octreotide therapy.
Pigment stones : The two types of pigment
stones namely the black and brown are also seen
in children. Calcium bilirubinate is the main
constituent, which interacts with mucin
glycoprotein to form pigment stones. Calcium
palmitate and cholesterol are present more in
brown pigment stones.
Black pigment stones: These are dark brown to
black in color, small, multiple, hard, radio opaque
stones located in gallbladder and are usually seen
in hemolytic disease, cirrhosis or following total
parenteral nutrition therapy.
Brown pigment stones: These are brown to
orange in color, soft, radio opaque and originate
in the common bile duct. The most important
association is infection of the biliary tree with
either parasites such as Clonorchis sinensis,
Ascaris lumbricoides or bacteria such as E.coli,
Staphylococcus and Enterobacter. Urosepsis can
be a predisposing factor in young infants.
Infected bile with stasis results in excessive
secretion of mucin, which serves as the
glycoprotein nidus for stone formation. The
enzymes released by bacteria act on the various
constituents of bile producing unconjugated
bilirubin, free saturated fatty acids and free bile
acids, which precipitate with calcium to form
stones. Biliary tree abnormalities such as Carolis
80
2006; 8(1) : 80
disease, choledochal cyst, sclerosing cholangitis
and strictures may also predispose to brown stone
formation.
The various conditions associated with
gallstones differ according to the age of the child
and are shown in Table 14. In some children,
however, no predisposing factor may be
identified.
Total parenteral nutrition (TPN): TPN induced
cholestasis may be seen in 80% of infants two
months following parenteral alimentation. The
absence of oral feeding reduces enterohepatic
circulation of bile acids, inhibits release of
cholecystokinin (CCK), gastrin, secretin, motilin
and glucagon leading to formation of stones in
infants. The gallstones are composed of a mixture
of bilirubin and cholesterol and belong to a
special group of TPN induced pigment stones.
The incidence of sludge formation six weeks after
therapy can be as high as 100% in adults1.
Ileal disease and ileal resection: Terminal ileal
disease results in interruption of bile acid
recycling and reduction in bile salt pool favoring
cholesterol supersaturation and formation of
gallstones that usually occurs after puberty.
Cystic fibrosis: Radiolucent cholesterol
gallstones have been found in 12.0 to 27.5% of
patients with cystic fibrosis. The gallbladder may
be hypoplastic micro gall bladder. In cystic
fibrosis, cholelithiasis has always been associated
with pancreatic insufficiency.
Obesity: The risk of cholesterol gallstone
formation in children with obesity is not clear
but is high in obese adolescent or pregnant
females. The biliary secretion of cholesterol is
increased relative to bile acid and phospholipid
secretion, thus predisposing to stone formation.
Drugs: Various drugs like furosemide, octreotide
and ceftriaxone have been associated with
gallstones (Table 2).
 2006; 8(1) : 81

Table1. Etiology of gallstones in children

0-12 months 1-5 years 6-18 years
Prematurity Hepatobiliary disease Cystic fibrosis
TPN Abdominal surgery Hemolytic disease
Abdominal surgery Artificial heart valve Obesity
Sepsis Drugs : Ceftriaxone Abdominal surgery
Bronchopulmonary dysplasia Malabsorption Oral contraceptives
Hemolytic disease Cystic fibrosis Hepatobiliary disease
Malabsorption Hemolytic disease TPN
Necrotizing enterocolitis TPN Malabsorption/IBD
Hepatobiliary disease Pregnancy

Furosemide: Furosemide has been implicated in
gallstone formation. In addition to the drug
numerous contributing factors such as
prematurity, sepsis and small bowel disease may
play a role in the formation of gallstones.
Octreotide: Gallstone formation has been
reported in 50% of patients receiving octreotide
for prolonged periods. It may be due to octreotide
induced gallbladder stasis or a direct effect of
octreotide on gallbladder mucosal absorption.
Ceftriaxone: Ceftriaxone is excreted in bile and
has the ability to displace bilirubin from albumin
binding sites. The sludge contains high
concentration of a calcium salt of ceftriaxone with
traces of bilirubinate and cholesterol thus
resembling pigment stone in its composition.
Fasting and children older than 2 years are
important risk factors for this pseudolithiasis.
The stones undergo spontaneous dissolution after
withdrawal of the drug5.
Table 2. Drugs causing cholelithiasis
1. Ceftriaxone
2. Furosemide
3. Octreotide
4. Cyclosporine
81
Cyclosporine: Cyclosporine has been implicated
in gallstone formation and is possibly related to
increased drug levels and hepatic toxicity.
Cirrhosis and chronic cholestasis: Children
with cirrhosis are at increased risk for pigment
gallstones. In Wilsons disease calcified pigment
stones can occur because of recurrent episodes
of hemolysis. Gallstones are also seen in Bylers
disease and inborn errors of bile salt metabolism.
Chronic Hemolytic Disease: Black pigment
stones are seen in patients with chronic hemolytic
disorders including hereditary spherocytosis,
sickle cell (S-S and S-C) disease, thalassemia
major and minor, pyruvate kinase deficiency,
glucose-6-phosphate dehydrogenase deficiency
and autoimmune hemolytic disease. The
prevalence of pigment stones in patients with
hemolytic disorders increases with age. In sickle
cell anemia the frequency is 14% in less than 10
years of age, 36% in the group 10-20 years and
by 33 years it is 60 to 85% .In hereditary
spherocytosis the range is from 4- 63%6.
Clinical features of gallstones
The classic symptom complex of acute
cholecystitis such as right upper quadrant pain
and vomiting is usually seen in older children
Indian Journal of Practical Pediatrics 2006; 8(1) : 82

Fever, if present, indicates associated

Fig 1. Ultrasound showing gallstones
and adolescents. Younger children tend to
present with nonspecific symptoms such as
incessant cry or poor feeding. Jaundice is a
presentation in symptomatic infants.
Intolerance to fatty food is uncommon in children.
cholecystitis. Complications like
choledocholithiasis, cholangitis, gallbladder
perforation and mucocele of the gallbladder are
less common in children. Pancreatitis has been
identified in 8% of children with gall stone
disease and probably is the most common
complication7.
Asymptomatic gallstones and its natural
history: More than 80% of the gallstones are
silent or asymptomatic and these are more
common during infancy and preschool years. The
natural history of asymptomatic gallstones in
adults has revealed that even after 15 years of
follow up, only 18% became symptomatic and
2 % per year had biliary pain for the first 5 years,
which decreased over time8. A similar natural
history is also possible in children.

Suspect gallstones in children with:

RAP (epigastrium and right hypochondrium)
Recurrent jaundice abdominal pain
Recurrent cholangitis / Pancreatitis
Family history of gallstone disease

USG abdomen

Gall stones + Hemoglobin Gallstone +

Intra hepatic biliary Total count IHBR dilated
radicle (IHBR) Reticulocyte count CBD stone +
normal Peripheral smear
No CBD stones Transaminases
Alkaline phosphatase
Lipid profile

Surgery (LAP or open Surgery / Endoscopic

cholecystectomy) intervention

Fig 2. Approach to gallstones in children

82

Gallstones
Gall bladder
Asymptomatic Symptomatic
Normal GB wall Hemolytic disease
Septate GB
Thickened and contracted GB
Porcelain GB
Observation Stones>2 cm
Surgery (LAP or
open cholecystectomy)
Fig 3. Management of asymptomatic / symptomatic gallstones in children
Diagnosis
Ultrasonography identifies gallstones as an
echogenic mass with acoustic shadows and is the
safe, sensitive and specific method (Fig 1). If a
gallbladder can be identified by ultrasound, the
stone identification rate is as high as 98%4. Biliary
microlithiasis are stones smaller than 2 mm that
are not detected by imaging techniques9. Plain
abdominal radiographs identify stones that have
high calcium content. Therapeutic ERCP is
reserved for choledocholithiasis.
Management
Symptomatic children presenting with any
of the following features namely recurrent
abdominal pain (RAP) localized to epigastrium
or right hypochondrium, recurrent jaundice with
or without abdominal pain, cholangitis or
pancreatitis and those with family history of
gallstones should be evaluated for gallstone
83
2006; 8(1) : 83
CBD
Asymptomatic
Surgery /
endoscopic
intervention
disease (Fig 2). An ultrasound of the abdomen is
the simple, safe, sensitive and specific
noninvasive test, which will help in diagnosis.
All children with symptomatic gallstones should
undergo cholecystectomy 4 . Prior to
cholecystectomy, an evaluation of the liver
enzymes, lipid profile and hemolytic work up
may be beneficial. If choledocholithiasis is also
detected on ultrasound, the common bile duct
stones should be removed before or during
cholecystectomy. Endotherapy with
sphincterotomy and basketting is recommended
for management of choledocholithiasis (Fig 2).
Asymptomatic children, in whom a
diagnosis of incidental gallstone is made on
routine ultrasound examination of the abdomen,
should not be subjected to prophylactic
cholecystectomy. Blood investigations such as
CBC, reticulocyte count, peripheral smear,
transaminases, alkaline phosphatase and lipid
Indian Journal of Practical Pediatrics 2006; 8(1) : 84

profile are done as a part of evaluation. Those
children with hemolytic disease, porcelain
gallbladder, congenital malformation of gall
bladder such as septate gall bladder should
undergo cholecystectomy even if asymptomatic
(Fig 3)
Medical dissolution of gallstones:
Ursodeoxycholic acid is recommended for oral
dissolution of small,radiolucent, cholesterol
stones. As the majority of children have pigment
gallstones, this form of therapy is not effective.
Prevention
Gallstones can be prevented in children on
TPN by initiating early limited enteral feeds.
Pancreatic supplements in cystic fibrosis will
prevent gall stone formation. Weight control in
obese children and using choleretics in chronic
cholestasis are some of the other methods in
preventing gallstones in children.
References
1. Gilger MA. Diseases of the gall bladder. In:
Wyllie R, Hyams JS, Eds. Pediatric
Gastrointestinal disease: Pathophysiology,
Diagnosis, management. WB Saunders,
Philadelphia, 1999; pp 651-656.
2. Friesen CA, Roberts CC. Cholelithiasis: clinical
characteristics in children, case analysis and
literature review. Clin Pediatr 1989;7: 294-298.
3. Ganesh R, Muralinath S, Sankaranarayanan
VS, Malathi S. Prevalence of cholelithiasis in
children-a hospital based observation. Indian J
Gastroenterol 2005; 24:85.
4. Heubi JE, Lewis LG, Pohl JF. Diseases of the
gall bladder in infancy, childhood and
adolescence. In: Suchy FJ, Sokol RJ, Balistreri
WF,Eds.Liver disease in children. Lipincott
Williams & Wilkins, Philadelphia, 2001; pp
343-362.
5. Robertson FM,Crombleholme TM,Barlow SE
et al. Ceftriaxone choledocholithiasis. Pediatr
1996; 98: 133-135.
6. Lackman BS, Lazerson J, Stashak RJ, et al.The
prevalence of cholelithiasis in sickle cell disease
as diagnosed by ultrasound and
cholecystography. Pediatr 1979; 64:501.
7. Reif S, Sloven DG, Lebenthal E. Gallstones in
children: Characteristics by age, etiology and
outcome. Am J Dis Child 1991;146:105.
8. Gracie WA, Ransohoff DF. The natural history
of silent gallstones: The innocent stone is not a
myth. N Engl J Med 1982; 307:798-800.
9. Choudhuri G, Srivastava A. Biliary
microlithiasis. Tropical Gastroenterol 1978; 19:
11-14.

NEWS AND NOTES

NNF Manual of Neonatal Care
Editors: Jayashree Mondkar & Ranjan Kumar Pejaver
Contributions from leading Neonatologists of India. Covers all the important aspects of Prevention, Diagnosis
and Management of various neonatal conditions.
Useful to Neonatal practitioners at all levels, may it be in Community practice or Hospital based units, also
to students of Neonatology.
Rs. 360/- ISBN : 81-7286-373-X
Available at all leading Medical Book Stores or Contact
PRISM BOOKS PVT LTD NATIONAL NEONATOLOGY FORUM
# 1865, 32nd Cross, BSK II Stage, 803, North ex Tower, Netaji Subash Place,
Bangalore-560 070, India Ring Road, Pitampura, Delhi - 110034
Tel: 26713991 / 26714108, Fax: 26713979 Tel : 27198647
E-mail: prism@vsnl.com

84
 2006; 8(1) : 85

RADIOLOGIST TALKS TO YOU

ACUTE ABDOMEN IN THE

CHILD-II
* Vijayalakshmi G
** Natarajan B
*** Ramalingam A
In continuation of our earlier article on
sonographic imaging in acute abdomen, we will
discuss a few more aspects of ultrasound in acute
gastrointestinal problems. Ultrasound is very
limited in identifying acute gastrointestinal
conditions because of the inteference by luminal
air. However, important clues can be obtained
Fig 1. Dilated bowel loops due to
from the state of distension and movement of
intussusception (I)
the bowel. This practical information is useful
in day to day practice .
Gastroenteritis and accompanying post
diarrheal ileus is a common problem in pediatric
practice. In abdominal distension due to paralytic
ileus, the ultrasound will demonstrate dilated
loops without peristalsis. To and fro non-
propulsive movement may also be seen. This is
just like listening for bowel sounds with the
stethoscope. With this sonographic information
the appropriate course of action can be followed.
In organic obstruction there are dilated
bowel loops with active peristalsis. Fig 1 shows Fig 2. Dilated bowel loop (B). Echogenic
dilated small bowel loops due to intussusception. mesenteric thickening (M) around appendix

* Addl Professor, Dept. of Radiology This is one condition where ultrasound help to
Chenglepet Medical College and Hospital. identify the cause of the obstruction and also in
** Lecturer the management. However when dilated small
*** Reader bowel loops are seen , as in this case it denotes
Dept. of Radiology that, there is an additional ileal component which
ICH & HC., Egmore, Chennai. is best treated surgically.
85
Indian Journal of Practical Pediatrics
Fig 3. Dilated aperistaltic loop over the
appendix (A)
Fig 2 belongs to a thirteen year old boy with
vomiting . Ultrasound of abdomen showed
dilated bowel loops with a clump of bowel loops
along with mesenteric thickening in the right iliac
fossa. There was also a lot of free fluid in the
peritoneal cavity. A diagnosis of appendiceal
perforation was made. A similar case (Fig 4)
which was also diagnosed as appendicular
pathology turned out instead to be ileal
perforation.
Free fluid in the peritoneal cavity is a very
important finding in acute abdomen . Perforation
and leakage of bowel content causes irritation
of the peritoneum and therefore there will always
be some peritoneal fluid. Segmental enteritis,
necrotizing enterocolitis and gangrene of bowel
NEWS AND NOTES
CME ON COMMON EMERGENCIES IN CHILDREN
th
Date: 19 March 2006 Venue: Chandigarh
Contact:
Dr.Arun K Baranwal
Department of Pediatrics, Govt. Medical College and Hospital, Sector 32 B, Chandigarh
Ph: 0172 2665253 Ext. 2514, 2503 (O), 9417402242 (M) and 0172 2647948 (R)
Fax: 91-172-2608488, 2609360. Email: baranwal1970@yahoo.com
86
2006; 8(1) : 86
Fig 4. Aperistaltic loop (L) overlying
thickened segment of bowel (B)
are also accompanied by peritoneal fluid.
Irreducible hernias with fluid collections adjacent
to the closed loop or in the general peritoneal
cavity should sound an alert for gangrene.
Minimal fluid in the pelvis is also seen at the
time of ovulation and is usually accompanied
with lower abdominal pain and tenderness . This
diagnosis can be made in a girl after exclusion of
other conditions.
Another feature that can be made out is a
loaded colon which might be a cause for acute
abdominal pain.
In conclusion, bowel loop distension,
peristalsis and free fluid in the peritoneal cavity
are useful findings that will help in decision
making in a child with acute abdomen

CASE STUDY
KLIPPEL TRENAUNAY
SYNDROME
* Dinesh Kumar J
** Anuradha D
*** Meena Jayashankar
**** Chandralekha K
Klippel-Trenaunay syndrome (KTW) is a
rare, non-heritable, sporadic, complex
developmental disorder characterized by
cutaneous angiomata, varicose veins,
pigmentation over trunk and limbs with an
asymmetric distribution and hypertrophy of
related bone and soft tissues. The diagnosis is
essentially based on clinical features.
Case study
We present this case, of a two and a half-
year-old male child referred to the Department
of Medical Genetics for evaluation of dysmorphic
features and multiple anomalies, for its rarity.
He is the first born child, to parents of non-
consanguineous marriage, delivered at term by
outlet forceps. Birth weight was 3.5 Kg and there
was no birth asphyxia or birth trauma. The mother
had noticed multiple red brown pigmented
* Special Trainee
** Assistant Professor
*** Reader in Medical Genetics
**** Professor and Head of Department (Retired)
Department of Medical Genetics,
Madras Medical College,
Institute of Obstetrics and Gynaecology,
Egmore, Chennai 600008.
87
2006; 8(1) : 87
patches all over the body and enlargement of both
upper limbs at birth. Pedigree analysis showed
no similar disorders in the family. Second
pregnancy was medically terminated. Develop-
mental history was normal with no history of
seizures, serious illnesses, hearing or visual
impairments.
Clinical examination revealed a conscious,
oriented, playful child with normal intelligence,
speech and behaviour. The child was afebrile with
no temperature difference between the limbs.
Vital signs were normal. JVP was not elevated.
Blood pressure recorded in the right upper limb
was 90/60 mm Hg with no significant difference
between the two sides. Height 85 cms, upper
segment to lower segment ratio was 1.4: 1, weight
12 Kg, appropriate for age.
Dysmorphic facies with blunt nose,
depressed nasal bridge and hypertelorism were
present. Head circumference was 49 cms, and
no plagiocephaly. Examination of the eyes
revealed no visual impairment, normal anterior
and posterior chamber contents and normal
intraocular tension. Dentition, hair and nails were
normal. A soft, pseudo-fluctuant swelling
measuring about 10x15x8 cms was present on
the left side of back, suggestive of
lymphangioma. Multiple cutaneous
hemangiomas (Port-wine stain) of variable size,
with overlying pigmentation, dark brown to black
in colour, diffuse and faded, predominantly on
the left side of the body were present. The areas
included lower abdomen, back, left arm, forearm,
dorsum of hand, left gluteal region, back of thigh,
leg, and dorsum of foot (Fig 1 and 2).
Indian Journal of Practical Pediatrics
Hypertrophy of both upper limbs with
macrodactyly of right ring, middle fingers and
left big toe. Anthropometric measurements and
x-ray of affected regions confirmed the
hypertrophy. There were no varicosities, signs
of chronic venous insufficiency, joint deformities,
or crease abnormalities. Signs of AV
malformations like bruits, thrills or pulsations
were absent. Abdomen examination revealed a
soft, non-tender spleen palpable just below the
left costal margin. Scrotum was well developed
with bilateral descended testes. Phimosis, with
superficial inguinal lympadenopathy was
observed. Other systems were clinically normal.
Routine biochemistry, blood counts, platelet
count were normal. Peripheral smear, ECG and
X-ray chest were normal. Ultrasound abdomen
revealed enlarged spleen, 9.9 cm in the greatest
dimension, with normal echo texture. Other
structures were normal and no vascular anomalies
were detected. Urine metabolic screening was
negative and CT scan brain was normal.
Karyotyping was normal (46, XY). Plain X-ray
of the affected limbs revealed soft tissue and bony
hypertrophy (Fig 3).
A diagnosis of Klippel Trenaunay Weber
Syndrome was made based on the presence of
multiple cutaneous hemangiomas, hypertrophy
of limbs with involvement of digits and presence
of lymphangioma. Manifestations at birth with
little progression, absence of skin thickening,
cardiac, renal or eye involvement are in favour
of the diagnosis.
It is a stable disease with normal life span
and minimal morbidity. Absence of mental
retardation, AV malformations, and visceral
involvement improves the prognosis. Since there
were no specific complaints or complications, no
active intervention was required, and regular
follow up was advised. The mother was advised
to continue the present pregnancy because the
risk of recurrence is small, but was advised to
88
2006; 8(1) : 88
undergo serial ultrasound examinations for
prenatal detection of KTW (limb anomalies and
vascular malformations).
Discussion
Klippel Trenaunay Syndrome was first
described in 1900 by French physicians Klippel
and Trenaunay in 2 patients presenting with a
port-wine stain and varicosities of an extremity
associated with hypertrophy of the affected
limbs bony and soft tissue1. In 1907, Parkes
Weber2, unaware of their report, described a
patient with the 3 aforementioned symptoms as
well as an arteriovenous malformation of the
affected extremity.
The exact pathophysiology of Klippel
Trenaunay Syndrome remains to be elucidated
and several theories exist. Bliznak and Staple3
suggested intrauterine damage to the sympathetic
ganglia or intermediolateral tract leading to
dilated microscopic arteriovenous anastomoses
as the cause. Servelle4 believed that primary deep
vein abnormality, with resultant obstruction of
venous flow, leads to venous hypertension and
subsequent development of varices and limb
hypertrophy. Baskerville et al5 contend that a
mesodermal defect during fetal development as
the etiology, while McGrory and Amadio6 believe
that mixed mesodermal and ectodermal
dysplasias as the likely cause of Klippel
Trenaunay Syndrome.
Klippel Trenaunay Syndrome otherwise
called Angio Osteo hypertrophy syndrome is
a rare entity. Most cases are sporadic although
some reports of autosomal dominant pattern of
inheritance have been reported 7,8. No racial
predilection is seen and affects males and females
equally. It usually presents at birth or during early
infancy. Most patients demonstrate all three
features of the triad. In a study conducted at Mayo
Clinic9 out of the 252 patients, only 63% of cases
manifested all three components of the triad. Port-

Fig 1.Front of the boy showing dysmorphic
facies, hypertrophied upper limbs,
macrodactyly of right ring finger and left big
toe, port wine stain on the dorsum of the left
hand.
wine Stain was the most common manifestation,
found in 98% of cases and varicosities were
present only in 72% of cases. However the
diagnosis can be made with any two of the three
features10.
Clinical features are protean in nature and
the management is mainly conservative with
emphasis on early detection and treatment of
complications9,11-15. Capillary hemangiomas are
usually confined to one side of the body, affecting
the lateral aspects of the limbs. They are present
at birth, may be limited to the skin or may extend
into deeper structures. Involvement of internal
organs portends greater morbidity and mortality,
manifesting as hematuria, hematochezia, seizures
and mental retardation. Cavernous hemangiomas
and lymphangiomas may also be present.
89
2006; 8(1) : 89
Fig 2. Back of the boy showing
lymphangioma, bilateral upper limb
hypertrophy
Varicose veins are congenital, but may not
manifest till the child ambulates, usually affecting
large, laterally situated superficial veins in the
lower limb. Underlying abnormalities in the deep
veins like agenesis or atresia may be present and
varicosities may involve internal organs. AV
anastomoses may be present rarely and worsen
the prognosis due to complications such as high
output cardiac failure.
Bone and soft tissue hypertrophy may result
in increased length and /or increased girth of
limbs. It may be present at birth and progress
during the first few years of life, resulting in limb
length discrepancies and joint abnormalities.
Macrodactyly, polydactyly, oligodactyly or
syndactyly may be present on the affected limbs.
Internal viscera and external genitalia may be
Indian Journal of Practical Pediatrics
Plain X-ray both hands showing soft tissue
hypertrophy of the right ring and middle
fingers, with widening of the web space
between them
enlarged and lymphedema can complicate the
situation.
Other features include mental retardation,
seizures, spina bifida, hypospadiasis,
hypertrichosis, hyperhidrosis, facial
dysmorphism, eye anomalies, macrocephaly, etc.
Complications include skin breakdown and
ulceration, leading to bleeding and secondary
infection of cutaneous hemangiomas and rarely
a syndrome of consumption coagulopathy.
Varicose veins may result in paresthesia, stasis
dermatitis, cellulitis, thrombophlebitis and
pulmonary emboli. Asymmetric hypertrophy of
a limb may lead to subsequent vertebral scoliosis,
joint or gait abnormalities.
A detailed history and clinical examination
is sufficient in most cases to arrive at the
diagnosis. Investigations may be required in
certain cases especially if complications are
present. These include X-ray of affected limbs,
doppler and duplex scan for varicose veins,
arteriography to delineate AV fistulas and USG,
CT scan or MRI for soft tissue, brain and visceral
90
2006; 8(1) : 90
involvement. Prenatal diagnosis by ultrasound is
possible. Previously Klippel-Trenaunay
syndrome and Parknays-Weber syndrome were
considered to be different spectrums of the same
syndrome. Arterio-venous malformations (AV
shunting and AV fistula) are the most imporant
components of ParksWeber syndrome and high
output cardiac failure may occur, but Klippel-
Trenaunay syndrome is a pure low-flow condition
without any significant fistula16. The distinction
of both entities is relevant since the natural
history, prognosis and treatment strategies differ
significantly 17. The two syndromes can be
distinguished by either Doppler study of the
vessels or Magnetic resonance projection
angiography.
The important differential diagnosis to be
considered is Proteus syndrome, which usually
manifests later in infancy, progressive and
associated with higher mortality and morbidity.
Subcutaneous thickening especially of palms and
soles, verrucous hyper-pigmented skin,
prominent skeletal changes and eye, cardiac,
renal and CNS involvement favour this diagnosis.
Other DDs include Maffucci syndrome,
Rubinstein Taybi syndrome, Beckwith
Wiedemann Syndrome, Cobbs disease and
Sturge Weber Syndrome.
Definitive surgical treatment is indicated
only in a few selected cases. Laser ablation
treatment 18,19 for disfiguring cutaneous
hemangiomas has been successful and
compression garments have been useful in the
management of capillary hemangiomas, chronic
venous insufficiency and lymphedema. Limb
length discrepancies, deformities etc may require
surgical correction. Significant arterio-venous
malformations can be removed but debulking
operations and varicose vein surgery may further
compromise the lymphatic and venous drainage
and hence not advised routinely20. Prognosis is
good and normal life span is expected.

Accurate diagnosis, proper genetic
counselling and early prenatal diagnosis helps
parents make an informed choice regarding the
birth of a child with KTW.
References
1. Klippel M, Trenaunay D. Du naveus variqueux
osteohypertrophique. Arch Gen Med 1900;
185:641.
2. Parkes Weber F. Angioma formation in
connection with hypertrophy of limbs and
hemi-hypertrophy. Br J Dermatol 1907;
19:231.
3. Bliznak J, Staple TW. Radiology of
angiodysplasias of the limb. Radiology 1974;
110(1): 35-44.
4. Servelle M. Klippel and Trenaunay syndrome.
768 operated cases. Ann Surg 1985; 201(3):
365-373.
5. Baskerville, et al., The etiology of Klippel-
Trenaunay Syndrome. Ann Surg 1985; 202(5):
624-627.
6. McGrory BJ, Amadio PC. Klippel-Trenaunay
syndrome: Orthopaedic considerations. Orthop
Rev 1993; 22(1): 41-50.
7. Aelvoet GE, Jorens PG, Roelen LM. Genetic
aspects of the Klippel-Trenaunay syndrome.
Brit J Dermatol 1992; 126(6): 603-607.
8. Ceballos-Quintal JM, Pinto-Escalante D,
Castillo-Zapata I. A new case of Klippel-
Trenaunay-Weber (KTW) syndrome: evidence
of autosomal dominant inheritance. Am J Med
Genet 1996; 63(3): 426-427.
9. Jacob AG, Driscoll DJ, Shaughnessy WJ, et al.,
Klippel-Trenaunay syndrome: spectrum and
management. Mayo Clin Proc 1998; 73(1): 28-
36
10. Jacob AG, Driscoll DJ, Shaughnessy AW, et
al. Klipper Trenaunay syndrome: Specttrum
and management. Mayo Clin Proc 1998; 73:
28-26.
91
2006; 8(1) : 91
11. Jones KL. Klippel-Trenaunay-Weber
Syndrome. In: Smiths Recognizable Pattern of
Human malformations, 5th ed: Eds. Jones KL,
Philadelphia, WB Saunders Company, 1997;
pp 512-513.
12. Esterly NB. Klippel-Trenaunay-Weber
Syndrome. In: Nelsons Textbook of Pediatrics,
14th ed: Eds. Behrman RE, Kleigman RM,
Philadelphia, WB Saunders Company, 1992;
pp 1630-1631.
13. Baskerville, et al., The Klippel-Trenaunay
syndrome: Clinical, radiological and
hemodynamic features and management. Brit
J Surg 1985; 72:232.
14. Samuel M, Spitz L. Klippel-Trenaunay
syndrome: clinical features, complications and
management in children. Br J Surg 1995; 82(6):
757-761.
15. Fishman SJ, Mulliken JB. Hemangiomas and
vascular malformations of infancy and
childhood. Pediatr Clin North Am 1993; 40(6):
1177-1200.
16. Moodie D, Driscoll D, Salvatore D. Peripheral
vascular Disease in children. In: Young J, Clini
J, Barthoilomew J, Eds, Peripheral vascular
Diseases. St.Louis, MOsby Yearbook
Publishers, 1996; 541-552.
17. Ziyeh S, Spreer J, Rossler J, et al. Parks-Weber
or Klippel-Trenaunay syndrome? Non-
invasive diagnosis with MR projection
angiography. Eur Radiol 2004; 2025-2029.
18. Spicer MS, Goldberg DJ, Janniger CK. Lasers
in pediatric dermatology. Cutis 1995; 55(5):
270-272.
19. Spicer MS, Goldberg DJ, Janniger CK. Lasers
in pediatric dermatology. Cutis 1995; 55(5):
278-280.
20. Gloviczki P, Stanson AW, Stickler GB, et al.,
Klippel-Trenaunay syndrome: the risks and
benefits of vascular interventions. Surgery.
1991; 110(3): 469-479.
Indian Journal of Practical Pediatrics
CASE STUDY
MIXED CONNECTIVE TISSUE
DISEASE IN CHILDHOOD
* Ganesh R
* Sathyaprakash.M
** Deenadayalan .M
*** Lalitha Janakiraman
Abstract: Mixed connective tissue disease
(MCTD) is uncommon in children and still
remains a controversial diagnosis. We herewith
report a 12-year-old girl who was diagnosed to
have mixed connective tissue disease and
responded to steroids.
Key Words: MCTD, children, steroids.
In 1972, Sharp and colleagues first proposed
mixed connective tissue disease as a separate
autoimmune disorder1. This was the first overlap
syndrome defined in terms of specific antigen-
antibodies to a ribonuclease sensitive extractable
nuclear antigen. We here with report one such
case.
Case study
A 12-year-old girl presented with fever and
rash involving the extensor surface of the arms
and legs for one month, along with pain and
stiffness of both small and large joints of one year
duration. She had noticed her fingers and toes
turning pale on exposure to cold for the last two
* Resident in Pediatrics
** Junior consultant in Pediatrics
*** Senior Consultant Pediatrician
Kanchi Kamakoti CHILDS Trust Hospital
Chennai - 600 034.
92
2006; 8(1) : 92
years and thickening of the skin of the face, trunk
and hands for the last one and a half years. She
had loss of appetite and weight during the last 6
months. There was no history of heartburn,
dysphagia, odynophagia, chestpain, dyspnoea or
decreased urine output. On examination, she was
febrile and emaciated. She weighed 28 kg (70%
of the expected) with height of 154 cms
(appropriate for age). She had maculopapular
rashes on the extensor surfaces of the arms and
legs with pressure ulcers over the elbow and ankle
joints with scleroderma of the skin over the face,
trunk and hands. On exposure to cold, she had
Raynauds phenomenon. There was proximal
muscle weakness with flexion contractures of the
knee joints. Systemic examination including eye
examination was normal.
Her WBC count was 5500 with normal
differential count, hemoglobin was12.8 g/dL
while PCV was 40%. Platelet count was 4.9 lakhs.
ESR at one hour was 40 mm and her CPK level
was 4348 IU/L (Normal: 15-135 IU/L). Renal
and liver function tests were normal. Chest
skiagram and ultrasound abdomen were normal.
Echocardiogram revealed normal pulmonary
arterial pressures with good ejection fraction
(74%). The forced vital capacity (FVC) and
forced expiratory volume in one second (FEV1)
were normal. Antinuclear antibody was strongly
positive (1:40 dilution by indirect fluorescent
antibody technique) and anti ds-DNA was
negative. HIV I and II were negative. Antibodies
against the U1 ribonucleoprotein (anti U1RNP)
was positive (immunoblot method)
while rheumatoid factor was negative.
Electromyography and muscle biopsy was not

Table 1: Alarcon-Segovia criteria for
diagnosis of MCTD
1.Serologic criteria:
Anti-RNP at heamagglutination titre of
>1:1600
2.Clinical criteria:
Swollen hands
Synovitis
Myositis(biologically proven)
Raynauds phenomena
Acrosclerosis
Note: MCTD is present if serologic criteria is
accompanied by three or more clinical criteria,
one of which must include synovitis or myositis.
done. In view of the above clinical features and
investigation findings, she was diagnosed to have
mixed connective tissue disease and started on
steroids following which she improved gradually.
Discussion
Mixed connective tissue disease (MCTD)
is a distinct entity, which has some manifestations
of scleroderma, dermatomyositis, systemic lupus
erythematosus and occasionally Sjogrens
syndrome2. It commonly occurs in the age group
of 5-18 years with female preponderance (F: M=
4:1). Its prevalence varies between 1-2 /1,00,000
population in US and 2.7/1,00,000 population in
Japan. MCTD has protean manifestations like
arthritis, arthralgia, alopecia, telengiectasia,
swollen hands, proximal muscle weakness,
scleroderma, Raynauds phenomena, fever,
acrosclerosis, myositis, rash, pleuritis,
pericarditis, esophageal hypomotility, pulmonary
hypertension and leucopenia. There are various
criteria to diagnose MCTD like Sharp (1972)
criteria, Kasukawa criteria, Kahns criteria and
Alarcon- Segovia and Villareal criteria. Alarcon-
Segovia, Villareal and Kahn criteria showed best
93
2006; 8(1) : 93
Table 2: Kahns criteria for diagno-
sis of MCTD
1.Serologic criteria:
High titre anti-RNP corresponding to
speckled ANA>1:1200 titre.
2.Clinical criteria:
Swollen fingers
Synovitis
Myositis
Reynauds phenomena
Note: MCTD is present if serologic criteria is
accompanied by Reynauds phenomena and two
or more of the three remaining clinical criteria.
sensitivity and specificity (62.5 and 86.2%
respectively), (Table 1 and 2)3. The defining
feature of MCTD is the presence of antibodies
against the U1 ribonucleoprotein complex
(U1RNP)4. All patients with MCTD have positive
ANA test and high titre of IgG antibodies against
the U1 ribonucleoprotein (U1RNP complex).
MCTD is a chronic and usually a mild disease
that responds to corticosteroids in the dose of
1-2mg/kg/day. NSAID provide symptomatic
relief for myalgia, arthralgia, edema and
tenderness. Diltiazem or nifedepine is the drug
used for Raynauds phenomena and
pentoxifylline may be added. Azathioprine is
given to children who have MCTD with mild
nephritis whereas cyclophosphamide with
corticosteroids is recommended for children who
have MCTD with WHO class III or class IV lupus
nephritis. Plasmapheresis is recommended as a
possible treatment for multiple organ damage in
MCTD 5.This girl was treated with IV pulse
methyl prednisolone followed by oral steroids.
Her symptoms improved and on follow up she is
doing well. Long-term studies on outcome have
documented that pulmonary hypertension as the
Indian Journal of Practical Pediatrics 2006; 8(1) : 94

most common disease related cause of death. The
mortality rate of juvenile MCTD seems to be in
the same range as that of juvenile systemic lupus
erythematosus, dermatomyositis and
scleroderma. However when compared with the
other connective tissue diseases, minor long-term
problems are seen mainly in surviving patients 6.
References
1. Marisa S Klein Gitelman. Mixed connective
tissue disease.Available from URL: http://
www.emedicine.com/ped/topic1466.htm.
Accesssed on November 11,2004.
2. Fraga A, Gudino J, Niembro FR. Mixed
connective tissue disease in childhood-Relation
ship to Sjogrens syndrome. Arch Pediatr and
Adolesc Medi 1978; 132(3) pp 263-265.
3. Bennett RM. Mixed connective tissue disorder
and other overlap syndromes. In: Shaun Ruddy,
Edward D.Harris, Clement B.Sledge
Eds.Kelleys text book of Rheumatology.Vol 2,
6th Edn, Philadelphia:WB Saunders;2000
p1241-1259.
4. Hoffman RW, Greidinger EL. Mixed
connective tissue disease. Curr Opin Rheumatol
2000; 12(s): 386-390.
5. Seguchi M, Soejima Y, Tateishi A, et al. Mixed
connective tissue disease with multiple organ
damage: Successful treatment with
plasmapheresis. Intern Med 2000; 39: 1119-
1122.
6. Michels H. Course of mixed connective tissue
disease in children. Ann Med. 1997; 29:359-
64.

NEWS AND NOTES

20th Congress of Asian Association of Pediatric Surgeons, New Delhi

Date: 12th to 15th November 2006

Pre-congress Live Operative Workshop on Anorectal malformation, New Delhi

Date: 11th & 12th November 2006

Post Congress Live Operative Workshop on Pediatric Urology, New Delhi

Date: 16th & 17th November 2006

Contact:
Prof. D.K.Gupta
Organizing Chairman
Head, Department of Pediatric Surgery
All India Institute of Medical Sciences
Ansari Nagar, New Delhi 110 029.
Tel: 011-26593309, 26594297
Fax: 011-26588663, 26588641
Email: aaps2006@gmail.com
Website: www.aaps2006.com

94

GLOBAL CONCERN
THE THREAT OF AVIAN
INFLUENZA (BIRD FLU)
Editorial Board - IJPP
Whats all the fuss about?
A small outbreak of avian influenza (bird
flu) in birds in Navapur Taluk of Nandurbar
District (Maharashtra) was widely published in
the media and caught the attention of the nation.
A brief summary of scientific facts is presented.
Influenza virus
There are many different subtypes of
influenza A virus. Human influenza virus
usually refers to those subtypes that spread widely
among humans by droplets, by direct contact and
by indirect contact (Fomites). There are only three
known A subtypes of influenza viruses (H1N1,
H1N2, and H3N2) currently circulating among
humans.
Influenza A (H5N1) virus also called
H5N1 virus is an influenza A virus subtype
that occurs mainly in birds (Avian influenza), is
highly contagious among birds and can be deadly
to them. H5N1 virus does not usually infect
people (the risk from avian influenza is generally
low to most people), but infections with these
viruses have occurred in humans. Confirmed
cases of human infection from several subtypes
of avian influenza infection have been reported
since 1997. The total number of cases reported
in the world till February 2006 is 175 and number
of deaths is 96 with the maximum from Vietnam
(93 cases and 42 deaths).
95
2006; 8(1) : 95
Most cases of avian influenza infection in
humans have resulted from contact with infected
poultry (e.g., domesticated chicken, ducks, and
turkeys) or surfaces (like egg shells)
contaminated with secretion/excretions from
infected birds. So far, the spread of H5N1 virus
from person to person has been limited and has
not continued beyond one person. Nonetheless,
because all influenza viruses have the ability to
change, scientists are concerned that H5N1 virus
one day could be able to infect humans and spread
easily from one person to another.
The H5N1 virus could either:
- adapt, giving it greater affinity for humans,
or;
- exchange genes with a human flu virus,
thereby producing a completely new virus
strain capable of spreading easily between
people, and causing a pandemic.
WHO Guidelines on Exposures that may
have put a person at risk of becoming
infected:
During the 7 days before the onset of
symptoms, one or more of the following:
- contact (within 1 metre) with live or dead
domestic fowl or wild birds
- exposure to settings where domestic fowl
were or had been confined in the previous 6
weeks
- contact (within touching or speaking
distance) with a person for whom the
diagnosis of influenza A(H5N1) is being
considered
Indian Journal of Practical Pediatrics
- contact (within touching or speaking
distance) with a person with an unexplained
acute respiratory illness that later resulted
in death.
Prevention of infection in humans
Countries or territories currently
experiencing outbreaks of highly pathogenic
avian influenza due to influenza A(H5N1) in
poultry should vaccinate health care workers
(HCWs) at risk with the WHO-recommended
seasonal vaccine. The rationale is to reduce
opportunities for the simultaneous infection of
humans with avian and human influenza viruses.
In turn, this reduces opportunities for
reassortment and for the eventual emergence of
a novel influenza virus with pandemic potential.
Reinforce standard precautions with droplet
and contact barriers.
Offer post-exposure prophylaxis (for
example, oseltamivir 75 mg daily orally for
7days) to any health care worker who has had
potential contact with droplets from a patient
without having had adequate personal protective
equipment.
Clinical features
The incubation period varies from 4 to 8
days. The spectrum of clinical manifestations
vary and may range from mild flu like illnesses,
sub-clinical infections and atypical presentations
(like encephalopathy and gastroenteritis) to
ARDS, multiorgan failure and sepsis syndrome.
Diagnosis
Antemortem diagnosis of influenza A
(H5N1) has been confirmed by viral isolation, the
detection of H5-specific RNA, or both methods.
Common laboratory findings have been
leukopenia, particularly lymphopenia, mild-to-
moderate thrombocytopenia and slightly or
moderately elevated aminotransferase levels.
Marked hyperglycemia and elevated creatinine
96
2006; 8(1) : 96
levels also occur. In Thailand, an increased risk
of death was associated with decreased leukocyte,
platelet, and particularly, lymphocyte counts at
the time of admission.
Management
Most hospitalized patients with avian
influenza A (H5N1) have required supportive
management for the systems affected. The H5N1
virus that has caused human illness and death in
Asia is resistant to amantadine and rimantadine,
two antiviral medications commonly used for
influenza. Treat with a neuraminidase inhibitor
such as oseltamivir (75 mg orally, twice daily
for 5 days) as early in the clinical course as
possible. Another antiviral medication
zanamavir, would probably work to treat
influenza caused by H5N1 virus. If a case is
assessed as not requiring hospitalization, educate
the patient and his or her family on personal
hygiene and infection control measures (e.g.
hand-washing, use of a paper or surgical mask
by the ill person, and restriction of social contacts)
and instruct the patient to seek prompt medical
care if the condition worsens.
Currently, there is no commercially
available vaccine to protect humans against
H5N1 virus that is being seen in Asia and Europe.
However, vaccine development efforts are taking
place.
Key Messages
There is no evidence, at present, from any
outbreak site that the virus has increased its ability
to spread easily from one person to another.
The spread of bird flu in affected areas can
normally be prevented.
People should avoid contact with chickens,
ducks or other poultry unless absolutely
necessary. This is the best way to prevent
infection with the bird flu virus.

Children are at high risk because they may
play where poultry are found. Teach your
children the following basic guidelines:
- Avoid contact with any birds, their feathers,
faeces and other waste.
- Do not keep birds as pets.
- Wash hands with soap and water after any
contact.
- Not to sleep near poultry.
If you unintentionally come into contact with
poultry in an affected area, such as touching the
birds body, touching its faeces or other animal
dirt, or walking on soil contaminated with poultry
faeces:
- wash your hands and feet well with soap and
water after each contact
- remove your shoes outside the house and
clean thoroughly with soap and water
- check your temperature for 7 days at least
once daily. If you develop a high temperature
(>37.5C), visit a doctor or the nearest health
care facility immediately.
If you need to handle dead or sick poultry,
make sure you are protected. Wear protective
clothing.
If you encounter sick and dead poultry for
the first time and are unsure of the situation,
inform the authorities immediately and do not
handle them.
Influenza viruses can survive for some time
in organic material, so thorough cleaning with
detergents is an important step in deconta-
mination.
WHO believes it is very important to prevent
human influenza from spreading in areas affected
by bird flu. Where the avian influenza viruses
and human influenza viruses come in contact with
each other, there is a risk that genetic material
will be exchanged and a new virus could emerge.
97
2006; 8(1) : 97
Anyone with flu-like illnesses should therefore
be careful with secretions from the nose and
mouth when around other people, especially
small children, in order not to spread human
influenza viruses.
In general, only apparently healthy poultry
should be prepared for food.
Chicken prepared hygienically and cooked
thoroughly, i.e. no pink juices should be
observed, can be considered safe to eat. However,
remember, if the bird has a transmittable disease,
such as bird flu, the person preparing the food is
at risk of becoming infected and the environment
may become contaminated.
Eggs, too, may carry pathogens, such as the
bird-flu virus inside or on their shells. Care must
be taken in handling raw eggs and shells. Wash
shells in soapy water and wash hands afterwards.
Eggs, cooked thoroughly (hard boiled, 5 minutes,
70oC) will not infect the consumer with bird flu.
In general, all food should be thoroughly
cooked to an internal temperature of 70C or
above.
Sources
1. World Health Organization. Pandemic and
epidemic alert and response (EPR) Available
from: URL: http://www.who.int/csr/disease/
avian_influenza/en/index.html (Accessed
March 8, 2006)
2. Avian Influenza A (H5N1) Infection in Humans
The Writing committee of the World Health
Organization (WHO) Consultation on Human
Influenza A/H5. New England Journal of
Medicine 2005; 353: 1374-1385 (Correction
New England Journal of Medicine 2006; 354:
884)
3. Guidelines for the use of seasonal influenza
vaccine in humans at risk of H5N1 infection:
http://www.who.int/csr/disease/
avian_influenza/guidelines/seasonal_vaccine/
en/
Indian Journal of Practical Pediatrics 2006; 8(1) : 98

XX SOUTH ZONE CONFERENCE OF IAP

SOUTH PEDICON 2006, SALEM
XXXI ANNUAL CONFERENCE OF IAP-TNSC

ORGANISED BY THE IAP-SLAME DISTRICT BRANCH

VENUE: HOTEL CENNEYS GATEWAY, SALEM

DATE: AUGUST 18TH 20TH 2006

G
reetings from IAP Salem District Branch, it is our privilege to welcome you in Salem, for the
South Pedicon 2006. A fabulous mixture of academics and cultural feast awaits everyone.
Salem is a renowned city for its education, business, steel and health care. Salem is surrounded
by a variety of tourist locations like Yercaud, Hogenakkal, Mettur Dam and Namakkal. Kindly
block these dates of the conference in your calendar and we urge you to register at the earliest.

ORGANIZING COMMITTEE

Dr.R.Ramalingam Dr.T.Srinivasan
Organising Chairman Organising Secretary
Mobile: 98427 11979 Mobile: 94437 24688

Dr.T.Madhubalan Dr.M.Javeed Khan

Jt.Organising Secretary Treasurer
Mobile: 984331 14165 Mobile: 98430 35115

Registration Fee for South Pedicon 2006

Category Before Before Before

31-3-2006 31-5-2006 15-7-2006 Spot
(Rs.) (Rs.) (Rs.) (Rs.)

IAP Member 1500 2000 2500 3000

Non IAP 1750 2250 2270 3500
PG Student 1250 1500 1800 2000
Accompanying Person 1500 1750 2250 2500

Mode of payment by Demand Draft, Drawn in favour of South Pedicon 2006 payable at Salem.

For Registration and other inquiries contact:

Organising Secretary, South Pedicon 2006, Pranav Hospitals Pvt.Ltd.,
108/38, Brindhavan Road, Salem 636 004.
Ph.No: 0427 2336787, 2336788 E-mail: southpedicon2006@rediffmail.com

For details regarding paper presentation please refer our website: www.southpedicon2006.com

98
 2006; 8(1) : 99

PICTURE QUIZ

This two months old male baby presented with irritability on handling, nasal discharge, muco
cutaneous lesions angle of mouth (Fig.1) and perianal area (Fig.2). Can you spot the diagnosis?
* Pramod Sharma, ** Chhangani NP, *** Randeep Singh, *** Ashok Pareek
* Assistant Professor, ** Associate Professor & Unit Head, *** Registrar,
Department of Pediatrics, Umaid Hospital, Dr. S.N. Medical Collee, Jodhpur.
Answer on page 101
99
Indian Journal of Practical Pediatrics
QUESTIONS AND ANSWERS
Q. 1 How to manage a child with dry
cerumen?
A. 1 Dry cerumen causes itching sensation in
the ear and the child is brought by the parents
with the complaint of frequent scratching of the
ears. The child is prescribed a wax softener
(Waxolve / Soliwax) for topical application, to
be used three times a day for 5-7 days, which
usually causes expulsion of the wax. If the wax
persists, ti is advisable to consult an ENT
Surgeon for cleaning the ear, either by syringing
with warm normal saline or suctioning.
Q. 2 What is the role of ear drops in pediatric
practice?
A. 2 (i) A wax softener is indicated when there
is impacted wax in the external auditory canal.
This softens the wax and helps in the removal of
the wax painlessly.
(ii) Antibiotic ear drops are indicated in
acute exacerbation of chronic suppurative otitis
media, when the child is brought with a history
of ear discharge following an attack of upper
respiratory tract infection. The efficacy of the
ear drops is increased when it is applied after
cleaning the ear of all secretions.
PICTURE QUIZ
Answer : Congenital Syphilis
100
2006; 8(1) : 100
(iii) Antifungal ear drops like clotrimazole
containing preparations are used for treatment of
otomycosis, ideally after cleaning the ear of all
the fungal debris.
(iv) Combination of antibiotic with steroid
ear drops is useful in severe inflammatory
conditions of the external auditory canal.
In view of the above facts, it is imperative
that the affected ear needs to be cleaned before
applying ear drops except if there is severe pain
or if there is impacted wax which cannot be
removed. After cleaning the ear, otoscopy should
be performed to assess the tympanic membrane
and the middle ear.
Prescribing antibiotic ear drops in acute
otitis media with an intact tympanic membrane
is not useful. Prescribing antibiotic ear drops in
a child with otomycosis will cause aggravation
of the fungal infection.
Prof. A.Ravikumar
Professor & HOD,
Department of ENT, Head & Neck Surgery
Sri Ramachandra Medical College &
Research Institute
Porur, Chennai 600 116.
 2006; 8(1) : 101

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

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101
Indian Journal of Practical Pediatrics 2006; 8(1) : 102

PEDICON 2007
44th Annual Conference of the Indian Academy of Pediatrics, 12-14 January 2007
&
IAP-AAP CME 2007, 11th January 2007

Registration form
IMPORTANT: Please note:

Registrations will be closed once the figures of 4000 delegates and 3000 accompanying delegates
have reached hence register early!
Registration fees for all categories have been mentioned in Indian rupees, except the categories
of foreign delegates which are in US dollars
Accommodation details follow in our first brochure, which will reach you soon. The payment
for travel and accommodation may be made later separately through official travel agent. The
following form and DD pertains to registration for the CME and conference only
Please note that only Demand drafts or cash will be accepted.

Registration fee

Category Early Bird up to 1st May 2006 to 1st August 2006 to After 1st
30th April 2006 31st July 2006 30th September 2006 October 2006
Member 3000/- 4000/- 5000/- 6500/-
Non member 4000/- 5000/- 6000/- 7500/-
Accompanying 3200/- 3700/- 4200/- 5700/-
Delegate
PG student 2700/- 3200/- 3700/- 4700/-
Senior citizen 2700/- 3700/- 4200/- 5700/-
SAARC 4000/- 5000/- 6000/- 7500/-
Foreign delegate 300 350 400 450
(US $)
Refund on 75% 50% 25% Nil
cancellation

102
 2006; 8(1) : 103

REGISTRATION FORM
Delegates Title [ ] Dr [ ] Prof [ ] Mr [ ] Mrs
Name
................................................................................................................................................................................
(First Name) (Middle Name) (Surname)
IAP Membership No:
Mailing Address
Building / Colony / House Name, Number & Floor
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Contact Numbers:
Office No.................................................... (Best time to contact) .........................................................................
Residence No............................................................. Cell phone no.......................................................................
Fax no........................................................... Email Address: .................................................................................
Diet preference Veg [ ] Nonveg [ ]
Accompanying person/s with details:

Name Age Sex

Final Registration details

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TOTAL
Mode of Payment: (DD in f/o PEDICON 2007)
Cash [ ] DD [ ] no. Bank dated-

Please mail duly filled form along with requisite DD by registered post to,
Conference Secretariat: C/o. Dr. Bharat Agarwal, Pediatric Hem/Onc Center, 63, Gandhi Nagar,
Bandra (East), Mumbai 400 051. Tel: 022-2643 0142, 2643 1902, 2642 6846. Email:
pedicon2007@iapindia.org
103
Indian Journal of Practical Pediatrics 2006; 8(1) : 104

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

IJPP
ADVERTISEMENT TARIFF
Official Journal of the Indian Academy of Pediatric - A quarterly medical journal
committed to practical pediatric problems and management update

Name ...................................................... FULL PAGE

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MANAGING EDITOR
Indian Journal of Practical Pediatrics
IAP-TNSC Flat, Ground Floor,
F Block, Halls Towers,
56 (Old No.33), Halls Road,
Egmore, Chennai - 600 008. India
Phone : 2819 0032
Email : ijpp_iap@rediffmail.com

104
 2006; 8(1) : 105

Indian Journal of
Practical Pediatrics IJPP
Subscription Journal of the
Indian Academy of Pediatrics

JOURNAL COMMITTEE NATIONAL ADVISORY BOARD

Editor-in-Chief President, IAP

Dr. A.Balachandran Dr.Nitin K Shah
Executive Editor
President 2007, IAP
Dr. K.Nedunchelian
Managing Editor Dr.Naveen Thacker
Dr. Malathi Sathiyasekaran Editor, Indian Pediatrics
Associate Editors
Dr. Panna Choudhury
Dr. N.C.Gowrishankar
Dr. P.Ramachandran Members

Dr. C.V.Ravisekar Dr. Arati Deka

Dr. V.Sripathi Dr. B.K.Bhuyan
Dr. S.Thangavelu
Dr. C.Kamaraj
Executive Members
Dr.Kul Bhushan Sharda
Dr. G. Durai Arasan
Dr. Mahesh Kumar Goel
Dr. Janani Sankar
Dr. S.Lakshmi Dr. M.A.Mathew
Dr. V.Lakshmi Dr. Mukesh Kumar Khare
Dr. (Major) K.Nagaraju Dr. Subhash Singh Slathia
Dr. T. Ravikumar Emeritus Editors
Dr. S.Shanthi
Dr. A.Parthasarathy
Dr. So.Shivbalan
Dr. B.R.Nammalwar
Dr. C.Vijayabhaskar
Dr. M.Vijayakumar
Dr. Deepak Ugra
(Ex-officio)

105
Indian Journal of Practical Pediatrics 2006; 8(1) : 106

Indian Academy
of Pediatrics
IAP Team - 2006 Kailash Darshan,
Kennedy Bridge,
Mumbai - 400 007.
President Jharkhand
Dr.Nitin K Shah Dr.Bijay Prasad
President-2007 Karnataka
Dr.Naveen Thacker Dr.M.Govindaraj
Dr.R.Nisarga
President-2005
Dr.Santosh T Soans
Dr.Raju C Shah
Kerala
Vice President Dr.Guhan Balraj
Dr.VN.Tripathi Dr.M.A.Mathew
Secretary General Dr.T.U.Sukumaran
Madhya Pradesh
Dr.Deepak Ugra
Dr.C.P.Bansal
Treasurer Dr.Mukesh Kumar Khare
Dr.Rohit C Agrawal Maharashtra
Editor-in-Chief, IP Dr.Anand K Shandilya
Dr.Panna Choudhury Dr.Tanmay Amladi
Dr.Vijay N Yewale
Editor-in-Chief, IJPP Dr.Yashwant Patil
Dr.A.Balachandran Manipur
Joint Secretary Dr.K.S.H.Chourjit Singh
Dr.Bharat R Agarwal Orissa
Dr.B.K.Bhuyan
Members of the Executive Board Punjab
Andhra Pradesh Dr.Kul Bhushan Sharda
Dr.P.Sudershan Reddy Rajasthan
Dr K.Umamaheswara Rao Dr.Ashok Gupta
Dr.P.Venkateshwara Rao Dr.Prem Prakash Gupta
Assam Tamilnadu
Dr.Arati Deka Dr.K.Chandrasekaran
Bihar Dr.M.P.Jeyapaul
Dr.Sachidanand Thakur Dr.K.Nedunchelian
Uttar Pradesh
Chhattisgarh
Dr.Mahesh Kumar Goel
Dr.Pradeep Sihare
Dr.V.N.Tripathi
Delhi
Dr.Vineet K Saxena
Dr.Ajay Gambhir
West Bengal
Dr.Sunil Gomber Dr.Nabendu Choudhuri
Gujarat Dr.Sutapa Ganguly
Dr.Baldev S Prajapati Services
Dr.Satish V Pandya Brig. Vipin Chandar
Haryana Presidents Spl. Representative
Dr.Verender N Mehendiratta Dr.Anupam Sachdeva
Jammu and Kashmir A.A.A.
Dr.Subhash Singh Slathia Dr.Kamlesh K Shrivastava

106
 2006; 8(2) : 105

INDIAN JOURNAL OF IJPP

PRACTICAL PEDIATRICS
IJPP is a quarterly subscription journal of the Indian Academy of Pediatrics
committed to presenting practical pediatric issues and management updates in
a simple and clear manner
Indexed in Excerpta Medica from January 2003

Vol.8 No.2 APR-JUN 2006

Dr. A. Balachandran Dr. K.Nedunchelian
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 107

TOPIC OF INTEREST - EMERGENCY MEDICINE

Approach to a child with respiratory distress 110
- Mahesh Babu
Acute asthma 116
- Krishan Chugh, Gurinder Arora
Endocrine emergencies in children 123
- Raghupathy P
Scorpion sting 134
- Mahadevan S
Snake bite 139
- Kulandai Kasthuri R
Acute poisoning in children 146
- Gautam Ghosh, Arun Kumar Manglik
Medico legal issues in emergency room 155
- Mahesh Baldwa
Journal Office: Indian Journal of Practical Pediatrics, IAP-TNSC Flat, F Block, Ground Floor, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for ordinary letters: The Editor-in-Chief, Indian Journal of Practical Pediatrics, Post Bag No.524,
Chennai 600 008.
Address for registered/insured/speed post/courier letters/parcels and communication by various authors:
Dr. A. Balachandran, Editor-in-chief, Indian Journal of Practical Pediatrics, F Block, No. 177, Plot No. 235,
4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
Indian Journal of Practical Pediatrics 2006; 8(2) : 106

PULMONOLOGY
Essentials of pediatric pulmonary function test 160
- Balachandran A, Shivbalan So, Vijayasekaran D, Gowrishankar NC
Subramanyam L
PRACTITIONERS COLUMN
Nutrition, health and well-being of children 167
- Meharban Singh
RADIOLOGIST TALKS TO YOU
Hepatomegaly and hepatic masses - I 176
- Vijayalakshmi G, Natarajan B, Ramalingam A
CASE STUDY
Abdominal epilepsy as a cause of recurrent abdominal pain 178
- Deshmukh LS, Pangrikar AG
Acquired velopalatopharyngeal palsy 181
- Rana K S, Dehera M K, Sood A
NEWS AND NOTES 122, 133, 145, 154, 166, 175, 180, 182

FOR YOUR KIND ATTENTION

* The views expressed by the authors do not necessarily reflect those of the sponsor or
publisher. Although every care has been taken to ensure technical accuracy, no responsibility is
accepted for errors or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are the
responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board

Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road, Egmore,
Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works, 9, Iyyah Street,
Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.

2

EDITORS DESK
Greetings from the Journal Committee of
IJPP. In this issue we have focussed some
more articles on Pediatric Emergency
Medicine. The Journal Committee profusely
thank Dr.P.Ramachandran and Dr. S. Shanthi
who have vast experience and rich knowledge in
Pediatric Intensive care, for formulating and
editing the articles on this important subject.
The Approach to a child with respiratory
distress is well narrated by Dr. Mahesh Babu.
He has stressed the need for proper history taking
and a good quick clinical examination which will
give clues to the cause of respiratory distress and
anatomical localisation of the problem in most
of the cases.
In his article on Acute asthma, Dr. Krishan
Chugh has reported that many a times it occurs
either due to non-compliance with treatment but
sometimes it may be the first episode. This article
deals with the management of acute episodes in
detail once the child presents in the emergency
department.
The Endocine emergencies in children is
discussed in detail by Dr.P.Raghupathy. He has
stated that endocrine emergencies in childhood
may not always be obvious in their clinical
presentation. Hence, one should have a high index
of suspicion for early clinical recognition and
confirmation of diagnosis and any delay in
diagnosis may lead to critically ill states with life
threatening complications.
The clinical features following
envenomation by the scorpion are dealt in detail
by Dr.S.Mahadevan. He has given the various
steps involved in managing children with
scorpion sting, which we hope may be useful for
practitioners, who are dealing with such cases.
A prior knowledge on the common poisonous
snakes in India will be helpful in the management
3
2006; 8(2) : 107
of children with snake bite. This topic is written by
Dr. Kulandai Kasthuri who has been handling
such cases in PICU of a tertiary care hospital.
She has given a detailed account of various steps
in the management of snake bite victims.
Dr. Gautam Ghosh, et al. have given the
various steps in the approach and management
of acute poisoning in children. He has also
highlighted the various pharmacological
antidotes for the ready reference for personnel
involved in the emergency room.
Dr. Mahesh Baldwa, Chairperson-IAP
Medico-legal group has given salient points on
medico legal issues with the help of past case
scenarios which will definitely guide all the health
managers looking after the emergency room and
intensive care.
In the practitioners column, Dr. Meharban
Singh, a senior pediatrician with repute, has
contributed an article on Nutrition, health and
wellbeing of children. This article will be useful
for all pediatric practitioners and also for family
physicians.
The Essentials of pediatric pulmonary
function test will be an eye opener for young
pediatricians and health personnel who are dealing
with pulmonary problems. The authors have done
their best to make it simple for IJPP readers.
Under the radiologist column
Dr.Vijayalakshmi, et al. have discussed the
assessment of hepatomegaly and hepatic masses
with the help of ultrasonogram. They have
reiterated that ultrasonogram is a non-invasive
primary screening technique and can be very
informative in dealing with such cases.
We sincerely thank all the contributors for
case study column. We welcome suggestions and
guidance from our readers to improve the quality
of the Journal and maintain the academic contents.
Indian Journal of Practical Pediatrics 2006; 8(2) : 108

INSTRUCTIONS TO AUTHORS

General
Print the manuscript on one side of standard size A4, white bond paper, with margins of at least 2.5 cm (1)
in double space typescript on each side. Use American English using Times New Roman font 12 size.
Submit four complete sets of the manuscript.
They are considered for publication on the understanding that they are contributed to this journal solely.
All pages are numbered at the top of the right corner, beginning with the title page.
All manuscripts should be sent to: The Editor-in-Chief, Indian Journal of Practical Pediatrics
Manuscript
1st Page
Title
Name of the author and affiliation
Institution
Address for correspondence (Email, Phone, Fax if any)
Word count
No. of figures (colour / black and white)
No. of references
Authors contribution
2nd Page
Abstract (unstructured, not exceeding 100 words) with key words (not exceeding 4)
3rd Page -
Acknowledgement
Points to remember (not more than 5 points)
Text
References
Tables
Legends
Figures should be good quality, 4 copies black & white / colour,*
(4 x 6 inches Maxi size) Glossy print
* Each colour image will be charged Rs........../- separately
Text
Only generic names should be used
Measurements must be in metric units with System International (SI) Equivalents given in parentheses.
References
Recent and relevant references only
Strictly adhere to Vancouver style
Should be identified in the text by Arabic numerals in parentheses.
Type double-space on separate sheets and number consecutively as they appear in the text.
Defective references will entail rejection of article
Tables
Numbered with Roman numerals and typed on separate sheets.
Title should be centered above the table and explanatory notes below the table.

4
 2006; 8(2) : 109

Figures and legends

Unmounted and with figure number, first authors name and top location indicated on the back of each
figure.
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5
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
APPROACH TO A CHILD WITH
RESPIRATORY DISTRESS
*Mahesh Babu
Abstract : One of the common presentations to
the emergency room is a child with respiratory
distress. This could be due to a upper respiratory,
lower respiratory or a non respiratory cause. A
proper history and a good clinical examination,
give the cause for respiratory distress in most of
the cases.
Keywords : Respiratory distress, Causes
The basic function of the respiratory system
is to provide oxygen and remove carbon dioxide
from the body, in technical terms called
oxygenation and ventilation respectively.
Whenever there is a clinical situation causing
compromise in either of these functions, the
respiratory tract has to work harder to try and
achieve its primary goal. This overactive
respiratory system is what a clinician recognizes
as respiratory distress.
Hence, a child with respiratory distress could :
1. Have normal gas exchange i.e. the child is in
a compensated phase of respiratory failure, when
he is working harder and maintaining his blood
gases. It is very important to recognize and treat
this child before he gets into frank respiratory
failure.
2. Have hypoxia and/or hypercarbia i.e. the
child is decompensated and is in frank respiratory
failure. This child needs emergent medical care.
* Pediatric Pulmonologist
Manipal Hospital, Bangalore
6
2006; 8(2) : 110
A child with respiratory distress can be
recognised by tachypnea, increased work of
breathing (chest indrawing), tachycardia and
abnormal sounds like stridor, wheeze or grunt.
A decompensated state (respiratory failure) can
be clinically suspected when there is altered
sensorium, cyanosis or ineffective breathing like
see - saw movements (described later).
The history: Evaluation of key clinical
symptoms
The clinician should ask focussed questions
based on the childs chief complaints and
significant findings, ensuring that one can elucidate
the onset, duration, character, alleviating and
exacerbating factors and treatment to date. The
impact that the symptoms have on everyday
activities, such as playing or exercise and the oral
intake of liquids and food are very important.
Measures of thriving and general feeling should
be elicited. Though the majority of ill children have
new and acute processes with short medical
histories, always consider the possibility of an acute
exacerbation of an indolent or more chronic process
that has not been uncovered till now. As there exists
a large number of children with special health care
needs and underlying medical problems (ie, asthma,
recurrent croup, cystic fibrosis, or
bronchopulmonary dysplasia), it is important to take
a detailed past medical history. Children with
known complex heart disease and those with any
chronic infectious or immunologic illnesses must
be investigated with high suspicion for
complications like infection. They may develop
acute respiratory distress associated with their
underlying condition. In children with their first
significant episode of acute distress from

bronchospasm secondary to asthma, a careful look
at their medical history may reveal recurrent though
mild symptomotology of reactive airway disease,
such as mild persistent cough with exercise or with
upper respiratory tract infections. Table 1 lists some
of the symptoms that are important to consider when
obtaining a focussed history.
Table 1. Symptoms associated with
respiratory distress
Breathing difficulty: Rapid breathing, retrac-
tions (subcostal, intercostal, supraclavicular),
abdominal wall muscle use and see-saw res-
piration, positional distress
Color change: Pale or cyanotic
Noisy breathing: Wheezing, stridor and
grunting
Non-Localized Symptoms
Fever, poor feeding or drinking
Weight loss or failure to gain weight, pain,
pallor, diaphoresis
The presence of important non-respiratory
symptoms, such as fever, often helps to direct
the evaluation to an inflammatory or infectious
etiology or trigger. One should also elicit the
history of other constitutional symptoms, such
as the impact of illness on dietary intake, activity
level, and weight loss to help judge the overall
severity of the process.
The physical exam: What are the important
signs?
It is useful to evaluate children for important
signs of respiratory disease in a logical
physiologic and anatomic order that assists in
localizing the primary etiology.
The respiratory rate of the ill child is a key
parameter that is often under-assessed. One
should correlate the respiratory rate to the age of
7
2006; 8(2) : 111
the child and to the sensorium of the child. Age
specific respiratory rates as per ARI protocols
(50 or more in 1-12 months and 40 or more in 1-
5 years old) might be a good reference guide. It
should also be appreciated that the respiratory
rate is faster in children who are awake than in
children who are asleep. A fast sleeping
respiratory rate, therefore, has a greater
significance.
The heart rate, temperature, state of
perfusion and blood pressure give supporting
evidence to the physiologic state of the child and
may help the clinician to identify early
cardiovascular compromise.
Sensorium is another important sign.
Children with hypoxia can either be irritable or
be drowsy, and sometimes slip into comatose
state. Hypercarbia also produces drowsiness and
hypersomnolescence.
When available, another useful measure in
the evaluation of respiratory disease is the oxygen
saturation, which can be obtained via pulse
oximetry. This may be a useful measure to
determine the presence of mild to moderate
hypoxemia that is not evident on physical
examination. It is useful to remember that pulse
oximetry may not be accurate if the probe is not
of the appropriate size for the childs small fingers
or toes, if the extremity is cold or has poor
perfusion or when the hemoglobin molecule is
saturated with something other than oxygen (such
as carbon monoxide) or if there is significant
methemoglobin.
It is useful to remember that in a child
presenting with tachypnea without increased
work of breathing (effortless tachypnea),
metabolic acidosis should be suspected. It is also
important to remember that in CNS disorders a
child may present with respiratory failure without
respiratory distress.
Indian Journal of Practical Pediatrics
Clinical Pearls
There are some important clinical signs
which can be considered as clinical pearls while
assessing a child with respiratory distress.
Indrawing
Supra-sternal indrawing: When present
suggests significant respiratory distress. It is a
non localizing sign and is present in upper airway
and lower airway pathologies. This sign suggests
the use of accessory muscles of respiration.
Sub-costal indrawing: When present
suggests much more significant distress. This is
also a non localizing sign. This sign suggests that
the diaphragm is working very hard. Normally,
the outward recoil of the chest wall and the inward
recoil of the subcostal area caused by the
diaphragmatic action, cancel each other.
However, when the diaphragmatic action is very
strong then the sub costal recessions appear.
Inter-costal indrawing: This is a localizing
sign. When present, intercostal indrawing
suggests decreased compliance of lung and hence
suggests parenchymal lung disease. Hence most
children with pneumonia will have intercostal
indrawing, as opposed to children with asthma
or pleural effusions who will not have intercostal
indrawing.
Sounds heard
(a) Stridor: Stridor is sine qua non of upper
airway pathologies. Stridor is produced by
passage of air through partially obstructed upper
airway structures which are predominantly extra
thoracic. These include structures comprising the
pharynx, larynx, subglottis and the upper trachea
till the thoracic inlet. Stridor is usually an
inspiratory noise, occasionally having a biphasic
component. The sound quality of stridor varies
with the site of obstruction, with nasopharyngeal
stridors having a low pitch quality and the sub-
8
2006; 8(2) : 112
glottic stridor having a high pitched quality.
Glottic problems usually cause biphasic stridor.
Acute onset stridor is always to be considered as
a medical emergency, since it suggests partial
obstruction of upper airway. Therefore protection
of airway is paramount before it gets worse.
(b) Wheeze: Wheeze is sine quo non of lower
airway pathologies. Wheeze is produced by
passage of air through partially obstructed lower
airway structures which are predominantly intra
thoracic. These include lower trachea, the major
bronchi and further generations of bronchi till
the respiratory bronchiole. Wheeze is usually an
expiratory noise. Trachea is the only structure
which has both an extra thoracic component and
an intra thoracic component, hence tracheal
pathologies can produce both stridor and wheeze.
Wheeze could be further classified as :-
Focal: when it is heard over only one part
of the chest. This suggests a local obstructive
pathology and one should think about foreign
body, or an extraluminal obstruction such as a
lymph node or vascular compression.
Generalized: When it is heard all over the
chest. This is further classified as
Monophonic wheeze: Where the quality of
sound heard all over the chest is the same, as in a
conducted sound. Monophonic wheeze suggests
large airway pathologies such as tracheomalacia
or broncho malacia or compression of main stem
trachea.
Polyphonic wheeze: where the quality of
sound heard is different in different parts of the
chest. Polyphonic wheeze suggests small or distal
airway disease such as asthma or bronchiolitis.
This is because the lumen of the affected
structures vary in different areas, and the pitch
of the sound produced is inversely proportional
to the diameter of the airway affected i.e smaller
the airway, higher the pitch of the sound.
 2006; 8(2) : 113

(c) Grunting: Grunting is sine qua non of
parenchymal lung disease. It is produced in
children with alveolar disease, where the child
tries to produce greater intrinsic PEEP to keep
their alveolus open. It is produced by a premature
glottic closure at the end expiratory phase.
Grunting suggests a parenchymal disease process
like pneumonia and should be taken seriously.
Localisation in respiratory distress
Another way of approaching a child with
respiratory disease is by considering the
respiratory system as individual components like
upper airway, lower airway or parenchymal
disease, problems of neuromuscular control or
mechanics and extra-pulmonary problems. Some
of the common diseases affecting individual part
are shown in Table 2.
First evaluate the upper airway, particularly for
signs of potential obstruction. Is there noisy
breathing on inspiration? Does the childs posture
have an important impact on the airway being
opened maximally (eg, leaning in the sniffing
position) and does it improve the condition? Is the
noise seal-like or barky (subglottic obstruction),
sonorous or harsh (nasal or pharyngeal) or high
pitched (tracheal and intrathoracic large airways)?
Upper airway conditions have the greatest risk of
sudden deterioration and significant morbidity and
mortality. Be careful to elicit enough history to
discern the components of common illnesses while
still looking for the clinical features that would cause
one to search for the less common and potentially
more risky condition. For example, focussing on
the obvious assessment of infectious croup too early
and missing the questions that might establish a
risk for foreign body aspiration is a potential trap.
Within the chest, the function of the lower
airways (central trachea to the small airways) can
be impacted from a variety of disorders, both
focal and diffuse. Clinical signs of lower airway
pathology include hyperinflation of the lung and
chest cavity, accentuation of the expiratory phase
of respiration, and wheezing (higher pitched,
continuous sounds on expiration). The presence
of inspiratory wheezing in addition to expiratory
wheezing is evidence of more severe lower
airway obstruction, which as it progresses can
lead to reduction of the tidal volume and the
quality of the inspiratory breath sounds on

Table 2. Location and conditions producing respiratory distress

Location of respiratory problem Examples of conditions
Upper airway Croup, epiglottitis, foreign body, tracheitis
Lower airway Asthma, bronchiolitis, foreign body, pneumonia
Neuromuscular control Seizure, CNS structural defects, acute encephalopathy
of various casues, head trauma, acute paralysis, myopathy
Mechanics Trauma, spinal or chest wall deformity
Pulmonary parenchyma Pneumonia, interstitial lung disease, BPD, cystic fibrosis
Extra-pulmonary : Heart failure, neurogenic hyperventilation, renal
Cardiac, CNS, renal, toxicologic, failure, drug overdose, Carbon monoxide (CO) poisoning,
Oxy-hemoglobin delivery system methemoglobinemia

9
Indian Journal of Practical Pediatrics
auscultation. All that wheezes is not asthma.
Consider entities such as an aspirated foreign
body, particularly with focal wheezing, or
something compressing the intra-thoracic airways
such as an enlarged lymph node or tumor, and
rarely, a left atrial problem causing cardiac
failure. In these instances, the physical exam may
reveal focal problems or an abnormal cardiac
examination. But more important is the history
of choking spell or acute or recurrent focal
wheezing at an age unusual for first asthma
episode.
The next component to discuss is the
pulmonary parenchyma. In general, one tends to
think of pneumonia as the prime pulmonary
parenchymal disease. When severe, one may
expect tachypnea, grunting, and retractions. Focal
findings may include splinting of the chest wall
when there is pain, changes in breath sound
quality, and crackles. The subtle alteration of
breath sounds in cases of pneumonia may range
from undetectable to harsh, bronchial, or the
classic tubular breath sounds. As the
pneumonia progresses, the physician may hear
crackles from the opening of small distal airways
closer to the alveoli. A complete physical
examination of the child may reveal other
important signs of chronic pulmonary
parenchymal disease, such as failure to thrive or
finger clubbing as seen in cystic fibrosis, or the
signs of prematurity or other neonatal
complications that may have accompanied
bronchopulmonary dysplasia. More difficult to
detect may be the subtle findings of pulmonary
interstitial diseasesuch as tachypnea and end-
inspiratory cracklesand constitutional
findingssuch as weight loss and fatiguein
the absence of fever. When the history does not
seem to fit common processes such as
pneumonia, one should dig deeper in the clinical
assessment at the first encounter or do so when
the patient does not respond to therapy as one
would have anticipated.
10
2006; 8(2) : 114
Assessment of neuromuscular control is
often delayed and forgotten. This system includes
the feedback loop encompassing the brainstem
respiratory centers, the connection to the muscles
of respiration and the internal receptors that
balance the measures of pH and PaO2. Disorders
that affect normal respiratory control are fairly
common and often lead to respiratory failure
without obvious respiratory distress like
increased work of breathing. Signs of central
nervous system-mediated respiratory problem
may be ascertained through an assessment of the
breathing pattern. Is the upper airway patent? Is
the respiratory rate slow or absent? Is the pattern
of respiration insufficient to move the chest wall?
Is there an unconscious state or active seizure
that may impair normal respiration? Is there
evidence of abnormal peripheral muscle tone or
lack of movement that would suggest metabolic
or neuromuscular weakness? Examples of
disorders of the central nervous system impacting
on effective respiration include generalized
seizures, an ingested poison or toxin, and a
number of acquired disorders (eg, infections,
trauma) and congenital nervous system problems
and for peripheral neuromuscular disorders like
muscle or nerve disorders.
The next location for the consideration of
pathology that can contribute to respiratory
distress is the effectiveness of the mechanics of
respiration. The mechanics of respiration can be
disrupted by the presence of upper airway
obstruction, lower airway obstruction, chest wall
or neuromuscular abnormality, and
extrapulmonary problems. Any of these may lead
to less than effective ventilation and respiratory
failure. Examples include a reduced lung volume
secondary to an intra-abdominal mass or large
pleural fluid collection or the air trapping and
large lung volume created by severe asthma.
Primary causes of mechanical problems include
congenital or acquired skeletal abnormalities and
trauma (eg, flail chest). The assessment should

focus on the observation of the chest wall
configuration and symmetry of the chest wall
movement with respiration. Appropriate effort
with ineffective respiration in the absence of an
upper airway problem or serious intrapulmonary
pathology is a sign of a mechanical problem.
Non-specific features of mechanical problems
include the presence and symmetry of retractions
and abdominal muscle use. Generally the
respiratory rate will be increased over normal in
attempts to compensate, but it may prove
ineffective.
Last but not least are the non-respiratory
problems that can lead to respiratory distress. The
list is long and can involve any of a number of
organ systems. Therefore, the physical
examination of the child with respiratory distress
should be complete. Is the cardiac exam
specifically abnormal? Is there primary heart
failure with secondary respiratory distress? Are
there signs of pericardial effusion with narrow
pulse pressure, pericardial rub, and distant heart
sounds? Is there any suggestion of pulmonary
embolus from history or from the normal chest
exam with significant hypoxemia if a blood gas
is measured? Is there evidence of acidosis (ie,
hyperpnea) or other metabolic abnormality (ie,
Kussmaul respiration with fruity breath) that may
cause respiratory distress? Is there evidence of
renal failure, liver disease, or a congenital
problem associated with respiratory distress? Is
there a suggestion of drug overdose or drug effect
that is leading to respiratory distress? This may
include miotic pupils with bradypnea from
narcotics or the drunken stupor of alcohol abuse
or small pupils, bronchorrhea, respiratory
distress, and overactive bowel sounds from an
insecticide exposure.
Laboratory assessment
No lab tests are required to make a diagnosis
of respiratory distress. However, they may be
11
2006; 8(2) : 115
required to quantitate the severity of respiratory
distress and sometimes to localize the cause of
distress. Some of the common tests done will
include a pulse oximetry, ABG and chest x-ray.
Pulse oximetry will give us the oxygenation status
and if greater than 90% in room it correlates with
a PaO2 of > 60mm/kg. Sometimes, children can
be maintaining their saturations with minimum
additional oxygen, but they could be having
dangerously high carbon dioxide. To know the
CO2 status, we will need to do arterial blood gas
analysis or end tidal CO2 monitoring.
Points to remember
1. Respiratory emergencies are quite common
and can be potentially life-threatening.
2. Rspiratory distress is characterised by
normal sensorium and increased work of
breathing.
3. Respiratory failure is present when there
is altered sensorium and respiratory
distress, except in CNS problems.
4. Respiratory failure is a clinical diagnosis
and does not need an ABG.
Bibliography
1. Baker MD, Ruddy RM, Pulmonary
Emergencies, In: Fleisher G, Ludwig S (eds).
Textbook of Pediatric Emergency Medicine,
4th edn, Baltimore, Williams and Wilkins,
1999.
2. Rusconi F, Castagneto M, Gagliardi L, et al.
Reference values for respiratory rate in the first
3 years of life. Pediatrics 1994; 94:350-355.
3. Hooker EA, Danzl DF, Brueggmeyer M, et al.
Respiratory rates in pediatric emergency
patients.. Emerg Med. 1992;10:407
4. Cherick V, Boat TF 9th Edn. Kendigs
disorders of the respiratory tract in Children.
Philadelphia, P.A, Saunders, 1998.
5. Foltin G, Tunik M etal: Teaching Resource for
Instructors in Prehospital Pediatrics, CPEM
TRIPP ALS
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
ACUTE ASTHMA
* Krishan Chugh
** Gurinder Arora
Abstract : Acute exacerbation of asthma is one
of the conditions which makes the parents rush
their children to the emergency room. Many a
times it occurs either due to non-compliance with
treatment but sometimes it may be the first
episode. All asthmatics should have a written
action plan for home management. This article
deals with the management of acute episode once
the child presents in the emergency department.
Keywords : Acute asthma, Drugs, Management.
Bronchial asthma is a common problem with
enormous medical and economic impacts. Despite
improved understanding of the disease and
pharmacological options, death and hospitalization
still occur. Appropriate emergency management
of acute asthma will have an impact on these
statistics. Most of the acute attacks are either the
first episode or due to non- compliance with the
treatment; acute events occurring because of the
treatment failure per se are uncommon. This
article reviews home management of an acute
attack, management in the Emergency Room (ER)
and in the Pediatric Intensive Care Unit (PICU).
Home management i.e. prior to arrival
in the emergency department1
All asthmatics should have a written action
plan that can help guide them in recognizing and
* Head of the Department of Pediatrics,
Sir Ganga Ram Hospital, New Delhi
** Consultant Intensivist, Department of Pediatrics,
Max Balaji Hospital, New Delhi.
12
2006; 8(2) : 116
assessing their overall asthma control and the
severity of acute asthma exacerbations.
Recognizing symptoms early and intensifying
treatment soon after symptoms worsen can often
prevent further worsening and can keep
exacerbations from becoming severe.
The National Asthma Education and
Prevention Program guidelines (NAEPP)
recommend immediate treatment with rescue
medication i.e. inhaled short acting agonist up
to 3 inhalations in 1 hour A good response would
be characterized by resolution of symptoms
within an hour, no further symptoms over the next
4 hours, and improvement in PEF to 80% or more
of the predicted or personal best.
If the child has an incomplete response to
initial treatment with rescue medication (i.e.
persistent symptoms and / or a PEF of 60-80 %of
predicted or personal best), an early arrival at the
emergency department (ED) would prevent the
attack progressing to severe stage.
At the emergency room the following
signs should be recorded for assess-
ment of severity of acute asthma:
1. Pulse: Increasing pulse rate generally denotes
worsening asthma; bradycardia occurs in life
threatening asthma as a pre-terminal event.
2. Respiratory rate and degree of breathlessness.
3. Use of accessory muscle of respiration: Best
noted by palpation of neck muscles
4. Degree of agitation and conscious level.
(NB: Clinical signs may correlate poorly with the
severity of airways obstruction. Some children

with acute asthma do not appear distressed.
Special care should be given in assessment of
adolescents).
Evaluation of the severity of an acute
episode of Asthma (BTS guidelines for
management of acute attack of Asthma
in children) 2
Assessment of acute asthma in children aged
over 2 years
Acute severe
1. Cannot complete sentences in one breath or
too breathless to talk or feed.
2. Pulse rate : > 130 (2-5 years) or
> 120 (beyond 5 years)
3. Respiratory rate: > 30 / min (beyond 5 years)
> 50 / min (2-5 years)
Life threatening
1. Hypotension
2. Exhaustion
3. Confusion
4. Coma
5. Silent chest
6. Cyanosis
7. Poor respiratory effort
Management upon arrival in the
emergency department
The key to managing acute episodes is to
stabilize the patient as rapidly and as effectively
as possible, ensure adequate oxygenation
(children with life threatening asthma or SpO2
of < 92 % should receive high flow oxygen via a
tight fitting face mask or nasal cannula at
sufficient flow rates to achieve normal
saturations), and reverse bronchial narrowing
with a minimum of side effects. Freedom from
wheezing and normal pulmonary mechanics take
a long time to achieve and need not be the primary
13
2006; 8(2) : 117
goal of acute therapy3. After the acute episode
has ended, the residual deficits can be addressed
with appropriate outpatient regimens. In this
situation, weeks may be needed to completely
stabilize all aspects of the disease.
Care paths
Care paths (practice guidelines) have been
developed to improve the efficiency. In ED
settings, the use of practice guidelines rapidly
identifies individuals at risk for adverse
outcomes, reduces admissions to both pediatric
wards and PICU, lowers the length of stay,
decreases the number of return visits in the next
48 hours, and lessens costs. On the inpatient side,
there is a decrease in length of hospitalization
and a better prognosis post discharge.
First line therapy in the emergency
department
Oxygen
Profound hypoxemia is rare in uncomplicated
acute asthma and few patients have oxygen
saturations less than 90%. A child of acute asthma
with SpO2 of < 92 % in the emergency department
should be started on supplemental oxygen.
Inhalation therapy with 2 agonists
Moderately short-acting 2-adrenergic agonists
such as salbutamol and terbutaline have rapid
onset of action and provide three to four times
more bronchodilatation than do methylxanthines
and anticholinergics, making them the first-line
treatment for acute illness4. Long-acting agents
such as salmeterol are not recommended in the
acute setting but formeterol, is undergoing
clinical trials to determine its efficacy.
Metered Dose Inhaler (MDI) with spacer
British Thoracic Society guidelines 2 for
management of acute asthma in children state
that, a MDI and spacer are the preferred option
in mild to moderate asthma.
Indian Journal of Practical Pediatrics
5-10 puffs may be required depending on the
severity. Each activation of MDI is followed by
8-10 normal breaths for the drug to be inhaled
completely. Improvement in peak flow rate was
as good5 or more6 with MDI and spacer compared
to nebulizer.
Nebulizer
Salbutamol is nebulized in doses of 0.5ml
(2.5mg) in children < 6 years and 1ml in > 6 years
mixed with 2ml of NS. The dose can be repeated
every 20 minutes three times.
Children with life threatening asthma may
deteriorate during 2 agonist nebulization due to
ventilation perfusion mismatch as salbutamol
may cause pulmonary vasodilatation. Hence,
during treatment always use O2 as a driving force
to nebulize along with close monitoring of patient
by a pediatrician.
Doseresponse effects are found with the
amounts commonly administered clinically. The
degree of improvement is a function of how much
medication is given, not of how it is delivered.
There does not seem to be any advantage in
giving larger quantities once pulmonary
mechanics approach the lower limit of normal7.
Continuous or intermittent nebulization
Review of literature suggests that in cases of
nonresponding asthma, continuous nebulization as
an option can be tried with good monitoring of
the patients for side effects8,9. The use of very
high doses of inhaled salbutamol (as high as 40-
80mg/hr), had the following side effects reported
hypokalemia, hyperglycemia, which were thought
to be because of the accentuation of these side
effects during acute exacerbations of asthma10.
Treatment for incomplete response
Individualize drug dosing according to
severity and the patients response.
The early addition of bolus dose of IV
salbutamol (15ug/kg) can be an effective
adjunct to treatment in severe cases.
14
2006; 8(2) : 118
Systemic (intravenous or oral)
corticosteroids should be used for all patients
who do not favorably respond to the initial
b-agonist therapy
Addition of anticholinergic may increase
lung function and may decrease hospital
admission rate
Corticosteroids
Recommendations for use of steroids in case
of acute asthma not responding to the initial
inhalation therapy2 :
To give prednisolone early in the treatment
of acute asthma attacks. Use a dose of 20 mg
prednisolone for children aged 2-5 years and a
dose of 30-40 mg for children > 5 years. Those
already receiving maintenance steroid tablets
should receive 2 mg/kg prednisolone up to a
maximum of 60 mg. Repeat the dose of
prednisolone in children who vomit and consider
IV steroids. Treatment up to three days is usually
sufficient, but tailor length of course to the number
of days necessary to bring about recovery. There
is no role for nebulized steroids in acute asthma
as per current guidelines.
Anticholinergics
If symptoms are refractory to initial 2
agonist treatment, add nebulized ipratropium
bromide (250 mcg / dose mixed with 2 agonist
solution). Repeated doses of ipratropium bromide
should be given early to treat children poorly
responsive to 2 agonists.
Ipratropium bromide or other
anticholinergics may be used as an additional
bronchodilator in conjunction with a 2 agonist
in cases of acute moderate to severe asthma. It is
nebulized in a dose of 250 mcg every 20 minutes
along with salbutamol. Its most beneficial effects
appear to be in multiple doses in more severe
exacerbations. Literature has been inconsistent,

but indicates that anticholinergic therapy may
increase FEV1 or PEF, may decrease hospital
admission rates slightly, may decrease the amount
of b-agonist needed, and may prolong
bronchodilator effect. There were no significant
adverse reactions, however. In view of this, it is
recommended to consider anticholinergic use in
moderate to severe asthma exacerbations, along
with 2 agonist.
Subcutaneous epinephrine
In children with poor tidal volume as in life
threatening asthma, epinephrine 1:10000 in a
dose of 0.1ml subcutaneously should be
administered and can be repeated every 20
minutes. After each dose child is reassessed and
if improving, continued on nebulized salbutamol.
Magnesium sulfate11
IV Magnesium sulphate is likely to be
effective in avoiding hospitalization and
improving bronchoconstriction and clinical
symptoms of acute severe asthma in children
when added to standard therapies of inhaled
bronchodilators and steroids. The possible
mechanism of action is by decreasing Ca++ uptake
leading to bronchodilation, inhibition of mast cell
degranulation and release of mediators, inhibition
of acetyl choline release and depression of muscle
fibre excitability11. The dose is 25-40mg/kg/day
(maximum of 2 grams) dissolved in 30ml NS and
administered over 30 minutes.
Aminophylline
Aminophylline is not recommended in
children with mild to moderate acute asthma.
Consider aminophylline in an High Dependancy
Unit (HDU) or PICU with severe or life
threatening bronchospasm unresponsive to
maximal doses of other bronchodilators and
systemic steroids with close and careful
monitoring. Aminophylline is used in a loading
dose of 5mg/kg as an infusion over 30 minutes
followed by 1mg/kg/hr as continuous infusion.
15
2006; 8(2) : 119
The loading dose is omitted if child is already on
theophylline.
High dose IV salbutamol in bolus form12
Statement from National Heart, Lung, Blood
Institute (NHLBI) regarding high dose
salbutamol given as a bolus sums up the current
status of this mode of therapy of acute severe
asthma :
Although inhaled 2 agonists and
corticosteroids have been the cornerstones of
acute asthma management, there remains a need
to develop new strategies to treat these patients
more effectively. An intravenous bolus of
salbutamol (15 ug / kg), given early in
conjunction with conventional therapy (oxygen,
inhaled 2 agonist, and intravenously
administered corticosteroids) results in more
rapid recovery, as measured by clinical
assessment scores and the need for inhaled 2
agonists and oxygen. The only side effect was
tremor. Intravenously administered 2 agonists
have been traditionally reserved for the patients
with the most severe exacerbations and given by
continuous infusion in an intensive care unit
setting. Single dose of 15 mg /kg of I.V.
salbutamol administered over 10 minutes in the
initial treatment of children with acute severe
asthma in the emergency department has been
shown to shorten the duration of severe attacks
and reduce overall requirements for inhaled
salbutamol maintenance13.
Intravenous terbutaline infusion in acute
severe asthma
Terbutaline is recommended as a useful
adjunct in asthma in those patients who fail to
respond to standard initial therapy. Terbutaline
was found to be effective and safe at doses of 1-
5 g /kg/ min14. Side effects of the drug reported
were increase in heart rate, significant fall in
diastolic blood pressure which may also require
inotropes and hypokalemia.
Indian Journal of Practical Pediatrics
Ketamine in acute asthma15
Ketamine promotes relaxation of airway
smooth muscle fibers probably via an epithelial-
independent mechanism.
The only randomized, double blind,
placebo-controlled trial to assess the efficacy of
ketamine in acute asthma carried out by Howton,
et al, concluded that intravenous ketamine at
doses low enough to avoid significant dysphoric
reactions demonstrated no increased
bronchodilatory effect over standard therapy.
Heliox16
Heliox, a blend of helium and oxygen,
reduces airway resistance and may be a
therapeutic option for severe refractory asthma
in intubated patients as there is a decrease in peak
inspiratory pressure and PaCO2. The effects of
heliox are transitory and disappear when air is
once again inhaled. Its temporary use, however,
may lower respiratory resistive work long enough
to forestall muscle fatigue and/or improve
ineffective mechanical ventilation until
bronchodilators and steroids can take effect. The
mixture may improve the distribution of inhaled
agents and lead to a faster rate of resolution of
obstruction. But there is insufficient evidence to
establish the utility of heliox in routine emergency
room treatment.
Anti-leukotriene agents17
There are limited data on the effects of
antileukotriene drugs in acute asthma. A clinical
benefit of the type noticed with salbutamol
definitely does not occur with antileukotrienes.
Ventilation in asthma 18, 19
Ventilatory assistance can be lifesaving.
Both noninvasive and invasive techniques are
available. Noninvasive facemask ventilation may
offer short-term support for some subjects with
hypercapnic respiratory failure who can
cooperate with their care and are able to protect
16
2006; 8(2) : 120
their airways. Its applicability, however, is limited
by its poor patient acceptance.
The generally accepted indications are
progressive CO 2 retention, obtundation and
impending cardiopulmonary collapse. Mere
presence of hypercapnia is not sufficient. The
goal of ventilatory support is to maintain adequate
gas exchange until bronchodilators and
corticosteroids relieve the airflow obstruction.
This usually entails sedation, and possibly
paralysis, as well as strategies to minimize
dynamic hyperinflation. Ketamine may be
necessary to supplement sedation with
neuromuscular blockade with pancuronium,
vecuronium, atracurium, or cisatracurium. All of
the paralytic agents can be associated with
myopathy, which is worsened by concomitant use
of corticosteroids and aminoglycoside antibiotics.
Dynamic hyperinflation (auto-PEEP) has
profound physiological effects. It rises directly
with minute ventilation and can compromise
cardiac output by reducing venous return. The
institution of positive-pressure ventilation in an
already hyperinflated thorax can markedly
worsen hemodynamics and cause abrupt falls in
blood pressure including cardiac collapse.
Because the airways are heterogeneously
narrowed, the less involved parts of the lungs may
undergo regional overdistension when exposed
to high inflation pressures and rupture .For these
reasons, ventilatory strategies that provide the
longest possible expiratory time are desired so
that dynamic lung inflation is minimized. This
goal is accomplished by combining the smallest
tidal volume with the slowest ventilatory rate and
fastest inspiratory time to keep a static end-
inspiratory pressure (plateau pressure) of less
than 30 cm H2O. Approaches designed to reduce
auto-PEEP often result in hypoventilation. The
resulting hypercapnia is well tolerated as long as
it develops slowly and the PaCO2 remains at 90
mm Hg or less. When necessary, the pH can be
defended pharmacologically. Once the

bronchospasm is relieved, the patient can be
weaned off rapidly.
Supportive treatment
Overall care of the child should also be given
due consideration, with maintainance of good
hydration status, control of temperature and strict
maintainance of the fluid and electrolytes
balance. Routine use of antibiotics in acute
asthma is not indicated.
Prognosis
Despite concerns about increasing mortality,
most patients survive acute episodes.
Points to remember
1. Parents should have a clearcut action plan
to follow whenever their children with
bronchial asthma worsen. This will
minimise the severity of acute
exacerbation.
2. In the emergency room, severity of acute
asthma can be assessed based on clinical
features and pulse oximetry on admission
and during re-evaluation.
3. Treatment is tailored to the severity of
acute episode.
4. In majority, administration of exygen,
aerosolised salbutamol and parenteral
steroids brings about good improvement.
5. Only in non-responders or those
presenting with life threatening episodes,
subcutaneous epinephrine followed by
IV magnesium sulphate or aminophylline
infusion may by required. IV salbutamol
in bolus form also may help in such severe
cases.
References
1. Liu AH, Spahn JD, Leung DYM. Childhood
Asthma. In:Behrman RE, Kliegman RM,
Jenson HB (eds). Nelson Textbook of
th
Pediatrics, 17 Edn, Philadelphia, Saunders,
2004; pp760-764.
17
2006; 8(2) : 121
2. British Guideline on the management of
Asthma, Scottish Intercollegiate Guidelines
Network, The British Thoracic Society, May
2004.
3. McFadden ER Jr, Elsanadi N, Dixon L, et al.
Protocol therapy for acute asthma: therapeutic
benefits and cost savings. Am J Med 1995; 99:
651-656
4. Rossing TH, Fanta CH, Goldstein DH, Snapper
JR, McFadden ER Jr. Emergency therapy of
asthma: comparison of the acute effects of
parenteral and inhaled sympathomimetics and
infused aminophylline. Am Rev Respir Dis
1980; 122:365371.
5. Cochrane Database Syst Rev 2002; CD 000052
6. Newman KB, Milne S, Hamilton C, Hall K. A
comparison of albuterol administered by
metered-dose inhaler and spacer with albuterol
by nebulizer in adults presenting to an urban
emergency department with acute asthma.
Chest 2002; 121: 1036-1041.
7. Emerman CL, Cydulka RK, McFadden ER Jr.
Comparison of 2.5 vs 7.5mg of inhaled
albuterol in the treatment of acute asthma. Chest
1999; 115:9296.
8. Rodrigo GJ, Rodrigo C. Continuous vs
Intermittent -Agonists in the Treatment of
Acute Adult Asthma. Chest 2002; 122:160-165
9. Reisner C, Kotch A, Dworkin G. Continuous
versus frequent intermittent nebulization of
albuterol in acute asthma: A randomized,
prospective study. Ann Allergy Asthma
Immunol 1995; 75:41-47.
10. Lipworth BJ, Clark RA, Fraser CG, McDevitt
DG. The biochemical effects of high dose
inhaled salbutamol in patients with asthma. Eur
J Clin Pharmacol. 1989; 36: 357-360
11. Cheuk DKL, Chau TCH, Lee SL. A meta-
analysis of intravenous magnesium sulphate for
treating acute asthma. Arch Dis Child 2005,;
90: 74-77.
12. Fan , Leland L. Randomized trial of intravenous
salbutamol in early mangement of acute severe
asthma in children, J Pediatr 1997; 131:
160-161
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13. Browne GJ, Lam LT. Single dose Intravenous
Salbutamol Bolus for managing children with
Acute Severe Asthma in the Emergency
department, Pediatr Criti Care Medi 2002; 3:
117-123.
14. Kamabalapalli M, Nilchani S, Upadhyayula S.
Safety of Intravenous Terbutaline in Acute
Severe Asthma, A Retrospective study. Acta
Paediatr 2005 ;94:1214-1217.
15. Reig DG, Rasansky MA. A Case Presentation
and Literature Review of Successful Ketamine
Administration in a Patient with Refractory
Status Asthmaticus. The Internet Journal of
Internal Medicine. 2004. Volume 5 Number
1.Available from URL.www.ispub.com:
th
Accessed on 5 December 2005.
16. Gluck EH, Onorato DJ, Castriotta R. Helium
oxygen mixtures in intubated patients with
status asthmaticus and respiratory acidosis.
Chest 1990; 98:693698.
17. Silverman RA, Chen Y, Bonuccelli CM,
Simonson SG. Zafirlukast improves emergency
department outcomes after an acute asthma
episode [abstract]. Ann Emerg Med 1999;
34:S1.
18. Slutsky AS. Mechanical ventilation: American
College Of Chest Physicians consensus
conference. Chest 1993; 104:18331859.
19. Meduri GU, Cook TR, Turner RE, Cohen M,
Leeper KV. Noninvasive positive pressure
ventilation in status asthmaticus. Chest 1996;
110:767774.

NEWS AND NOTES

FIRST NATIONAL CONFERENCE OF IAP COMMUNITY PEDIATRICS SUBCHAPTER

COMMPEDICON 2006
ORGANIZED BY
IAP CHHATTISGARH STATE BRANCH & IAP RAIPUR BRANCH.
ON
11 & 12 NOVEMBER 2006
th th

Two days conference on community pediatrics will be held at Raipur. Eminent speakers of
National and International repute will give their deliberations.
Registration fee for delegates is Rs. 1000/- & for postgraduate student is Rs. 800/- till
31st October 2006.
After 31st oct. & on spot Rs. 1200/- [for everybody]
Demand draft should be send in favor of COMMPEDICON 2006 payable at Raipur.
No cheque please.
Contact:
Dr. ASHWANI AGRAWAL Organizing Secretary,
C/O Swapnil Nursing Home, Civil Lines, Raipur (c.g.) 492001.
Phone no. 0771-2424111, 0771-2593093.
Mobile no. 94252 08789
E-mail: drakagr_r@yahoo.co.in, anoopve@yahoo.com

18

EMERGENCY MEDICINE
ENDOCRINE EMERGENCIES IN
CHILDREN
* Raghupathy P
Abstract : Endocrine emergencies in childhood
may not always be obvious in their clinical
presentation. Hence a high index of suspicion is
required for clinical recognition and
confirmation of diagnosis. Needless to say, any
delay in diagnosis can lead to critically ill states
with life-threatening complications. Some of
these conditions may be the initial manifestation
of a previously undiagnosed endocrine condition
which makes it all the more difficult to think of
the diagnosis. These emergencies may also arise
in a known case as a result of stress situation,
emotional crises, intercurrent infections,
accidents etc. For example, diabetic ktoacidosis
may be the presenting feature of type 1 diabetes
mellitus. This complication may also arise in a
child with established disbetics owing to non-
compliance with the prescribed insulin therapy.
In the enthusiam to save the child during an
emergency, one should not miss an important
aspect of management, which is to collect the
critial blood samples as these will help to confirm
the diagnosis of a lifelong condition.
Keywords : Diabetic ketoacidosis, Cerebral
oedema, Adrenal insuficiency, Syndrome of
inappropriate ADH secretion.
Endocrine emergencies such as diabetic
ketoacidosis, adrenal insufficiency and syndrome
of inappropriate ADH secretion will be discussed
* Senior Consultant in Pediatric Endocrinology
Sagar Apollo Hospital, Bangalore - 560 041.
19
2006; 8(2) : 123
in this article. Metabolic emergencies such as
hypoglycemia, hyponatremia, hypernatremia,
hypocalcemia, hypercalcemia, hypokalemia,
hyperkalemia and metabolic acidosis may also
have an endocrine aetiology.
Diabetic ketoacidosis
Among the endocrine emergencies in
children, diabetic ketoacidosis (DKA) is
relatively common. Severe insulin deficiency is
the primary cause of DKA. Lack of insulin
decreases the activity of GLUT4 glucose
transporter and hence glucose cannot enter the
cells (except in the brain which has a non-insulin
regulated glucose transporter). As a result,
intracellular low glucose level induces counter-
regulatory hormone production and
hyperglycemia raises serum osmolality causing
osmotic diuresis. The combination of insulin
deficiency and counter-regulatory hormone
excess sets into motion the vicious cycle of
excessive lipolysis and uncontrolled fatty acid
oxidation with ketoacids (ketone bodies)
production in the liver leading to metabolic
acidosis, ketosis, dehydration, electrolyte
depletion and ketonuria. Ketoacids often cause
nausea and vomiting which increase the severity
of dehydration. Dehydration in turn reduces renal
clearance of glucose and ketoacids, further
worsening the hyperglycaemia and acidosis. In
effect, all these compensatory metabolic changes
also contribute towards a significant risk of
mortality making DKA a life-threatening
emergency.
DKA generally occurs as a presenting
manifestation at the time of initial diagnosis in
Indian Journal of Practical Pediatrics
nearly 40% of children with type 1 diabetes mellitus
(T1DM), especially in those under 5 years of age.
This is mainly because the parents are too slow
to recognize the childs symptoms even when these
develop over a few days or weeks. Such delayed
diagnosis may be the cause of DKA even in the
absence of a precipitating infection. DKA may
also occur in an established case of T1DM during
a stress situation, commonly a severe infection, or
when insulin injections were omitted for various
reasons, despite detailed parental education on
home management of T1DM parents seeking
herbal and other indigenous therapies; omission of
insulin during a severe infection, often influenced
by poorly informed relatives with wrong
concepts regarding chronic therapy; depressed
or rebellious adolescents especially with lack of
parental supervision.
Although DKA is potentially life-
threatening, it is rarely fatal when the condition
is promptly recognized and appropriate treatment
is given. However, the best approach is its
prevention through early recognition of
symptoms such as polyuria, polydipsia, enuresis,
lethargy, weight loss in a new case of T1DM and
by education of families in confirmed cases
regarding the importance of regular insulin
therapy, the absolute need to provide increased
insulin dosages during an intercurrent infection
and the futility of the promises made by
indigenous practitioners who do not have any
effective alternative for insulin therapy.
Besides providing insulin, urgent treatment
is required for the profound fluid and electrolyte
deficits, hyperosmolarity and acidosis seen in
DKA. This therapy should be carried out under
close supervision and monitoring, as rapid
treatment may by itself lead to complications such
as cerebral oedema especially in infants and very
young children.
The clinical features of DKA are polyuria,
polydipsia, weight loss, lethargy, malaise,
20
2006; 8(2) : 124
anorexia (or polyphagia in some), nausea,
vomiting and abdominal discomfort or colicky
pain which may even be mistaken for a surgical
abdomen. Children may present with severe
dehydration, hypotension and shock, drowsiness,
unconsciousness or coma. Rapid deep breathing
(Kussmauls respirations) suggestive of
metabolic acidosis is a common presentation.
There may be a fruity odour to the breath.
DKA is often precipitated by an infection
and hence this should be actively searched for,
evaluated and treated appropriately. Sinusitis,
urinary tract infection, cutaneous infections or
pneumonias are the common causative illnesses
but may not be obvious on physical examination
or x-rays. Even fever may be absent in the
presence of dehydration. Interestingly,
leucocytosis and a shift to the left observed on
differential WBC count are observed consistently
even if infection is not present. These changes
are due to elevated levels of adrenaline and
cortisol in DKA.
Emotional and psychosocial factors may
also predispose to the onset of DKA in children
with T1DM. However, in our country, where
mostly family support is widely available for the
children, psychological factors do not contribute
to the evolution of DKA.
Diagnosis of DKA is made when the following
are present.
1. Blood glucose 300 mg/dl,
2. Acidosis is present with arterial pH < 7.3
and serum bicarbonate < 15 mEq/L,
3. Serum bicarbonate < 18 mEq/L,
4. Marked glucosuria (+++ or ++++),
5. Severe ketonuria (++ to ++++).
Classification of DKA
MildpH > 7.2 and serum bicarbonate
10-15 mEq/L

Moderate pH 7.1 - 7.2 and serum
bicarbonate 5-10 mEq/L
Severe pH < 7.1 and serum bicarbonate
< 5 mEq/L
Treatment
Urgent and prompt treatment is essential but
at the same time, it should be optimal and
monitored closely to avoid the risk of cerebral
oedema. This is an important complication of
therapy, more often seen in infants and young
children under the age of five. Children with
DKA are best managed in an institutional setting
with intensive care facilities. However, if a large
centre is away at a considerable distance, these
children can be managed quite effectively at even
lower level hospitals. If the patient is referred to
another hospital, it is always a wise practice to
administer one dose of rapid acting insulin
subcutaneously before sending away the child,
to avert any further deterioration during the
journey.
At admission, a blood sample is collected
for blood glucose, urea, serum sodium,
potassium, bicarbonate, venous blood gases and
glycosylated hemoglobin. Urine is examined for
the presence of glucose and ketones.
Fluid and electrolyte replacement (Table 1)
This is an important step in the treatment
and is carried out after initial assessment of the
patient. DKA is invariably associated with severe
dehydration and should be treated so, even in the
absence of all the signs of dehydration. Since
hyperosmolarity is the rule in DKA, the initial
hydrating fluid chosen is usually normal saline.
Hypovolemic shock requires immediate
commencement of rehydration over the next hour
to expand peripheral circulation. An isotonic fluid
such as normal saline or Hartmann Ringer Lactate
solution may be administered at 15-20 ml per kg
body weight. Moisture of mucous membranes
21
2006; 8(2) : 125
and capillary refill time are useful in assessing
hydration. When the hydration improves,
glomerular filtration increases favouring glucose
excretion. Hence, the blood sugar level keeps
falling even prior to commencement of insulin
infusion.
In a typical DKA case, the fluid deficit is
calculated as 6% (60ml/kg) of body weight and
10% (100 ml/kg) for a child < 2 years of age.
Using this volume, rehydration is done carefully
over a period of 36 to 48 hours to avoid the
complication of cerebral oedema. In a child
presenting with clinical signs of severe
dehydration, fluid deficit is calculated at 9%
(90ml/kg) of body weight and 15% (150ml/kg)
for a child < 2 years of age. It should be
remembered that if the initial blood sugar value
is 800 mg% or higher, or if the corrected serum
sodium level is in the hypernatremic range, fluid
deficit must be calculated for more severe
dehydration. Measured hypernatremia will be
another pointer to severe dehydration. The initial
fluid chosen is normal saline and should be
continued until the blood sugar level approaches
250 mg%, when a change to 5% dextrose saline
solution may be done. Monitoring of all fluid
intake and output during treatment and recording
is essential. The temptation for overzealous
treatment to correct the dehydration rapidly in
the case of children who look very ill should be
resisted.
A gradual decline in serum osmolality is
desirable to avoid the complication of cerebral
oedema. Hence 50-60% of the total calculated
deficit is replaced within the initial 12 hours and
the remainder over the next 24 hours.
Maintenance fluids are calculated by carefully
monitoring urine output during treatment.
Total body depletion of potassium occurs as
a rule in DKA. Besides, during insulin therapy
there is a risk of severe hypokalemia and requires
careful potassium replacement. Serum potassium
Indian Journal of Practical Pediatrics 2006; 8(2) : 126

level is estimated initially and monitored regularly.
When serum potassium reaches the normal range,
and urine output is good, potassium chloride is
added to the intravenous fluids after the first hour
of rehydration, usually at the rate of 10-20 mEq/L,
but may need upto 40-60 mEq/L if there is
protracted vomiting, hypokalemia or persistent
acidosis. If the child is oliguric at the end of the
first hour of rehydration, potassium chloride is
added only if the serum potassium is < 4 mEq/L or
if the ECG shows evidence of hypokalemia. Sodium
deficit present in DKA is mainly due to osmotic
diuresis. By its osmotic force, hyperglycemia draws
intracellular water into the vascular space. The
increased vascular volume dilutes the sodium
content of the blood giving rise to
pseudohyponatremia. Hence a correction is
applied to arrive at the true level of serum sodium.
For every 100 mg% rise in blood sugar, 1.6 mEq/L
must be added to the actual value of serum sodium.
The sodium deficit is taken care of by the normal
saline solution used in initial rehydration and
continued subsequently. Normal saline with added
potassium is used as the hydrating fluid initially
and later with 5% dextrose. Higher concentrations
of sodium in the intravenous fluids will be needed
in children who are at a high risk of developing
cerebral oedema. Bicarbonate losses are huge in

Table 1. Guidelines for management of diabetic ketoacidosis

Initial investigations:
Blood glucose, serum Na, K, Cl, HCO3, blood gases, creatinine
Search for a precipitating infection may need urine culture, blood culture, throat culture,
chest radiograph
Indications for ICU care:
Unconscious child
Severe DKA
pH <7
Age < 2 years
Blood glucose > 1000 mg%
Initial therapy:
20 ml/kg of 0.9% saline over 1 hour
Assess level of dehydration, calculate fluid replacement required, add maintenance fluids and administer
intravenously over 36-48 hours Use normal saline solution as the initial intravenous fluid
Begin insulin infusion 0.1 unit/kg/hour after initial bolus of NS. Aim for fall of blood sugar at the rate of
100 mg%/hr and rise of blood pH by 0.03 / hr
Constantly monitor the patients vital signs, intake and output, 2-hourly blood sugars, pH,
electrolytes,creatinine, urine ketones on all urine samples till negative on 2-3 consecutive samples
Continue insulin infusion till acidosis improves, even if the blood sugar level drops to 300 mg/dL
Change normal saline IV infusion to 5% dextrose saline when blood sugar is ~ 250mg/dL
Subsequently insulin infusion may be reduced by 0.05 units/kg/hr
Reassess the patient hourly at first, then every 2-3 hrs
Later therapy:
When the child has regained consciousness, feels hungry, is clinically more stable, offer clear fluids orally
If oral fluids are tolerated well, change to 6-hourly short acting regular insulin SC when the childs condi-
tion is stable. When ketonuria has disappeared completely, mixed split insulin regime with intermediate
and short acting insulins may be commenced

22

DKA, yet bicarbonate replacement is not usually
required unless the pH is very low, (< 7.0).
Correction of ketoacidosis can be achieved with
initiation of insulin treatment and fluid replacement
and bicarbonate infusion does not hasten this. On
the other hand, bicarbonate infusion may increase
the risk of cerebral oedema, worsen hypokalemia,
and reduce tissue oxygenation. Phosphate losses
are also high in DKA and to correct this, it is
recommended that one half of potassium
replacement may be given as potassium phosphate
and the other half as potassium chloride. But in
clinical practice, hypophosphatemia causing
complications is extremely rare.
Insulin therapy
Continuous intravenous insulin infusion with
regular insulin is recommended to ensure reversal
of hyperglycemia to normal. The time to achieve
this can be controlled by insulin infusion in such a
way that it is not too slow or too rapid, as both
can be risky. Insulin infusion is prepared by adding
50 units of short acting insulin (e.g. Actrapid,
Humulin-R) to 500 ml of normal saline, so that 10
ml of the solution will contain one unit of insulin.
This solution is prepared afresh every 24 hours
and used in a pediatric microdrip set or infusion
pump. The usual rate of insulin infusion is 0.1
unit/kg/hour and if acidosis is not corrected in the
first few hours of insulin therapy, the rate of the
drip may be increased by 0.05 unit/kg/hour, until
acidosis improves. Generally, acidosis improves
more slowly than hyperglycemia. If the rise of
pH during therapy is slower than 0.03 per hour,
higher rate of intravenous rehydration or insulin
infusion may be tried. This drip is given separately
from the other intravenous fluids used so that the
insulin infusion can be regulated independently.
Precaution is taken to prevent rapid fall of blood
glucose to hypoglycemic levels by increasing the
rate of glucose infusion rather than reducing the
insulin administration. An important aim of therapy
is to avoid cerebral oedema.
23
2006; 8(2) : 127
Intermittent subcutaneous injections of
regular insulin can be used for milder cases of
DKA. It should be remembered that even in small
towns, where there are no intensive care facilities
or infusion pumps, children with DKA can be
managed quite effectively with intermittent
multiple intramuscular injections of insulin
initially and later by subcutaneous doses of
insulin with very good results. This may be
particularly useful in a situation wherein the child
presenting with life-threatening DKA may be
stabilized first in this manner before referring the
child to a large medical centre. Thus mortality
during the travel can be successfully prevented.
Blood sugar monitoring must be carried out
throughout the treatment to ensure a steady and
gradual fall of blood sugar by 100 mg/dL per
hour, to avoid hypoglycemia and to decide the
switch over to a dextrose containing intravenous
fluid. Insulin infusion is reduced when the
acidosis is showing improvement and blood sugar
continues to fall despite administration of
dextrose infusion intravenously.
When the childs consciousness also
improves along with improvement of all the
laboratory parameters, clear fluids are at first tried
orally. If tolerated well, one can switch over to
subcutaneous 6-hourly short acting insulin and
solid food may be given. Every sample of urine
is checked for ketones throughout this treatment
and when ketones are consistently negative on
2-3 samples, short acting insulin may be replaced
by a mixture of intermediate and short acting
insulins, preferably before breakfast or dinner.
Cerebral oedema
This is an unusual (in 1% of cases) but major
complication of treatment for DKA, more often
seen in infants and young children below the age
of 5 years at the time of initial presentation. As it
carries a high mortality, great care is taken to
avoid this complication as best as possible.
Indian Journal of Practical Pediatrics
Prompt clinical diagnosis, initiation of treatment
with mannitol or other hyperosmolar agents,
hyperventilation and respiratory support are
essential to manage this life threatening
complication. It often occurs after 4-6 hours after
treatment has begun when biochemical
abnormalities are improving. The clinical features
are: recurrence of drowsiness following improved
alertness with treatment, recurrence of vomiting,
bradycardia, hypertension, headache, abnormal
CNS findings, such as irritability, disorientation,
unequal dilated or unreactive pupil,
papilloedema, coma, and respiratory arrest with
herniation of the brain stem. CT or MR scans
done when the patient is sufficiently stable will
detect the changes in the brain.
The head end of the bed is raised by 30
degrees, airway is secured, respiratory support
is by endotracheal intubation with paralysis and
sedation, and hyperventilation is commenced.
The intravenous fluid rate is reduced to
maintenance or less. Mannitol (0.5 to 1 gram/kg
intravenously over 5 minutes) is an important
aspect of the management and is repeated in half
the dose once or twice till a response is obtained.
Hyperventilation and deep sedation may be
required for 24-48 hours.
The adverse prognostic factors in DKA are:
young age, delay in diagnosis and treatment,
severe dehydration, low PCO2, elevated serum
creatinine, treatment with bicarbonate, failure of
rise of serum sodium with treatment, rate of fluid
infusion > 4.0 L/M2/day.
Adrenal insufficiency
Adrenal insufficiency may occur in primary
adrenal conditions which may be due to enzymatic
block as in congenital adrenal hyperplasia (CAH),
acquired causes (autoimmune or idiopathic cases,
termed Addisons disease) or due to pituitary
causes such as ACTH deficiency. In the newborn,
transient adrenal insufficiency may occur with
24
2006; 8(2) : 128
maternal glucocorticoid therapy in antenatal period
or may be due to adrenal haemorrhage following
breech presentation, hypoxia or sepsis. Congenital
adrenal hypoplasia is a rare cause of hypoadre-
nalism in the neonatal period primarily affecting
boys but this condition may also present in later
childhood. Autoimmune adrenalitis causing
adrenal insufficiency is unusual in childhood.
Adrenal insufficiency may also occur with
adrenal haemorrhage in infectious conditions such
as meningococcemia (Waterhouse-Fridericksen
syndrome), in hypovolemic shock and hypoxia.
In some children with severe hypothyroidism,
adrenal insufficiency may be coexisting and
requires caution during thyroxine therapy.
Attaining euthyroid status may precipitate acute
adrenal insufficiency with vascular collapse. Some
rare conditions with adrenal insufficiency are:
adrenoleucodystrophy, Smith-Lemli-Opitz
syndrome (a disorder of cholesterol synthesis with
abnormally low cholesterol, elevated 7-
dehydrocholesterol and adrenal insufficiency) and
Wolman disease (presenting with adrenal
calcifications, intra lysosomal accumulation of
cholesterol esters in many organs). Certain drugs
such as the antifungal ketoconazole, rifampicin,
phenytoin, phenobarbital and mitotane are also
known to suppress the adrenal cortex.
Clinical manifestations
A high index of suspicion is necessary for
diagnosis as otherwise vague symptoms such as
fatigue and weakness may be missed. In severe
cases, acute vascular collapse (shock) may occur
but may still be mistaken for septic and other
causes of shock. Neonates with CAH commonly
due to salt losing form of 21-hydroxylase
deficiency may present with hyperpigmentation,
vomiting, polyuria (which is difficult to detect in
a newborn), ambiguity of genitalia in a female
infant, failure to gain weight, unexplained
dehydration and acute onset of hypotension and

shock. Occasionally, 3-hydroxysteroid
dehydrogenase deficiency also manifests with salt
losing symptoms in the neonatal period. Older
children and adolescents with adrenal insufficiency
present with apathy, confusion, vomiting,
dehydration, muscle weakness, abdominal pain,
orthostatic hypotension and may need intravenous
fluid resuscitation during a stress situation such
as an asthmatic episode, a lung infection or even
a minor infectious illness. Hypoglycemia is a
prominent feature. When this induces breakdown
of fat and mobilization of fatty acids as an alternate
source of energy, ketosis results giving rise to
anorexia, nausea and vomiting. The illness may
be mistaken for an episode of gastroenteritis.
Weight loss, growth failure and hyperpigmentation
may be features of chronic primary adrenal
insufficiency.
Investigations
Serum cortisol, ACTH, electrolytes, blood
sugar, renin and aldosterone levels are measured
at 0800 hours. Hyponatremia, hyperkalemia,
hypoglycemia and ketosis are the findings that
should suggest the possibility of adrenocortical
insufficiency. ACTH level is high, urinary
excretion of sodium and chloride is increased.
Low basal cortisol with elevated plasma ACTH
values indicates primary adrenocortical
insufficiency as against low ACTH in secondary
cases. Hyponatremia and hyperkalemia with
elevated plasma renin concentration suggests
mineralocorticoid deficiency. Elevated serum
17-hydroxyprogesterone will suggest CAH.
Short synacthen stimulation test is the
confirmatory test for adrenal insufficiency. The
basal value of serum cortisol is low and does not
rise after a intravenous bolus of injection ACTH
in a case of primary adrenal disorder. If the resting
level is normal and there is a significant response
to ACTH, secondary adrenal insufficiency should
be suspected. Elevated very long chain fatty acid
25
2006; 8(2) : 129
level in the plasma is diagnostic of
adrenoleucodystrophy. Anti adrenal antibodies
suggest an autoimmune pathogenesis.
Treatment
Blood samples must be collected for
confirmation of diagnosis before any treatment is
given. If the patient is in a stable condition, ACTH
stimulation test may be carried out while the child
is receiving fluid replacement therapy. Urgent
replacement with water soluble hydrocortisone
sodium succinate (100 mg/m2 intravenously at 6-8
hour intervals) intravenously is essential in acute
adrenal crisis along with fluids, electrolytes and
glucose to replace fluid and electrolyte deficit, and
to correct hypoglycemia. Normal saline solution
with 5% dextrose is given intravenously to correct
the situation and this will provide adequate fluid
and sodium. If hyperkalemia is severe, treatment
with IV calcium and/or bicarbonate or a cation
exchange resin will be needed. Hydrocortisone
(cortisol) replacement is continued orally in
maintenance doses (10 mg/m2/24hours) after the
acute manifestations of adrenal insufficiency are
treated. Although thrice daily dosage is
recommended, compliance is always a problem.
A larger dose is given in the morning to match
the physiological circadian rhythm of cortisol
secretion. In the presence of mineralocorticoid
deficiency, fludrocortisone is given orally in a dose
of 50 to 300 micrograms daily in two divided doses.
These maintenance doses are increased 2-4
folds temporarily during any acute stress situation
such as surgery, infection or an accident. If oral
cortisol is not tolerated during an emergency,
intramuscular injection of hydrocortisone is
essential and needed urgently. Monitoring the
efficiency of the replacement therapy is done by
periodic evaluation of serum cortisol levels and
plasma renin activity. Overdose with glucocorticoid
will produce all the manifestations of Cushings
syndrome and with mineralocorticoid one can
expect tachycardia, hypertension, fluid retention
and occasionally hypokalemia.
Indian Journal of Practical Pediatrics
Syndrome of Inappropriate
Antidiuretic Hormone Secretion
The syndrome of inappropriate antidiuretic
hormone (SIADH) secretion is the most common
cause of euvolemic hyponatremia in pediatrics.
The characteristic findings in this syndrome are:
hyponatremia and hypo-osmolality resulting from
inappropriate continued secretion and/or action
of antidiuretic hormone (ADH) despite normal
or increased plasma volume and low serum
osmolality.
Arginine vasopressin (AVP), the naturally
occurring ADH in humans, is synthesized in the
cell bodies of neurons in the supraoptic and para-
ventricular nuclei of the anterior hypothalamus
and carried along the supraopticohypophyseal
tract into the posterior pituitary, where it is stored
in association with a carrier protein, neurophysin.
ADH is released from here directly into the
circulation.
The release of ADH from the posterior pituitary
is dependant on:
1. Osmoreceptors which detect changes in
the extracellular fluid (ECF) osmolality. ADH
release results from a 2% increase in the serum
osmolality perfusing the supraoptic nuclei and
ADH secretion diminishes with a 1.2% decrease
in the serum osmolality, halting completely at
plasma osmolality < 280 mOsm/kg.
2. Baroreceptors, located in the carotid
sinus, aortic arch, and left atrium, induce a
significant release of ADH with a 8-10%
reduction in plasma volume.
These two sets of receptors normally act in
close coordination to increase or decrease ADH
release, although intravascular volume may be
the major stimulus. ADH release is also affected
by several drugs and stress situations such as pain
or anxiety.
26
2006; 8(2) : 130
ADH mainly favours the reabsorption of
water in the tubular fluid from the distal tubules
and collecting ducts and has no effect on sodium
reabsorption. ADH also exerts a pressor effect
by causing arteriolar vasoconstriction and a rise
in arterial blood pressure.
Pathophysiology
The basic defect in SIADH is uncontrolled
excess of vasopressin secretion giving rise to
water retention and volume expansion, presenting
as puffiness of the face and increase in body
weight. The clinical manifestations are often
obvious when the patient continues to drink or
has a fluid overload. Urinary sodium content will
be high although the serum sodium and
osmolality values are low. Increased extracellular
fluid volume elicits decreased proximal tubular
sodium absorption in an effort by the kidney to
excrete sodium and decrease intravascular
volume.
Hypervolemia suppresses the renin-
angiotensin-aldosterone system during the water
retention phase, but later, levels of renin and
aldosterone rise again, perhaps in response to
hyponatremia. The main mediator of the
natriuresis in SIADH is probably the atrial
natriuretic peptide (ANP), which may suppress
proximal tubular reabsorption of sodium in
response to expanded ECF volume. Sodium
balance is maintained in SIADH, and the sodium
output equals the intake.
Causes
CNS disorders : SIADH in children is most often
observed in association with intracranial disease
or injury (i.e., bacterial or tuberculous meningitis,
brain abscess, encephalitis, head injury) and in
postoperative patients.
Neoplasms: Malignancies producing excessive
ADH secretion are uncommon in children.

Pulmonary disorders: Pneumonia and
pulmonary tuberculosis causing SIADH are less
common causes in children than in adults.
Excessive administration of vasopressin in the
treatment of central diabetes insipidus.
Drugs : Vincristine, cyclophosphamide,
carbamazepine
Clinical features
It is good to remember that in a vast majority
of cases (~90%), it is a self-limiting condition,
remitting spontaneously within 2 3 weeks of
the initial event. Overt clinical manifestations of
SIADH are largely related to the cellular swelling
and cerebral oedema associated with
hyponatremia. Most patients with SIADH are
asymptomatic if the serum osmolarity remains
above 240 mOsm/kg of water. The net result in
SIADH is that the child is unable to excrete water.
Hence the clinical manifestations of SIADH are
those of water intoxication. Symptoms are more
likely to develop in young children and elderly
patients with hyponatremia.
SIADH occurs most frequently in children
with central nervous system infections,
intrathoracic disease, and in postoperative
patients.
Among premature neonates, the syndrome
most often accompanies brain injury and is
closely associated with intracranial
hemorrhage.
Signs and symptoms of SIADH, as a rule,
are those of hyponatremia and often are
vague and nonspecific nausea, vomiting,
headaches, blurred vision, disorientation.
The clinical manifestations of SIADH are
usually related to the degree of the
hyponatremia and to the rate at which
hyponatremia develops.
27
2006; 8(2) : 131
SIADH is often first recognized on finding
hypotonic hyponatremia in a child without other
major symptoms and in the absence of
dehydration.
Puffiness of face and weight gain of nearly
5% may seen. Skin turgor and blood pressure
usually are normal. Obvious hypervolemia is
absent.
Deep tendon reflexes are depressed and
pathologic reflexes, such as positive Babinski
reflexes, may be present. Altered sensorium with
asymmetric pupils may be seen. Pseudobulbar
palsy and seizures may occur. Cheyne-Stoke
respirations may be present.
Diagnostic clues
Hyponatremia (serum sodium <135 mmol/L)
with corresponding hypoosmolality (serum
osmolality <280 mOsm/kg) is characteristic.
There is continued renal excretion of sodium with
urinary sodium level > 25 mmol/L. Urine is less
than maximally dilute with urine osmolality >
100 mOsm/kg (more than plasma) and urine
volume is low. Serum potassium remains
unchanged. Other causes of hyponatremia such
as adrenal insufficiency, congestive heart failure,
pituitary deficiency, renal disease, hepatic disease
and use of diuretic are absent.
Treatment
Treatment of hyponatremia in SIADH
depends on the presence or absence of symptoms,
the severity of hyponatremia, and its duration.
Asymptomatic patients are usually treated in the
immediate period with water restriction. Patients
with CNS symptoms usually require more rapid
correction of the hyponatremia and water
restriction alone may not be sufficient.
Fluid restriction
Reduced water excretion by the kidneys is
responsible for the physiological and biochemical
Indian Journal of Practical Pediatrics
abnormalities in SIADH, such as hyponatremia,
volume expansion, and sodium depletion.
Therefore, water restriction corrects all these
abnormalities and is the most important step in
treatment of patients with SIADH. Fluid
restriction to less than 75% of maintenance (i.e.,
1000 mL/m 2/d) usually allows for the slow
excretion of retained excess fluid and results in a
decrease in ECF volume with a concomitant fall
in urinary sodium excretion.
If no improvement occurs in 4-6 hours,
further fluid restriction to 50% of maintenance
(i.e., 700-800 mL/m2/d) or lower is necessary. A
few children may require more severe fluid
restriction to as little as 10% of maintenance (i.e.,
150-200 mL/m2/d). Sodium chloride intake is
maintained during fluid restriction. 5% dextrose
in 0.45 isotonic sodium chloride solution or 5%
dextrose in lactated Ringer solution can be used,
if intravenous fluids are indicated.
In most children with SIADH with mild to
moderate symptoms, fluid restriction helps within
24 hours. Fluid intake can be increased as serum
electrolytes and osmolality normalise.
Hypertonic sodium chloride solution
Use of hypertonic sodium chloride solution
(3%) in children with SIADH is not often helpful
and is indicated only when severe neurologic
disease is present, viz., seizures or coma induced
by hyponatremia (serum sodium <120 mmol/l).
It may worsen the underlying condition by
expanding the ECF volume further, resulting in
greater decrease in sodium reabsorption by the
proximal tubule and excretion of the administered
sodium. A risk of heart failure exists in a patient
who already is volume expanded.
Corticosteroids are of no direct benefit in
SIADH. Vasopressin analogs with intrinsic
antidiuretic antagonism are very promising but
still experimental. Thiazides decrease free water
28
2006; 8(2) : 132
excretion at the cortical diluting segment and can
severely aggravate hyponatremia in patients with
SIADH.
Complications
Fluid overload
o Pulmonary oedema
o Hypertension
o Anasarca
Acute extracellular hypoosmolality
Cerebral edema (may be observed at rates
of plasma osmolality decrease faster than 10
mOsm/kg/hr)
Permanent brain damage
Cerebral herniation (has been observed in
postmortem examination in both humans and
experimental animals)
Prognosis
Prompt recovery usually follows water
restriction.
Prognosis of SIADH is usually that of the
underlying disease.
Points to remember
Diabetic ketoacidosis
Although diabetic ketoacidosis is potentially life-
threatening, it is rarely fatal when the condition
is prompltly recognized and appropriate
treatment is given.
Early recognition of symptoms such as polyuria,
polydipsia, enuresis, lethargy, weight loss will
certainly help in the diagnosis of type 1 diabetes
mellitus which if treated promptly will avoid
presentation with diabetic ketoacidosis.
In children with type 1 diabetes mellitus, the
following points are to be emphasized to avoid
preceipitatiing diabetic ketoacidosis: the

importance of regular insulin therapy, the
absolute need to provide increased insulin
dosages during an intercurrent infection and
the false promises made by indigenous
practitioners.
Adrenal insufficiency
A high index of suspicion is necessary for
diagnosis as otherwise vague symptoms such as
hyperpigmentatiion, fatigue and weakness may
be missed.
Older children and adolescents with adrenal
insufficiency present with apathy, confusion,
vomiting, dehydration, muscle weakness,
abdominal pain, orthostatic hypotension and
may need intravenous fluid resuscitationduring
a stres situation such as an asthmatic episode,
a lung infection or even a minor infectious
illness.
Syndrome of inapprpriate ADH secsretion
Signs and symptoms of syndrome of
inappropriate ADH secretion, as a rule, are
those of hyponatremia and often are vague and
nonspecific - nausea, vomiting, headaches,
blurred vision, disorientation.
The clinical manifestations of SIADH are
usually related to the degree of the
hyponatraemia and to the rate at which
hyponatraemia develops.
NEWS AND NOTES
INTERNATIONAL CONFERENCE ON PEDIATRIC TRANSPLANTATION
DELHI, AUGUST 19-20, 2006
Enquiries to : Dr. Anupam Sachdeva, Organising Chairman
Dr. Neelam Mohan, Organising Secretary
E-mail : anupamace@yahoo.co.in
Website : WWW.mpades.org.my
29
2006; 8(2) : 133
Asymptomatic patients are usually treated with
water restriction. patients with CNS symptoms
usually require more rapid correction of the
hyponatraemia and water restriction alone may
not be sufficient.
Bibliography
1. Felner EI, White PC. Management of diabetic
ketoacidosis. Recent Adv Pediat 2003; 20:
113-124.
2. Mathai, S, Raghupathy P. Fluid and electrolyte
management of endocrine disorders in
childhood. Ind J Pract Pediatr 2004; 6: 151-
159.
3. Ten S, New M, Maclaren N. Clinical review:
Addisons disease 2001. J Clin Endocrinol
Metab 2001; 86: 2909-2922.
4. Murray JS, Jayarajsingh R, Perros P. Onset of
symptomatic adrenal insufficiency during
treatment of hypothyroidism. Brit Med J 2001;
323: 332-333.
5. Zimmerman D, Lreif AN. Thyrotoxicosis in
children. Endocrinol Metab Clin North Am
1998; 27: 109.
6. Weetman AP. Graves Disease. N Engl J Med
2000; 343: 1236-1248.
7. Segni M, Leonardi E, Mazzoncini B, et al.
Special features of Graves disease in early
childhood. Thyroid 1999; 9: 871.
8. Robertson GI. Syndrome of inappropriate
antidiuresis. N Engl J Med 1989; 321: 538-
539.
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
SCORPION STING
* Mahadevan S
Abstract : The clinical features of scorpion sting
are predominantly due to autonomic stimulation.
Significant systemic manifestations are more
commonly encountered in young children
compared to adults in whom local effects
predominate. Prazosin acts like a specific
phyiological antagonist and is indicated early in
presence of systemic manifestations. In refractory
cardiogenic shock and pulmonary oedema,
ventilatory support with inotrope and vasodilator
infusion in an intensive care setting may be life-
saving.
Keywords : Scorpion sting, Child, Prazosin,
Autonomic storm.
Scorpion sting is a common problem
worldwide and often, children are victims of fatal
stings. The clinical features following
envenomation by the Indian red scorpion
(Mesobuthus tamulus) are predominantly due to
the effect of autonomic stimulation on the cardio
vascular system1. The steps involved in managing
these children are outlined below.
Diagnosis
Step1
Confirmation of the sting is done by history
given by the eye witness or by observing the
killed scorpion.
* Professor
Department of Pediatrics
JIPMER, Pondicherry 605 006
30
2006; 8(2) : 134
Step 2
Differentiation of a benign sting from
potentially fatal envenomation. Severe local pain,
local sweating and mildly raised blood pressure
and no autonomic storm, indicate a non poisonous
sting.
Step 3
Identification of autonomic storm which is
evident soon after the sting (minutes to 4 hours).
Vomiting, profuse sweating, cold extremities,
excessive salivation, saliva as a rope, priapism
in males and paresthesia all over and around the
mouth are features of autonomic storm.
Cardiovascular signs include hypertension
or hypotension, cardiac arrhythmias, sinus
bradycardia or tachycardia, S3 gallop, transient
non sustained ventricular tachycardia, transient
systolic murmur and left ventricular failure.
Oculogyric phenomenon, propped up eyes, puffy
face and abdominal colic are seen in those with
hypertension.It is observed that in children with
scorpion sting profuse sweating may last for 7-
20 hours, priapism / mydriasis for 6-18 hours,
hypersalivation for 2-12 hours and tachycardia
alone for 12-18 hours. Anuria, pulmonary edema
presenting with pinkish froth and cyanosis ,
hypotension, convulsions and shock are late
manifestations. Persistent tachypnea is an early
sign of pulmonary edema in children.
The cause of hypotension in these children
can be due to any one of the following factors.
Early short lasting: Hypovolemia (due to
profuse sweating and vomiting), peripheral
cholinergic or central vagal.

Delayed long lasting: Myocardial failure or
decreased vascular resistance.
Asymptomatic ( 72- 96 hours) : Exhausted
catecholamine stores.
Central nervous manifestations are infrequent.
Intra cerebral hemorrhage is invariably fatal. Late
presentations include, hemiplegia and choreo
athetosis which may appear as late as 10 days
after recovery from acute symptoms.
Management
Close monitoring of the following parameters
is an essential part of management, viz cold
peripheries, pulses, respiratory rate, heart rate,
blood pressure and S3, S4 gallop. ECG and chest
x-ray are needed in any child with significant
features of systemic envenomation. Common
ECG changes encountered include, premature
ventricular contraction, bigeminy, tented T wave,
acute myocardial infarction like pattern, ST
depression, injury to conducting system i.e left
anterior hemiblock, left or right bundle branch
block and QT >500 msec.
For non poisonous sting: Pain relief is done by
cooling of the affected part or local anesthetic
agent; oral paracetamol and oral diazepam may
be used.
Poisonous sting : Hospitalize for frequent
monitoring and stabilisation of hemodynamics.
Key clinical features determining the need for
management in a High Dependency Unit or
Inensive Care Unit are severe tachycardia,
palmoplantar sweating, S3 gallop, hypotension,
shock, pulmonary oedema and ECG changes.
Correction of dehydration is important.
Vomiting, salivation and sweating contribute to
dehydration. Confused agitated child can be
given fluids by NG tube. Restriction of fluid due
to fear of pulmonary edema is a common mistake.
Hypovolemia correction is a priority. Oral
31
2006; 8(2) : 135
rehydration or intravenous crystalloids to be
given as dictated by the clinical picture.
Prazosin, a post synaptic adrenergic
receptor blocking agent, should be given in a dose
of 30g/kg in children which should be repeated
three hourly until there are signs of clinical
improvement in tissue perfusion such as warming
of extremities, increase in urine output, appearance
of severe local pain at the site of sting which was
absent or tolerable on arrival, disappearance of
paresthesias, reduction or improvement in heart
rate and pulmonary edema, reduction in
hypertension or improvement in blood pressure
in case of hypotension without hypovolemia,
reduction or disappearance of murmur and earliest
most important subjective feeling of better or
decreased restlessness in a small child. This is
because the drug has 1000 times more affinity
towards the activated alpha-1 receptors. Then
dose is to be repeated six hourly till extremities
become dry and warm. If the initial dose has been
vomited (one should see the vomit carefully), it
should be repeated. In a confused, agitated, non-
cooperative child, prazosin should be administered
by nasogastric tube. Prazosin is life saving drug
hence attending doctor himself should administer
the drug to the hospitalized patient and it should
be clinically confirmed by noting the signs and
symptoms that drug is absorbed in circulation and
started acting. First dose phenomenon (fall in
blood pressure following an intial dose of prazosin)
is due to postural fall in blood pressure and is
rare. This can be prevented by avoiding lifting
the child and not allowing getting up from bed.
Postural hypotension should be treated by giving
head low position and intravenous fluid. Oral
prazosin may be repeated every 3 hours till
extremities are warm. After prazosin therapy, the
following should be closely monitored to identify
good response: Dilated peripheral veins, good
volume pulse, warm extremities, reappearance of
pain, adequate urine output, no paresthesia and
natural sleep without sedation.
Indian Journal of Practical Pediatrics
Pulmonary edema is a life threatening time
limiting emergency, often fatal and needs rapid
intervention. Patient should be in propped up
position if there is no hypotension. Intravenous
aminophylline 5mg/kg diluted in dextrose is given
as a slow bolus to counter the associated
bronchospasm2. If available isosorbide buccal
spray is useful or powder of nitroglycerine should
be rubbed on gum3 and intravenous furosemide
should be given to reduce the preload and
pulmonary congestion. In cases of massive
pulmonary edema (blood stained froth from
nostrils and mouth), intravenous sodium
nitroprusside (SNP) drip 0.5 microgram per kg
per minute is started and dose raised continuously
according to patients response and blood pressure
upto 8 g/kg/min. Blood pressure should be closely
monitored and maintained at 80-90 mm mg of
systolic blood pressure. SNP has to be prepared
from fresh powder every four hours; the bottle
and saline set should be protected from light. At
times a severe case may require 15-36 hours of
SNP drip to clear pulmonary edema. Patient
should be given oral or injectable cynacobalamine
to avoid cyanide toxicity whenever SNP is given
for long time. Before starting SNP, IV furosemide
is given to avoid sudden fall of intra-ocular
pressure and ocular bleed due to SNP drip3. IV
nitroglycerine can be used in a dose of 0.5-5
Table 1 - Management of scorpion sting
GROUP I Local symtoms only : Analgesics.
GROUP II Systemic manifestations but hemodynamically stable :
Prazosin and oral fluids
GROUP III Systemic manifestations and stable at admission with subsequent
destabilization : Prazosin+dobutamine +/- Sodium Nitroprusside
GROUP IV Life threatening complications and hemodynamic compromise at admission :
ICU protocol (Fig 1)
32
2006; 8(2) : 136
microgram per kg per minute if SNP is not
available. In case of shock or hypotension, early
administration of dobutamine 5-15 microgram per
kg per minute along with SNP drip may be life
saving. In children, after 20-24 hours of sting,
marked tachycardia (130 and above), warm
extremities, pulmonary edema or air hunger
respond to IV dobutamine drip, which may be
required for 48 hours3.
Presence of pulmonary edema has no
relationship to intravascular volume. One should
not assume such patients to be fluid overloaded.
Diuretics may be harmful. Cardiac output can
be improved with dobutamine. Morphine is
contraindicated.
In occasional victims with myocardial
dysfunction, ventricular premature contraction or
R on T phenomenon and ventricular tachycardia
respond to intravenous lidocaine.
Triaging, categorizing victims of scorpion
sting for appropriate management are
summarized in Table 1.
Key instructions for the ICU staff handling
scorpion envenomation are : (a) Propped up
position, oxygen, sublingual nitroglycerin or
isosorbide spray in patients with pinkish froth.
(b) Prepare SNP from fresh powder every 4
 2006; 8(2) : 137

1. Oxygen By Mask / Nasal Prongs

+
2. Maintenance Intravenous Fluids after careful initial boluses of crystalloid
+
3. Intravenous Dobutamine Infusion (5 15 g/Kg/min)
+
4. -Adrenergic Blocker (oral or through NG tube) : Tab Prazosin (30 g/Kg/dose)

No improvement in 4 6 Hours/ Deterioration

Steps 1, 2 & 3 as above

+
5. Intravenous infusion of Nitroglycerine (0.5 5 g/Kg/min) if hypotensive
(or) Sodium Nitroprusside (0.5 8 g/Kg/min) if normotensive/ hypertensive

6. Mechanical Ventilation CPAP/ IMV

Improvement

Taper and stop Dobutamine infusion

+
Taper and stop Nitroprusside/ Nitroglycerine infusion (1 hour before stopping vasodilator infusion
start oral prazosin. To be given Q6h for the next 24 hours)

Fig 1. Intensive care unit protocol for children with scorpion envenomation with
hemodynamic compromise and / or pulmonary edema
33
Indian Journal of Practical Pediatrics
hours. (Dose : SNP 0.5 8 g / kg/ min).
(c) Protect bottle and IV line from light.
(d) Nitroglycerine, another alternative. (NTG :
0.5-5 g/kg/min) upto 12 - 36 hours.
(e) Ventilatory support can be life saving.
(f) Dobutamine 5-15 g/kg/min as infusion.
Atropine, steroids, antihistamines, beta-
blockers, calcium channel blockers, excessive
diuretics, adrenaline and narcotics should be
avoided. They do more harm than good in
scorpion envenomation. Newer reports of
carnitine for myocardial dysfunction in scorpion
sting victims tend to shift the focus towards costly
therapy for this rural emergency. Such
uncontrolled observations could lead to
neglect of life-saving cheaper alternatives like
prazosin.
Indian experience is limited in the use of
scorpion antivenin, though benefits are reported
from USA, Mexico, Saudi Arabia and Brazil
(Centruroides species) 4,5,6. Trials in Tunisia
(RCT) found no useful role for antivenin in severe
envenomation7.
Conclusion
Alpha blockade effect of Prazosin prevents
the evolution of serious cardiovascular morbidity
in victims of scorpion sting. The interval between
sting to administration of prazosin is an important
prognostic factor. A standard intensive care
protocol with dobutamine, sodium nitro prusside/
nitroglycerin has been successfully adopted for
this emergency8.
Points to remember
1. Significant systemic effects of scorpion
envenomation in children are due to
outpouring of catecholamines and
CONTRIBUTOR TO CORPUS FUND OF IJPP
Contribution of Rs. 1000/- Dr. Jayanta Bandyopadhyay, Durgapur, West Bengal
34
2006; 8(2) : 138
predominentaly involve the cardiovascular
system.
2. Prazosin acts like a physiological
antagonist and its early administration
when systemic manifestations appear,
ensures a better outcome.
3. Escalated therapy in the form of ventilatory
support, inotropes and vasodilators in an
intensive care unit may be required in
cardiogenic shock or massive pulmonary
oedema.
Reference
1. Bawaskar HS, Bawaskar PH. Management of
scorpion sting. Heart 1999; 82: 253 - 254.
2. Bawaskar HS, Bawaskar PH. Cardiovascular
manifestations of severe scorpion sting in Inida
(review of 34 children) Ann Trop Pediatr 1991;
11(4): 381-387.
3. Bawaskar H. Scorpion sting, current
management. Pediatric on call website
www.pediatriconcall.com. Last updated
January 1, 2006. Accesssed June 14, 2006.
4. Freire-Maia I, Campos JA, Amaralk CF.
Approaches to the treatment of scorpion
envenoming,. Toxicon 1994; 32: 1009-1014.
5. El-Amin EO, Sultan OM, al-Magamci MS,
EidrissyA. Serotherapy in the management of
scorpion sting in children in Saudi Arabia. Ann
Trop Pediatr 1994; 14: 21-24.
6. Sofer M, Shahak E, Gueron M. Scorpion
envenomation and antivenom thrapy. J Pediatr
1994; 124: 973-978.
7. Belghith M, Boussarsar M, HaguigaH,
Abroug F. Efficay of serotherapy in scorpion
sting: A matched pair study. J Toxicol Clin
Toxicol 1999; 37: 51-57.
8. Mahadevan S. Scorpion sting (Personal
practice).Indian Pediatr 2000; 37: 504 - 514.

EMERGENCY MEDICINE
SNAKE BITE
* Kulandai Kasthuri R
Abstract : Snake bite, a predominantly rural
problem, mainly occurs in older children with
increasing outdoor activity. Out-of-hospital
management is limited to immobilizing the limb
and transporting to a centre where assessment
and if necessary, ASV administration can be
done. In the hospital, initial stablization and
supportive measures are a priority. ASV is
required only if there is systemic manifestation
and significant local reaction. The dose is based
on grading of clinical manifestations and children
require as much dose as adults.
Keywords : Snake bite, Snake envenomation,
Anti-snake venom.
There are about 3500 known species of
snakes seen worldwide, of which about 500
species are poisonous. Among the 330 species
of snakes found in India,70 species are poisonous
(40 land snakes and 30 sea snakes). Annually
India records about 10,000-15,000 deaths due
to snake bite1. The case fatality rate being 2-10%.
The mortality rate is higher in children.
The most common Indian venomous
snakes referred to as the Big Four are the
common krait, common cobra, saw-scaled
viper and Russells viper. The clinical
manifestations are mainly due to the venom
having hemotoxic, neurotoxic and myotoxic
components1,2 (Table 1).
* Associate Professor and Head
PICU., ICH & HC., Chennai.
35
2006; 8(2) : 139
Table 1. Predominant toxicity of
different species
Predominant
toxicity Snake species
Hemotoxic Viperidae
- Saw scaled Viper
- Russells Viper
Neurotoxic Indian Cobra
Common Krait
Coral snakes
Myotoxic Sea snake
Pathophysiology of venomous snake
bite
Among the various species, the average
yield per bite in terms of dry weight of lyophilized
venom is 60mg for cobras, 63 mg for Russells
viper, 20mg for krait and 13mg for saw scaled
viper. The respective fatal doses are much
smaller viz. 12mg, 15mg, 6mg and 8mg
respectively. However, clinical features and
outcome are not that simple to predict because
every bite does not result in complete
envenomation 3. Between 20% and 80% of
venomous snake bites, even with puncture marks
may not result in signs of envenomation4.
Snake venom is a complex mixture of
enzymatic and non-enzymatic compounds,
nontoxic protein, carbohydrates and metals.There
are 20 different enzymes like phospholipases A2,
D-hydrolases, proteases, hyaluronidase,
nucleotidase and ATP ase. The non enzymes
are neuro-toxins and haemorrhagins. The
pathogenesis and effects are given in Table 25.
Indian Journal of Practical Pediatrics
Table 2. Mode of action of snake venom
Pathological process
Direct cytolytic action
Procoagulants leading to intra vascular coagulation
consumption coagulopathy
Platelet function defect qualitative and
quantitative
Postsynaptic blockage preventing depolarisation
(cobra and krait)3
Presynaptic blockage preventing release of
acetylcholine at neuromuscular junction (krait)
Increased capilary permeablility
Reduction in intravascular volume
Cardiotoxicity
Hemotoxic features are predominantly due
to viper bites and neurotoxic features are due to
cobra and krait bites. Local effects are seen both
in viper and cobra bites.
Approach to an individual allegedly
bitten by a snake
Determine whether the patient is actually
bitten by the poisonous snake: Elicit focussed
history. Look for fang marks which may vary from
a few millimeters to as much as 4 cm, depending
upon the species. The depth of the bite varies
anywhere from 1-8 mm. In some cases of bites,
fang marks may not be visible at all. Time of onset
of poisoning may be as early as 5 minutes in cobra
bites or as late as 10 hours in krait bites. In viper
bites the mean duration of onset of symptoms
may be 20 minutes. In sea snake bites the myotoxic
features occur within 2 hours5.
Factors determining the severity of
envenomation
1. Age: Younger the child, more severe the features
36
2006; 8(2) : 140
Effect
Local necrosis and secondary infection
Bleeding
Bleeding
Neurotoxic
Neurotoxic
Oedema
Shock
Hypertension, ECG changes,
acute myocardial infection
2. Location: Bites on face and neck and directly
into the blood stream are more dangerous
3. Activity: Running or active movement of the
limb after the bite increases the risk of venom
absorbtion.
Clinical manifestations
Apart from non-specific symptoms like
severe vomiting, headache, myalgia, vertigo,
tingling and numbness over tongue, mouth and
scalp and hypersalivation, there may be specific
local and systemc manifestations. When the child
is brought to the hospital, a rapid clinical
examination of vitals (airway, breathing and
circulation) and features of local and systemic
envenomation is done6.
Local
Local-pain, tenderness, oedema within 6 to
8 minutes up to 30 minutes.
Local bleeding including petechial and
purpuric rash and blistering are common in
viper bites

Wet gangrenous lesions, blistering and
compartment syndrome can occur in cobra
bites
Regional lymphadenopathy has been
reported as an early and reliable sign of
systemic poisoning.
Local effects are minimal in krait bite.
Systemic Manifestations
Neurological symptoms : Mostly seen in
bites by cobra and krait. Ptosis is the earliest
followed by external opthalmoplegia,
hyperaccusis, weakness of muscles of palate,
jaw, tongue, larynx, neck and muscles of
deglutition. Generally cranial nerves are
involved earlier, followed by drowsiness,
coma and finally respiratory muscle
paralysis. Diaphragm is affected terminally
followed by respiratory failure.
Bleeding manifestations are seen in bites by
vipers characterized by prolonged clotting
time, bleeding at the site of bite, skin bleeds,
bleeding from gum, GIT, urinary tract and
cerebral haemorrhages
Cardiotoxic features like tachycardia, hypo-
tension and hyperkalemic cardiac arrest can
occur in viper bites. Myocardial infarction
and sudden cardiac arrest may be seen in
cobra and krait bites. ECG changes of
hyperkale-mia can occur in renal failure due
to bites by Russels viper and sea snakes.
Acute renal failure may occur in Russels
viper bite due to various reasons (prolonged
hypotension, intravascular hemolysis or DIC
with clinical picture like Hemolytic Uremic
Syndrome). Muscle necrosis and myoglobin-
uria occur in sea snake bite which may also
lead on to acute tubular neerosis.
Transient severe abdominal pain may be ssen
in krait bite.
37
2006; 8(2) : 141
Recurrent manifestations of poisoning may
occur due to ongoing action of the venom which
has a half life of 26 to 96 hours. So, daily
evaluation of the patient is essential for 3 to 4
days. Delayed manifestations in an initially
stabilized patient can occur even after 3 weeks,
the venom being released from local blebs which
act as venom depots not accessible to anti-venom3.
Investigations
Laboratory tests are useful for monitoring,
prognosticating and determining type of
intervention. ELISA studies are now available
to identify the species involved based on the
antigens5 but these tests are expensive and not
freely available.
1. CBC-May show anemia, leucocytosis and
thrombocytopenia
2. Peripheral smear-May show evidence of
hemolysis (particularly in viperine bites) and DIC
3. Coagulation profile-Prothrombin time (PT),
partial thromboplastin time (PTT), fibrinogen,
fibrin degration products (FDP) and clotting time
may be defective. Clot lysis which indicates the
quality of clot formed may be a better indicator
of coagulation capability than the actual time
required for formation, since clot lysis has been
observed in several patients who have normal
clotting time. Prothrombin time (PT) is more
sensitive for assessing coagulopathy. Clotting
time by Lee White method (6-8 hourly till values
normalize) is useful for periodic assessment of
state of coagulation.
20 minute whole blood clotting time 7:
Incoagulable blood is a cardinal sign of systemic
envenomation by most of the viper bites. A simple
bed side test is adequate for clinical purpose. This
test is useful to monitor the effectiveness of ASV
therapy when more sensitive tests of coagulation
are not easily available. 2 to 3 ml of blood is taken
and kept in a new, clean, dry, test tube undisturbed
for 20 minutes. At the end of 20 minutes the tube
Indian Journal of Practical Pediatrics
is tilted once to check if clotting has occurred. If
blood is clotted it rules out significant coagulation
disturbance.
4. BUN, creatinine, electrolytes-azotemia,
hyperkalemia may be present
5. Urine analysis for hematuria, proteinuria,
hemoglobinuria, or myoglobinuria
6. ECG : Changes are usually nonspecific and
include bradycardia, AV block with ST segment
elevation or depression, features of hyperkalemia
if present
Management
i. Out-of-Hospital care (first aid)
ii. Supportive therapy
iii. Specific therapy
iv. Local wound management
Out-of-Hospital care (First Aid)
Out-of-Hospital care should focus on
stabilization and rapid transport of victim to a
health care facility with the capability of anti
venom administration8. This includes:
1. Immobilization of the bitten extremity in a
neutral position in every case with the help of a
splint and not allowing the victim to walk or run
is important. The patient should maintain strict
rest, as movement of even the unbitten extremities
increases the lymphatic absorption from the bitten
side. He should be transported in a vehicle or on
a stretcher in a lying down position. Constriction
bands or pressure-immobilization method are
recommended during transport of the victims.
Constriction bands: These are broad, flat
bands applied proximal to the bite site to exert a
pressure great enough to occlude superficial veins
and lymphatics (>20 mm Hg) but, with enough
space between the band and limb to admit one
finger. It should not be so tight to obliterate the
peripheral arterial pulse8.
38
2006; 8(2) : 142
Pressure-immobilization method: Firmly
wrap the bitten extremity with an elastic bandage.
The tightness of the wrap is described as
approximating an elastic wrap for an ankle sprain.
This technique slows the systemic absorption of
the venom by trapping it at the bite site8.
2. Avoid incision and excision over the bite,
chemical application, cauterisation, suction,
cryotherapy, tourniquet and electric shock as
these may cause more tissue injury leading on to
gangrene and uncontrolled bleeding.
3. Avoid giving the patient food or drink, as there
is a potential danger of vomiting due to
envenomation
4. If the snake has been killed, it should be
brought carefully to the hospital for species
identification. It should not be touched with bare
hands as some snakes may sham death and even
severed head can inject venom4.
Supportive therapy
This is the most important aspect of the
therapy.
1. Reassure the patient
2. Take care of airway, breathing, circulation
(ABCs)
3. Monitor vitals, urine for hematuria and clotting
time; monitor heart rate, respiratory rate, chest
expansion and sensorium periodically. Close
observation for early neurotoxic effects such as
ptosis, ophthalmoplegia, speech and swallowing
difficulty is periodically carried out.
4. Ventilatory support may be needed for
respiratory failure or unstable airway.
5. Vascular access should be obtained in the
unbitten limb. Treat shock with IV fluid boluses
(NS or RL).
6. Fluid management and inotropes as needed to
maintain normal perfusion.
 2006; 8(2) : 143

7. Avoid IM injections effective against the Big Four (common cobra,

8. Anti-convulsants for seizures
9. Keep the pressure immobilization/constriction
band in place till the antivenom is administered.
When child is brought to hospital without
constriction band or pressure immobilization, a
sphygmomanometer cuff inflated 25-35mm Hg
placed atleast 2-4 inches proximal to the bite site
or leading edge of swelling may be applied and
kept during intra-hospital transport8.
10. Sedation and analgesics for pain; avoid
NSAIDs.
11. Send blood for grouping, typing and cross
matching before administering anti-venom.
12. Neostigmine may be tried in Indian cobra
and krait bite presenting with neurological
manifestations - dose 50 -100 g/kg IV every 4
hours with atropine 0.02 mg/kg IV five minutes
prior to neostigmine
Specific therapy (Anti-venom)
Anti snake venom (ASV) ingredients:
Polyvalent snake anti-venom manufactured by
Haffkine Bio-pharmaceutical Corporation Ltd is
lyophilized powder. It is of equine origin and is
common krait, Russells viper and saw scaled
viper). King Cobra bite will not respond to the
commonly available ASV. So, specific monovalent
ASV shoud be used. Each ml of the reconstituted
snake anti-venom neutralizes 0.6 mg each of the
Indian cobra and Russells viper venom,0.45mg
of krait and saw scaled vipers venom. ASV is
also available in liquid form (10ml/vial).
Indications: Every snake bite, even by poisonous
species does not warrant snake anti-venom. The
empirical use of anti-venom should be avoided
due the risk of hyper sensitivity reactions. So
ASV is indicated only if there are signs of local/
systemic envenomation. When indicated,
antivenom should be administered without delay.
Dose: Depends on the severity of the
envenomation.The ideal dose is not known and
there is no universally accepted standard
regarding optimum dose of ASV. The
recommended dose of ASV based on severity of
clinical features is given in the Table 3. It should
be remembered that the envenomation grade is
only for the initial guidance for ASV therapy, as
the severity can change over time. ASV doses
may have to be repeated based on reassessment.

Table 3. Recommended for different severities of envenomation

Severity of Cliical features Amount of
envenomation anti-venom
No No fang marks, no local/systemic reactions NIL
envenomation
Mild Fang marks, local swelling and pain with/wihtout lymphadenitis 5 vials
envenomation and local ecchymoses/purpura, no systemic signs
Moderate Above features + swelling progressing beyound the site of the bite 10 vials
envenomation mild systemic symptoms like nausea, vomiting and paresthesia,
mild coagulation defect (clotting time more than 10 mins, clot size
<50% of whole blood in the tube, a small speck)
Severe Marked swelling of extremity, subcutanesous ecchymoses, severe 15-20 vials
envenomation systemic signs and symptoms, DIVC, proteinuria, hematuria,
encephalopathy, shock, paralysis incoagulable blood
39
Indian Journal of Practical Pediatrics
Preparation and administration of anti-venom
Mix 1 vial of anti-venom (lyophilised
powder) with 10ml of distilled water and rotate
it between the palms of the hands till the
antivenom is fully dissolved and appears clear.
Dont shake vigorously.If foam appears or if the
solution is turbid or milky, it indicates denatured
protein and there is a greater risk of anaphylaxis
if this is used. Before administering anti-venom
ask for history of previous administration of anti-
serum, allergy, bronchial asthma and urticaria
Sensitivity test is done only if ASV
administration is planned. Inject subcutaneously
0.1ml of the antivenom diluted 1:10. Observe the
patient for 20-30 minutes for local/general
reactions of hypersensitivity.If no reaction is
seen, dilute the content of 1 vial (10 ml) with 40
ml NS(1:4 dilution).Administer this slowly over
1 hour. Watch for any reaction; if no reaction
occurs, then the required dose is administered
over 3-4 hours.
Continued administration of anti-venom : After
initial bolus,depending on clinical response, 2
vials of anti-venom are infused in 100ml of fluid
every 4-6 hours till all signs of envenomation
disappear and clotting time is less than 10
minutes.
Reaction : Hyper sensitivity reactions may occur
in 3-4% of cases usually within 10 minutes to 3
hours after starting the infusion. Reactions range
from urticaria, hypotension to acute life
threatening anaphylaxis. Drugs and equipment
for cardiopulmonary resuscitation and for
anaphylaxis should be kept ready. Serum
sickness occurs after 1-4 weeks.
Treatment of anaphylaxis :
1. Give 0.01 ml/kg of 1:1000 IM adrenaline
(maximum 0.5 ml). Repeat doses may be
needed
2. Volume replacement for shock-NS
40
2006; 8(2) : 144
3. Chlorpheniramine maleate 0.2 mg/kg/dose IV
4. Hydrocortisone 6mg/kg/dose IV
5. Oxygen and intubation facility should be ready
If patient found sensitive to the equine ASV
de-sensitization may be necessary by
administering graded dose of anti-venom at
regular and adequate intervals.
Timing of anti-venom : Best effects are
observed within 4 hours of bite.But it is never
too late to start ASV in viper bites as some times
neutralizable venom is found even after 3 weeks.
Local wound management9
Clean the wound
Leave the wound open
If swelling or tenderness is apparent- mark
the proximal edge and time it so that
progression can be easily monitored.
Measure the circumference of the injured
extremity at the level of oedema and record
progression of oedema hourly.
Wound debridment may be required after 3-
5 days.
Fasciotomy may be done for massive
oedema due to compartment syndrome after
careful assessment. It is ideal to substantiate
elevated intracompartmental pressure by
compart-mental pressure monitoring.
Compartment syndrome10
Swelling of muscles within the tight fascial
compartment of the limb may raise the
intracompartmental pressure leading on to
ischemic damage and neurological dysfunction.
The features are severe pain, weakness of the
limb, distal anesthesia, pallor and tenseness of
the limb on palpation. Fasciotomy is done to
relieve the intracompartmental pressure after
coagulation is corrected with adequate ASV.

Other supportive measures
1. A booster of Tetanus toxoid if appropriate.
2. Broad spectrum antibiotics with anaerobic
coverage
3. Blood transfusion-whole blood or plasma as
needed in DIC.
4. Management of ARF if present is usually
conservative.
5. Peritoneal dialysis may occasionally be
necessary.
Points to remember
1. Most of the snake bites are due to non-
poisonous snakes.
2. Some bites even by poisonous snakes may
not cause symptoms. Reassurance, allaying
of anxiety and hospitalization for 24-48
hours are all that is required in such cases.
3. The main clinical features of systemic
envenomation will be bleeding
manifestation (hemotoxic) due to viper bites
and bulbar or respiratory paralysis
(neurotoxic) due to cobra or krait bites.
4. If signs of envenomation are present the
emphasis is on stabilization of ABCs,
adequate antivenom administration with
continuous and repeated monitoring for
3 to 4 days will be life saving.
NEWS AND NOTES
NATIONAL CONFERENCE OF IAP CHAPTER ON GROWTH, DEVELOPMENT &
BEHAVIORAL PEDIATRICS 2006
DELHI, SEPTEMBER 9-10, 2006
Enquires to :
Dr. Anju Seth, Organizing Secretary, Dept. of Pediatrics,
Kalawati Saran Childrens Hospital, Bangla Sahib Marg, New Delhi 110001.
Email: anju_seth@yahoo.com
41
2006; 8(2) : 145
References
1. Pillay VV. Comprehensive Medical
Toxicology, 1st Edn. Hyderabad, Paras Medical
Publishers. 2003; pp 548-569.
2. Whitaker R. Common Indian Snakes - A Field
Guide. 1st edn. New Delhi. Macmillan India
Ltd. 1978; pp 94-99.
3. Dutta TK, Ghotekar LM. Rational use of Anti-
snake venom (ASV). Medicine update. 1998;
8: 760-765.
4. Warrel DA. Animal toxins. In : Cook GC,
Zumla A, Eds. Mansons Tropical Diseases.
21st Edn, London, Saunders Elsevier, 2003; pp
583-603.
5. Auerbach PS, Norris RL. Disorders caused by
reptile bites and marine exposure. In : Kasper
DL, Fauci AS, Longo DL, Braunwald E, Hauser
SL, Jameson JL, Eds. Harrisonss Principles of
th
Internal Medicine. 16 Edn. New York,
McGraw-Hill, 2005; pp 2593-2595.
6 Dutta TK,Vijetha SR. Snake bite. In : Shankar
PS, Ed. API Medical Update. 1995; 5:
pp 309-312.
7. Bavaskar HS. Snake venom and anti venoms.
Critical supply Issues. JAPI. 2004; 52: 11-12.
8. McKinney PE. Out-of-Hospital and
Interhospital Management of Crotaline
Snakebite. Ann Emerg Med 2001;37:2.
9. Hall EL. Role of Surgical Intervention in the
Management of Crotaline Snakebite
Envenomation. Ann Emerg Med 2001; 37:2
175-180.
10. Sullivan Jr JB, Boyer L. Snake envenomations.
In : Fuhrman BP, Zimmerman JJ, Eds. Pediatric
Critical care. 2nd Edn. St. Louis, Mosby, 1998;
pp 1171-1180.
Indian Journal of Practical Pediatrics
EMERGENCY MEDICINE
ACUTE POISONING IN CHILDREN
* Gautam Ghosh
** Arun Kumar Manglik
Abstract: A poison has been defined as a
substance (including medicines) which when
introduced into or absorbed by living organisms,
causes injury or death. Majority of the accidental
poisoning occurs below 5 years and at home. A
poisoned child may present as an emergency with
or without multi-system involvement. Toxidromes
(constellation of signs and symptoms seen
commonly with a particular poison) help in
diagnosis of unknown poisons. Management
constitutes of resuscitation, evaluation,
detoxification and removal phases. Special
emphasis is given to the two common poisons
namely organophosphates and kerosene.
Key words: Poisons, Diagnosis, Management,
Organophosphate, Kerosene.
The peak incidence of accidental poisoning
is in the second year of life as the childs instincts
lead him to explore everything around, as he/she
acquires the ability to do so1. This tendency starts
decreasing after 4-5 years of age as he/she tends
to be selective in choosing things for the purpose
of ingestion, putting to good use his/her
experience. Male children due to greater activity
and children from poor socio-economic class due
to less supervision and more access to common and
carelessly stored chemicals and drugs, are
more prone to poisoning. The second group is
adolescents who fall prey to suicidal poisoning
* Park Clinic, Kolkata & Shree Jain Hospital, Howrah
** Sishu Sanjivan Hospital, Salt Lake City, Kolkata
42
2006; 8(2) : 146
due to emotional stress. The exact incidence of
acute poisoning is not known in India but it is
quite common and often unreported in children2.
According to WHO the mortality due to poisoning
ranges from 0.3%- 0.7% worldwide3. There are
six basic methods of exposure in children: oral,
inhalational, dermal, ocular, envenomation, and
transplacental. Most poisonings are acute.
Poisoning should be viewed as a multiple chemical
trauma. Animal bites e.g. scorpion and snake bites
are excluded from the present discussion.
Approach to poisoning
I. Primary survey and stabilization
The general approach to evaluation and
support of cardio-respiratory functions is the
same as practised in PALS (Pediatric Advance
Life Support) courses. Assessment and
resuscitation are carried out simultaneously in the
primary survey.
II. Secondary survey
Evaluation
i) History: It is necessary to know that only less
than 10% of poisoning may be symptomatic at
presentation4. History of acute onset, prior nor-
mal status, child left unsupervised, drugs con-
sumed by other family members, spillage of drugs
and chemicals and emotional stress of the child
(usually adolescent) must be considered. Suspi-
cion is most important for diagnosis. A history
of poison ingestion has to be searched for. Con-
sidering the general presentations of common
poisoning in children, one or more of the follow-
ing should alert towards possible poisoning:

Disturbed consciousness without a cause
Abnormal behavior of sudden onset
Arrhythmias without a heart disease
Respiratory distress without pneumonitis
Shock, mostly third space loss
Unusual odor from mouth.
Cyanosis, without heart disease or distress
Severe vomiting and/or diarrhea without
gastroenteritis
Seizures without a reason
Metabolic derangements, often acidosis
Identification of the toxin, its form and dose,
time lapsed after exposure, route of exposure, any
underlying medical condition and home
management given before arrival are important
histories one should take. Appearance of
symptoms chronologically and similarity of
symptoms in all involved children are to be
recorded.
ii) Physical examination: Some findings on
clinical examination may give a clue to the
identity of the poison.
a) Odour : Smell of kerosene (kerosene, petroleum
products), garlic (organophosphates, arsenic) and
acetone (salicylate, methanol) may be suggestive.
b) Skin and mucous membrane: Cyanosis may
indicate methemoglobinemia due to dapsone or
nitrates and carboxy hemoglobinemia due to
carbon monoxide (CO) poisoning. Sweating and
lacrimation (organophosphates, amphetamines,
cocaine and barbiturates), dry and hot skin
(dhatura, anticholinergics, tricyclic anti-
depressants) and pallor (sympathomimetics,
insulin) may be the other clues.
c) Temperature: Hypothermia may suggest
poisoning due to sedatives, phenothiazines,
barbiturates, carbamazepine or nimesulide.
43
2006; 8(2) : 147
Hyperthermia may indicate anti-cholinergics,
tricyclic antidepressants(TCAs), salicylates or
theophylline.
d) Pulse rate : Unexplained bradycardia (digitalis,
sedatives, organophosphates, -blockers, calcium
channel blockers), tachycardia (anti-cholinergics,
TCAs) or arrhythmia (anti-cholinergics, TCAs
organophosphates, digitalis) may be suggestive
of poisoning.
e) Respiration: Bradypnea or depressed respiration
due to barbiturates or narcotics, tachypnea due to
salicylates or amphetamines, Kussmaul breathing
due to salicylates or methanol and pulmonary
edema because of aspiration, narcotics and TCAs
may be useful findings.
f) Central nervous system : Seizures may occur
in ingestion of organophosphates (OPs),
sympathomimetics, camphor, INH, theophylline
and anti-cholinergics. Fasciculation (OPs),
nystagmus (phenytoin, carbamazepine),
hypertonia and myoclonus (anticholinergics),
weakness and paralysis (OPs, botulism, heavy
metals), ataxia (barbiturates, phenytoin,
carbamazepine, sedatives), delirium (anti-
cholinergics, alcohol, cocaine), and coma
(anticholinergics, alcohol, OPs, anticonvulsants,
CO and salicylates) are other neurological
findings. Eye signs like miosis (narcotics, OPs,
mushrooms, barbiturates), and mydriasis
(anticholinergics, cocaine, TCAs) should be
looked for.
g) GIT: Vomiting and diarrhea may occur in iron,
mushroom and OP poisoning
h) BP: Hypertension may be seen in
sympathomimetics, OP, TCA, cocaine and
amphetamine poisoning.
iii) Toxidromes: The characteristic clinical
manifestations of a specific drug or toxin or a
group of drugs is called toxidrome. Table 1 lists
some common toxidromes.
Indian Journal of Practical Pediatrics
Table 1. Toxidromes 4,5
(Specific features of some common poisons)
Drugs
Anticholinergic toxidrome (Atropine, TCA,
Antihistaminics, Mushrooms)
Cholinergic toxidrome (insecticides like organophosphates, carbamates) : These are discussed
separately
Opiates / Narcotics / Clonidine
Sedatives / Hypnotics / Barbiturates
Salicylates
Phenothiazines
Sympathomimetics (Amphetamines,
Ephedrine, Cocaine, Aminophylline)
iv) Laboratory tests that can suggest poisoning4,6
1) Hypoglycemia: Insulin, Ethanol, Acetami-
nophen, Salicylates
2) Hyperglycemia: Salicylates, Organo-
phosphates, Iron.
3) Hypocalcemia: Methanol, Ethylene glycol
4) Elevated anion gap metabolic acidosis: Methyl
alcohol, Ethanol, Salicylates, CO, INH
5) Urinalysis: Oxalic acid crystals (Ethylene
glycol), Ketonuria (Ethanol, Salicylates).
The clinical management is based on history
and clinical findings. Toxicology screening
2006; 8(2) : 148
Clinical manifestations
Agitation, hallucination, coma, extrapyramidal
symptoms, mydriasis, flushed warm dry skin and
mucus membrane, tachycardia, arrhythmia, hypo/
hypertension, paralytic ileus (Hot as a hare,
Blind as a bat, Dry as a bone, Mad as a hatter).
Bradycardia, hypotension, pulmonary odema,
bradypnea, hypothermia, coma, miosis,
Hypothermia, bradypnea, nystagmus, ataxia, coma,
hypotension, miosis / mydriasis, vesicles, bullae
Vomiting , hyperpnea, fever, lethargy, coma,
acidosis
Hypotension, tachycardia, tachypnea, hypother
mia, lethargy or coma, tremor, miosis, extra
pyramidal symptoms (torsion of head and neck,
occulogyric crisis, trismus, ataxia, back arching,
tongue protrusion)
Tachycardia, arrhythmia, psychosis, hallucination,
delirium, nausea, vomiting, abdominal pain,
piloerection.
(from urine and blood) is rarely needed for
immediate management. It may be useful for
confirmation of poisoning, on-going management
and medico-legal purposes.
Management
More than 75% of the poisoning may be
managed at home as majority of poisons are non
toxic (Table 2) and amount of ingestion is
insufficient.5
Indications for admission: The presence of
disturbed consciousness, seizures, shock, severe
vomiting and/or diarrhea, cyanosis, respiratory
distress mandate admission, preferably in
intensive care unit .
44
 2006; 8(2) : 149

Table 2. Common household items: Are they poisonous?

Category
Nontoxic substances
Potentially toxic substances
Name
Inks, mosquito repellants, incense, saccharine, calamine lotion,
candle, chalk, pencil lead (graphite)
After shave lotions (ethanol), aspartame (sweetener), sindoor
(lead, mercury salts), kajal (lead salt), jewellery cleaners
(caustics), bleach / detergent (alkali), disinfectant (phenol,
lysol) toilet cleaners (acid), varnish, nail polish cleaner
(acetone), rat poisons (aluminium phosphide, zine phos-
phide, warfarin like compounds, arsenic or thalium), button
batteries (acid/alkali/lithium), hair bleach (hydrogen peroxide)

1. Resuscitation and stabilization hospital setting it is not available freely. Emesis

The classical PALS protocol (ABC) is
followed with special emphasis on keeping the
airway open and intubating children with loss of
protective airway reflexes. Oxygen, glucose and
naloxone may be used as a therapeutic trial.7
The initial gastric aspirate is kept for
chemical examination.
2. Symptomatic and supportive therapy
Specific management may be needed in the
following situations: shock and electrolyte
abnormalities, cardiac arrhythmia, seizures,
hypothermia, pulmonary edema, rhabdomyolysis.
3. Detoxification1
i. Removal of unabsorbed poison
Skin or eyes, if they are source of exposure
need to be thoroughly washed and clothes
removed. Remove the person from the site if
that environment can lead onto further exposure.
Gastrointestinal detoxification8
1. Emesis: Syrup of Ipecac: 10ml (6-12 months),
15ml (1-12yrs) followed by water. It is no more
used in a hospital setting. Even for use in out of
45
is contra indicated in young infants < 6 months
of age, in corrosive and hydrocarbon ingestion
and in children with altered sensorium.
2. Gastric lavage : Orogastric lavage allows direct
irrigation and removal of unabsorbed poison. If
gag reflex is absent the airway must be protected
by endotracheal intubation. Size of tube used is
30F between 2-5yrs (biggest tube which can be
safely inserted is selected). It is done with warm
0.9% saline in the dose of 15ml/kg cycles until
the return lavage fluid gets clear. The lavage return
should approximate the amount of fluid given to
avoid fluid retention. It is useful in removing highly
toxic substances e.g. organophosphate. It is
contraindicated in unconscious and unstable
patients and hydrocarbon and corrosive poisoning.
Side effects may be fluid retention and aspiration.
Gastric lavage is found to be useful if it is done
within one hour of ingestion of the toxin (32% of
ingested drug removed).
3. Reduction of absorption (activated charcoal)9:
Activated charcoal is produced from wood,
petroleum which is heated to 900oC with steam
and CO2. The net result is marked increase in
total absorptive surface as high as 1600m2/gm.
The dose is 1-2 gm/kg, total average 30-60 gms,
Indian Journal of Practical Pediatrics
given as a suspension of 20% activated charcoal
in 70% sorbitol base. If only tablets are available,
they can be crushed and mixed with water or fresh
juice in the form of a thick soup. It acts within 30
minutes. It is useful in poisoning with many toxins
like TCA, INH, digoxin, barbiturates, dapsone and
anticonvulsants. If is not useful in iron and OP
poisoning. Multiple doses may be required when
the drug is excreted into gut after initial absorption
(phenobarb, carbmazepine, theophylline,
dapsone). The use of activated charcoal is
considered an important method of gastrointestinal
decontamination. The main constraint is that it is
not freely available. It is contraindicated in
intestinal perforation or ileus or when oral antidote
like N-acetyl cystine is used.
4. Whole bowel irrigation (WBI)10: It refers to
mechanical cleansing of the entire bowel by large
volumes of colonic lavage solution. Polyethylene
glycol (EZLAX, PEGLEC), a non absorbable
vehicle mixed in a balanced electrolyte solution
is run at 25-40ml/kg/hr by naso-gastric or rectal
route for 4-6hrs, keeping the child in a semi-
fowler position until the rectal effluent gets clear.
A dose of anti-emetic may help. It is indicated
where activated charcoal is not useful. It is a
recent armamentarium in poisoning and may be
used in iron, lithium, theophylline, cocaine,
heroin and sustained release drug poisoning. It
is contra-indicated in ilues, intestinal obstruction,
perforation and GI bleeding.
5. Catharsis: Magnesium citrate / Disodium
phosphate. Not used nowadays.
Gastric lavage, use of activated charcoal and whole
bowel irrigation are the only currently recom-
mended methods for GIT decontamination.
ii. Elimination of absorbed poison
This may be achieved by
(a) Forced Diuresis 4: may be alkaline
(sod.bicarbonate) for salicylate /phenobarbitone /
46
2006; 8(2) : 150
isoniazid poisoning or acid (ammonium.chloride
1.5gm in 5%dextrose.) for amphetamine /
quinidine poisoning. But it is of limited clinical
value. It is not recommended because of potential
volume overload and electrolyte abnormalities.
Just alkalinisation of urine (urine pH maintained
at 7.5 or slightly more) with IV sodabicarb may
enhance urinary excretion of weak acids like
salicylates and phenobarbitone. It is also indicated
in TCA poisoning. Sodabicarb is administered in
a dose of 2-3 ml/kg by slow infusion 4 to 6 hourly.
(b) Dialysis: indicated in severe apnea / a critical
toxin level / failure of other measures / prolonged
coma / delayed drug toxicity 4 due to Salicylates,
Lithium, INH, Methanol, Ethylene glycol and
Phenobarbitone (SLIME-P). Hemodialysis is
more effective.
(c) Hemoperfusion: Blood flows through charcoal
or ion exchange resins. It is used in theophylline,
phenobarbitone, phenytoin and carbamazepine
poisoning. This may damage the platelets.
iii. Antidotes1
Physical: Demulcents like oil and egg prevent
absorption by forming a coating on mucous
membrane of stomach and may be used in heavy
metal poisoning.Currently they are not used.
Activated charcoal is the only physical antidote
recommended.
Specific antidotes : These are available only for
a few poisonings (Table 3).
Hydrocarbon poisoning
There are four groups of hydrocarbons according
to viscosity e.g. Very low (furniture polish), low
(benzene, toluene), moderate (kerosene, gasoline)
and high (petroleum, paraffin).
Kerosene poisoning4
The toxicity of these substances is primarily
due to pulmonary aspiration and not due to
systemic absorption. The risk of aspiration is
 2006; 8(2) : 151

Table 3. Pharmacological antidotes11,12

Poison Antidote Indication Dose of antidote
Acetaminophen N-Acetyl cysteine Serum level > 200mcg/ml 140mg/kg PO, then 70mg/kg
(Paracetamol) (Mucomyst) within 4hrs. every 4hrs (17 doses in 3-4days)
Anticoagulant Phytomenadione Bleeding 5-10mg IM / IV
( Warfarin ) (VitK1)
Beta-blocker, Glucagon Bradycardia 0.05-0.1 mg/kg bolus, then 0.05mg/kg/hr
Titration accordingly
Calcium channel Isoproterenol / Bradycardia 0.1 to 2.0 mcg/kg/min Isoprotenenol
blockers (CCB) Epinephrine, 0.1 to 1 mcg/kg/min Epinephrine
IV calcium 0.5 ml/kg/bolus-calcium for CCB poisoning
Benzodiazepine Flumazenil Sedation 0.2mg over 30 sec. repeat q 1min (1 mg max.)
Ethylene Glycol Ethanol Serum level > 20mg/dl; 750mg/kg as 10% Ethanol in 5% GDW
Or osmolar gap with (loading) 80-150mg/kg/hr(maintenance) to
Methanol metabolic acidosis maintain blood ethanol level 100-150 mg/dl
Fomepizole It inhibits 15mg/kg (load), 10mg/kg q12hr 4doses for
alcohol methanol and until level < 20 mg/dl for
dehydrogenase ethylene glycol.
Heavy metals Calcium EDTA Pb/Mn/Ni/Hg/Cu EDTA 1-1.5g/m2/day IV(2dd) x 5 days
BAL Pb/As / Cu /Au / Hg BAL - 12-24mg/kg/day deep IM (6dd) x 3 days
Penicillamine Cu / Pb /Au / Hg Penicillamine - 20-40mg/kg/day PO
DMSA Pb / Hg / As DMSA - 10mg/kg/dose q8hrly PO for 5days,
q 12 hr 14 days
Isoniazid Pyridoxine Seizures Same dose as INH ingested or if amount not
known, 25-50 mg/kg IV every 30 minutes till
seizures controlled
Iron salts Desferoxamine Serum level> 15mg/kg/hr IV infusion or 50mg/kg/IM repeat
350mcg/ml / every 4-8 hr until urine color normal
(no more vin rose color),
serum iron and clinical condition normal
Methemoglobinemia Methylene Blue Symptomatic / 1-2 mg/kg of 1% soln. in 5-10min repeat
(Dapsone / nitrites/ level > 30-40% q 30-60min. Maximum total dose 7 mg/kg
nitrates / sulphonamides)
Narcotics Naloxone Symptomatic 0.01mg/kg /dose; if no response repeat
0.1 mg/kg every five minutes till response.
Organophosphates, Atropine Muscarininc 0.05 mg/kg IV; repeat every 5-10 mins to
carbamates effects reverse muscarinic effects; maintain
atropinisation for 24 to 48 hours
Organophosphates Pralidoxime Nicotinic 25-50 mg/kg in NS over 30 mintues; repeat after
effects 30-60 minutes; then q 12 hr if symptoms persist
Phenothiazine Diphenhydramine Oculogyric crisis 5mg/kg/day 3 dd (max. 300mg/ day) oral or IV
Sulphonylureas Octreotide Hypoglycemia 25 mcg SC 8th hourly as required
(Antidiabetics)

As = Arsenic, Au = Gold, Cu = Copper, Hg =- Mercuy, Mn = Magnese, Ni = Nickel, Pb = Lead, dd = divided doses

47
Indian Journal of Practical Pediatrics
higher with moderate viscosity, highly volatile
compounds (gasoline, kerosene) than with low
viscosity less volatile ones (petroleum, paraffin).
Clinical features
1) Respiratory: Cough, respiratory distress, fever,
dyspnea, wheeze, cyanosis and rarely hemoptysis.
This occurs within 6-24hrs of aspiraton. One gets
the smell of kerosene from the childs breath.
2) CNS: Somnolence, depression which may be
secondary to hypoxia or due to additives (blue
pigment in commercial kerosene!).
3) Gastrointestinal: Nausea, vomiting, abdominal
pain and diarrhea.
4) Hematological: Hemolysis, hemoglobinuria.
It occurs rarely with gasoline ingestion due to
red cell damage.
Laboratory findings: Chest X-ray within 24 hours
may confirm chemical pneumonia. Complete
blood count and ABG are rarely needed.
Treatment : Is usually supportive and includes
resuscitation and stabilization Emesis, activated
charcoal and lavage are contraindicated for
kerosene poisoning.The child with respiratory
distress requires oxygen, IV fluids and close
monitoring. Respiratory failure is a rare
complication and requires ventilatory support.
The outcome is usually good.
Organophosphate poisoning11 (OP):
OPs include malathion, parathion and
fenitrothion (Tik 20). Absorption occurs through
skin, eyes, inhalation and ingestion. Stronger
concentrations (40-50%) are present in industrial
formulations than in domestic (1-2%) ones.
OPs act by phosphorylating the active or
esteric site of acetyl cholinesterase leading to
irreversible inhibition of the enzyme and excessive
accumulation of acetylcholine. Carbamates like
48
2006; 8(2) : 152
propoxur (Baygon) cause reversible inhibition of
cholinesterase and cause less CNS effects. The
clinical signs are due to muscarinic, nicotinic and
central nervous system effects.
a)Muscarinic (post-ganglionic parasympatho-
mimtic): D(diarrhea), U(urinary incontinence),
M(miosis), B(bradycardia), B(bronchorrea),
E(emesis), L(lacrimation), S(salivation)
DUMBBELS
b) Nicotinic (sympathetic and skeletal muscle):
Muscle twitching, fasciculation, paralysis,
tachycardia, hypertension (most dangerous),
hyperglycemia
c) Central nervous system effects : Confusion,
slurred speech, ataxia, seizures, periodic
breathing, coma etc.
RBC cholinesterase < 50% of value is diagnostic
(rarely done)
Treatment
Stabilization
Rapid cardiopulmonary asessment and
support is the priority. Treat seizures, if present.
Decontamination
Removal of contaminated clothes and cleaning
the skin and eyes (by irrigation) are carried out
wherever appropriate. Gastric lavage is done as
soon as possible protecting the airway.
Specific Treatment
Atropine (in doses 5-10 times greater than
usual dose): It blocks muscarinic action only.
Initial dose: 1-2mg IV (>12yrs) and 0.05mg/kg
IV every 5-10min (<12yrs). It may be doubled
every 5 min until response. End point is drying
of mucosa and and respiratory secretions (not
pupil size or heart rate!). Maintenance dose is
required for 24-48 hrs depending on symptoms
to prevent rebound phenomenon.

Pralidoxime : Counteracts nicotinic symptoms
only and hence should be added to atropine. It
has to be given within 48 hrs (preferably within
12 hours) as it has poor action against aged acetyl
cholinesterase. Dose is 25-50mg/kg in N.saline
IV in 30 mins. It may be repeated after 30-60
minutes and then 12-24 hrly if symptoms
reappear. Pralidoxime does not have effect on
CNS manifestations. Atropine is used for CNS
effects of OP. Pralidoxime is not indicated in
known carbamate poisoning.
Drugs contraindicated in OP poisoning are
morphine, phenobarbitone, frusemide,and
theophylline.
Sequelae :
a) Prolonged memory loss, peripheral
neuropathy, personality changes
b) Intermediate syndrome: Respiratory failure,
bulbar or nuchal or proximal limb weakness
24-96 hrs after resolution
c) Delayed neurotoxicity or neuropathy :
Sensorimotor polyneuropathy occurring 1-3
weeks after poisoning. Flaccid paresis and
wasting may ensue after 12-15 months.
Medicolegal issues : Doctor, Poisoning and
13
Law:
a) A doctor should give information about his
patient to police or legal authority especially in
i) severe toxicity or death ii) strong suspicion of
homicidal poisoning (Sec 39 IPC).
b) He should supply all records to the police or
magistrate if asked for under Sec. 175 Cr. IPC.
Noncompliance of such obligation (Sec. 202
IPC.) or deliberate concealing of facts or lying
(Sec. 193 IPC) will make him liable to
prosecution.
c) He should always suspect homicidal causes in
each case (though extremely rare in childhood in
49
2006; 8(2) : 153
our country) and seek a second opinion if needed.
He should keep all the records for future
references.6
Prevention 1
Childhood poisoning in our country is mostly ac-
cidental. This makes this hazard preventable by
good social education. A large proportion of ac-
cidental poisoning is trivial. A few hours of hos-
pital observation is only needed. These children
can be sent home after providing anticipatory
poison prevention guidelines.
Key Messages:
1) Strongly suspect poisoning in acute but un-
explained symptoms suddenly appearing in an
otherwise healthy child.
2) Clinical features are the key to diagnosis as
confirmatory tests are usually not available in
most of the cases.
3) Stabilization of vital parameters in the initial
phase, evaluation of the poison (identification
and severity assessment) and detoxification are
the key points in management.
4) Activated charcoal is the mainstay of non-
specific gastrointestinal decontamination.
Whole bowel irrigation is a new armamen-
tarium. Specific antidotes are available for a few
poisons only. Hence supportive therapy remains
the mainstay in management.
References
1. Singh UK, Layland FC, Suman S, Prasad R.
Introduction and General Symptoms and Signs
nd
of Poisoning. In: Poisoning in Children, 2 Edn,
Eds Singh UK, Layland FC, Suman S, Prasad
R, Jaypee Brothers, New Delhi 2001; pp 1-31.
2. Gupta S, Taneja V. Poisoned child: emergency
room management ; Indian J Pediatr 2003, 70:
S2-S8.
Indian Journal of Practical Pediatrics 2006; 8(2) : 154

3. Rai BS. Poisoning in Children. IAP J Pract
Pediatr,1995; 3: 267-269.
4. Berkowitz ID. Drug Intoxication. In: The
Handbook of Advanced Pediatric Life Support,
Eds Nicholas DG, Yaster M, Lappe DG, Buck
JR , Mosby Year Book, 1991; pp201-241.
5. Mofenson HC, Caracio TR. Toxidromes.
Compr Ther 1985; 11: 46-52.
6. Osterloh JD. Utility and reliability of
emergency toxicological testing. Emerg Med
Clin North Am 1990; 3: 693-723.
7. Hoffman JR, Schrigr Luo JS. The empiric use
of naloxone in patient with altered mental
status; A reappraisal. Ann Emerg Med 1991;
20: 246-252.
8. Rodgers GC Jr, Matyunus NJ. Gastrointestinal
decontamination for acute poisoning. Pediatr
Clin North Am 1986; 33: 261-285.
9. Levy G. Gastrointestinal clearance of drugs
with activated charcoal. N Engl J Med 1982;
307: 676-678.
10. Tenenbein M, Cohen S, Sitar DS. Whole bowel
irrigation as a decontamination procedure after
acute drug overdose. Arch Intern Med 1987;
147: 905-907.
11. Goldfrank LR, Fomenbaum NE, Lewin, et al.
eds. Goldfranks Toxicological Emergencies,
th
5 edn. East Norwalk, CT, Appleton &
Lange,1994; pp 301-322.
12. Rodgers CC Jr, Matyunas NJ. Poisoning drugs,
chemicals, and plants. In : Nelson Textbook of
th
Pediatrics, 17 Edn, Eds Behrman RE,
Kligman RM, Jenson HB, Philadelphia,
Saunders 2004;704:2363-2375
13. Ghosh DK. Consumer protection act & the
medical profession: Toxicology. In: Forensic
Medicine and Toxicology, Ed Mukherjee JB,
Nu Printers, Kolkata 2000; (Vol2); pp 177-200.

NEWS AND NOTES

November 11-12, 2006.

Pre-congress Live Operative Workshop on Anorectal Malformation
(led by Prof Alberto Pena), AIIMS, New Delhi.

November 12, 2006,

Pediatric intensive nursing care, including neonatal resuscitation and safe transport
Conference Hall, AIIMS, New Delhi

November 12-15, 2006, .

20 CONGRESS OF ASIAN ASSOCIATION OF PEDIATRIC SURGEONS with Executive
th

Meeting of WOFAPS,
Taj Hotel and Convention center, New Delhi.

November 16-17, 2006

Post Congress Live Operative Workshop on Pediatric Urology ( VUR, Intersex and Hypospadias)
( Prof Prem Puri, Prof Snodgrass, Mr A.Bracka, Prof. John Hutson, Prof Asopa), AIIMS,
New Delhi.

50

EMERGENCY MEDICINE
MEDICO - LEGAL ISSUES IN
EMERGENCY ROOM
* Mahesh Baldwa
Abstract: Enactment of Consumer Act along with
inclusion of medical professional in its ambit has
put cases of alleged medical negligence under
fast tract of judicial remedy. A number of tertiary
care centers in the form of intensive neonatal care
units and intensive pediatric care units with huge
investment in infrastructure have come up. State
of art infrastructure costs a fortune and escalates
cost of quality care in pediatric treatment. Heavy
cost of emergency and critical care treatment has
made this emerging pediatric subspecialty, a
hotspot of litigations. In todays scenario doctors
are health risk managers for their critically sick
patients who need vigilant monitoring and timely
treatment to avert further crisis and
complications that are common and foreseeable.
So, the corollary is that doctors are expected to
chart the course of the health of their critically
ill patients with minimal health hazards by use
of state of art and costly monitoring equipment.
Any action or inaction of doctor in emergency
room that accelerates or increases the health
risks may result in allegation of breach of duty
of doctor. Courts take lenient view regarding
making errors in diagnosis but take very strict
view, if there is deficiency in procedure or
conduct of a treatment.
Key words: Emergency room care, duty of care
in emergency, omission of duty, death, disability
* Senior Consultant Pediatrician
Baldwa Hospital, Mumbai and
Chairperson - IAP Medico-legal Group.
51
2006; 8(2) : 155
Introduction
The monitoring facilities and advancement in
maintaining vital parameters in a critically ill
child till the basic pathology is taken care of by
appropriate treatment, are significant advances in
the field of pediatrics. This has ushered in a new
era of critical care and emergency in pediatrics.
In todays scenario doctors are health risk
managers of their critically ill patients1. Any action
or inaction (act of omission or commission) of
the doctor that accelerates or increases the health
risks of a critically ill patient may result in an
allegation of breach of duty of doctor 2.
Establishment of consumer courts has put the
cases of medical negligence on fast tract remedy.
There is no limit for asking of compensation for
alleged medical negligence. The amount of money
quoted is mind-boggling3. Patients may sue a
doctor for compensation by asking usually lakhs
of rupees and some times in crores4. Medical
indemnity insurance policy is the only way out to
practice emergency and critical care pediatrics
peacefully in such an odious scenario by which
these risks of litigations could be managed and any
claim if arises could be paid5.
Likely situations of medico-legal
importance
There are situations where it is mandatory
to inform the law enforcers and/or legal
authorities (usually it is local police station6)
regarding patients seen in emergency room.
Because doctors duty is to treat the patient and
duty of police7 is to find out whether any crime
was committed on victim/patient for making him/
her suffer from problems listed below:
Indian Journal of Practical Pediatrics
A) Tetanus, gas gangrene, significant burns, head
injuries, significant violence8 needing inpatient
treatment, motor vehicular and other accidental
fractures, accidental falls needing inpatient
treatment, attempted suicides 9, attempted
poisoning, attempted homicide 10, human or
animal or snakebite, rape11, minors pregnancy
and MTP 12, battered baby. In case of death
doctors should insist for post mortem in all of
the above situations.
B) In case of attempted poisoning or poisoning,
doctor is duty bound to collect a specimen of
stomach wash (usually 100ml or more in a clean
glass bottle), blood samples in EDTA and plain
bulbs (usually 2ml each), as applicable and feasible
and hand it over to the police with proper labeling
of name, sex, age, time of collection, brief history
and treatment given13. In case of death due to
poisoning always insist for post mortem.
C) There are situations apart from this that may
require information to police or post mortem
depending upon facts and circumstances of a
case. Doctor should continue to treat with
meticulous history recording, examination,
investigations needed and treatment as per
reasonable norms of medical practice.
1. Indoor admitted child falling from cot or in
the bathroom and getting significant injury
and needing inpatient treatment.
2. Operation table deaths or post operative
critically ill child dying
3. Child developing gas gangrene and gangrene
due to infused fluids or intravenous lines
4. Almost instant intra muscular nerve palsy
5. Deaths resulting from anaphylaxis or Steven
Johnson syndrome due to a drug
6. Post procedure death like for example after
lumbar puncture, liver biopsy and other
biopsies.
52
2006; 8(2) : 156
7. Deaths due to bleeding and disseminated
intra vascular coagulation, reason not
obvious.
8. Post anesthesia critical child dying.
What is the procedure if a child is brought dead
by a mob (or lot of relatives):
1. If there is a mob (or lot of relatives)
immediately divide doctors working team to two
parts. One team shall explain to the parents that
child is dead yet if you permit we may give some
treatment but situation may not change. Second
team tackles the mob that wants the child to be
treated anyhow. Tell them he is already dead but
the team of doctors is doing their best.
2. Declaration of death in a child brought dead
by mob should be essentially preceded by rapid
assessment and an attempt at resuscitation after
talking to the groups as mentioned above. This
will buy time and wisdom for medical team to
declare death at the terms and conditions desired
by medical team rather than be swept away with
unruly behaviour of mob.
3. When a child is brought by mob, who are not
amenable for explanation then one should surely
inform police for protection and then only declare
final death. The situation will be considered all
the more serious, if the child is brought dead.
Avoid loose talk which may spark problems and
may lead to physical abuse of medical team.
What is the procedure if the child is brought dead
by parents:
1. Declare death, inform police and ask for
postmortem.
2. If mob gathers later on, then inform police,
hold talk with mob leader, be empathetic,
sympathetic, humanistic and soft-spoken. Let
some one senior handle the situation.
What to do if child is brought dead who was under
your treatment for a serious disease?

In such a case one may have to issue death
certificate. In United kingdom (U.K. rule of 21)
if patient is under treatment for 21 days then one
may have to issue death certificate.
How should we transport the sick and serious
child?
1. Doctor and nurse team should accompany the
patient14.
2. Ambulance should be equipped with adequate
doses of emergency medicines, injections,
intravenous fluids and oxygen15.
3. Monitoring equipments like stethoscope, blood
pressure instrument, cardiac monitor machine with
preferably a defibrillator and a ventilator16.
Standard of medical care in emergency room
should be high because emergency room17 care
claims giving state of art services, as mentioned:
1. Duty of care in emergency room (which means
actively avoiding all kinds of dangers i.e. health
risks from all sources i.e. from disease, drugs and
surgery, all the time) to your patients by
continuous monitoring of all relevant vital
parameters and investigations18.
2. Law requires proportionate degree of care in
emergency room. Higher the risk undertaken,
higher is the standard demanded by law in caring
for critically ill.
3. If there is any lack of care, on the part of
medical practitioner in monitoring or treatment
of a critically ill, doctors actions which cause
acceleration of disease process leading to death
or disability is actionable under law.
4. Under law for actionable negligence, such an
acceleration should be caused by breach of duty
of a doctor (lack of due care of critically ill and
lack of caution in monitoring critically or
delaying or omitting to give treatment to critically
ill) which should result in actual (proved) physical
or mental damage to patient.
53
2006; 8(2) : 157
5. There should be close nexus between such
acceleration of disease process caused by
negligence of doctor and not because of inherent
nature of disease. Such acceleration should cause
disability or death due to breech of duty (lack of
due care and caution) resulting in damage.
6. Legally if there is no resultant damage due to
lack of care, then no compensation can be given
to patient19.
Consent, Dissent, Assent, Counselling,
Forewarning
1. In emergency rooms standards for informed
consent are lower than usual cold situations. In
dire emergency, courts waive off consent in favour
of giving lifesaving treatment, even though nature
of treatment may amount to adventure20. In a case
of a road traffic accident, victims (In case of
accident victim court takes very strict view if no
attempt is made to save life) vitals were stabilized
by giving emergency treatment before shifting to
higher center, where one limb had to be amputated
because of delay in referral; court did not hold
doctor negligent in causing delay in referring
because stabilization of vitals was crucial before
transfer of patient otherwise patient would have
been dead during transit21,22. In another case of
vehicular accident, a reasonable delay in preparing
for operation and arranging for 19 bottles of blood
was permitted by court even though patient died
postoperatively23.
2. Some times in emergency, omission to
perform operation for want of consent may
amount to negligence 24 . An emergency
appendicectomy was not done, for want of written
consent or dissent from patient. The doctor was
held liable on this as patient died of burst
appendix. Remember written dissent is more
important than consent for invasive procedure,
surgery, investigation, transfer and referral in
emergency situations25.
Indian Journal of Practical Pediatrics
Prevention or detection of complications,
monitoring, treating or transferring serious
patients
Monitoring and record keeping
1. Monitoring serious patients by keeping record
and using available gadgets and investigations
or referral by providing ambulance to transfer18,26.
Basic minimum for monitoring is recording pulse,
respiration, temperature, blood pressure, intake
and output chart.
2. Remember proper record is a valid defence
in medical negligence case as the law asks for a
show of care rather than cure27.
Critically ill patients where known
complications which cannot be
prevented is present
A boy was bitten by a cat and was given
anti-rabies vaccine. He developed neuro-paralytic
reaction28, for which he was hospitalized and died
in ICU. In this case there is no negligence as
standard textbooks and WHO report of 1984
mention neuro-paralytic reactions as a well
known complication of ARV. Here a proper ICU
treatment was given with care.
Cases related to anaphylaxis29
If a doctor neither does penicillin test dose
nor have emergency medicines for treating
anaphylaxis and fails to treat complications
resulting in the patient, the doctor is held
negligent.
Cases related to improper drug
administration resulting in complication
a) A practitioner inadverdently administered a
medication intra arterially instead of
intravenously. The patient developed gangrene
of the thumb, index and middle fingers. The local
court held the doctor as negligent and the patient
was entitled to receive adequate compensation30.
54
2006; 8(2) : 158
b) Analgin was given intravenously to a 16 year
old boy resulting in gangrene of the leg resulting
in amputation; the doctor had to pay a compen-
sation31.
c) Emergency drugs such as pentazocine,
diazepam and atropine were given by an
ayurvedic physician to a patient with abdominal
pain; the patient developed severe pain in fingers
and subsequent gangrene, requiring amputation
of three fingers. The ayurvedic physician not
qualified to administer allopathic drugs had to
pay compensation.
d) In another case though the patient developed
gangrene of right hand requiring amputation
following IV pentazocine and promethazine
given in the right arm, the doctor was not
considered negligent32.
Emergency blood transfusion:
Some times emergency blood transfusion of
a wrong blood group may cause mismatch33
transfusion reactions; rarely AB positive child
may be given B positive blood 34 . Blood
transfusion in emergency rooms have been the
source of transmitting hepatitis B and HIV
infections35,36. It is better to be safe than be sorry
later by following proper blood checking norms.
Summary: This article is intended to provide the
emergency care provider and those who deal with
critically ill patients with the required knowledge
and wisdom regarding the relevant laws applicable
to practicing critical care. It will also help to
prevent, solve and understand the day-to-day legal
problems related to emergency care. All of us are
aware and have experienced that ignorance breeds
and feeds uncertainty. Uncertainty breeds and
feeds unfounded fears. We also know that
unfounded fears usually never become true, but
only make life stressful and unlivable. In the light
of basic legal knowledge, let us dispel these
unfounded legal fears and do the right deeds in the
 2006; 8(2) : 159

right direction. Let us not give up and practice 9. S.309 of Indian Penal Code,1860.
defensive medicine for fear of legal wrangles. 10. S.299 of Indian Penal Code, 1860.
Points to remember 11. S.375, 376 of Indian Penal Code, 1860.
12. Medical termination of pregnancy Act,1971
1. Do not forget to take medical indemnity 13. The Poisons Act, 1919
policy and keep renewing yearly and then 14. Mr. S Vs Dr PI & Ors. 1999(2)CPR 515
only keep on handling emergencies.
15. PSG Vs GM, Int CF & Ors., 1993 (2) CP J
2. Document parameters monitored with 1211(TNSCDRC)
respective time and date on indoor case 16. DC BP Vs KNH, 1997 (I) CPJ 483 (Karn.
paper. SCDRC)s
3. Do not forget to xerox the thermal paper 17. LBJ Vs TBG, 1968 ACJ 183 (SC): AIR 1969
printout readings of ECG, ABG etc. as the SC 128: 1969 (1) SCR 206
readings fade by the time they are viewed 18. GTBSH Vs DKN, 2002 (I) CPR 442 Punj.
in court of law. SCDRC)
19. AT Vs SMC, 2002 (1) CPJ 75 (NCDRC)
4. Do not forget to inform local police station
20. L Vs BNH & Anr, 1998 (2) CPJ 335 (Punj.
regarding cases which necessitate this
SCDRC)
procedure.
21. PBKMS & Ors, Vs WB & Anr, 1996 (4)
5. Keep ready formats of consent, dissent, Supreme 260: AIR 1996 SC 2426: 1996 (4)
assent, counseling, forewarning and get it SCC 37: IT 1996 (6) 43 (SC)
signed, dated and timed. 22. PK Vs UI, 1989 (4) SCC 286: AIR 1989 SC
6. If you need to transport sick and serious 2039: 1989 ACl 1000: 1989 (4) SCC 286
patients in ambulance do in well-equipped 23. AAS Vs SJ MCH, Bangalore, 1996 (1) CPJ
ambulance with qualified doctor and nurse 169: 1995(3) CPR 174 (Karn. SCDRC)
to handle emergency situations. 24. TTT Vs Smt.E 1987 Ker.-HC 52: 1986 Ker.
LT 1026:
7. In case of death in emergency room,
25. PNSG Vs AVNH, 1997 (1) CPJ 266
declare death only when you have
completed indoor case records and talked 26. SP Vs GCO, 2001 ACJ 874 (Ori.) (DB)
empathetically to relatives. 27. VCS Vs MHL, 2001 (I) CPJ 137: 2001 (I),CPR
628 (TN SCDRC)
References 28. DDS Vs SAI & Ors, 1993 (1) CPR 640:1993(2)
1. The Consumer Protection Act 1986 as amended CPJ 1289 Orissa SCDRC
up to date in 2002 29. CK Vs GOM, 1967 ACJ 379 P.C.
2. IMA & Ors, Vs VPS & Ors. JT 1995(8) SC 30. Dr. GCA Vs DD, Punjab SC DRC 1(2002)
119: AIR 1996 SC 550: 1995 (6) SCC 651: CPJ,351.
1995 (3) CPJ 1 (SC): 1995 (3) CPR 412(SC) 31. GS Vs Dr. JS, 1996(3) CPJ, Punjab SCDRC.
3. SM Hosp & Anr, Vs HA & Anr., 32. SD Vs Dr. CKM, 1998(3) CPJ7, Haryana SC
1998(3)CPR1(SC):1998(I)CPJI:JTI998(2)SC620 DRC.
4. CS Vs HT Hosp & Ors, 2003 (2) CPR 95: 2003 33. CMRI Vs BC & Ors., 1999 ( 1) CPR 3
(3) CPJ 62: 2003(6)CLD46(NCDRC) (NCDRC)
5. The Indian Insurance Act, 1937. 34. SIK Vs CTH, 1994 (3) CPR 233 (TN SCDRC)
6. S. 154 of The Criminal Procedure Code,1973 35. HN Vs Dr. PA,1995(1)CPJ 220(Ker SCDRC)
7. S. 173 of Code of criminal procedure, 1973. 36. SVH & Ors Vs MMC, 1994 (2) CPJ 544: 1994
8. S.319 to 338 of Indian Penal Code, 1860. (3) CPR 214 (Mah. SCDRC)
55
Indian Journal of Practical Pediatrics 2006; 8(2) : 160

PULMONOLOGY

BASICS IN PEDIATRIC Spirometry

PULMONARY FUNCTION TEST
The instruments used for spirometry tests
*Balachandran A are called spirometers. The tracing generated
**Shivbalan So by the spirometer is called a spirogram. Spirometry
***Vijayasekaran D is the timed measurement of dynamic lung volumes
***Gowrishankar NC during forced expiration and inspiration. Four
*Subramanyam L indices are mainly used to interpret spirometry1,2.
a) Forced vital capacity (FVC): This is the total
Abstract : Pediatricians utilise a wide variety of
amount of air expelled after a maximal
laboratory tests including radiography in day-
inspiration. The normal value is 100 20%.
to-day practice to facilitate diagnosis and
treatment of pulmonary disease. However b) Forced expiratory volume (FEV1): This is the
pulmonary function tests (PFT) are not commonly amount of air that can be expelled in one second
used despite the high incidence of asthma and after a maximal inspiration i.e. the fraction of
chronic cough seen in office practice. The under forced vital capacity expired during the first
utilization is probably due to decreased second. The normal value is 100 20%.
awareness and lack of understanding of PFT. c) Forced expiratory ratio: This is the ratio of
This article discusses the basic principles FEV1 with FVC (FEV1/FVC). The normal value
involved in the interpretation of PFT. is more than 80%.
Keywords: Spirometry, Peak flow metry,
Pulmonary function test, PEFR, Children
Pulmonary function testing is one of the basic
tools for evaluating a patients respiratory status.
A basic knowledge of the normal lung volumes and
capacities is essential for proper understanding of
the pulmonary function tests (Fig.1)1. In day-
to-day practice, PFT includes spirometry and peak
expiratory flow metry (PEFM). These are usually
performed in children above 5-6 years of age.
* Consultant Pediatric Pulmonologist,
IRV- inspiratory reserve volume, TV- tidal
Dr.Mehtas Hospitals Pvt. Ltd, Chennai. volume, ERV- expiratory reserve volume,
RV- residual volume, TLC- total lung capacity,
** Consultant Pediatrician,
SMF, Dr.Rangarajan Memorial Hospital, Chennai. FRC- functional residual capacity. IC- inspira-
tory capacity, VC- vital capacity
*** Assistant Professor in Pediatric Pulmonology,
Institute of Child Health and Hospital for
Children, Chennai. Fig 1: Normal lung volumes and capacities
56

d) Forced expiratory flow (FEF25%-75%): This is
the percentage of FVC calculated between the
first 25% and the last 25% of FVC and is also
called maximal mid expiratory flow (MMF 25-
75%). It is useful to evaluate small airways. The
normal value is 100 35%.
Spirometry is reported as both absolute values
and as predicted percentage of normal. Predicted
spirometric values depend on various factors like
race, sex, age and height. There is no single
standard reference value and the predicted values
has to be in accordance to the target population.
The spirometer cannot measure static lung
volumes and capacities like residual volume
(RV), functional residual capacity (FRC) or total
lung capacity (TLC), in which airflow does not
play a role. These parameters can be measured
using gas dilution and body plethysmography
techniques, but they are not required in routine
assessment of common lung problems.
Spirometry Test
The success of spirometry is in producing
an acceptable with/without reproducible FVC
curve. With adequate training and encouragement
children above 5 to 6 years of age can produce
an acceptable FVC curve. The environment for
testing should be child friendly. Before
attempting spirometry, it is important to make
the child and attenders familiar with the
laboratory, instruments and persons.
Criteria for acceptability are: a) There should be
no artifact due to cough, glottic closure or
equipment leak, b) The start should be without
hesitation and c) There should be at least six
seconds of smooth continuous exhalation and/or
a plateau in the volume time curve of at least one
second, or a reasonable duration of exhalation
with a plateau3.
Criteria for reproducibility are 3: From the
acceptable spirograms the difference between the
57
2006; 8(2) : 161
2 largest FVC and FEV1 should not be more than
0.2L.
Procedure2
The childs torso and head should be erect
during the procedure. The study may be done
either in sitting or standing position.
Occasionally few may experience syncope
or dizziness while performing the forced
expiratory maneuver. Thus, sitting position
is preferred.
The mouthpiece is held in between the lips
to form an airtight seal. The use of nose clip
for all spirometric maneuvers is strongly
encouraged.
The child should take a slow, full and deep
inspiration followed by a brief hold of the
breath and then a sustained forceful
expiration (with maximum effort) without
coughing or quitting during the procedure.
The child should be taught and encouraged
during expiration to achieve a complete
forced vital capacity i.e., blowing as long
as possible or at least 6 seconds. FVC
maneuver in spirometry is similar to blowing
of a balloon. Application of nose clips may
yield better results.
The child is allowed atleast three but not
more than eight attempts to meet acceptability
and reproducibility criteria, as fatigue might play
a role in the results. An acceptable spirogram
should not be discarded even if it is not
reproducible, as FEV1 from such spirogram may
be valid and the volume expired may be an
estimate of the true FVC. However FEV1/ FVC
and FEF25-75% may be overestimated3. The highest
FEV1 and FVC can be reported from 2 different
spirograms. But FEF25-75% and instantaneous
expiratory flow rates, such as FEFmax (i.e. PEFR)
should be obtained from the same best acceptable
spirogram. The best accepted curve is the one
that has the largest sum of FEV1 and FVC. Test
Indian Journal of Practical Pediatrics
acceptability is best determined by examining the
flow volume loop and volume time curve.
Variable effort, cough and early glottic closure
can be seen on the graphs but may not be apparent
by simply looking at values for FEV1 and FVC.
Reproducibility criteria helps to ensure that
adequate effort has been made as maximal patient
effort leads to reproducible spirograms. The same
person, preferably a medical personal should
perform and interpret spirometry, as the
spirogram is effort dependent..
Types of spirogram
The spirogram produced depends on the
machine used but the measurement technique,
principle and interpretation of results remains the
same. There are 3 types of spirograms2 :
a) The standard spirometric curve is a volume
time curve i.e. plot of volume Vs time. This
records only the expiratory phase. (Fig2)
b) A flow volume curve plots flow Vs volume.
This also records only the expiratory phase.
c) A flow volume loop includes the forced
expiratory and inspiratory effort. At the beginning
of the procedure the subject exhales as forcibly
Fig 2: Volume time curve
58
2006; 8(2) : 162
as possible, the result is an FVC curve. At the
end of FVC maneuver the subject inhales, as
rapidly and forcefully as possible, the result is
an inspiratory curve. The expiratory and
inspiratory curves together describe a flow
volume loop (Fig 3).
Most of the commercially available
spirometers have both volume time curve and
flow volume loop tracings.
Interpretation of spirometry
Spirometry for lung is akin to ECG for heart.
In most cases it does not give us the etiological
diagnosis but give us the physiological status with
clues for diagnosis. Ideally spirometry should be
interpreted with the flow volume loop, volume
Fig 3: Flow volume loop

time curves and absolute values for flows and
volumes. As clinicians we must be able to identify
an abnormal spirogram and should be able to
diagnose whether it is obstructive or probable
restrictive pattern depending on the values and
shape. The primary abnormality detected by
spirometry is airway obstruction while restrictive
lung diseases cannot be diagnosed by spirometry
alone. To diagnose restrictive lung disease the
lung volumes (including RV/ FRC/ TLC) have
to be confirmed. This could be done by closed
circuit helium dilution/ gas dilution techniques,
open circuit nitrogen washout method, body
plethysmography and radiographic planimetry.
In obstructive pattern it is necessary to
differentiate extrathoracic (upper airway) and
intrathoracic (lower airway) obstruction.
Interpretation of spirometry depending on
spirogram values2:
The spirometry values of the child are
compared against the nomograms available for
the population. In restrictive lung disease the
child is not able to inhale the expected amount
of air as compared to his or her peers, but is able
to exhale the inhaled air normally. In obstructive
lung disease (e.g. asthma) the child is not able to
breath out as expected like his or her peers (i.e.
air trapping).
Disproportionate reduction in the FEV1 as
compared to the FVC and therefore reduced
FEV1-to-FVC ratio (due to slow rate of airflow)
is the hallmark of obstructive lung diseases.
Reduction in the FVC, FEV1 that is a fraction of
the FVC, is also proportionally reduced, with
FEV 1 /FVC being normal (proportionally
reduced) or elevated (as there is no impedence
in expiration) in restrictive lung diseases.
In early or mild asthmatics because of air
trapping the TLC will increase and the FEV1 and
FEV1/FVC ratio is deceptively normal. In such
conditions, the measurement of FEF25-75% may be
59
2006; 8(2) : 163
diagnostic. If the child quits before the end of
the FVC manoeuvre, the FVC is underestimated
and in the early stages of obstruction, the FEV1/
FVC ratio may be normal resulting in a wrong
interpretation as restrictive lung disease instead
of obstructive disease.
Interpretation of spirometry depending on
spirogram shape:
In restrictive lung disease, all lung volumes
and flows (inspiratory and expiratory) are
reduced resulting in a small loop without any
change in the shape i.e shape maintained but size
is altered. In obstructive lung disease, the shape
of the loop is altered. In intrathoracic (lower
airway) obstruction the shape of the expiratory
limb (upper loop) is altered. Whereas in extra
thoracic (upper airway) obstruction the shape of
the inspiratory limb (lower loop) is altered
without changing the shape of the upper loop.
For easy interpretation of spirometry results the
algorithm in fig 4 may be followed4. The overall
validity of spirometry depends on eqipment
caliberation, patients cooperation and effort to
produce an acceptable and reproducible
spirogram.
Peak Expiratory Flow Metry (PEFM)
Peak flow meter is a handy, portable device
used for recording peak expiratory flow rate
(PEFR). The Peak flow value is measured in liters
per minute. In children with asthma, peak flow
can be monitored and recorded at home. It may
be useful in the diagnosis and monitoring of
asthma patients on follow-up.
Technique for measuring a peak flow
The pointer on the meter is moved to zero
The meter is held horizontally, the childs
torso and head should be erect during the
procedure. This could be done in either
sitting or standing position
Indian Journal of Practical Pediatrics 2006; 8(2) : 164

Step 1 : Time Volume Curve

Acceptable No Repeat the procedure

Yes

Step 2a : FEV 1 >80% Normal (if FEV1 /FVC>80% &
FEF 25-75 >65%)

<80 %

Step 2b : FEV1/FVC >80% s/o Restrictive lung disease

<80 %

Obstruction

Step 2c : FVC

>80 % (pure obstruction) <80 % (Obstruction and Restriction)

Step 3 : Flow volume loop

Look for e/o upper or lower airway obstruction

Upper / Extrathoracic Obst: Lower / Intrathoracic Obst:
Lower limb (inspiratory) Upper limb (expiratory)
loop involved loop involved

Fig 4. Algorithm for interpretation of spirogram

60

The fingers should be kept away from the
vent holes and marker
Maximum air is inspired with the mouth
wide open
The mouthpiece is placed in the mouth with
lips pursed around it
Blow out as hard and fast as possible with a
short, sharp blast (like blowing a candle)
The pointer is moved to zero after each
recording
The recording is done thrice waiting at least
2 seconds in between each recording
The best of the three values is recorded and
not the average.
A record of the value obtained in the morning
and evening is maintained
Peak expiratory flow rate (PEFR) correlates
with FEF (max) in spirometry. The PEFR reading
is correlated with the predicted values from
standard normogram based on height of the child.
Ideally this again has to be population based and
in routine office practice a formula: {(Ht in cms
100) X 5} + 100= PEFR Lt/min, can be used5.
PEFM in office practice
In a child with suspected asthma PEFM may
help to confirm the diagnosis. PEFR values <80%
of predicted values (by nomogram or the best
personal recording of the patient during a
symptom free period, whichever value is higher)
are considered abnormal. Further confirmation
is by doing a bronchodilator reversibility test i.e.
either 3-4 puffs of short acting beta-2- agonist
via MDI or a single dose beta-2- agonist via
nebuliser is given and PEFR is recorded every 5
minutes for the next 15 minutes. If there is 15%
improvement in the recording, it confirms
reversible bronchospasm.
61
2006; 8(2) : 165
Subjects who use inhaled short-acting
bronchodilators should be tested at least 4 to 6
hours after the last use of their inhaled
bronchodilator to allow proper assessment of
acute bronchodilator response (long-acting
inhaled bronchodilators may need to be withheld
for a more extended period) either for spirometry
or PEFR. The length of the interval between
administration of the bronchodilator and
postbronchodilator testing varies, however a
interval period of 15 minutes is being practiced.
If the PEFR values are normal in a suspected
case of asthma, the patient is asked to record
PEFR atleast twice a day (8am and 8pm
preferably) to check for diurnal variation.
Normally the PEFR values are less in the
mornings as compared to the evening values and
the variation is normally less than 10%. If the
diurnal variation is more than 20%, the possibility
of asthma is considered6.
Exercise test: The initial PEFR is recorded and
the patient is asked to exercise vigorously for 5
to 6 minutes (e.g. by running up and down stairs).
The PEFR is recorded every five minutes for the
next 15 minutes post-exercise. In normal
individuals there is no change in PEFR reading;
however in asthmatics there will be a fall in PEFR
by at least 15% at the end of the test. This fall in
PEFR will be improved after inhaled
bronchodilator. This test is especially useful for
patients with exercise-induced asthma. A fall in
PEFR value is usually said to precede an acute
exacerbation of asthma. This can be used to
predict an impending exacerbation in children
who perceive symptoms of asthma poorly and
can be helpful in initiating early reliever therapy
to prevent acute exacerbation.
PEFR zones (Tri colour cards)
These are colour-coded zones that are based
on the traffic light concept. They can be used as
home monitor to check the well being of airways:
Indian Journal of Practical Pediatrics 2006; 8(2) : 166

a) Red zone: Danger i.e. PEFR <50% of
childs best. This is a medical emergency and
warrants hospitalization.
b) Yellow zone: Alert i.e. PEFR 50-80% of
childs best. The advice is to eliminate triggers
and use reliever (bronchodilator) medicine.
c) Green zone: Safe i.e. PEFR >80% of childs
best. The advice is to avoid triggers.
In all 3 zones if the child is on preventor
medication, it should be continued.
PEFR recording is an objective assessment
in asthma like temperature recording in fever.
PEFR monitoring is a useful tool in home
management of asthma. In acute exacerbation of
asthma, PEFR monitoring may worsen symptoms
due to collapse of peripheral airway during forced
expiration. Cough during recording can depict
an abnormally high value of PEFR despite severe
airway obstruction.
Conclusion
Spirometry and PEFM recording are both
effort dependent. With proper calibration of the
equipment, correct technique and interpretation
of results, they are valuable tools in the
assessment of lung diseases.
References
1. Subramanyam L, Balachandran A, Somu N.
Interpretation of pulmonary function tests. In;
Somu N, Subramanyam L, Eds. Essentials of
nd
pediatric pulmonology. 2 Ed. Siva & Co,
Madras, 1996; p 229- 237.
2. Vijayasekaran D, Subramanyam L,
Balachandran A, Shivbalan So. Spirometry in
clinical practice. Indian Pediatr 2003; 40(7):
626-632.
3. AARC Clinical Practice Guideline:
Spirometry. Respir Care 1996; 41(7): 629-636.
4. h t t p : / / w w w . v h . o r g / a d u l t / p r o v i d e r /
internalmedicine/Spirometry/Algorithm.html
(Browsed on 25th December 2004).
5. Balasubramanian S, Ravikumar NR,
Chakkarapani E, Shivbalan So. Peak expiratory
flow rate in childrena ready reckoner. Indian
Pediatr 2002; 39(1): 104-106.
6. Indian Academy of Pediatrics- National
guideline. Asthma By Consensus. Consensus
statement on the diagnosis and management of
asthma in children- Update 2003. Long-term
management. An IAP Respiratory chapter
publication. pp 6-16.

NEWS AND NOTES

JOHAR, AUGUST 18-20, 2006

1st ASEAN Congress of Pediatric Surgery in conjunction with 28th Annual Congress of the
Malaysian Pediatric Association & 2nd Annual Congress of the Malaysian Association of Pediatric
Surgeons.
Enquiries to : Malaysian Pediatric Association 3rd Floor (Annexe Block), National Cancer
Society Building, 66, Jalan Raja Muda Abdul Aziz, 50500 Kuala Lumpur, Malaysia.
E-mail : mpaeds@po.jaring.my
Website : www.mpades.org.my

62

PRACTITIONERS COLUMN
NUTRITION, HEALTH AND
WELL-BEING OF CHILDREN
* Meharban Singh
Abstract : Health and well being of children
depends upon an interaction between their
genetic potential for physical growth and mental
development and intake of optimal nutrition,
exposure to safe and stimulating environment and
freedom from common day-to-day infections. The
last 3 months of fetal life, first 3 years of post-
natal life (pre-school years) and adolescence are
most critical and vulnerable to the adverse effects
of malnutrition. Due to control of florid or severe
cases of malnutrition, the child survival has
improved but the quality of life and human
resource development has not improved due to
wide-spread prevalence of subclinical or
biochemical deficiencies of micronutrients.
Keywords : micro nutrients, child health
Mothers are creators of progeny and their
health and wellbeing is closely interlinked with
the health of their children. Therefore, a life-
cycle approach should be followed to provide
optimal nutrition and health care to girl children
from infancy through childhood, adolescence,
pregnancy and lactation.
Breast feeding is the best feeding for every
baby and must be promoted and universalized to
provide a best start in life. Nursing mother should
receive nutritional supplements to improve the
* Consultant Pediatrician,
Child Care and Dental Health Center
Noida, Uttar Pradesh.
63
2006; 8(2) : 167
quality of breast milk. Breast feeding should be
continued as long as feasible and adequate intake
of home-cooked cereal-based semi-liquid
complementary feeds should be introduced at six
months of age taking due precautions to prevent
bacterial contamination and infections. Food
fussiness should be prevented by intelligent and
relaxed handling of pre-school children during meal
times. School-going children and adolescents
should be encouraged to take a balanced nutritious
diet to prevent both undernutrition as well as
obesity. The practice of missing the breakfast must
be condemned and all efforts should be made to
ensure that breakfast is the most wholesome meal
of the day. Children should be discouraged to
follow the unhealthy dietary practices like
consumption of soft drinks and junk food and
instead encouraged to become more milk-friendly.
Children should be encouraged to take a
balanced nutritious diet to ensure adequate intake
of macronutrients (carbohydrates, proteins and
fats), micronutrients (vitamins and minerals),
phytonutrients, antioxidants and fiber. But many
a times, it is not possible to ensure intake of 100%
RDAs of micronutrients from dietary sources alone
because most children do not like to take green
leafy vegetables or fruits, and they are fussy,
choosy and rebellious in their food habits. The
situation may be worse among vegetarians because
of poor availability of iron, zinc, vitamin B12, and
decosa hexaenoic acid (DHA). In view of high
prevalence of subclinical deficiencies of
micronutrients, it is thus mandatory that nutritional
supplements should be given to children (especially
during pre-school years and adolescence) to ensure
that their full genetic potential for physical growth
Indian Journal of Practical Pediatrics
and mental development is achieved in order to
provide a solid foundation to our society.
The health and well being of children depends
upon the interaction between their genetic potential
and exogenous factors like adequacy of nutrition,
safety of environment, social interactions, physical
activity and stimulation. Nutrition has a global role
to promote physical growth, enhance neuromotor
development, boost host defences to ward off
common day-to-day infections, retard the process
of aging, and prevent occurrence of age-related
degenerative diseases and thus improve the quality
of life.
Nutritional status of children
Unlike offsprings of other mammals who
are on their feet at birth and can search for their
food, human babies are entirely at the mercy of
their care takers for atleast 3-5 years of life. They
have high energy and nutrient requirements due
to rapid growth velocity and neuromotor
development. Because of high incidence of low
birth weight babies and unsatisfactory feeding
practices, nutritional disorders are common in
developing countries. Nutritional status is further
compromised due to occurrence of recurrent
respiratory and GI infections because of poor
environmental sanitation, overcrowding and lack
of safe drinking water.
The florid cases of kwashiorkor, severe
protein-energy malnutrition and various
syndromes due to gross deficiencies of single
nutrients (like scurvy, rickets, pellagra, beri-beri
etc.) have become rare. Nevertheless, there are
still wide spread diseases of public health
relevance due to deficiency of micronutrients like
iron deficiency anemia, iodine deficiency
disorders and milder forms of vitamin A
deficiency 1. However, though deficiency of
isolated or single nutrient is rare in clinical
practice an individual is more likely to have a
deficiency of multiple micronutrients.
64
2006; 8(2) : 168
Due to control of florid or severe cases of
malnutrition, the child survival has improved but
the quality of life and human resource
development has not improved. Over 50 percent
of under-5 children in India are stunted due to
intrauterine growth retardation and post-natal
protein-calorie malnutrition. According to
National Nutrition Bureau of India, 80-90%
children take less than 30% RDA of green leafy
vegetables. Therefore, iron consumption is
inadequate in 90% of individuals in India. Dietary
surveys have shown that two-third of adolescents
consume less than 70% RDA of vitamin A and
riboflavin. Intake of calcium, vitamin B complex
and vitamin C is also inadequate. 2 Studies
conducted at National Institute of Nutrition,
Hyderabad have shown that over 50% of
apparently healthy school going children have
subclinical or biochemical deficiencies of
micronutrients. There is increasing evidence that
deficiency of certain micronutrients may
adversely affect the physical and mental growth
of children. With progressive elimination of
protein-energy deficits in the diets, deficiencies
of micronutrients are emerging as the major
bottleneck to compromise optimal physical
growth and mental development of children.3
Nutritional status and infections
Studies during the past two decades have
demonstrated the importance of optimal nutrition
for the functional integrity of the immune system.
Both under nutrition and over-nutrition as well
as deficiencies and excess of single nutrients have
been shown to have adverse effects on the
immune system. Recently, studies have shown
that immunological dysfunction is the earliest
marker of deficiency of micronutrients. Every
few days our body replaces one quarter of our
immune cells. For example, neutrophils have a
half life of merely 36 hours! Therefore, the
immune system needs continuous supply of
vitamins and minerals for their regeneration.

A large number of vitamins (vitamins A, E,
C, pyridoxine, folic acid) and trace minerals (iron,
zinc, selenium, copper) are credited to enhance
cell-mediated and humoral immune responses4.
There is increasing clinical and laboratory evidence
to suggest that children with subclinical deficiencies
of various micronutrients are more vulnerable
to develop a variety of common day-to-day
infections. They are likely to have more severe
infections with prolonged convalescence. Infective
illnesses are recognized to adversely affect the
nutritional status by causing anorexia, tissue
catabolism and enhanced utilization of
micronutrients, thus setting up a vicious cycle of
undernutrition, recurrent infections and
unsatisfactory physical growth (Figure 1)5. During
antigen-antibody fight, there is increased
production of reactive oxygen-free radicals which
may further adversely affect the integrity of
immune cells by damaging their mitochondria.
There is enough clinical and laboratory evidence
to suggest that deficiency of micronutrients is
associated with increased incidence and severity
of common day-to-day infections which can be
prevented or controlled by giving nutritional
supplements6-10.
Physical growth
Over 50 percent of under-five children are
stunted in India. They have sub-optimal vigour
and stamina, poor neuromotor coordination,
learning skills and mental capabilities. Vitamins
and trace minerals are required for production of
various enzymes, hormones and biochemical
mediators for regulation of biological processes.
They are required for energy production, synthesis
of RNA and DNA and for providing protection
against reactive oxygen-free radicals. Interaction
between sub-optimal nutrition and occurrence of
repeated infections is the leading cause of growth
retardation in children in developing countries11.
Dietary inadequacies and recurrent infections,
interact in a mutually reinforcing manner to further
65
2006; 8(2) : 169
Inadequate Dietary Intake
Anorexia, utilization Growth faltering,
of nutrients,
weight loss, reduced
malabsorption immunity,
altered metabolism mucosal damage
Increased incidence and
severity of infections
Fig. 1. Vicious cycle of malnutrition-infections
aggravate nutritional status. Calcium, phosphorus,
vitamins A, C, D and K are required to maintain
the integrity and mineralisation of bones.
Brain development
It is not generally realized that neurons are
more sensitive to nutrients and dietary chemicals
compared to other body cells. Optimal nutrition
during pregnancy and first 3 years of life is most
crucial because 70 percent of the human brain
develops during fetal life and remaining 30
percent during pre-school years. Micronutrients
are required for production of several enzymes
and co-factors for a number of metabolic
pathways. It has been well known that pellagra
(niacin deficiency) leads to reduced cognition and
dementia. A number of other B-complex vitamins
especially B1, B2, B6, B12 and folic acid are needed
for synthesis of several neurotransmitters12-13.
Deficiency of folate, B6, B12 and choline are
associated with elevation of plasma
homocysteine level which may lead to
thromboembolic complications and stroke. Iodine
is required for synthesis of tri-iodothyronine and
thyroxin. Iron is required for proper functioning
of neurotransmission system by production of
dopamine, serotonin and GABA. Iron deficiency
has been shown to adversely affect brain stem
Indian Journal of Practical Pediatrics
auditory activity and visual evoked potentials
which may persist even after correction of iron
deficiency anemia. Zinc is a component of a large
number of metalloenzymes and there is high
concentration of zinc in the brain. Copper is an
important component of cytochrome-C oxidase
and superoxide dismutase in the brain. Fish and
fish oils are important sources of omega-3 fatty
acids and decosahexaenoic acid (DHA). Omega-
3 fatty acids are credited to reduce cellular and
vascular inflammation in the brain, promote
vasodilatation and ensure integrity of brain cell
membranes to keep them soft and pliable. DHA
is the building material for fabrication of synaptic
communications and constitute almost one-half
of the total fat in the brain cell membranes. It
increases the level of feel good neurotransmitter
serotonin and the memory boosting chemical
acetylcholine. According to WHO, pregnant
women and nursing mothers should take 2.6g
omega-3 fatty acids and 100-300 mg DHA per
day to meet the nutritional needs of the baby in-
utero and her breast fed infant. The brain-friendly
nutrients are listed in Table 114, 15.
Table 1. Smart nutrients for the brain
Omega-3 fatty acids, decosahexaenoic acid
(DHA) and arachidonic acid.
Vitamin B complex, folic acid, vitamin C,
vitamin E
Iodine, iron, zinc, copper and selenium
Essential amino acids including taurine
Glucose
Choline
Antioxidants
Life-cycle approach for the care of girl
children
Health and well being of mothers and their
children are intimately linked. Healthy mothers
66
2006; 8(2) : 170
produce healthy babies while sick and
malnourished mothers produce high-risk and low
birth weight babies. The health and growth of the
fetus in the womb is dependent upon the health,
well being and nutritional status of the mother
(rather than the father!) because she is both the
seed as well as the soil where baby is nurtured for
9 months. Moreover, healthy, educated and well-
informed mothers are in a better position to look
after the health needs of their children. Therefore,
a life-cycle approach should be followed to
provide optimal nutrition and health care to girl
children from infancy through childhood,
adolescence, pregnancy and lactation (Figure 2).
During adolescence, girls must be given balanced
nutrition with supplements of iron, folic acid,
calcium and phosphorus to build adequate
nutritional stores to meet the nutritional demands
of pregnancy and lactation16.
Breast feeding
Breast milk is nutritionally complete and
biologically most compatible drink and every baby
must receive exclusive breast feeding during first
6 months of life17. Breast milk is a nutritionally
complete food for infants and contains several
brain-friendly nutrients like lactose, DHA, zinc,
choline, iodine and taurine. Breastfed babies have
been shown to have 8 IQ points higher cognition
compared to bottle fed infants.18 The baby should
be put to the breast as soon as the mother has
recovered from labor. Prelacteal feeds should not
be given and colostrum should never be discarded
because it is replete with protective antibodies.
The baby should be given demand feeding and each
breast should be completely emptied so that
the baby gets both the fore milk as well as the
hind milk. The nutritional quality of breast milk
can be enhanced by improving the diet and
providing nutritional supplements to the lactating
mother. During the period of exclusive breast
feeding, there is no need to provide any nutritional
supplements to the baby.

Fig. 2
Complementary feeds
Milk alone is a complete food to meet all
the nutritional requirements during first 6 months
of life. Most nutritional problems start at weaning
time due to delay or unsatisfactory weaning foods
and risk of contamination. There is a potential
risk of occurrence of diarrhea and growth
faltering during the process of weaning. Breast
feeding should be continued for atleast 1 year or
even longer and semi-solid cereal-based weaning
foods should be introduced around 6 months of
age. During weaning, bottle feeding should not
be introduced but milk-products can be given.
Milk can be offered with a cup or a glass after
one year of age when breast feeding is gradually
tapered off.19 The child should be offered calorie-
dense, home-cooked, properly mashed cereal-
based foods. A variety of food items which are
67
2006; 8(2) : 171
liked and enjoyed by children should be offered
like khichri, ragi, soft porridge, suji kheer, rice
kheer, custard, rice and dal, bread and dal,
mashed vegetables, yoghurt and banana. Butter
and ghee should be added to increase caloric
density. Mother should be advised to start with
1-2 teaspoons of semisolid foods at a time and
gradually increase the quantity. Egg can be
introduced at 6 months and minced meat, chicken
and fish can be offered after the age of 9 months.
The weaning foods should be given atleast 4-5
times/day by the end of first year. During weaning
safe drinking water should be offered while
maintaining strict personal hygiene to prevent
contamination and risk of bacterial infection.
WHO has published international guidelines for
best feeding practices during the early years of
life.20
Indian Journal of Practical Pediatrics
During weaning period supplements of
micronutrients should be provided. All efforts
should be made to provide optimal nutrition to
children during first 3 years of life which are
most crucial for optimal physical growth and
mental development. It is well recognized that the
stature achieved by the child at 3 years of age is a
good predictor of ultimate adult height. During
this period growth parameters should be monitored
on Road-to-Health charts. The National Center
of Health Statistics (NCHS) has published revised
growth charts which should be used21.
Table 2 highlights the common myths and
food fads which must be discouraged by health
education and awareness programs to promote
optimal nutrition of children22.
Table 2. Common myths and food fads
Children with diarrhea are often starved to give
rest to the gut.
Weaning for some mothers implies stopping
breast feeding.
Weaning is commonly delayed until Anna
Prasana ceremony is held.
Many mothers have a fancy for fruit juices
which are useless to provide energy and pro-
teins. They are associated with a high risk of
bacterial comtamination.
Mothers often give watery soups and dal ka
pani which has poor nutritive value.
Children with fever are often starved or given
only grapes and pomegranate!
Food fussiness
Due to excessive concern and over protection
because of one or two child norm in the society,
feeding of preschool children demand considerable
art and tact to tackle the problem of food fussiness
and food preferences. The development of food
fussiness should be prevented by avoiding
overindulgence and not paying excessive concern
68
2006; 8(2) : 172
and attention to the childs food. The individual
likes and dislikes of the child should be identified
and honored and he should be offered a variety
of food items to break the monotony. Parents
should adopt a relaxed attitude at meal times and
let the child enjoy what he likes to eat. There
should be intelligent neglect of the child. Children
do have a rebellious attitude and many a times a
negative statement like Kabir would not get his
food today may evoke a positive response. The
best way to make the child eat is not to try.
The child should be encouraged to self-feed even
if he creates a mess. Most children would like to
eat when other family members are eating or even
take a bite from their plate. After giving a
reasonable time, the plate should be quietly
removed even if the child has not finished without
showing any concern and anxiety. The whole
family including grandparents must participate in
the mission approach to change the blackmailing
behavior of the child. Because food fussiness is a
behavior disorder and it is not due to weak liver
or loss of appetite, the role of tonics and appetizers
is doubtful. The emphasis should be placed on
changing the attitude of the family19.
Diet of school-going children
During adolescence, there is a rapid spurt of
physical growth and sexual maturation. Almost
20% of stature and 50% of bone mass are laid down
during adolescence. Adequate intake of
calories (3000 kcal/d) should be ensured by
consumption of plenty of pulses, legumes, fresh
green leafy vegetables, seasonal fruits, milk and
dairy products. It has been shown that well-
nourished girls have higher premenarcheal growth
velocities and reach menarche earlier while
undernourished girls continue to grow more slowly
for a longer period because menarche is delayed.
During this period, junk food should be avoided
and children given extra calories, proteins and
micronutrients like calcium, iron, iodine and zinc.
Intake of soft drinks should be discouraged due to

their health hazards and efforts should be made to
make children more milk-friendly.
Soft drinks and junk food
Most children hate to take milk and find it
boring, colorless, insipid and conventional. They
usually get hooked to take soft drinks due to
catchy and aggressive advertisements. In some
children milk may cause abdominal pain and
flatulence. Soft drinks provide empty calories and
are devoid of wholesome nutrients. Caffeinated
drinks may cause restlessness, insomnia and
addiction. They may predispose to development
of osteoporosis due to calciuria and displacement
of milk intake. Dental caries may occur due to
exposure of teeth to the acidic pH of soft drinks.
The coloring agents in the drinks may cause
allergic disorders. The presence of phosphoric
acid, fizz and bubbles may cause damage to the
mucosa of the gut. According to the reports
published by Bhabha Atomic Research Centre,
there may be excessive production of a toxic
agent called hydroxyl methyl furfural when soft
drinks are stored in room temperature in hot
summer months. And there is an issue and
controversy regarding the presence of excessive
amounts of pesticides in soft drinks. In view of
the aforementioned facts children should be
discouraged to take soft drinks, and there is a
need to print a statutory warning on soft drink
bottles that excessive intake of soft drinks may
be hazardous to the health of children. Instead
children should be encouraged to take milk and
dairy products. Milk drinks should be made
available in different flavours in tetrapacks
having attractive and catchy motifs. Nutritional
supplements can be added to the milk to change
its color, taste, flavour and nutritional value to
make children more milk-friendly. When a child
dislikes to take milk or milk intake is associated
with bloating or abdominal discomfort, he should
be encouraged to take milk products like
youghurt, kheer, porridge, custard and cheese.
69
2006; 8(2) : 173
Due to changes in life-style, indulgence in
soft drinks and junk food, adoption of sedentary
habits, almost 25% of adolescent children
belonging to well-to-do urban families are
overweight or overtly obese. They are also an
important cause of constipation due to lack of
fiber. Junk food like hot dogs, hamburgers,
French fries, pizzas, samosas, pakoras,
kachories, milk shakes, soft drinks, desserts etc.
are loaded with calories, saturated fats, transfatty
acids and excessive amount of omega-6 fatty
acids leading to obesity and adverse health
consequences later in life. Studies have shown
that fast foods provide additional 187 kcal/day
leading to additional weight gain of 3 kg/
year23.Children should be discouraged to take
junk food or alternatively fast food items should
be made more health-friendly by reducing their
content of saturated fats and ensuring liberal use
of health-friendly omega-3 fatty acids, vegetables
and fruits in their production.
Meal proportions and their distribution
There is a popular saying that Eat breakfast
like a king, lunch like a prince and dinner like a
pauper. Breakfast should be the most wholesome
meal of the day because it is taken after a long
gap of fast and it must have enough calories and
essential nutrients to start the day with optimal
energy and enthusiasm. Instead, studies have
shown that over 50% of school going children in
our country miss their breakfast because they sleep
late, get up late in the morning and there is not
enough time to take breakfast before leaving for
school. There is evidence to suggest that skipping
of breakfast may adversely affect their vigour,
zest, memory, learning capability, academic
performance, emotional and psychological well
being. Hungry children are also more likely to have
headaches and tummy aches. Parents must be
informed about the health hazards of missing the
breakfast and they should be motivated to provide
wholesome breakfast to their children. The habit
Indian Journal of Practical Pediatrics
of taking snacks (like potato wafers or chips,
French fries, namkeens, biscuits etc) in-between
meals, binging and fasting must be condemned
because of potential risk of causing obesity.
Conclusion
All efforts should be made to ensure that
children take a well balanced nutritious food by
encouraging them to consume green leafy
vegetables, lentils, soyabeans, seasonal fruits,
milk and dairy products, eggs, fish, chicken etc.
However, the prevailing dogma in nutritional
science that a balanced diet is sufficient to meet
all the nutritional requirements has been
challenged. According to the recommendations
of United Nations Sub-committee on Nutrition it
is not possible to meet the requirements of 100%
recommended dietary allowances (RDAs) of
micronutrients from dietary sources alone24. The
situation is worse among vegetarians and young
children because they are fussy, choosy and
rebellious in their food habits. Nutritional
supplements are thus mandatory to improve
physical growth and mental development and
prevent occurrence of common day-to-day
infections. Healthy children do provide a solid
foundation to the society inorder to ensure
optimal human resource development of a
country and focus on their optimal nutrition is of
fundamental importance to achieve that goal.
References
1. Trace Elements in Human Nutrition and Health.
World Health Organization, Geneva 1996.
2. National family Health Survey (NFHS II) 1998-
99. International Institute for Population
Sciences, Mumbai 2000: 266-274.
3. Enriching Lives. Overcoming vitamin and
mineral malnutrition in developing countries.
World Bank Publication, Washington DC,
1994; pp 6-13.
4. Scrimshaw NS, SanGiovanni JP. Synergism of
nutrition, infection and immunity : An
overview. Am J Cl Nutr 1997; 66:464S-477S.
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2006; 8(2) : 174
5. Kelley DS, Bendich A. Essential nutrients and
immunologic functions. Am J Cl Nutr 1996;
63:994S-996S.
6. Herrera MG, Nestel P, El Amin A, et al. Vitamin
A supplementation and child survival. Lancet
1992; 340:267-271.
7. Hussey GD, Klein M. A randomized controlled
trial of vitamin A in children with severe
measles. N Engl J Med 1990; 323: 160-164.
8. West KP, Pokhrel RP, Katz J et al. Efficacy of
vitamin A in reducing pre-school child
mortality in Nepal. Lancet 1991; 338:67-71.
9. Bhutta ZA, Black RE, Brown KH, et al.
Prevention of diarrhea and pneumonia by zinc
supplementation in children in developing
countries : pooled analysis of randomized
controlled trials. Zinc Investigators
Collaborative Group. J Pediatr 1999; 135 (6):
689-697.
10. Singh M. Nutrition, immunity and infections
in children. SriLanka. J Child Health 2003;
32:35-39.
11. Gershwin ME, Beach RS, Hurley LS. The
potential impact of nutritional factors on
immunological responsiveness. In : Nutrition
and Immunity. Academic Press, 1985; pp 1-7.
12. Kretchmer N, Beard JL, Carlson S. The role of
nutrition in the development of normal
cognition. Am J Clin Nutr 1996; 63:997S-
1001S.
13. Carper J. Your Miracle Brain. Harper Collins
Publishers, New York 2000; p15-25.
14. Singh M. Nutrition, brain and environment.
How to have smarter babies? Indian Pediatr
2003; 40:213-220.
15. Singh M. Essential fatty acids, DHA and human
brain. Indian J Pediatr 2005; 72:35-38.
16. Singh M. Role of micronutrients for physical
growth and mental development. Indian J
Pediatr 2004; 16 (Suppl 2) : pp1-4.
17. Singh M. Breast feeding. In : Care of the
th
Newborn. 6 Edn. Sagar Publications, New
Delhi 2004; pp162-170.
18. Lucas A, Morley R, Isaacs E. Nutrition and
mental development. Nutr Rev 2001; S24-32.
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19. Singh M. The Art and Science of Baby and
nd
Child Care. 2 Edn. Sagar Publications, New
Delhi 2004; pp 86-90.
20. WHO (2000). Malnutrition the global picture.
Geneva, WHO.
21. Ogden C L, Kuczmarski R J, Flegal K M, et al.
Center for Disease Control and Prevention
2000 Growth Charts for United States :
Improvements to the 1977 National Center
for Health Statistics Version. Pediatrics
2002, 109:45-60 (http://www.cdc.gov/
growthcharts).
22. Singh M. Optimal nutrition of children : A
practical approach. Indian J Pract Pediatr 2001;
3:44-49.
23. Bowman SA, Gortmaker SL, Ebbeling CB,
Pereira MA, Ludwig DS. Effects of fast food
consumption on energy intake and diet quality
among children in a national household survey.
Pediatrics 2004; 113: 112-118.
24. Allen L, Gillespie S. What works? A review of
the efficacy and effectiveness of nutrition
interventions. United Nations Administration
Committee on Nutrition, Asian Development
Bank, September 2001; pp 23-41.

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Indian Journal of Practical Pediatrics 2006; 8(2) : 176

RADIOLOGIST TALKS TO YOU

HEPATOMEGALY AND HEPATIC

MASSES - I
*Vijayalakshmi G
**Natarajan B
**Ramalingam A
Mass lesions in the liver may be solid or
cystic, single or multiple, they may be incidental
findings, or present as hepatomegaly. Ultrasound
is the primary screening technique and can be
very informative.
Abscesses are the commonest space
occupying lesions (SOL) encountered in an Fig. 1. Liver abscess (SOL)
enlarged liver (Fig.1). They may present acutely
with pain and fever. The ultrasound appearance
may vary depending on the duration of the
abscess. Evolving abscesses tend to have an
appearance that resemble a solid lesion. As the
pus liquefies they become cystic or hypoechoic.
Doppler ultrasound will help in differentiating
between an abscess and a mass lesion; vessels
will be seen traversing through a mass lesion due
to increased vascularity, whereas in an abscess
they may be splayed out. On plain CT, an abscess
is hypodense relative to the surrounding liver,
similar to other cystic lesion. Contrast CT
however shows the pathognomonic feature of
an enhancing ring around the non-enhancing Fig. 2. Hydatid Cyst - US
collection of pus in an abscess.
multilocular (a single large cyst with multiple
Hydatid cyst is another hypoechoic cystic daughter cysts within it). Degeneration or damage
lesion (Fig 2). These may be unilocular or of the cyst wall leads to a contained internal
* Addl.Professor, Department of Radiology,
rupture of the membranes. The detached
Chenglepet Medical College Hospital, Chenglepet membranes float within the cyst, an appearance
** Lecturer, Department of Radiology, likened to a serpent. Later, the cyst wall
Institute of Child Health & Hospital for Children, undergoes calcification which is seen as white
Egmore, Chennai. curvilinear rim. A hydatid cyst may also get
72

Fig. 3. Polycystic kidneys with cysts( C ) in
the liver
Fig. 5.Mesenchymal hamartoma (M)
L- liver - US
infected and at that stage it is not possible to
differentiate it from an abscess, even by CT.
Cysts can also be a part of the autosomal
dominant polycystic kidney disease (Fig 3).
Simple bile cysts are rare and can be mistaken
for the unilocular type of hydatid cyst. One
differentiating feature that will help is the margin
of the cysts. Bile cysts tend to have a scalloped
edge (Fig. 4).
Another rare lesion is the mesenchymal
hamartoma, a developmental anomaly which arises
from the mesoderm of the portal tract. They
present in children less than 2 years of age as
painless hepatomegaly. They are slow growing but
73
2006; 8(2) : 177
Fig. 4. Bile Cyst
Fig. 6. Mesenchymal hamartoma (m)-
CT (g-Gall bladder)
can suddenly increase in size due to rapid fluid
collection. On ultrasound, there is a well defined
mass which is either cystic or solid. It is clearly
demarcated from the surrounding liver and is
usually found on its undersurface. On real time
ultrasound the mass moves with respiration along
with the liver. The mass shown in Fig 5 is cystic
with some solid elements. The intrahepatic biliary
radicals are normal. CT supports the sonographic
findings and shows the extent of the mass with thick
enhancing septae running between the low
attenuating cystic parts (Fig. 6). In MRI, the solid
mesenchymal component is hypointense while the
cystic parts are hyperintense in T2W images.
Indian Journal of Practical Pediatrics
CASE STUDY
ABDOMINAL EPILEPSY AS A CAUSE
OF RECURRENT ABDOMINAL PAIN
*Deshmukh LS
**Pangrikar AG
Abdominal pain or discomfort with or
without nausea and vomiting or other sensations
sometimes occurs in association with a convulsive
disorder. A concept that abdominal epilepsy is an
entity has been proposed by number of authors in
the past. Recent reports are few and the criteria
for diagnosis have become hazy. Trousseau first
described abdominal epilepsy in 1868.1
The association of abdominal symptoms
with epilepsy has been recognized for many
years. The invention and clinical application of
electroencephalogram (EEG) in 1920s shifted
the focus of medical attention from abdomen to
brain where, for the most part, it has remained
to this date. Modern medical science has
rediscovered abdominal connection in epilepsy.
Common clinical features of abdominal epilepsy
include abdominal pain, nausea, bloating, and
diarrhoea with nervous system manifestations
such as headache, confusion and syncope.2
We report a 10 year male child presenting
with recurrent abdominal pain of long duration
who had undergone several investigations and
treatments at various hospitals before being
diagnosed as having abdominal epilepsy.
* Associate Professor
** Lecturer
Department of Pediatrics,
GMC, Aurangabad, Maharastra.
74
2006; 8(2) : 178
Case Report
10 year male child born of third degree
consanguinity was brought for episodic pain in
abdomen since last five years. Pain was localized
to upper abdomen and periumblical region as a
feeling of upward thrust, lasting for 2 to 3 minutes
and subsided on its own. Pain was associated
with lacrimation, palpitation, unresponsiveness
and incontinence of bowel with each episode.
Initially such episodes occurred at monthly
intervals, frequency increased to every fortnightly
and now since last 6 months twice a week. There
was no incontinence of urine, vomiting,
emotional insult or any association with specific
foodstuff or altered pattern of defecation.
When child reported to us, he had already
undergone following investigations. Plain x-ray
abdomen, ultrasonography of abdomen thrice by
different persons and were reported normal.
Urine and stool examinations revealed nothing
abnormal. Barium meal followthrough done at
other hospital did not reveal any abnormality.
He had repeated antihelminthic, antiamoebic
and antispasmodic treatments but had no
response. He is a school going child with average
school performance with normal development.
His anthropometric measurements, physical
examination and hemogram were normal. Urine
examination was negative for porphobilinogen.
With the typical history, we did his
electroencephalogram (EEG) which revealed
focal spike and sharp waves around left temporal
region (Fig. 1). CT brain was normal. Child was
started on anticonvulsant carbamazepine. After
one year of starting anticonvulsants, he is totally
symptom free.
 2006; 8(2) : 179

Discussion Many a times abdominal epilepsy is

misdiagnosed as psychogenic pain, however, a
Abdominal epilepsy is a rare disorder, triad of paroxysmal pain, abnormal
difficult to diagnose. It is paroxysmal in nature electroencephalogram (EEG) and remarkable
and may be confused with abdominal migraine.3 response to anticonvulsants confirms the
One area of particular concern for diagnosis.5
pediatrician is proper diagnosis of abdominal Though the condition is rare, it should be
epilepsy. The epigastric aura (with or without a considered in differential diagnosis in a child with
rising sensation) as seen in our case is the most unexplained paroxysmal abdominal pain.6 It is
common premonitory symptom in complex suggested that no one symptom satisfies the
partial seizure. Vomiting and abdominal pain may requirement for diagnosis. The rigid criteria
occur in association with altered responsiveness, required for the diagnosis of other forms of
other signs of epilepsy and abnormal EEG
findings. The onset of the attack is usually
paroxysmal and postictal sleepiness is the rule.
Attacks of abdominal epilepsy usually lasts
for minutes and usually responds to
anticonvulsants.3
The pathophysiology of abdominal epilepsy
remains unclear. Temporal lobe seizure activity
usually arises in or involves the amygdala. It is
not surprising therefore that patients who have
seizures involving temporal lobe to have GI
symptoms, since discharges arising in amygdala
can be transmitted to gut via dense direct
projections to the dorsal motor nucleus of the
vagus. In addition, sympathetic pathways from
amygdala to GI tract can be activated via
hypothalamus. On the other hand, it is not clear
that the initial disturbance in abdominal epilepsy
arises in brain. There are direct sensory pathways
from the bowel via vagus nerve to the solitary
nucleus of medulla which is heavily connected
to amygdala. These can be activated during
intestinal contractions.2
Usually, abdominal epilepsy is idiopathic.
However it may be rarely secondary to develop-
mental brain disorders like polymicrogyria.
Hence computed tomographic scan as well as Fig.1: Showing Polygraphic EEG record with
MRI may be indicated in patients with abdominal paroxysmal spikes and waves in the left
epilepsy.4 temporal region.
75
Indian Journal of Practical Pediatrics 2006; 8(2) : 180

epilepsy should also be applied to this syndrome.
The conclusion that abdominal pain is of central
origin should be made on positive rather than
negative ground.1
References
1. Eustance F Douglas, Philip T White.
Abdominal epilepsy a reappraisal. J Pediatr
1971;78(1):59-67.
2. Peppercorn MA, Herzog AG. The spectrum
of abdominal epilepsy in adults. Am J
Gastroenterol 1989;84(10):1294-12
3. Martin H, Ulshen, Stableba. Recurrent
adominal pain In: Practice of Pediatrics, Ed,
Vincent C Kelley, Harper and Row Publisher,
Philadelphia, 1985 Vol 5, (15) Pp 15.
4. Garcia Herrero, G Fernandez Torre JL,
Barrasa J, Calleja J, Pascual J. Abdominal
epilepsy in an adolescent with bilateral
perisylvian polymicrogyria. Epilepsia
1998;39(12):1370-137.
5. Singhi PD, Kaur S. Abdominal epilepsy
misdiagnosed as psychogenic pain. Postgrad
Med J 1988;64(7):281-82.
6. Peppercorn MA, Herzog AG, Dichter MA,
Mavman CI. Abdominal epilepsy, A cause of
abdominal pain in adults. JAMA
1978;240(22):2450-24.

NEWS AND NOTES

XX SOUTH ZONE CONFERENCE OF IAP

SOUTH PEDICON 2006, SALEM
XXXI ANNUAL CONFERENCE OF IAP-TNSC
ORGANISED BY THE IAP-SALEM DISTRICT BRANCH
VENUE: HOTEL CENNEYS GATEWAY, SALEM
DATE: AUGUST 18TH 20TH 2006
Greetings from IAP Salem District Branch. It is our privilege to welcome you in Salem, for the South
Pedicon 2006. A fabulous mixture of academics and cultural feast awaits everyone.
Salem is a renowned city for its education, business, steel and health care. Salem is
surrounded by a variety of tourist locations like Yercaud, Hogenakkal, Mettur Dam and Namakkal. Kindly
block these dates of the conference in your calendar and we urge you to register at the earliest.
ORGANIZING COMMITTEE
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Organising Chairman Organising Secretary Jt.Organising Secretary Treasurer
Mobile: 9842711979 Mobile: 9443724688 Mobile: 98433114165 Mobile: 9843035115
Registration Fee for South Pedicon 2006
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For Registration and other inquiries contact: Organising Secretary, South Pedicon 2006, Pranav Hospi-
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Ph.No: 0427 2336787, 2336788 E-mail: southpedicon2006@rediffmail.com
For details regarding paper presentation please refer our website: www.southpedicon2006.com

76

CASE STUDY
ACQUIRED
VELOPALATOPHARYNGEAL PALSY
* Rana K S
** Behera M K
*** Sood A
Abstract : Unilateral velopalato pharyngeal
palsy is rare. The exact etiology of this condition
is not known, though a post viral immune
mediated response has been postulated. The
present case developed features of isolated 9th
nerve palsy after a viral illness. Rest of the
neurological and local examination of the neck
was normal. Neuro imaging of the head and neck
was normal. He has completely recovered after
a course of steroid.
Key words : Velopalatopharyngeal palsy.
Unilateral palatal palsy is uncommon. The
etiology and pathogenesis of this condition remains
unclear till date. This is usually a benign and a
self-limiting condition. Viral infections have been
postulated as a possible cause1. We report a male
child with multiple neurofibromas, who developed
acute onset right-sided velopalatopharyngeal palsy
and subsequently recovered completely.
Case Report
An eight years old male child was admitted
with history of sudden onset nasal regurgitation
of fluids in right nostril, nasal intonation of voice
and difficulty in swallowing of seven days duration
* Associate Professor
** Professor and Head
*** Resident in Pediatrics,
Dept. of Pediatrics,
Armed forces Medical Colelge, Pune.
77
2006; 8(2) : 181
with history of running nose and dry cough, a
week before the onset of illness. His symptoms
increased over the next few days and then was
static. There was no history of any visual and
auditory difficulty, drooling of saliva and
difficulty in chewing, breathing or coughing.
Examination revealed absent palatal movements
on a deviation of uvula to left while demonstrating
gag reflex. There was no other neurological deficit.
Examination also showed that he had multiple
neurofibromas measuring 10 to 30mm on the inner
aspect of left arm. He did not have any other
neurocutaneous markers or dysmorphic features.
Local neck examination and that of the ear, nose
and throat including laryngoscopic examination of
larynx was normal.
Hemogram and metabolic parameters were
normal. CSF anaylsis, Brainstem Auditory
Evoked Response, Magnetic Resonance Imaging
and Angiography (BAER, MRI & MRA) of the
brain and neck revealed no abnormality.
He was managed with oral prednisolone
(1.5mg/kg) initially for two weeks and
subsequently tapered over the next two weeks.
The child started improving within the first week
of treatment and the nasal regurgitation and nasal
intonation subsided. He is being followed up and
is presently asymptomatic.
Discussion
Acquired velopalatopharyngeal hemi-
paralysis, a rare condition, is seen mostly in children
with a male preponderance and is usually unilateral2.
It was first described by Edin in 1972. Most cases
(>96%) had acute onset of nasal intonation,
Indian Journal of Practical Pediatrics
unilateral nasal escape of fluids with varying
degrees of dysphagia3. The present child had all
these symptoms. No definite etiology has been
found out but post viral immune mediated
involvement of the ninth nerve has been postulated.
Viral studies have always been negative. CSF
examination has shown elevated IgG and IgG/
albumin ratio. Respiratory infection prior to the
illness has been documented in 35% cases4.
Although unilateral absence of palatal reflex
mostly indicates IX cranial nerve lesion, vagal
involvement can also rarely result in unilateral
palatal paralysis5. For definite diagnosis of isolated
velopalatopharyngeal palsy, vocal cords
involvement must be excluded. Hoarseness of
voice and a bovine cough indicate a vocal cord
palsy. A direct laryngoscopic examination is
essential to rule out vocal cord involvement. A
meticulous clinical search should be done for
multiple cranial nerve palsies due to brainstem
involvement because of vascular causes, tumors,
syringobulbia, motor neuron disease and
inflammatory diseases. Lesions around the ears
and pharynx can also cause multiple cranial nerve
palsies because of the close proximity of extra
cranial course of the last four cranial nerves after
their exit from cranial foramina. Isolated lesion of
nucleus ambigus leads to a combined
palatopharyngeal and laryngeal palsy. Rarely an
isolated injury to cephalic portion of the nucleus
can lead to isolated palatopharyngeal palsy with
laryngeal sparing 5. Velopalatopharyngeal
insufficiency secondary to local causes like
submucosal cleft palates easily differentiated by
long history and by local examination. The cranial
MRI (with angiography) is the diagnostic modality
NEWS AND NOTES
NATIONAL CONFERENCE OF PEDIATRIC RHEUMATOLOGY
SURAT, SEPTEMBER 30, 2006
Enquires to: Dr. Ketan Shah
Email : ketanhet@mail.com
78
2006; 8(2) : 182
of choice and is invariably normal. In the present
case also, MRI with angiography of the head and
neck was normal.
No specific treatment is required. Prognosis
is excellent. Steroids have been used empirically.
Recurrence is rare in children. A self limiting
course is the norm with complete recovery in
>85% cases over 2-3 weeks3. Multiple neuro
fibromas in this child were an incidental finding.
To conclude, sudden onset unilateral
velopalatopharyngeal palsy in children is rare.
It is a benign and self- limiting condition with
almost complete recovery. Post viral infectious
immune reaction is one possibility and that is why
some people recommend short course of steroids.
Reference
1. Cuvellier JC, Cusset JM, Nuyts JP, Vallee L.
Acquired and isolated asymmetrical palatal
palsy. Neuropediatrics 1998; 29(6):324-325.
2. Izzat M, Sharma PD. Isolated bilateral paralysis
of the soft palate in an adult. J Laryngol Otol
1992;106(9):839-840.
3. Auvin S, Cuvellier JC, Vallee L. Isolated
recurrent palatal palsy in a child.
Neuropediatrics 2003;34(5):278-279.
4. Villarejo GA, Camacho SA, Penas PM, Garcia
RR, et al. Unilateral isolated paraysis of the soft
palate: a case report and a review of literature.
Rev Neurol 2003; 36(4):337-339.
5. Cranial nerves IX and X (The
Glossopharyngeal and Vagus Nerves) In:
Brazis PW, Masdeu JC, Biller J. (editors)
th
Localization in clinical neurology 4 edn,
Lippincott Williams & Wilkins, Philadelphia,
2001; pp 329-336.
 2006; 8(2) : 183

PEDICON 2007
44th Annual Conference of the Indian Academy of Pediatrics, 12-14 January 2007
&
IAP-AAP CME 2007, 11th January 2007

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79
Indian Journal of Practical Pediatrics 2006; 8(2) : 184

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 ADVT
2006; 8(2) : 185

NCPCC- Bangalore 2006

8th National Congress on Pediatric Critical Care
NIMHANS Convention Center, Hosur Road, Bangalore, 10-12 November 2006

Organized by: Co-Organized by: IAP-Bangalore BPS

IAP-Intensive Care Chapter IAP-Intensive Care (Karnataka Subchapter)
MAIN SCIENTIFIC PROGRAMME (11th & 12th Nov)
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Indian Journal of Practical Pediatrics 2006; 8(2) : 186

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Indian Journal of Practical Pediatrics 2006; 8(2) : 188

Indian Journal of
Practical Pediatrics IJPP
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Indian Academy of Pediatrics

JOURNAL COMMITTEE NATIONAL ADVISORY BOARD

Editor-in-Chief President, IAP

Dr. A.Balachandran Dr.Nitin K Shah
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President 2006, IAP
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 2006; 8(2) : 189

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IAP Team - 2006 Kailash Darshan,
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 2006; 8(3) : 187

INDIAN JOURNAL OF IJPP

PRACTICAL PEDIATRICS
IJPP is a quarterly subscription journal of the Indian Academy of Pediatrics
committed to presenting practical pediatric issues and management up
dates in a simple and clear manner
Indexed in Excerpta Medica, CABI Publishing.

Vol.8 No.3 JUL.-SEP. 2006

Dr. A. Balachandran Dr. K.Nedunchelian
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 189

TOPIC OF INTEREST - VACCINES

Issues in EPI /IAP immunization schedule 190
- Raju C Shah, Bharat Prajapati
Newer vaccines (I) 197
- Nitin K Shah
Adverse events following immunization 208
- Indra Sekar Rao M
Polio Eradication / How near and how far? 220
- Vipin M Vashishtha, Naveen Thacker
Hepatitis vaccines - Current concepts 232
- Ashish Bavdekar, Sheila Bhave
Rabies vaccines - Current concepts 239
- Tapan Kumar Ghosh
Medico legal issues in emergency room 155
- Mahesh Baldwa
Journal Office: Indian Journal of Practical Pediatrics, IAP-TNSC Flat, F Block, Ground Floor, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for ordinary letters: The Editor-in-Chief, Indian Journal of Practical Pediatrics, Post Bag No.524,
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Plot No. 235, 4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
Indian Journal of Practical Pediatrics 2006; 8(3) : 188

RADIOLOGIST TALKS TO YOU

Hepatomegaly and hepatic masses - II 246
- Vijayalakshmi G, Elavarasu E, Porkodi, Malathy K, Venkatesan MD
CASE STUDY
Milroys disease 250
- Farzana Beg, Ajit Saxena, Imteyaz Ahamed Khan, Siray N Huda,
Faisal Haque
Necrotizing Fascitis 252
- Shrishu R Kamath, Anjul, Rajeswari, Balaji V, Suchitra Ranjit,
Radha Rajagopalan
Mckusick - Kaufman: Hydrometrocolpos polydactaly -
A rare syndrome 256
- Sridharan S, Pradip Vincent, Ramesh S.
PRACTITIONERS COLUMN
Is there a need for regular ultrasound in every infant? 262
- Janani Sankar, Alka Sophia Rao, Nammalwar BR, Vijayakumar M,
Muralinath S.
PICTURE QUIZ 265
EMERGING EPIDEMICS
Chikungunya - Is it a threat? 266
QUESTION AND ANSWER 268
NEWS AND NOTES 196, 207, 219, 231, 238, 245, 249,
251, 255, 261, 264, 267

FOR YOUR KIND ATTENTION

* The views expressed by the authors do not necessarily reflect those of the sponsor or publisher.
Although every care has been taken to ensure technical accuracy, no responsibility is accepted for errors
or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are the
responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board

Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road, Egmore,
Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works, 9, Iyyah Street,
Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.

2

EDITORS DESK
Greetings from the Journal Committee of
IJPP. This issue is dedicated to important topics
on Vaccines. The journal committee sincerely
thanks Dr.Nitin K Shah, President, IAP - 2006
for accepting to be the Guest Editor for this issue.
With his vast experience and rich knowledge in
immunization, he has carefully chosen the topics
and authors for this current issue.
Issues on EPI and immunization schedule
is compiled by Dr.Raju C Shah, et al. They have
covered the general principles to be followed in
vaccination, various schedules, principles of
vaccine scheduling, and immunzation in special
circumstances.
The topic on Newer vaccines has been
written by Dr.Nitin K Shah. He has stated that
H.influenzae b and pneumococcus are common
causes of invasive bacterial infections in children.
He has mentioned that conjugated Hib vaccine
has good immunogenicity and efficacy and it can
be given as 3 primary doses and 1 booster dose
along with DPT and OPV and the conjugated
pneumococcal vaccine given as 3 primary doses
at 2, 4, 6 months and a booster at 15 months has
high efficacy against invasive disease. He has
also stated that Influenza virus A can lead to severe
illness,hospitalization and even deaths among high
risk populations, and they should be targetted with
inactivated influenza vaccine.
In his article on Adverse events following
immunization Dr.Indra Sekhar Rao has discussed
the various adverse events that can occur
following the routine immunization. He has
warned all medical personnel handling vaccines
to be aware that no vaccine is perfectly safe and
adverse events can occur following any
immunization.
3
2006; 8(3) : 189
The topic on Polio eradication / How
near and how far? is well narrated by
Dr.Vipin Vashishtha, et al. The main aim of the
polio eradication programme is to interrupt wild
polio virus (WPV) transmission globally. They
have warned that failure to achieve this will pose
a threat to all the nations as evidenced by the
recent reporting of large number of cases in non-
endemic countries. The various problems
pertaining to this and the possible solutions for
present and future are discussed by them.
The article on Hepatitis vaccines - Current
concepts is contributed by Dr.Ashish Bavdekar,
et al. They have stated that some regions in the
country have shown an epidemiologic shift of HAV
infection from early childhood to adolescents and
adults. They stress the definite role of HA vaccine
in these regions to prevent epidemics and protect
against severe HAV infection in adulthood. The
effectiveness of the vaccine in reducing the burden
of hepatitis B disease is well demonstrated in
countries adopting the universal immunization
program. Hepatitis B vaccination not only prevents
HBV infection but also associated chronic liver
disease and hepatocellular carcinoma.
Rabies is said to be a disease of antiquity
known to mankind from time immemorial.The
prevention of rabies by vaccination dates back to
Louis Pasteur. Dr.Tapan Kumar Ghosh has given
a detailed account in the article Rabies vaccine -
Current Concepts.
We thank all the authors for their
contributions to Practitioners column, Case
study and Question and Answer column. Our
sincere thanks to Dr.Vijayalakshmi, et al. for their
continued, contribution to Radiologist talks to
you column. The next issue will also cover some
more topics on vaccines.
Indian Journal of Practical Pediatrics
VACCINES
ISSUES IN EPI / IAP IMMUNIZATION
SCHEDULE
* Raju C Shah
** Bharat Prajapati
Abstract : Immunization programme should be
epidemiologically relevant, immunologically
competent, technologically feasible, economically
viable and socially acceptable. This article covers
general principles in vaccination, various
schedules, principles underlying vaccine
scheduling, and immunization in special
cicumstances.
Key words : Schedules, Principles, Special
Circumstances.
Every nation designs its own immunization
schedule depending on epidemiology, health
infrastructure and socio economic conditions of
the country. For any immunization programme to
be successful the national schedule should be such
that it is epidemiologically relevant,
immunologically competent, technologically
feasible, economically viable and socially
acceptable.
EPI was proposed by WHO in 1974. In India
it was launched in 1978. In 1985 Government of
India launched Universal Immunization
Programme (UIP). Under this the emphasis was
shifted from under five to under one.
* Immediate Past President, IAP
** Junior Consultant
Ankur Institute of Child Health,
Ashram Road, Ahmedabad 380009
4
2006; 8(3) : 190
Schedule means a time table which is
necessary for achieving uniform and regular
response and optimal coverage. It is a way of
ordering priorities in accordance with childrens
ability to acquire immunity, the epidemiology of
disease and antigenic qualities of the vaccine.
Certain general principles should be observed
while performing vaccination.
1. An interval of 4 weeks is necessary between
two doses or two different vaccines unless
specific short interval is stated for a vaccine.
2. Vaccines can be given at all ages as per
requirement.
3. Generally the child should not be very sick
at time of vaccination.
4. Separate syringes and needles are required
for each prick.
5. Vaccine must be properly preserved
maintaining the cold chain.
6. While giving more than one vaccine at a time,
their compatibility must be known.
Universal Immunization Programme (UIP)
launched in 1985 in India covers six vaccine
preventable diseases. BCG, OPV, DPT and
Measles are the vaccines administered totalling
five injections during infancy. With the launch of
Pulse Polio Programme, an infant may receive,
up to 7 doses of OPV. The Indian Academy of
Pediatrics-Committee on Immunization (IAPCOI)
has suggested that EPI should be supplemented
by hepatitis B, MMR, and typhoid vaccines.

Principles underlying vaccine
scheduling
Optimal response to a vaccine depends on
multiple factors. These include the following.
Nature of vaccine
Certain vaccines (Inactivated vaccines,
toxoids, recombinant subunit and polysaccharide
conjugate vaccines) require administration of more
than two doses for development of an adequate
and persisting antibody response. Toxoids (i.e.
tetanus and diphtheria) require periodic
reinforcement of booster doses to maintain
protective antibody concentrations. Unconjugated
polysaccharide vaccine does not induce T-cell
memory and hence repeated doses do not produce
substantial boosting. However, when conjugated
with a protein carrier, the effectiveness of
polysaccharide vaccine improves by inducing
T-cell dependent immunity.
Immunogenicity and potential
interference by passively transferred
maternal antibody
The timing of the first immunization is a
compromise between the developing immunity by
the infants immune system and the risk of infection
from virulent organisms. Maternal transplacental
IgG antibodies are protective in the first few
months of life. In early infancy the protection is
partial for some diseases (pertussis), and
satisfactory against others (measles and rubella).
BCG (Bacille Calmette Guerin), OPV (Oral
Polio Vaccine) and Hepatitis B (Hep. B) vaccines
can be given at birth. BCG elicits a CMI and
maternal CMI is not transferred transplacentally.
Maternal antibodies in the babys circulation
against OPV are weakly inhibitory in nature and
hence OPV can establish local gut infection in a
significant proportion of recipients. Hepatitis B
vaccine is strongly immunogenic and can
overcome the maternal antibodies. Live measles
vaccine, mumps and rubella are inhibited by
maternally derived antibodies till around 9 to 12
months of age.
5
2006; 8(3) : 191
Local disease epidemiology
The optimal age for starting immunization
depends upon both immunological maturity and
local disease epidemiology. In developing countries
where tuberculosis and poliomyelitis may affect
young children, immunization should be started
soon after birth. In communities where pertussis
and diphtheria are still a problem this vaccine
should be given as DTP (diphtheria, tetanus,
pertussis) early in infancy since cases before
6 months of age have a greater morbidity and
mortality. When measles is a major threat, vaccine
should be given early, despite the risk that the
response may not be optimal. The most
appropriate age for measles vaccination depends
upon the age-specific measles attack rate in a
particular county. In India this age is 9 months.
Changing epidemiology of diseases
With effective vaccination program, there is
a shift to the right in the age group affected by
some vaccine preventable disease. It has been
observed that now measles is affecting older
children and whooping cough is being seen more
in adults. These changes may make vaccination
programs prolonged or even lifelong.
Simultaneous administration of
vaccines
The simultaneous administrations of live and
inactivated vaccines have produced
seroconversion rates and rates of adverse reactions
similar or those observed when the vaccines are
administered separately. Routinely simultaneous
administration of all vaccines is recommended for
children who are of the appropriate age to receive
them and for whom no specific contraindications
exist at the time of the visit.
Combination vaccines
Use of combination vaccines can reduce the
number of injections required at a single visit. Use
of licensed combination vaccines is preferred over
separate injection of their equivalent component
vaccines.
Indian Journal of Practical Pediatrics 2006; 8(3) : 192

Adverse reactions Table 2: National immunization

schedule of India (UIP)
Certain vaccines produce increased rates of
local or systemic reactions in certain recipients Age Vaccine
when administered too frequently. This has been
At birth BCG, OPV
observed with adult tetanus-diphtheria toxoid (dT),
pediatric diphtheria-tetanus toxoid (DT), and 6 Weeks DTP1, OPV1
tetanus toxoid (TT). 10 Weeks DTP2, OPV2
14 Weeks DTP3, OPV3
Vaccine failure
9 Months Measles
Approximately 90-95 percent recipients of a
16-18 Months DTP booster, OPV4
single dose of MMR vaccine develop protective
antibody within 2 weeks of the dose. Similarly, a 5 Years DT
second dose of varicella is recommended in 10 Years TT
recipients of >13 years of age, since 16 Years TT
approximately 20 percent fail to respond to the
first dose and 99 percent of recipients seroconvert
after two doses. Table 3: Indian Academy of
Pediatrics Immunization Schedule
Issues in schedule for specific
vaccines Vaccine Age Recommended

1. DTP: IAP recommends that all children less BCG Birth 2 weeks
than 1 year should be actively immunized with OPV Birth, 6, 10, 14 weeks,
three doses of DTP vaccine followed by 2 booster 16 18 months, 5 years
doses at 18 month and 5 year of age. IAP DTP Birth, 6, 10, 14 weeks,
recommends DTP at 5 years (2nd booster), which 16 18 months, 5 years
is logical looking at its comparative safety in recent
Hepatitis B Birth, 6 weeks, 6 months
or 6 , 10, 14 weeks
Table 1: WHO Expanded program on
Immunization Hib Conjugate 6, 10, 14, weeks
16 18 months
Age Vaccine
Measles 9 months plus
Birth BCG, OPV0, Hep. B1
MMR 15 months
6 Weeks OPV1, DTP1, Hep. B2
Typhoid 2 years
10 Weeks OPV2, DTP2
TT/Td 10, 16, years
14 Weeks OPV3, DTP3, Hep. B3
2 doses of TT Pregnancy
6 Months Measles*
9 Months Measles* Additional Vaccines*
10 Months Yellow fever Varicella Above 1 Year
18 Months DTP 4 Hepatitis A Above 1 Year
* Extra early dose given in situation of high risk * These are not routinely recommended
given in all countries at risk
6

studies. DT is recommended after 7 years of age
whenever there is need to give even one antigen
and Td/TT after 10 years of age. Surveys also
indicate that tetanus tends to infect more people
as they age . Hence, booster doses shall be given
in adults also at regular interval of 10 years or on
exposure to serious injury.
2. Polio vaccine: IAP recommends the five dose
schedule, ZERO DOSE at birth, 3 doses at 6,
10 and 14 weeks and fifth dose at 9 months along
with measles vaccine. Although IAP finds the need
and requests for the availability of IPV in India, it
has not been licensed in the country till date. A
five dose OPV regimen plus two to three dose
pulse would increase the number of doses to 7 to
8 in infancy, 10 to 11 by second year and so on.
This approach, although recommended for
adoption in India was rejected in favour of the
3 dose regimen and multiple NIDs and subnational
IDs.
3. Hepatitis B vaccine: HB vaccine may be given
in any of the following schedules.
(i) Birth, 4 to 6 wks and 6 months
(ii) Birth, 6 and 14 weeks
(iii) 6,10, and 14 weeks
If the mother is known to be HbsAg negative,
HB vaccine can be given along with DTP at 6,10
and 14 weeks. If the mothers HbsAg status is
not known, it is important that HB vaccination
should begin within a few hours of birth so that
peinatal transmission can be prevented. Any one
of the following schedules may be used for this
purpose-birth, 6 and 14 weeks or birth, 1 and 6
months. If the mother is HbsAg positive (and
especially HbeAg positive), the baby should be
given Hepatitis B immune globulin (HBIG) within
24 hours of birth, along with HB vaccine (at birth,
6 and 14 weeks, or birth, 1 and 6 months). If
HBIG is not available (or is unaffordable), HB
vaccine may be given at 0,1 and 2 months with
an additional optional dose between 9-12 months.
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2006; 8(3) : 193
It has been suggested that in infancy the third
dose of HB vaccine should be given at least
16 weeks after the first dose, at least 8 weeks
after the second dose and not before 6 months of
chronological age, as it presumably gives longer
lasting immunity. The vaccination schedule need
not be changed for preterm and small-for-dates
babies.
4. Measles vaccine: Ideal vaccination strategy is
to choose the right time so as to close the gap of
vulnerability to natural wild virus infection.
Vaccination given too early, before waning of
maternal antibodies would result in failure of
vaccine uptake. On the other hand delayed
vaccination will leave many children predisposed
to measles infection. Considering all these factors
IAP has advocated two dose schedule where
second dose is recommended as MMR at
15 months of age.
Immunization in special
circumstances
1. Immunization in preterm infants
In general, all vaccines may be administered
as per schedule according to the chronological age
irrespective of birth weight or period of gestation.
Very low birth weight babies can be given
immunization after initial stabilization.
2. Children receiving corticosteroids
Children receiving oral corticosteroids in high
doses (e.g. Prednisolone 2 mg/kg/day) for more
than 14 days should not receive live virus vaccines
until the steroid has been discontinued for at least
one month. Killed vaccines are safe but may not
be completely effective in such situations. Patients
receiving small doses, short course, on topical or
inhaled steroid therapy should not be denied their
age appropriate vaccines.
3. Children awaiting splenectomy
Children with loss of splenic function are at
high risk of serious infections with encapsulated
Indian Journal of Practical Pediatrics 2006; 8(3) : 194

organisms. If splenectomy is being planned,
immunization with pneumococcal, Hib and
meningococcal vaccines should be initiated 2 to 4
weeks prior to splenectomy.
4. Vaccination in children with HIV infection
Children infected by HIV are particularly
vulnerable to severe recurrent or unusual
infections by vaccine preventable pathogens. It
must be emphasized that routine immunizations
seem to be generally safe in such children, but
the immune responses may be suboptimal.
Development of an immune response following
vaccination would depend upon the degree of
immunodeficiency at that point of time. Immune
attrition associated with viral replication may
particularly interfere with memory responses.
Consideration should be given to re-administering
childhood immunization to such children when
their immune status has improved following anti-
retroviral therapy.
Table no. 4 summarizes the recommendations of
WHO/UNICEF and the Advisory Committee on
Immunization Practices (ACIP).
5. Vaccination schedule for children not
immunized in time
It may be noted that vaccination catch-up
regimens may be difficult to construct for older
children and must necessarily be individualized.
Table 5 depicts the suggested schedule which may
be followed in cases of children who have not
been offered any immunization.
It may be noted that Measles/MMR vaccines
may as well be given at the first visit itself (along
with the other vaccines). The third dose of HB
vaccine may be given 6 month after the first dose,
if patient compliance is not a problem.

Table 4. Vaccination recommendations in HIV infected children

VACCINE WHO/UNICEF ACIP
Symptomless Symptomatic Children with
HIV infection HIV infection HIV/AIDS
BCG Yes* (At birth) No No
DTP Yes (At 6,10,14weeks) Yes Yes (but use DTPa)
OPV Yes (At 0, 6,10, 14 Yes No (use inactivated polio
weeks) vaccine)
Measles Yes (At 6 & 9 months) Yes Yes (but contraindicated
if CD4+ is < 15%)
Hepatitis B Yes (As for Yes Yes
uninfected children)
Hib Yes
Pneumococcal Yes
Influenza Yes (but not below
6 months of age)
Varicella Yes
Meningococcal Yes
Empty cells imply there are no current recommendations

8
 2006; 8(3) : 195

6. Lapsed immunization illnesses (e.g. fever, diarrhea, respiratory infection)

There is no need to restart a vaccine series
regardless of the time that has elapsed between
individual doses. Immunizations should be given
at the next visit as if the usual interval had elapsed
and the immunization schedule should be
completed at the next available opportunity. In
case of unknown or uncertain immunization status,
however, it is appropriate to start the schedule as
for an unimmunized child.
7. Missed opportunity for immunization
This is defined as a situation when child visits
a health care facility and is not immunized. Minor
and malnutrition should not be construed as
contraindications to immunization. Any dose not
given at the recommended age should be given at
any subsequent visit when indicated and feasible.
8. Simultaneous administration of multiple
vaccines.
Both killed and live vaccines can be
administered simultaneously without decreasing
the efficacy of the individual vaccines. However,
prudence demands that the vaccines be
administered at different sites using separate
needles for each component.

Table 5. Vaccination schedule for an unimmunized child

Age Less than 5 years More than 5 years

First visit BCG, OPV, DTP, HBV TT/Td, HBV

2nd visit (1 month later) OPV, DTP, HBV TT/Td, HBV

3rd visit (1 month later) OPV, DTP, HBV HBV, MMR

Measles/MMR, Typhoid Typhoid

1Yr later OPV, DTP -

Every 3 Years Typhoid booster Typhoid booster

Table 6. Vaccination schedule in adolescents

Vaccine Age
1. Diptheria/Tetanus Toxoid (Td) Boosters at 10 and 16 Years
2. Rubella vaccine 1 dose to girls at 12-13 years of age
OR
MMR Vaccine 1 dose at 12-13 years of age, if not given earlier
3. Hepatitis B Vaccine 3 doses at 0,1 and 6 months, if not given earlier
4. Typhoid Vaccine Vi-polysaccharide vaccine every 3 years
5. Varicella Vaccine* 1 dose upto 13 years, and 2 doses (at 4-9 weeks interval)
after 13 years of age (if not given earlier)
6. Hepatitis A Vaccine* 2 doses 0 and 6 months
* Only after discussing with the parents on a one-to-one basis

9
Indian Journal of Practical Pediatrics
9. Immunization of adolescents
Adolescence should be considered an
appropriate age for top-up immunization as well
as for administration of certain vaccines which
may not have been indicated earlier. However,
this should always be done after careful counseling.
10. Vaccination of children with bleeding
disorders or those receiving anticoagulants
23G or smaller needles should be used for
injection and the parents should be asked to apply
firm and sustained pressure, without rubbing, for
at least 5 minutes.
11. Breastfeeding and vaccination
Breastfeeding does not adversely affect
immunization and is therefore, not a
contraindication for any vaccine. Neither
inactivated nor live vaccines administered to a
lactating woman affect the safety of breastfeeding
for infants. There is no risk of transmission of
Hepatitis B virus from an HBsAg carrier mother
to her baby through breast milk.
Points to remember
* National Immunization schedule is
designed according to disease epidemiology,
health infrastructure and socio economic
conditions.
* General principles should be observed while
performing vaccination.
* It may be necessary to adopt some
modifications under special circumstances
like immuno compromised states, lapsed
immunisation, etc.
NEWS AND NOTES
PPSA: Pediatric Procedural Sedation and Analgesia Course 3rd December, 2006
Course Director: Dr. Suresh Gupta, Sir Ganga Ram Hospital, New Delhi - 110 060.
Phone : 9811426628, 28312656, 28312591 Email: drguptasuresh@yahoo.co.in
10
2006; 8(3) : 196
Bibliography
1. Committee on Immunization and infectious
diseases. Immunity, Immunization &
Infectious diseases. 1994. 16-32.
2. IAPCOI Update on immunization policies,
guidelines and recommendations. Indian
pediatircs. 2004 : 41 : 239-244.
3. WHO Global programme for vaccines and
Immunization. Immunization policy. Geneva:
WHO,1996.
4. IAP Committee on Immunization 2003-2004.
IAP Guide Book on Immunization, 3rd ed. New
Delhi, Cambridge Press, 2005; pp 39-45.
5. Obaro SK, Pugatch D, Luzuriaga K.
Immunogenicity and effficacy of childhood
vaccines in HIV-1 infected children. Lancet
Infect Dis 2004; 4(8): 510- 518.
6. Colditz GA, Brewer TF, Brekey CS, et al.
Efficacy of BCG vaccine in the prevention of
tuberculosis. JAMA 1994;271 (9):698-702.
7. Seth V, Kumar M, Lodha R. BCG vaccination.
In: seth V, Kabra SK (Eds).Essentials of
nd
Tuberculosis in children 2 ed. New Delh,
Jaypee Brothers Medical Publishers (P) Ltd,
2001;371-581.
8. Fine PE, Rodrigues LC. Modern vaccine
Mycobacterial disease. Lancet 1990;335:
1016-1020.
9. CDC vaccine Adverse Event Reporting
systemUnited States, MMWR 1990;39:
730-733.
10. Fritzell B.Polysaccharide vaccine against
Haemophilus influenzae b conjugated to
tetanus protein. Immunol Med 1991;8:176-
183.
11. CDC. Prevention of varicella. Recommen-
dations of the Advisory Committee on
Immunization Practices (ACIP). MMWR
1996;45(RR-11):1-36.

VACCINES
NEWER VACCINES (I)
*Nitin K Shah
Abstract: H.influenzae type b and pneumococcus
are common causes of invasive bacterial
infections in children. Conjugated Hib vaccine
has good immunogenicity and efficacy. The
recommended schedule is 3 primary doses and
one booster dose along with DPT and OPV.
Polyvalent polysaccharide pneumococcal vaccine
cannot be used in children less than 2 years of
age and in healthy adults it has an efficacy of
70% against invasive disease. Conjugated
pneumococcal vaccine given as 3 primary doses
at 2, 4, 6 months and a booster at 15 months has
high efficacy against invasive disease. Influenza
virus A can lead to severe illness, hospitalization
and even deaths among high risk populations,
who should be targetted with inactivated
influenza vaccine. Due to frequent antigenic drift
of the virus, the development of vaccine also
would require periodic changes. Intranasally
administered live cold adapted influenza trivalent
(CAIV-T) vaccine is also found to be effective.
Key words: Hib, Pneumococcal, Influenza,
Vaccines
H. Influenzae b vaccine
H. Influenzae type b infection is a common cause
of invasive and non-invasive severe bacterial
infections in children less than 5 years of age like
* President, Indian Academy of Pediatrics, 2006
Co-chairperson,
IAP Committee on Immunization, 2005-06
Mumbai
11
2006; 8(3) : 197
bacteremia, meningitis, pneumonitis, arthritis,
epiglottitis etc. The pathogen is a commensal in
the upper respiratory tracts of healthy
humans1,2. In the developing countries it is still a
major cause of morbidity and mortality due to
non-inclusion of Hib in the national immunization
schedule.
Disease burden: 3-5% of children in west are
carriers of Hib, whereas this figure is as high as
15%-30% in developing countries. 95% of the
Hib infection occurs before the age of
5 years. IBIS study done in India has shown that
76% of Hib occurs before the age of 1 year with
the peak at 6-9 months3. It is estimated that the
incidence of invasive Hib disease in India is
around 50-60/100,000 children less than 5 years
of age2. It is estimated that 3 million cases of Hib
infection occur every year world over and 0.375
million of them die due to Hib1,4. In India only
hospital based data is available which have shown
that 30-45% of cases of pyogenic meningitis and
8-12% of cases of pneumonia in children are due
to Hib disease as shown in Table I 2,5. This is
similar to data from Europe before mass
vaccination in these countries.
Meningitis: Of the cases of pyogenic meningitis,
30% is caused by Hib as per IBIS study and
30-45% as per the study done in Vellore. The
mortality in developing countries is as high as
30-50% as compared to 3-5% in the West. Of the
survivors, 30-40% have some sequelae like
deafness, epilepsy or motor deficiencies1,3.
Pneumonia: Up to 40% of cases of Hib present
as pneumonia in developing countries1. Various
studies done from India have shown Hib as a cause
Indian Journal of Practical Pediatrics
of pneumonia in 8-46% 2. It is difficult to prove
the etiological agent as blood culture is positive in
less than 10% of cases as most of the pneumonia
cases are non-invasive.
Others: 8-12 % of total Hib cases present as
epiglottitis. It is commonly seen in developed
countries but virtually not seen in developing
countries. Similarly skin infections involving face
is rarely seen in countries like India but was
commonly seen in west before mass
vaccination 1.
Drug resistant Hib: Since 1970, drug resistant
Hib strains have emerged posing therapeutic
challenges. In India, initial cases of drug resistant
Hib disease were reported from Chandigarh in
19901. Since then Vellore has reported that 42.5%
of the Hib isolates were MDR strains in 19922, 5,
Nagpur reported 80% MDR isolates in 19966 and
IBIS reported 56% resistance to chloramphenicol
and 40% resistance to ampicillin in 19993.
Prevention: 3 million cases with 0.37 million
deaths world over is a huge toll due to Hib disease
in children. Increasing drug resistance has added
to the mortality and cost as 3 rd generation
cephalosporins are required now to treat these
patients. Excellent vaccines are available in the
form of conjugate Hib vaccines since 1980. The
western world has eliminated Hib disease with
universal immunization. That makes this vaccine
a strong contender as the 8th vaccine to be included
in to the National Schedule for immunization.
Hib vaccines
The newer conjugated Hib vaccines have
been highly successful with excellent tolerance,
safety, immunogenicity and efficacy as proved in
several trials world over.
There are 4 types of conjugate Hib vaccines
depending on the protein carrier used; PRP-OMP
(using outer membrane protein of meningococcus)
is not used due to poor immunogenicity, PRP-D
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2006; 8(3) : 198
(using diphtheria toxoid) is also given up for
primary schedule due to poor immunogenicity,
HbOC (using CRM 197 mutant diphtheria toxin)
and PRP-T (using tetanus toxoid). HbOC and
PRP-T are the only vaccines available in India.
There is one more brand available which has
HbOC with adjuvant.
Immunogenicity and clinical efficacy: 98-100%
of the vaccinees achieve anti-PRP antibody titers
of > 0.15 mcg/ml in the serum which is taken as
protective in a short term basis and nearly 100%
of them achieve the same after the booster dose
given at 15 months. The GMC achieved at the
end of 4 dose series is as high as 60-90 mcg/ml1.
These high titers translate into near 100% clinical
efficacy as shown in various trials world over1.
High coverage with the vaccine has also resulted
in significant drop in the carrier state not in those
vaccinated but even in un-vaccinated children
which means that routine vaccination program
leads to herd immunity1. This also means that it
is possible to eradicate Hib by including it in the
National Schedule. In US there was 95-98% drop
in the incidence of Hib disease with the use of
HbOC and PRP-T vaccines1. Similar experience
was noted in Finland and UK which almost
eliminated Hib disease with mass vaccination in
just 2-3 years of its use 1,7.
Schedule: Hib vaccines are available as ready to
use liquid (HbOC) or as lyophilized powder
(PRP-T) in 0.5 ml of volume. It is given by IM
route over the antero-lateral aspect of the thigh or
over deltoid region. It should be preserved at
2-80C in the refrigerator. It should not be frozen
and if frozen by mistake, it should be discarded.
The cost of the vaccine at present is Rs. 250-300
per dose. It is available as unit dose or as a
multi-dose vial. 3 primary doses are given at 6,
10 and 14 weeks along with the OPV/DTP vaccine
followed by a booster at 15-18 months. If the
child comes after 6 months of age only 2 primary
doses at 4-6 weeks interval are given followed by

the booster at 15 months. Similarly if the child
comes after 1 year he receives only one primary
dose followed by a booster at 15-18 months. After
the age of 15 months, only one dose is required1.
It is preferable to use Hib/DPT/Hepatitis B
combination vaccine instead of giving these
vaccines separately as appropriate.
Side effects: Hib conjugate vaccines are one of
the safest vaccines proved in many studies.
Local : 3-5% of the vaccinees develop local pain,
10% develop redness, 2-4 % develop swelling.
These are mild in nature and lasts for 1-2 days.
One can use paracetamol for pain 1,8.
Systemic : 10-15% of the vaccinees develop fever
which is mild, lasts for 1-2 days and responds to
paracetamol. Other side effects include loss of
appetite in 15-20%, restlessness in 15-20%,
excessive crying in 20-22%, vomiting in 7-10%
and diarrhea in 10-15% of cases. Again these
symptoms are mild and self limiting 1,8.
IAP recommendation: Indian Academy of
Pediatrics Committee of Immunization strongly
recommends that Hib vaccine needs serious
consideration for inclusion in the national
immunization schedule, while awaiting disease
burden studies. However, the cost of vaccination
is considered prohibitive9.
Pneumococcal vaccine
Pneumococcus is a common organism causing
invasive bacterial disease, especially in children
less than 2 years and elderly adults (above the
age of 65 years). In west, now it is the commonest
organism causing invasive bacterial disease in
children, as Hib is virtually eradicated with
universal Hib vaccination. Interest existed in
developing pneumococcal vaccine since 1940s till
penicillin became available. With the emerging
resistance to penicillin and other drugs of late,
there is resurgence of interest in pneumococcal
vaccine, especially after the success of conjugation
13
2006; 8(3) : 199
technique used for Hib vaccine. This has led to
availability of highly efficacious conjugate
pneumococcal vaccine which is creating history
in western world.
Pneumococcus: Pneumococcus has more
than 90 serotypes grouped into more than
45 serogroups. Most serotypes do not have cross
protection. Of these, 10 serotypes cause more than
90% of childhood infections and include serotypes
4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 3, 7. Of
these, type 1 is the commonest serotype seen in
India as per IBIS study10.
Disease spectrum: Pneumococcus can lead to
invasive diseases like bacteremia, meningitis,
pneumonitis or local infections like non-bacteremic
pneumonia, acute otitis media (AOM), cellulitis,
arthritis, peritonitis etc. 30-50% of school age
children are carriers for one or more serotypes.
In adults, carrier rate varies from 6-30%. From
nasopharynx it can spread locally or systemically
leading to various types of clinical diseases. In
west, the first contact with pneumococcus occurs
at 6 months of age whereas in developing countries
it can occur as early as 17 days! The peak
incidence of pneumococcal disease is seen at
6-24 months of age.
Incidence of invasive disease in children less than
5 years varies from 25-50 per100,000 in Europe
to 90/100,000 in USA to 500/100,000 in Gambia
and Apache Indians11.
90% of bacteremia, 30-50% of pneumonia,
30-45% of pyogenic meningitis and 30-60% of
all bacterial AOM are caused by pneumococcus.
The mortality rate of invasive disease is 6% to
20% and there are sequelae like CNS sequelae in
survivors of meningitis and deafness in children
with recurrent AOM.
In India, it is estimated that pneumococcus leads
to 50,000 - 75,000 cases of meningitis11. IBIS
study showed that of the pneumococcal invasive
Indian Journal of Practical Pediatrics
diseases 30% present as meningitis, 30% as
pneumonia and 30% as bacteremia, peritonitis and
others10. At this rate one expects pneumococcus
also to cause 50,000 - 75,000 cases of invasive
pneumonia, 50,000 - 75,000 cases of other types
of invasive disease, 10 times more cases of non-
bacterial pneumonia and 100 times more cases of
AOM.
Bacterial resistance: Cases of penicillin resistance
were reported first in 1970s. Since then the
resistance has spread world over. More than 40%
of the isolates from invasive diseases and nasal
carriers are penicillin resistant in countries like Sri
Lanka and Taiwan, whereas the same in USA
and Europe is 10-40%. In India and Australia it is
less than 10%. IBIS study done in India showed
that intermediate penicillin resistance was seen in
1-4 % of serotypes in India. The resistance has
been increasing over last two decades. In USA it
increased from 4% in 1980 to 30% in 1990.
Pneumococci are resistant to other drugs too like
TMP/SMX, chloram-phenicol, and even 3 rd
generation cephalosporins.
Serotypes 6B, 9V, 14, 19F and 23F are
responsible for most of the resistant infections and
are covered by the 7 valent conjugate vaccine.
Infection with resistant forms means use of higher
dose of antibiotic or use of alternate drugs like
cefotaxime or vancomycin to prevent mortality.
One of the main reasons for increasing drug
resistance is misuse of antibiotics10, 11.
Unconjugated pneumococcal vaccines
23 valent plain polysaccharide vaccine is
available since last few decades. Being non-T cell
dependent it cannot induce good immune
response. The immune response is IgM type, short
lived, has low titers, affinity and avidity, does not
induce local IgA immunity and does not have
boosting effect in spite of repeated doses.
Hence, this vaccine cannot be used in children
below 2 years of age when it is most required. At
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2006; 8(3) : 200
best it has efficacy of 70% in healthy adults against
invasive disease and only 56% in those > 65
years of age. It has poor efficacy against non-
bacteremic pneumonia and doubtful, if any,
efficacy against AOM, carrier state or immune
compromised hosts.
Conjugated pneumococcal vaccine
7, 9 and 11 valent conjugated pneumococcal
vaccines have been developed and of this 7 valent
CRM 197 conjugated vaccine is commercially
available in the west. Other carrier proteins tried
include tetanus toxoid, diphtheria toxoid and outer
membrane protein of meningoccus. None of them
are commercially available at present.
Content : 7 valent vaccine contains 2 ug of each
serotypes 4, 9, 14, 18C, 19F, 23F and 4 ug of
6B, that is total of 16 mg of antigen in 0.5 ml of
vaccine. 9 valent vaccine contains additional
serotypes 1, 5 and 11 valent vaccine in addition
has serotypes3,7,10,12.
Safety : 7 valent conjugate vaccine given to infants
is a very safe vaccine. Mild local reactions are
seen in 30-35% of patients and include redness,
warmth, pain, induration and tenderness. Severe
local reactions of > 2.5 cm diameter are seen in
5-6% of patients. The reactions are less than those
seen with DPwT and same as seen with DTaP,
Hib/MMR vaccines 12,13.
Fever of > 38oC is seen in 25-35% of recipients
whereas fever of > 39oC is seen in < 5% of
patients. Rare adverse reactions like febrile
convulsion, breath holding spasms are same as
seen with any other vaccine and are more of a
coincidence. Severe adverse reactions are
unknown to occur with this vaccine 12,13.
Immunogenicity: Rise in GMT following
3 primary doses is statistically better than controls
for each serotype with 4.4 to 27.0 fold rise in
titers. 92-100% of vaccines develop GMT of
> 0.15mg/ml and 90-91% >1.0 mg/ml. Pre

booster titers are better than pre-primary titers
for all serotypes. Post-booster titers rise by 5-15
fold. GMT rises to 2.3-9.7 mg/ml and 96-100%
recipients have GMT of > 0.15 mg/ml and
84-100% > 1.0 mg/ml. Types 4 and 6B are the
most immunogenic serotypes 13.
Clinical Efficacy
Invasive disease: In a study done by Black et al
in California, USA, children were given 3 primary
doses at 2, 4, 6 months followed by a booster at
15 months of 7 valent conjugate pneumococcal
vaccine. The efficacy against invasive
pneumococcal disease was 97.4% which remained
as high as 97.4% at 1 year follow up12.
Pneumonia: The same study done by Black
et al also looked at efficacy against clinically
diagnosed pneumonia 12. The efficacy was 11.4%
against any pneumonia diagnosed clinically, 13.8%
against any pneumonia with X-ray taken, 33%
against any pneumonia with some abnormalities
on X-ray and 63% against pneumonia with
consolidation of > 2.5 cm on X-ray of chest (which
is likely to be caused by pneumococcus more than
other pathogens).
Acute Otitis Media: Besides the study done by
Black et al, one more study by Eskola et al looked
at efficacy against AOM. They studied culture
proven cases of AOM by doing myringotomy in
patients diagnosed to have AOM with middle ear
fluid as per WHO guidelines 14. Both the studies
found nearly similar efficacy of 57 66.7%
against vaccine serotype AOM. It was 7.8 -8.9%
against any AOM episode. It was more efficacious
against recurrent AOM especially the ones that
need tube placement in the middle ear.
Carrier state and herd immunity: Studies have
shown nearly 50% reduction in the carriage with
vaccine types which however is counterbalanced
by similar 50% increase in the non-vaccine types
carriage leading to no net change in the prevalence
of carriage rates 15.
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2006; 8(3) : 201
Schedule : Children presenting before 7 months
of age are given 3 primary doses at 2, 4 and
6 months or 2, 3, 4 months or at 6, 10, 14 weeks
depending on local schedule, and a booster at
12-15 months. Children coming for the first time
between 7-12 months are given 2 primary doses
at 4-8 weeks interval and a booster at 12-15
months. Children presenting between 12-24
months for the first time are given 2 doses at 4-8
weeks interval. It is given IM over deltoid or lateral
aspect of thigh. It is to be stored at 2-8o C and the
shelf life is 2 years.
Coverage in India and other problems: Main
problem is coverage of prevailing serotypes.
7 valent vaccine will have coverage of > 90%
serotypes in USA, 75% in Europe, 51% in India,
and 45% in Pakistan. Similar figures with 9 valent
vaccine will be 71% in India, 30% in Dhaka
(Bangladesh) and 61% in Pakistan and with
11 valent vaccine 75% in India, 51% in Dhaka,
and 61% in Pakistan. Hence we need 9 or
11 valent vaccine or even more valent vaccine
for good global coverage 10.
The other problems are high cost which needs to
come down. There may be need to increase the
dose of some antigens like 19F serotype. Long
term follow up will prove the efficacy over years
and need for further booster if any. For timely
completion it has to be given simultaneously along
with other childhood vaccines. Some studies of
combined CRM 197 vaccine along with HbOC/
DPT have proved to be safe and efficacious. We
need more studies on such combinations. We also
need clear cut studies showing its benefits in older
children, adults and immune compromised hosts
especially HIV infected patients. Study done in
Africa using 9 valent vaccine has shown good
efficacy in spite of high local prevalence of HIV
in children13 Lastly, we need to update information
on the prevailing serotypes. For this, we need
continued surveillance of pneumococcal disease
globally.
Indian Journal of Practical Pediatrics
Influenza vaccines
After the discovery of influenza A virus in
1933, efforts were on to develop a vaccine against
influenza as it was realized that the disease could
be devastating during pandemics and epidemics
amongst military forces. The first influenza vaccine
was invented in 1945 and since then the mankind
is in the search of the ideal flu vaccine. Currently
there is a lot of interest generated in the influenza
vaccine due to the fear that the next pandemic of
influenza is long overdue and it could be due to
spread of avian influenza [A (H5N1)].
Disease burden: 30-50% of influenza cases can
be asymptomatic. Classical influenza is a mild but
bothersome illness with 3-5 days of high fever,
respiratory tract symptoms, myalgia and
GI symptoms which are more commonly seen in
children. It also leads to morbidity, school
absenteeism and loss of work hours. At times the
disease can lead to complications like acute otitis
media (AOM), croup, sinusitis, pneumonia,
exacerbation of underlying chronic conditions like
respiratory or cardiac disease, Reyes syndrome
in patient on long term aspirin therapy, toxic shock
syndrome, myocarditis or pericarditis, myositis
and myoglobinuria, and rarely CNS morbidity like
encephalitis, GBS or chronic encephalopathy as
reported from Japan. These complications are
more common in certain high risk populations
leading to more severe illness, morbidity,
hospitalization and even deaths. These at risk
groups are the ones which are the target for
influenza vaccination at present 16.
In temperate climate influenza typically has onset
in winter, whereas in tropics it is seen throughout
the year with one or two peaks during winter and
summer. While pandemics do lead to sudden
increase in the number of cases and mortality,
cumulatively more cases and deaths occur in the
inter-pandemic interval. Type C influenza is very
mild and hence is not included in the vaccine.
Type B influenza is significant and hence is a part
of the vaccine. Fortunately type B virus does not
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2006; 8(3) : 202
mutate easily and hence does not need change
from year to year. Type A virus mutates easily
and constantly due to point mutations in the HA
and NA antigens called as antigenic drift. This
ensures that enough pool of susceptible population
is available for the epidemics to occur from time
to time. This also means the need to change the
vaccine and the need to vaccinate annually.
Exchange of genes between two different types
of type A viruses in a host like pig co-infected
with both the viruses leads to antigenic shift which
leads to pandemics. The worst pandemic was the
Spanish flu in 1918-1919 caused by type A
(H1N1) which killed more than 20 million people,
mainly young adults. This was then followed by
Asian pandemic due to type A (H2N2) in 1957,
Hong Kong flu pandemic due to type A (H3N2)
in 1968, and partial pandemic due to reintroduction
of type A (H1N1) in 1977 which still co-circulates
with type A (H3N2) even now. Another pandemic
was possibly averted by culling millions of
chickens infected with type A (H5N1) avian virus
which had threatened to transmit directly to
humans. The cases of avian flu keep on occurring
still since then and epidemic within the birds is
rapidly spreading in the world keeping the threat
of another pandemic alive 16.
During an epidemic 10-20% of the population
suffers from disease which can be as high as
40-50% in an institutional breakout. Usually the
cases start in the school going children which then
spreads to the older individuals. The attack rates
are 19-20% in general population, 30-40% in
school age children, 1-19% in elderly population
and 80-90% in institutionalized people.
Hospitalization, complications and mortality are
higher in children < 2 years old besides the elderly
> 65 years of age. This has led to recent
recommendation of routine annual vaccination of
healthy children aged 6 months 23 months by
the Advisory Committee on Immunization
Practices (ACIP) in US and other western
countries 16.

Influenza Vaccines
The first influenza vaccine was invented in 1945
for use during World War II. The initial vaccine
was whole virion vaccine which though effective
was highly reactogenic with lots of side effects
especially in children. Since 1970s only sub-virion
vaccines like the split or the sub-unit vaccines are
used especially in children. Sub-virion vaccines
are prepared by using a solvent which dissolves
or disrupts the lipid layer of the virion which leads
to availability of the HA and NA without the
envelope or the other proteins like NP and M
proteins which are known to lead to side effects.
Of late safer, more convenient and more efficacious
live intra-nasal cold-adapted vaccines have been
made available and licensed for use. The vaccines
are grown on chicken eggs. Now the
manufacturers also use MKCD or the Vero cell
lines. It is also possible to make the HA and the
NA antigens by DNA recombinant technique;
however this has not been tried commercially.
Though the virions have many antigens,
hemagglutinin (HA) is the most important antigen
as the anti-HA antibodies are protective in nature.
Anti-NA antibodies though can not prevent the
disease, can reduce the severity of the disease.
Other proteins like the nucleoprotein (NP) or the
matrix protein (M) can lead to side effects as also
the intact lipid envelope. Hence anti-HA antibodies
are measured as a immune correlate of efficacy.
Inactivated influenza vaccine
Contents : The current vaccine is a trivalent
vaccine. It contains inactivated type A (H3N2),
type A (H1N1) and type B viruses. In children
whole virion vaccines are not recommended.
Current vaccines are subunit or split vaccines
manufactured by disrupting the whole virion
envelope by chemical process. The vaccine
contains 7.5 mg of HA of each of the virus type/
dose in 0.25 ml of volume for children < 3 years
and 15 mg/dose in 0.5 ml volume for older children
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2006; 8(3) : 203
and adults. It also contains traces of thiomerosal
as preservative. Since 1990s type B virus is
showing two different HA antigens leading to the
question whether we need now a quadrivalent
vaccine 16.
Vaccine manufacture and time frame : The
manufacture of influenza vaccine is literally a race
against time. The seed virus representing the
current circulating virus for both the northern and
the southern regions is provided by WHO and
the manufacturing of the vaccine is completed in
the next 6 months so that it is available in time for
the next influenza season 16.
Dose and route: The vaccine is given by IM
route. SC and ID routes lead to less efficacy and
more side effects. The dose is 0.25 ml for a child
<3 years and 0.5 ml for >3 years of age. Children
< 8 years of age are given 2 doses for the first
time at 6-8 weeks interval and one dose in the
subsequent years, whereas > 8 years old are
always given only one dose.
Stability and storage: The vaccine should be
stored at 2-80C. The vaccine is stable at this
temperature for at least 2 years. However as the
vaccine is changed every year due to mutation of
the virus, the shelf life of the vaccine is only one
year.
Immunogenicity: Anti HA titers of > 1:32-40 are
protective. More than 90% of the young vaccinees
sero-convert. Vaccine also may produce secretory
IgA antibody acting locally. The Japan model has
shown that herd immunity may develop if
sufficient target population is vaccinated.
Efficacy and effectiveness: The efficacy of the
study depends on the match between the vaccine
types and the circulating types, outcome measure
used to calculate the efficacy and from year to
year. It is difficult to compare studies with one
another as the outcome measure used to calculate
efficacy differs from study to study. In one study
Indian Journal of Practical Pediatrics
the efficacy was found to be 86% against culture
proved cases, 34% against clinical definition using
influenza like illness and 10% against any upper
respiratory tract infections 17.
A meta-analysis done on effectiveness in > 65
years old showed the effectiveness to be 33%
against Influenza like illness, 33% against
hospitalization due to pneumonia or influenza and
50% against mortality due to any cause 18. In
studies done in < 65 years the effectiveness has
been shown to be 56-70 % against influenza like
illness in a military population, 70-79% in culture
proved influenza illness. The overall efficacy
appears to be as high as 70-90% in young
people 16,19.
In elders > 65 years with chronic medical illnesses
the effectiveness against hospitalization has been
shown to be 29% in those with chronic heart and
lung disease, 32% in those with metabolic diseases
like diabetes, rheumatologic disease, renal diseases
or strokes compared to 49% in those who were
healthy. Same study showed a decrease in
mortality of 49%, 64% and 55% in respective
groups 20.
Various studies have been done in children. In a
study done in US over 5 seasons, the effectiveness
against influenza like illness was found to be 77-
91% in 1-15 years old, 54% in 3-6 years old and
100% in 10-18 years old. Similar efficacy of
70-83% has been found in studies done in Italy,
UK and Japan 16. Efficacy seems to be lower in
children, 2 years old. The efficacy against
influenza acute otitis media has been found to be
30%. There are very few studies of efficacy in
children with chronic medical illnesses. In one
study the efficacy against influenza was found to
be 22-54% in 2-5 years old and 60-78% in 7-14
years old 16.
Duration of immunity: Natural infection leads
to long term immunity for decades. Vaccine leads
to sero-conversion in 90% of the vaccinees. The
immunity lasts for 1-3 years. The second dose
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2006; 8(3) : 204
does not lead to boosting effect. The antibody
levels drop by next 6 months in 50% of the
vaccinees. In any case due to high level of mutation
the vaccine has to be changed every year, and in
that sense the protection lasts for only 1 year
needing revaccination annually.
Safety: 65% of the vaccinees develop local side
effects like pain, induration and redness for
24-48 hours which usually is mild and responds
to paracetamol. Less than 15% develop systemic
side effects like fever, myalgia etc, usually in
young children with first dose. Rare side effects
include acute GBS (excess of 1/100,000 doses)
which was first noticed with the Swine vaccine
used in 1976. The current vaccines are safe and
do not lead to increase in cases of acute GBS 16.
Contraindications: The vaccine is
contraindicated in children < 6 months of age,
pregnant women in the first trimester, those with
severe reactions with previous doses and those
with severe egg allergy.
Cost: There are 3 brands available commercially.
Each dose costs Rs.700.
Indications: Influenza vaccine is used liberally
in the Western world. In fact is considered an
under-utilized vaccine in US. Initially the focus
was on vaccination of those who are at high risk
for complications following influenza and those
who are in contact with these at high risk people
as they can transmit influenza to them. As the
epidemiological studies in US have shown that
even healthy children < 2 years are at as much
risk of complications, hospitalizations and deaths
following influenza as the other at risk elders, in
2000 vaccination was encouraged for routine
use for all children < 2 years of age. In 2004 it is
now recommended for all children < 2 years of
age. The current recommendations of ACIP in
US are shown in Table 1 16. Many other western
countries also follow these guidelines and vaccinate
routinely all children < 2 years of age.

IAP Recommendations: IAP does not
recommend routine influenza vaccination of
children < 2 years old. It recommends to use
influenza vaccine for all the children with high
risk diseases as listed in Table 1 except asthma
unless oral steroid dependant. This is partly
because of lack of data of disease burden and its
severity in Indian children and partly because
influenza is in the lower priority in childhood
vaccination program where we are still struggling
to include more important vaccines like MMR,
Hib, HepatitisB and Typhoid vaccines in our
national schedule.
Live Cold Adapted Influenza Vaccine - Trivalent
(CAIV-T):
Live attenuated influenza vaccines are made
to make it more safe, efficacious, physiological
and convenient. The cold adapted live vaccine
CAIV-T is licensed since June 17, 2003 in US
and other western countries. It is still not marketed
in India. It is adapted by serial passages in such a
way that there is limitation to its replication only
in the colder upper airway and not in the lower
airway when given intra-nasally. This leads to local
immunity in airway without chances of systemic
infection or side effects. It contains
107 TCIDs/dose of each of the type A (H3N2),
type A (H1N1) and type B influenza viruses in
0.5 ml volume to be given intra-nasally by a
syringe like device in the dose of 0.25 ml in each
of nostrils21.
Efficacy and effectiveness: In a study done on
15-71 months old children over 2 years, the
efficacy against type A (H3N2) was found to be
95% in first year and 100% in the second year;
against type B it was 91% in first year and 100%
in the second year; against any type it was 93%
in first year and 100% in the second year. Type
A/Sydney variant not included in the vaccine was
seen in the second year and the efficacy against
that variant was 86%. Type A (H1N1) was not in
19
2006; 8(3) : 205
circulation during the study period and hence was
tested for challenge after vaccination, the efficacy
against such challenge was found to be 83%.
Efficacy against culture proved acute otitis media
was found to be 98% and that against culture
proved LRTI was 95%22.
Safety : 20 trials done on over 20,000 subjects
Table 1: ACIP recommendations for
influenza vaccination (modified)
A) At risk group:
a) > 65 years of age
b) Residents of nursing homes or chronic care
facilities
c) 6 months - 64 years of age with chronic
medical conditions like:
i) Chronic pulmonary condition including
asthma
ii) Chronic cardiac conditions
iii) Chronic metabolic conditions including
diabetes mellitus
iv) Chronic renal diseases
v) Hemoglobinopathies
vi) Immune compromised including HIV
infected
d) 6 months 18 years on long term aspirin
therapy
e) Pregnant women after the first trimester
f) Children of 6 months 23 months
B) Persons who can transmit influenza to as
risk group patients:
a) Health care workers
b) Employees of the nursing home and other
chronic health care facilities
c) Home care workers looking after the at
risk group at home
d) Contacts at home for all those at risk
including contacts of children 6 months
23 months
C) 50-64 years old
Indian Journal of Practical Pediatrics
using over 28,000 doses which included 15,000
children has shown that local side effects were
similar to the placebo and < 10% subjects
developed mild side effects like URI, low fever
or lethargy. Study in high risk group showed that
the side effects were not more in asthmatics, HIV
patients or elderly patients with high risk diseases.
In asthmatics there was no change in any of the
scores of asthma after the use of the live vaccine21.
Indications: At present this vaccine is indicated
only in healthy people between 5-49 years of age.
It is not indicated for < 5 years, > 50 years and
those with high risk diseases. Hence the inactivated
influenza vaccine is indicated for the prevention
of influenza and related complications in those at
high risk, whereas the live vaccine is primarily
indicated for prevention of influenza in healthy
young adults.
Contraindications: The live vaccine is
contraindicated in the following:
a) < 5 years old
b) > 50 years old
c) 5-50 years old with high risk diseases
d) Any one with reactive airway disease
e) Any one on long term aspirin therapy
f) Pregnant women
g) Patient with acute GBS
h) Immune compromised individuals
Points to remember
Conjugated Hib vaccine has good
immunogenicity and efficacy.
Conjugated pneumococcal vaccine given in
a schedule of 3 primary doses and 1 booster
dose is found to have high efficacy.
High risk populations should be targetted
with influenza vaccine.
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NEWS AND NOTES
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circumstances of incomplete antigenic and
genetic match. Vaccine 2001; 19:3252-3260.
20) Nochol KL, Wouremna J, Stenberg T. Benifits
of influenza vaccination for low-,
intermediate- and high-risk senior citizens.
Arch Intern Med 1998; 158: 1776-1998.
21) Robert BB, Husein FM, Paul MM. Influenza
vaccine - Live. In Plotkin SA, Orenstein WA
(eds): Vaccines. USA, Elsevier Inc, 2004; pp
371-388.
22) Belshe RB, Gruber WC, Mendelman PM, et
al. Efficacy of vaccination with live attenuated,
cold adapted, trivalent, intranasal influenza
virus vaccine against a variant (A/Sydney) not
contained in the vaccine. J Pediatr 2000;
136:168-175.

8th NATIONAL CONGRESS ON PEDIATRIC CRITICAL CARE (NCPCC)

Dates : 10th, 11th and 12th November 2006
CONFRENCE FEES Till June Till August Till October
15th 2006 15th 2006 15th 2006 Spot
IAP Intensive Care Member Rs.2000 Rs.2500 Rs.3000 Rs.4000
IAP Member Rs.2250 Rs.2750 Rs.3250 Rs.4000
Non IAPMember /
Foreign delegate Rs.2500 Rs.3000 Rs.3500 Rs.4000
PG Student Rs.1400 Rs.1700 Rs.2000 Rs.4000

Payment is by Demand Draft only, payable to NCPCC Bangalore. Cheques not accepted.
Contact for further details: Dr.Girish HC, Organizing Secretary, NCPCC Bangalore KR Hospital, 979,
25th Main Road, BSK 1st Stage, 50 Feet Road, Bangalore 560050. Mobile: 98452-72933
21
Indian Journal of Practical Pediatrics
VACCINES
ADVERSE EVENTS FOLLOWING
IMMUNIZATION
* Indra Shekhar Rao M
Abstract : Several scientific, ethical and statutory
obligations are fulfilled before introducing a
vaccine in the field. However no vaccine is
perfectly safe and adverse events can occur
following immunization. The adverse events may
be minor or major, true or coincidental. The various
adverse events that can occur following the routine
immunization are dicussed in this article.
Guidelines for vaccinations, reporting of adverse
events following immunization (AEFI), parent
education and efficient resuscitation equipments
are vital components essential to make
immunization a most effective public health tool
in child survival programme.
Keywords : AEFI, Safe Vaccination.
The success story of child health in the last
century attributes to immunization as the main
component which has enhanced and improved the
child survival all over the world. Vaccines used in
National Immunization Programmes are extremely
safe and effective. Several scientific, ethical, and
statutory obligations are fulfilled by the
manufacturers; elaborate field trials regarding safety
and protection offered by individual vaccines are
established before it is recommended for routine
use. However no vaccine is perfectly safe and
adverse events can occur following immunization.
In addition to the vaccines themselves, being
* Professor & Head, Dept. of Pediatrics,
Institute of Child Health, Niloufer Hospital,
Hyderabad, A.P.
22
2006; 8(3) : 208
products of biological nature, the process of
immunization is also a potential source for
adverse events1-3.
An adverse event following immunization
(AEFI) is any adverse event that is believed to
be caused by immunization. Reported adverse
event can be a true adverse event or a
coincidental event. For the purpose of these
guidelines AEFIs are classified into five
categories as shown in Table 1.
Immunization can cause adverse events
from the inherent properties of vaccine (Vaccine
reaction) or some error in Immunization process
(Programme error) The event may be unrelated
to the immunization but have temporal
association (Coincidental event). Anxiety
related reactions can raise fear or pain of the
injection rather than the vaccine. In some cases
the cause of AEFI remains unknown.
The adverse event following the
immunization may be minor and is the one
which is expected but not severe enough to
cause discomfort during short duration of time,
e.g. pain or fever after DPT vaccination;
whereas a severe or rare event following the
vaccine may be in the form of unexpected
anaphylactic shock or introduction of active
disease e.g. anaphylaxis following measles
vaccine. Another type of hypothetical and
vaccine related scare has casual rather than
causal relationship with the adverse effect and
usually are concerning the issues which are of
controversial nature occurring in vaccinated
children though not directly related to the vaccine
as shown in Table 2.
 2006; 8(3) : 209

Table 1. Classification of adverse events following immunization (AEFIs)

Vaccine reaction Event caused or precipitated by the vaccine when given correctly,
caused by the inherent properties of the vaccine.
Programme error Event caused by an error in vaccine preparation, handling, or
administration.
Coincidental Event that happens after immunization but not caused by the vaccine
a chance association.
Injection reaction Event from anxiety about, or pain from, the injection itself rather than
the vaccine
Unknown Events cause cannot be determined.

Table 2. Adverse events following immunization

Anticipated reaction (Minor reaction) Pain, fever following DPT vaccination
Severe reaction (rare event) Disseminated BCG infection, anaphylaxis
Vaccine controversies and casual relationship MMR vaccination and autistic syndrome.

Table 3. Common, minor vaccine reactions and treatment

Vaccine Local reaction Fever>380C Irritability, malaise
(pain, swelling, and systemic
redness) symptoms

BCG 90-95% - -
Hib 5-15% 2-10% -
Hepatitis B Adults 15% 1-6% -
Children 5%
Measles / MMR / MR 10% 5-15% 5% (Rash)
Oral Poliomyelitis (OPV) - <1% <1%
Tetanus / DT / Td 10% 10% 25%
Pertussis (DTP-Whole cell) Upto 50% Upto 50% Upto 55%
Treatment Cold compress at Give extra fluids Give extra fluids
injection site Tepid sponge or Paracetamol
Paracetamol bath
Paracetamol

23
Indian Journal of Practical Pediatrics 2006; 8(3) : 210

The common vaccine reactions are due to
the immune response of the host and sometimes
due to vaccine components (e.g. Aluminium
adjuvant and preservatives). An ideal vaccine
reduces these reactions to a minimum while
inducing the best possible immunity. These
anticipated reactions occur within a day or two of
immunization and they are listed in Table 3.
The rare vaccine reactions usually do not lead
to long-term problems. Anaphylaxis while
potentially fatal is treatable without leaving any
long-term effects. These are listed in Table 4.
The vaccine scare related adverse events
have a very casual link and are most often
hypothetical. These are listed in Table 5.
Another notable component of adverse
events following immunization is due to
programme errors that result from errors and
accidents in vaccine preparation, handling or
administration. The identification and correction
of these errors are of great importance which
would otherwise lead to a cluster of other events
associated with immunization. The most common
programme error is an infection as a result of non

Table 4. Rare vaccine reactions, onset interval and rates

Vaccine Reaction Onset Number of
interval reactions per doses
BCG Suppurative lymphadenitis 2-6 months 1 in 1000-10000
BCG osteitis 1-12 months 1 in 3000 to 1 in
100 million
Disseminated BCG infection 1-12 months 1 in 1 million
Hib None known
Hepatitis B Anaphylaxis 0-1 hour 1 in 6-900000
Measles / MMR / Febrile seizures 6-12 days 1 in 3000
MR Thrombocytopenia 15-35 days 1 in 30000
Anaphylaxis 0-1 hour 1 in 1000000
Encephalopathy 6-12 days <1 in 100000
OPV Vaccine associated paralytic 4-30 days 1 in 2.4-3 million
poliomyelitis
Tetanus Brachial neuritis 2-28 days 0.5-1 in 100000
Anaphylaxis 0-1 hour 1 in 100000 to
1 in 2500000
Tetanus- None extra to tetanus
Diphtheria reactions
Pertussis (DTP- Persistent (>3 hours 0-24 hours 1 in 15 to 1 in 1000
Whole cell) inconsolable screaming)
Seizures 0-2 days 1 in 1750 to
1 in 12500
Hypotonic, hyporesponsive 0-24 hours 1 in 1000-33000
episode (HHE)
Anaphylaxis 0-1 hour 1 in 50000
Encephalopathy 0-2 days 0-1 in 1 million
(note: risk may be zero)

24
 2006; 8(3) : 211

sterile injection e.g. abscess which may have a Each vaccine administered in the
systemic effect or blood borne infection e.g.HIV, immunization programme has specific
Hepatitis B etc. These are listed in Table 6. complications most of which are anticipated and

Table 5. Vaccination scares

Hepatitis B Multiple sclerosis, lupus, diabetes
Whole-cell pertussis Encephalopathy, epilepsy, learning disorders
Diphtheria, tetanus and pertussis
Cot death/Sudden Infant Death Syndrome (SIDS)
Inactivated polio vaccine HIV infection
Influenza Diabetes mellitus
Hemophilus influenza type b Diabetes mellitus
Measles, Mumps and Rubella Autistic spectrum disorder, inflammatory bowel disease,
Childhood arthropathy
Rubella Ethical concerns because grown in cells from an aborted fetus
Thiomerosal containing vaccines Neuro-developmental disorders, autism
Aluminium containing vaccines Muscular fibrosclerosis
Various vaccines Diseases of unknown, or only partially understood etiology, e.g.
asthma, autism, inflammatory bowel disease, cot death, chronic
fatigue syndrome, immune deficiency, leukemia, autoimmune
diseases, learning disorders, increase in violent crime.
Table 6. Programme errors leading to adverse events
Non-sterile injection Infection
Reuse of disposable syringe or needle Local suppuration at injection site,
Improperly sterilized syringe or needle abscess, cellulitis, systemic infection, sepsis,
Contaminated vaccine or diluent toxic shock syndrome, transmission of blood
Reuse of reconstituted vaccine at subsequent borne virus (HIV, hepatitis B or hepatitis C).
session
Vaccine prepared incorrectly
Vaccine reconstituted with incorrect diluent Local reaction or abscess from inadequate
shaking
Drugs substituted for vaccine or diluent. Effect of drug (e.g. muscle relaxant, insulin)
Immunization injected in wrong site
Subcutaneous instead of intradermal for BCG Local reaction or injection site abscess.
Too superficial for toxoid vaccine
(DPT, DT, TT)
Gluteal region (
Sciatic nerve damage vaccine efficacy.
)
e.g. hepatitis B
Vaccine transported/stored incorrectly. Increased local reaction from frozen vaccine
(and ineffective vaccine).
Contraindications ignored Avoidable severe vaccine reaction.

25
Indian Journal of Practical Pediatrics
mild. However some of them are serious adverse
reactions which have to be anticipated and
immediate remedial measures must be given.
Vaccine complications and their management:
BCG
Anticipated Reactions: Nodule formation at
the site of vaccination (3-6 weeks) which liquefies,
ulcerates and heals by tiny scar (10-12 weeks)
Adverse Reactions
Local:
a) Persistent discharging sinus at the site of
vaccination
b) Regional axillary adenitis (below 2 cm, no
treatment). Fluctuant, more than 2 cms- INH
(3-6 months) / Excision.
c) BCG Complex: Local lymphadenitis +
Positive Mantoux reaction + Paratracheal
Lymphnode. Treat with RHZ (2 months) +
RH (7 months)
Systemic: Disseminated infection, T.B.
Osteomyelitis, Scrofuloderma. Treat like
tuberculosis.
Table 7. Differential diagnosis of anaphylactic shock
Anaphylaxis These reactions must be distinguished from syncope, breath holding spells,
anxiety which are common benign reactions which only require
symptomatic treatment.
Syncope (Fainting) Breath holding spells Anxiety
Sudden onset of pallor, Occurs after 6 months
loss of consciousness, of age
collapses to ground. Follows a painful
stimuli
Continuous cry, holds
his breath, cyanosis,
convulsion.
2006; 8(3) : 212
DPT
Anticipated Reactions: Pain, discomfort,
fever, induration (treatment-analgesics +
antipyretics paracetamol 15 mg/kg/dose).
Adverse Reactions: Incessant cry (more than
3 hours), febrile convulsions, hyperpyrexia,
hyporesponsive hypotensive shock like state
acute encephalopathy, anaphylactic shock. (The
differential diagnosis of anaphylactic shock
following DPT or any other vaccine is discussed
in Table 7.
Treatment of anaphylactic shock : Place the
patient in recumbent position and elevate the feet.
a) Clear the airway, establish breathing
(O2 supplementation and bag valve mask
application) and maintain circulation.
b) Injection Adrenaline (1:1000) 0.01 ml/kg.
S.C./I.M. (severe cases). Repeat dose at 20
min. intervals.
c) Volume expanders (20 ml / kg normal saline
or R.L. 20 ml/kg over 20 minutes) followed
by plasma or fresh blood 20 ml / kg.
Anaphylaxis
Sweating Itchy urticarial rash, facial flushing
Panic Progressive edema involving face,
mouth and body parts
Excessive Respiratory symptoms: Sneezing,
crying coughing / wheezing, airway
obstruction.
Hypotension: Shock
26

d) Dopamine (5-10 micro grams/kg/minute) and
Dobutamine (5-40 micro grams/kg/min).
e) Monitor vital signs.
f) Other measures: To reduce the absorption of
vaccine from injection site:
a. Placing a tourniquet above vaccination site.
b. Local adrenaline to reduce vaccine
absorption (only in vaccines given through
S.C. route).
OPV
AEFI almost none
Very rarely vaccine associated paralytic
poliomyelitis (VAPP)
In contacts: 1 in 3 million vaccine doses
In recipients: 1 in 2 million vaccine doses.
IPV
Local reactions: Erythema, induration,
Patients sensitive to streptomycin/neomycin might
develop hypersensitive reactions as IPV contains
streptomycin and neomycin.
Measles
Anticipated Reactions: Mild fever, rash,
coryza (upto 4-7 days following vaccination)
Treatment: Paracetamol
Adverse Reactions:
a) Toxic shock syndrome (TSS) due to
contamination of measles vaccine by Staph.
aureus.
b) Exaggeration of T.B.
c) Encephalitis
Toxic shock syndrome: It occurs due to
contamination of measles vaccines with Staph.
aureus due to usage of unsterile syringes, needles/
and using a reconstituted vaccine vial for more
than one session.
27
2006; 8(3) : 213
Clinical features: (can occur after 30 minutes to
few hours after vaccination) Fever, vomiting,
diarrhea, shock.
Treatment: Should be treated as medical
emergency.
a) ORS, paracetamol (home treatment)
b) I.V. fluids (RL or Normal Saline), Antibiotics
(Cloxacillin 100 200 mg/kg/day in divided
doses), steroids, antipyretics, supportive
therapy
MMR
Anticipated Reactions: Mild fever, rash, febrile
seizures
Mumps
Adverse reactions: Fever (Rarely, encephalopathy,
seizures, G.B.S, parotid swelling, hemolytic uremc
syndrome, aseptic meningitis).
Rubella
Adverse reactions: Arthralgia, lymphadenopathy,
fever, sore throat; rarely thrombocytopenia and
peripheral neuropathy
Hepatitis B vaccine
Local reactions: Soreness at the site of injection
Systemic reactions: Mild fever, myalgia, arthralgia,
rarely anaphylaxis
Hepatitis A vaccine
Local reactions: Soreness, induration
Systemic reactions: Headache, nausea, loss of
appetite
Typhoid vaccine
1) A.K.D. vaccine (Acetone Killed)
Local reactions: Pain, swelling, tenderness
Systemic reactions: Headache, nausea, fever and
relapse of chronic diseases like rheumatoid arthritis
and compensated cardiac conditions
Indian Journal of Practical Pediatrics
2) Vi capsular polysaccharide vaccine
Local reactions: Mild pain, swelling for 1 day
3) Ty 21 A (Oral)
Local reactions: Diarrhea, vomiting
Systemic reactions: Transitory exanthema
Tetanus Toxoid (T.T.):
Repeated TT injections after trivial injuries
can lead to reduced immunogenecity,
hypersensitivity, hemolytic anemia, amyloidosis.
Also increase risk to hemorrhagic disease of
newborn.
Hib vaccine
Local reactions: Mild redness, pain and swelling
Varicella vaccine
Local reactions: Papulo vesicular eruption in less
than 4% of vaccinees.
Systemic reactions: Mild fever, headache,
pneumonitis, arthropathy.
Rabies Vaccine
1) Nervous tissue vaccine
Local reactions: Pain, redness, itching, abscess
formation
Systemic reactions: Fever, headache, giddiness,
palpitation, shock, generalised urticaria.
Neuro-paralytic complications (1:5,500): Cranial
nerve paralysis, paralysis of limbs, ascending
paralysis, encephalopathy
Treatment of complications: Discontinue the
vaccine, bed rest, steroids, further vaccination if
required by tissue culture vaccine.
2) Tissue culture vaccine
Local reactions: Soreness
Systemic reactions: Headache, fever, anaphylaxis,
rarely transient neuroparalytic illness (Guillain
Barre type)
28
2006; 8(3) : 214
Meningococcal vaccine
Local reactions: Inflammation
Systemic reactions: Anaphylaxis rarely
Pneumococcal vaccine
Local reactions: Swelling, redness, pain
Systemic reactions: GBS, anaphylaxis, relapse of
ITP
Japanese Encephalitis vaccine
Local reactions: Redness, swelling, pain
Systemic reactions: Fever, headache
Influenza vaccine
Local reactions: Pain, swelling
Systemic reactions: Rarely GBS (1 in 100,000)
Vaccines and controversies
Thiomerosal and Vaccines: Thiomerosal, a
mercury based preservative used in some vaccines,
is an organic compound containing 49.6% of
ethylmercury by weight. It has been used in very
small amounts in some vaccines to prevent
bacterial and fungal contamination. This organic
compound of mercury is in two forms,
ethylmercury (Thiomerosal) which doesnt
accumulate in the body because its half life is 7-
10 days and is rapidly converted in the body to
inorganic mercury which is excreted in the stool;
and methylmercury which is more potent as it
accumulates in the body because the time taken
for the body to eliminate it is about 50 days.
The safe level of mercury consumption lies
somewhere between 0.7 gs/kg/week (Environ-
mental protection agency, USA) to 3.3 gs/kg/
week (WHO). The total intake of 175 micrograms
of ethylmercury occurs in a child who is given all
routine vaccines, is equivalent to 1.9 gs/kg/week.
This level is well below the WHO limit for
methylmercury which is converted to
ethylmercury and rapidly excreted4.
 2006; 8(3) : 215

The Global Advisory Committee on Vaccine a single study that has shown a risk of MMR
safety ( GAVSC ) of WHO has concluded that vaccine causing autism but there have been many
There is currently no evidence of mercury toxicity studies that cant find a risk. No correlation exists
in infants, children or adults exposed to Thimerosal between the prevalence of MMR vaccination and
containing vaccines, and there is no reason to the rapid increase in the risk of autism over the
change current immunization practices with time7. The surveys revealed that the apparent rise
Thimerosal containing vaccines on grounds of in cases of autism substantially reflects the
safety5. adoption of a much broader concept of autism
and improved identification of children with
Various studies in Denmark, Sweden, United
autism8.
States and UK and the evidence there upon
indicated that autism and neurodevelopmental In conclusion, there is no epidemiological
disorders are not associated with Thimerosal in evidence for a casual association of Measles,
the vaccines. Mumps and Rubella vaccines with autism. MMR
vaccination is not associated with an increased
MMR and autism risk of pervasive developmental disorders in
Autism is a developmental disorder, a children 9.
situation where childs growth and development, Vaccines and contraindications
physically and emotionally doesnt progress as it
is expected, which usually appears in second year Vaccines might cause adverse reactions. It
of life and MMR is given around that age of is often difficult to prove definite cause effect
1-2yr6. relationship between the act of vaccination and
subsequent complication. However, following
Autism is well known condition long before guidelines will help in deciding vaccine
the MMR vaccine was used. There has not been administration as shown in Table 8.
Table 8. Vaccines and contra-indications
1. Avoid: Live vaccine a) Immunodeficient individuals
b) Immuno suppressant therapy
c) Chronic debilitating illness
Avoid: DPT (1st dose) a) Progressive neurologic disease
b) Uncontrolled seizure disorder
Avoid: Rubella vaccine during pregnancy
Avoid: Antibiotics effective against S. typhi: 1 week prior / after Ty 21a vaccination
If person is sensitive to vaccines containing egg protein (eg. Measles vaccine) should not be given
2. Delay: Live vaccine a) Measles / MMR for 6 weeks following
immunoglobulin therapy
b) Severe febrile illness.
3. Discontinue: DPT in case of severe post-vaccinial reactions
4. Do not stop vaccination in: a) Malnutrition
b) Moderate fever
c) Respiratory infections
d) Mild diarrhea
e) Any benign ailment

29
Indian Journal of Practical Pediatrics
Guidelines for safe vaccination
1) Select proper vaccine. Follow manufacturers
instructions (dose / route / administration)
2) Maintenance of cold chain.
3) Informing the mother regarding vaccine
benefits and their anticipated reactions.
4) Obtain consent before vaccination.
5) Keep the child under observation for 30 min.
after vaccination. Be equipped and gear up
to treat any untoward reactions. Have always
resuscitation kit ready.
6) Use desired injection procedure i.e. load the
vaccine into appropriate syringe size, discard
the needle used for drawing and use a fresh
needle for injection (1 syringe and 2 needles
for each vaccination)
7) Dont mix vaccines in single syringe unless
permitted by the manufacturer and the drug
authorities Use different syringes for different
vaccines. Use different sites for injection.
8) Once a live vaccine has been administered
wait for 4-6 weeks period for another vaccine
administration.
9) Use zig-zag method of administration or Z
technique to prevent track formation.
10) Always use anterolateral aspect of thigh in
young children and deltoid area for older
children for injections. Avoid gluteal region.
11) Avoid fomentation/ vigorous rubbing after
vaccination.
12) Document every vaccination procedure in the
immunization card and keep a copy of it.
13) Complete the vaccination schedule as per
immunization calendar. Remind the mother
regarding next date.
30
2006; 8(3) : 216
14) There is no need to restart immunization
within a year of administering the first dose
of multidose vaccine e.g. HIB, DPT etc., if
the child is not brought for immunization on
suggested date.Continue and complete the
schedule.
The best way to minimize the adverse events
following the immunization is to anticipate the
expected type of reaction for a specific vaccine
and to identify the events that are probably
unrelated to the vaccination.
Prevention and Treatment of Vaccine
Reaction
It is mandatory for the person administering
the vaccine to have sufficient knowledge regarding
vaccines and expected side effects and to inform
parents thoroughly regarding such adverse effects
which may however occur very rarely. It is also
essential to be prepared and to always have a kit
with life saving drugs and equipments at each place
of vaccination.
Advice on managing the common reactions
should be given to parents as well as the
instructions to return if there are more serious
symptoms. This will help to reassure parents
about immunization and prepare them for common
reactions. Programme errors are preventable and
detract from the overall benefit of the
Immunization Programme. Identification and
correction of these errors are of great importance.
WHO guidelines to avoid programme errors are
as follows:
Vaccines must only be reconstituted with the
diluent supplied by the manufacturer.
Reconstituted vaccines must be discarded at
the end of each immunization session and
never retained.
No other drugs or substances should be stored
in the refrigerator of the immunization centre.
 2006; 8(3) : 217

Immunization workers must be adequately
trained and closely supervised to ensure that
proper procedures are being followed.
Careful epidemiological investigation of an
AEFI is needed to pinpoint the cause and to
correct immunization practices.
Reporting AEFIs
The reportable AEFI must include any death
or serious event believed by the public or health
worker to be caused by Immunization. Table 9
gives the list of reportable AEFIs. The minor
common reactions such as local reactions, fever,
and self limiting systemic symptoms need not be
reported. It is important for the persons
administering the vaccine to advise the parent /
patient at the time of immunization that these
reactions are expected and advise them how to
manage these common reactions (e.g. paracetamol
to treat fever). For more serious problems patient
should be advised to return or to seek medical
attention and to allow detection of AEFI. More
importantly they should be advised not to delay
treatment of a coincidental illness falsely attributed
as vaccine reaction. Severe local reactions
especially if occurring in clusters should be
reported as they can be markers for programme
errors or for problems with specific vaccine lots.
When to report? Who should report?
Reporting should be done as quickly as
possible so that an immediate decision on the need

Table 9. List of Reportable AEFIs

Occurring within 24 hours of
immunization
Occurring within 5 days of
immunization
Occurring within 15 days of
immunization
Occurring within 3 months of
immunization
Occurring between 1 and 12 months Lymphadenitis
after BCG immunization
No time limit
Anaphylactoid reaction (acute hypersensitivity reaction)
Anaphylaxis
Persistent (more than 3 hours) inconsolable screaming
Hypotonic hyporesponsive episode (HHE)
Toxic shock syndrome (TSS)
Severe local reaction
Sepsis
Injection site abscess (bacterial/sterile)
Seizures, including febrile seizures (6-12 days for measles/
MMR; 0-2 days for DTP)
Encephalopathy (6-12 days for measles / MMR; 0-2 days
for DTP)
Acute flaccid paralysis (4-30 days for OPV recipient; 4-75
days for contact)
Brachial neuritis (2-28 days after tetanus containing
vaccine)
Thrombocytopenia (15-35 days after measles / MMR)
Disseminated BCG infection
Osteitis/Osteomyelitis
Any death, hospitalization, or other severe and unusual
events that are thought by health workers or the public to be
related to immunization

31
Indian Journal of Practical Pediatrics
for action and investigation can be made. Private
physicians and hospitals should also report events
that come to the notice. In the community,
peripheral health worker or supervisor should
report to the district office.
The report should contain at a minimum:
Description of the event
Timing of the event in relation to
immunization.
Vaccines given
Patients identifying details.
The routine vaccination programme should
continue while awaiting the completion of the
reporting and investigation.
Responding to AEFIs
Private physicians and the health workers
need to know how to recognize, treat and report
AEFI-immediately as per the guidelines discussed
earlier. It is always wiser to keep the community
informed, investigate fully and avoid making the
premature statement about the cause of the event.
Always safeguard the public during investigation
with continuing immunization.
Communicating with the media
The media plays an important role in public
perception. The media are more interested in
stories that will attract attention, hence there is
tendency to dramatize and personalize the event.
It is easy for the media to create sense of panic
and outrage about the events which are unrelated
to immunization (co-incidental). The guiding
principle dealing with media must be one of
honesty and building of trust and one should show
empathy and caring, honesty and openness,
dedication and commitment, whenever possible
positive terms like immunization safety or vaccine
safety should be used. Key messages have to be
32
2006; 8(3) : 218
prepared before media contact and they should
include some of these facts.
That benefit of immunization in preventing
disease is well proven
It is very risky not to immunize (risk of
disease and complications)
Vaccine-preventable diseases caused millions
of death and/or disability before the
introduction of vaccines, and that situation
would return without continued use of
vaccines.
Vaccines do cause reactions, but these are
rarely serious and hardly ever cause long-
term problems.
Immunization safety is of paramount
importance, and any suspicion of a problem
is investigated (Advantage of well established
immunization safety surveillance)
The AEFI is currently being investigated, but
is likely to be coincidental/due to a local
problem (depending on type of event), and
the immunization programme must continue
to keep the population safe from disease.
The Immunization Safety and Safe Injection
Practices
The issues concerning the practices and
policies dealing with various aspects of correct
administration of vaccines focus on minimizing
the risk of transmission of disease and maximizing
the effectiveness of the vaccine. The term
encompasses the spectrum of events from proper
manufacture to correct administration which
includes both injection safety and vaccine safety.
The Immunization safety project includes the
WHO, UNICEF, UNAIDS, World bank, PATH,
Bill and Melinda Gates Children Vaccine
Programme, USAID and CDC who are the main
partners and financial supporters.

The project has main areas of focus.
1) Vaccine safety
2) Research and development of safe thermo
stable vaccines.
3) Access to safe vaccine delivery and safe
disposal.
4) Identification and management of risks related
to immunization, development of resource
material, training of all EPI managers in the
surveillance and management of adverse
events following immunization.
5) Strengthening of monitoring system for
vaccine adverse event reporting system
(VAERS).
Conclusion
The Immunization focus as established by
the WHO has objective to eliminate sickness and
death caused by vaccine preventable diseases
through the development of strong, sustainable
National Immunization Programmes, capable of
delivering high quality vaccines in a safe and
effective way to all children.
Points to remember
No vaccine is perfectly safe and adverse
events can occur following any vaccination
Effective resuscitation facilities should be
available to tackle and adverse event if
occurs.
Safe and efficient immunization practices
with thorough knowledge of the vaccines,
well maintained cold chain, proper parent
education and efficient resuscitation
equipment are vital components essential
to make immunization most cost effective
public health tool in child survival
programmes.
NEWS AND NOTES
NATIONAL CONFERENCE OF PEDIATRIC RHEUMATOLOGY, SURAT, SEPTEMBER 30, 2006
Enquiries to: Dr.Ketan Shah, Email: ketanhet@mail.com
33
2006; 8(3) : 219
References
1. Rao I. Vaccination complications, their
management and contraindications. Pediatr
clini India 2001; 36:30-35.
2. Immunization safety surviveillence.
Guidelines for managers of immunization
programmes on reporting and investigating
adverse events following immunization.
Manalia: WHO: 1999.
3. Adverse events following immunization. In:
Parthasarathy A, Lokeshwar MR, Shah NK
st
(Eds). Immunization digest.1 edn. New Delhi.
Jaypee Brothers Medical Publishers (P)
Ltd.2004;pp59-62.
4. Ball LK, Ball R, Pratt RD. An assessement
thimerosal use in childhood vaccines:
Pediatrics. 2001;107:1147-1154.
5. Clements CJ, Ball LK, Ball R, Pratt RD.
Thimerosal in vaccines: Is removal warranted?
Drugs safety. 2001;24:567-574.
6. Madsen KM, Lauristen MB, Pedersen CB, et
al. Thimerosal and the occurrence of autism:
negative ecological evidence from Danish
population- based data. Pediatrics
2003;112:604-606.
7. Taylor B, Miller E, Lingam R, Andrews N,
Simmons A, Stowe J. Measles, Mumps and
Rubella vaccination and Bowel Problems or
Developmental Regression in children with
Autism: Population Study. Brit Med J 2002;
324:393-396.
8. Kaye J et al. Mumps measles and rubella
vaccine and the incidence of autism recorded
by general practitioners: a time trend analysis.
Bri Medi J 2001;322:460-463.
9. Taylor V, Miller E, Farrington CP, Prtropoulos
MC, Farot-Mayaud I, LI J, Waight PA. Autism
and meales, mumps and rubella vaccine : No
epidemiological evidence for a causal
association. Lancet 1999;353:2026-2029.
Indian Journal of Practical Pediatrics
VACCINES
POLIO ERADICATION / HOW NEAR
AND HOW FAR?
* Vipin M. Vashishtha
** Naveen Thacker
Abstract : In the on-going struggle on polio
eradication the main aim is to interrupt wild
polio virus (WPV) transmission globally. Failure
to achieve this will pose a threat to all the nations
as evident by the recent reporting of large number
of cases in non-endemic countries. Evaluation
initiative has made good impact in the two most
stubborn states of Bihar and Uttar Pradesh in
India with substantial reduction in the number
and geographical areas with WPV. The threats
to ongoing eradication initiative may be in the
form of importation of WPV and vaccine
associated paralytic poliomyelitis. Reasons
behind delay in achieving polio erradication like
vaccine failure, programmatic set backs,
peculiarity of type 1 virus in endemic regions,
neglect of routine imminization and accessibility
problems are discussed and possible solutions
for present and future are offered.
Key words : Polio eradication, Situation
analysis, India, Worldwide
In 1988, when poliovirus was endemic in
more than 125 countries, World Health Assembly
resolution 41.28 established the goal of global
eradication of poliomyelitis by 2000. In 1999, the
Health Assembly, in resolution WHA 52.22, urged
* Consultant Pediatrician,
Mangal Children Hospital, Bijnor, UP
** Consultant Pediatrician,
Convener, IAP Committee on Polio Eradication
IAP President-Elect, 2006
Gandhidham
34
2006; 8(3) : 220
all member states to accelerate eradication
activities. At that time, three of the six WHO
regions - the Americas, Europe and Western
Pacific- had successfully interrupted transmission
of poliovirus. By 2003, the number of polio
endemic countries decreased to six (Afghanistan,
Egypt, India, Niger, Nigeria and Pakistan) from a
high of 125 in 19881. At the beginning of 2006,
this number has further reduced to an all time
low of four as so far Egypt and Niger have not
had indigenous poliovirus for more than 12
months2. However, during 2002-2005, a total of
21 previously polio free countries were affected
by importation of wild poliovirus (WPV) type 1
from the six remaining endemic countries
(primarily Nigeria). Four countries (Indonesia,
Somalia, Sudan and Yemen) had out breaks of
more than 100 polio cases3. For the first time in
the history of Global Polio Eradication Initiative
(GPEI), the number of cases in the non-endemic
countries was higher than in the endemic countries
(1048 vs 848 as of February, 2006). This reflects
progress in endemic countries and the great
vulnerability of polio free countries, where low
coverage of routine immunization (RI) failed to
protect their polio-free status4.
Hence, the current overall scenario provides
mixed signals- there are ample indicators of
achieving ultimate objectives and goal in
immediate future where as continued setbacks
tend to dampen the euphoria and remind us to
tread the path with utmost caution.
The Goal and Objectives of Eradication
The original targets of GPEI when the
initiative was undertaken in 1988 were:
 2006; 8(3) : 221

No cases of clinical poliomyelitis associated

Containment of all polioviruses

with wild poliovirus, and

Stop AFP surveillance after 3yrs

Stockpile & Response
No WPV circulation world wide (including

Coordinated cessation of OPV after 3 yrs of

Interruption of wild Poliovirus transmission

in sewage or drinking water) in presence of
the ability to detect one should it be

Surveillance & Response

? IPV use in RI/ No IPV/
circulating.
Since then various elaborate modifications
were made to final goal and the most recent
published goal is to ensure

of last VDPV
that poliovirus transmission is interrupted
globally through coordinated national and
international action;
that the full humanitarian and economic
benefits of eradication are realized;

last wPV
that the lessons and infrastructure from its
implementation are utilized in the
strengthening of health systems and control
of other important diseases5.
There is definite, perceptible shift from the
original goal. The enforcing agencies and polio-
partners are no longer talking of complete absence
of WPV from the world including the environment, Fig 1. Proposed cascade of events to be observed
which was far more ambitious and unrealistic goal before achieving true eradication of polio
as the world has come to realize now.
This new strategic plan has identified four The state of polio eradication - Situation
key objectives and milestones5 analysis

1. Interruption of WPV transmission, In 2005, the world moved several critical

2. Achieving certification of Global Polio
Eradication,
3. Developing products for the Global OPV
Cessation Phase,
4. Mainstreaming the Global Polio Eradication
Initiative
The strategic plan, 2004-2008 has also set a
timeline for all the above-enumerated objectives.
A modified step-ladder type figure
demonstrating each important event is depicted
in Figure 1.
35
milestones closer to polio eradication, including
the successful introduction of the powerful new
monovalent OPV(mOPV) vaccines, visible
progress in the hardest endemic areas, and an end
to west and central Africas epidemic (outside
Nigeria/ Niger). As stated earlier, the number of
countries with indigenous polio has dropped to 4,
as Egypt and Niger have not had indigenous
poliovirus for more than 12 months now2.
Between 1988 and 2004, global eradication
efforts reduced the number of polio cases from
350,000 annually to a low of 1,189 cases. In 2005,
Indian Journal of Practical Pediatrics 2006; 8(3) : 222

the number of cases rose again to 1932 (as of 21st fundamentalist religious organizations of the
February 2006), at the peak of the epidemic country severely affected the drive against polio
originating in northern Nigeria and infecting 21 eradication and at least ensured that the project is
previously polio free countries between 2003 and going to be delayed for further few years4,6. This
20053. temporary suspension resulted not only in huge
immunization gap in young children in northern
Nigeria (40.7 %), Yemen (24.8 %), states of the country where between 40-50 % of
Indonesia (15.7 %) and Somalia (9.6 %) are the children have not received any doses of OPV
countries responsible for more than 90% of global but also introduced wild poliovirus (type 1) in to
wild poliovirus cases in 2005 (Table 1). 21 previously polio free countries, followed by
Table 1: Polio cases from 22 February intercontinental spread to Middle East and Asia
2005 to 21 February 2006 (Fig. 2). Out of these 21 countries, in 8 countries
imported virus did not result in sustained
Name of Status Number of transmission and they either had only 1case
country WPV cases (Botswana, Eritrea, Lebanon, Togo) or had
Nigeria Endemic 788 detected a small number of separate cases not
Yemen Importation 478 directly linked genetically or epidemiologically
Indonesia Importation 302 (Benin, Cameroon, Nepal, Saudi Arabia). In the
Somalia Importation 184 remaining 13 countries, imported WPV caused
India Endemic 66 multiple case outbreaks. In 8 of these 13 countries,
Pakistan Endemic 27 transmission is considered to have stopped
Sudan Importation 27 (Burkina Faso, Central African Republic, Chad ,
Ethiopia Importation 22 Cote dIvore, Ghana, Guinea, Mali, Sudan). The
Angola Importation 10 remaining 5 countries (Yemen, Indonesia,
Niger Importation 10 Somalia, Angola and Ethiopia) are still having
Afghanistan Endemic 7 sustained transmission and 3 of them (Yemen,
Nepal Importation 4 Indonesia, and Somalia) are still contributing wild
Mali Importation 3 virus cases and already had large out breaks7.
Chad Importation 2
The Progress in India and the Sub-continent
Eritrea Importation 1
Cameroon Importation 1 The eradication initiative has made handsome
Total cases 1932 progress in India till last year, particularly in the
states of Bihar and to some extent in Uttar Pradesh
Nigeria continues to be the greatest obstacle (U.P.)- the two most stubborn endemic foci in
in making world free from polio. Extensive the country. The number of WPV cases declined
transmission of both type 1 and type 3 poliovirus from 1600 cases in 2002 to 66 cases in 2005, and
continues in the northern part of the country. With number of infected districts has gone down from
788 cases reported in 2005, Nigeria accounted 159 districts in 2002 to only 35 districts in 20058.
for >40 % of global cases. The southern part of
the country is polio free, as no indigenous polio However, 2006 brought us disappointing news as
transmission has occurred in 20052. Suspension far as situation in UP is concerned. Already by
of all forms of polio activities during 2003-2004 mid-July the number (136) has reached double
period owing to fierce resistance from some that of the whole year of 2005. The wild virus

36

tally in UP now reflects a staggering figure of 185
cases (as of 18th August 2006). Cases in UP are
concentrated around Moradabad district.
Moradabad, JP Nagar, Bareilly, Badaun, and
Rampur account for 80% of the cases to date in
UP and 70% of cases in India as a whole.
Moradabad and JP Nagar alone have reported 56
cases, greater than 50% of the UP total. While
cases have been concentrated in a fairly restricted
area of western UP, more recently geographical
spread has occurred and it is likely that there will
be numbers of cases reported across UP in the
9
coming months .
The situation in Bihar stands in marked contrast
to UP. 12 of the 13 cases from Bihar had onset in
the first 4 months of the year. Since
April 19 only one case has been reported, in Patna.
9
Transmission in Bihar is clearly very restricted .
There is dj vu of what we had seen in 2002. In
2000 and 2001 there was promise, with the then
Fig. 2. Wild poliovirus (WPV) cases in 2005 and WPV importation routes during 2002-2005 worldwide
Source : CDC
37
2006; 8(3) : 223
lowest numbers on record namely 265 and 268,
that things were going well, but 2002 turned out
an outbreak year. Four years later, the situation
looked good towards the end of 2005, but then
and outbreak has developed now. So, there is
growing anxiety, as we are not able to reach the
goal of eradication even in 2006, six years overdue
from the original target year of 2000. Previously
1998 and 2002 were years of upswing in numbers
of cases; now 2006 shows the same pattern
4 years later. This is disconcerting. Had
transmission continued but the number of cases
was less than in 2005, optimism would have
10
prevailed .
Bihar, the other hot spot polio endemic state,
has for the first time surpassed the U.P. tally last
year (30 vs. 29 cases). The situation in Bihar
stands in marked contrast to UP. 12 of the 13
cases from Bihar had onset in the first 4 months
of the year. Since April 19 only one case has been
Indian Journal of Practical Pediatrics
reported, in Patna. Transmission in Bihar is clearly
very restricted. The wild virus activity, it seems,
has confined to only these two states. The AFP
surveillance sensitivity has improved substantially
since mid 2004, and genetic sequences data
indicate that transmission is substantially restricted,
with only two P-1 genetic clusters circulating in
2005 (down from 10 in 2003 and 4 in 2004),
whereas only one cluster of P-3 virus was
responsible for all four P-3 cases in western U.P .
9 Apart from Pakistan and Afghanistan, two
Pakistan (27 cases) and Afghanistan (7 cases),
the other two endemic countries of the
subcontinent, have shown remarkable progress in
2005. In 2005, 27 cases were reported in Pakistan
compared with 53 of the same period in 2004.
The primary risk to Pakistans polio eradication
efforts remains restricted access due to insecurity
in some areas of the country, most notably the
2
tribal areas bordering Afghanistan .
However, while Pakistan continued to show good
control (only 13 cases in 2006, till 18th August),
the situation in Afghanistan deteriorated
alarmingly. Afghanistan has seen a six-fold rise in
the number of polio cases over last year
(25 cases confirmed in 2006, compared to 4 cases
in the same period in 2005). All but one of these
cases is in the southern region of the country,
where the current security situation has made it
nearly impossible for health teams to reach
11
children . The transmission of virus is made easier
by frequent population movements into and from
neighbouring Pakistan, one of the three other
polio-endemic countries. This corridor of
transmission stretches from the Southern Region,
into Pakistans Balochistan and northern Sindh/
southern Punjab. In response, Afghanistan and
Pakistan continue to synchronize Supplementary
Immunization Activities (SIAs) .
11
Pakistan has only reported 13 cases so far in 2006.
In Pakistan, wild poliovirus is surviving only in
minority-underserved populations, including
nomadic groups and other mobile populations,
38
2006; 8(3) : 224
generally in less well-populated areas.
Transmission survives in these groups because
children have not been consistently reached during
immunization activities. The priority for the
programme in Pakistan now is to identify these
groups and access them during the remaining
rounds in 2006, to ensure that transmission is
completely stopped by the end of the year.
other countries of the sub-continent-Bangladesh
(10 cases so far till 18th August 2006) and Nepal
(1 case) have reported importation of wild virus
from India. Bangladesh had been polio-free for
five years before the first case was confirmed in
March of this year-an importation from India
(Bihar). That one case sparked the three NIDS
which reached 96% of the 22 million children aged
under five. This, however, has not stopped the
outbreak with a further 10 cases being confirmed
in the past month11. Nepal has also reported one
case again an imported wild virus from Bihar
(India).
The new strategies to tackle imbroglio in
western UP
The first necessary step is to realize that higher
quality performance is essential in western UP
than everywhere else10. The primary players are
the government, the health system officers, the
staff and the volunteers, facilitators, social
mobilisers and monitors. It is not that they have
not done their job reasonably well, but that they
must do it even better. All partner agencies must
work harder and work together and work in
unison.
The second step is to maximize the use of the
monovalent OPV, which has better efficacy for
the given type (here type1), than trivalent OPV.
The government has already progressed in this
direction. A birth dose of OPV has been introduced.
Monovalent OPV will replace trivalent OPV in
the endemic communities. It will certainly

improve vaccine efficacy of OPV but perhaps not
to the level that will result in herd effect and
interruption of transmission10.
A third step to improve protection in the very
young is to give the inactivated polio vaccine
(IPV), which is highly immunogenic with 3 doses
and sufficiently immunogenic even with 2 doses10.
The Drugs Controller General of India has
appreciated this need and has very recently
licensed IPV for use in India. IPV has potential
role in the long term, but let us look at the short-
term need, opportunity and tactic. Ideally IPV
should be enmeshed with routine vaccination
schedule, 3 doses per infant, but we know that
the coverage will be dismally low. In the
immediate future we can use IPV to expedite the
process of infant immunization and thereby
supplement the vaccine efficacy. For that purpose
a campaign mode may be the only way. The
introduction of IPV, if and when it comes, should
be an additional intervention, without in any way
diluting whatever is being achieved by OPV9,10.
Threats to ongoing eradication initiative
The polio eradication initiative is
characterized by multiple setbacks, frequent
delays, scarcity of funds, and religious opposition.
However, the greatest threat to on going program
is now posed by the following phenomena.
1. Importation of wild virus to polio free
countries
As stated earlier, the most significant
development of 2005 was importation of large
number of WPVs from endemic countries to polio
free countries. This phenomenon will continue to
occur until endemic WPV transmission is
interrupted globally. It is simply not sufficient to
achieve zero polio status; more arduous task
would be to maintain this status, year after year.
As happened in Indonesia- after remaining polio
free for 10 consecutive years, the country
39
2006; 8(3) : 225
witnessed first case of imported WPV in May
2005 and before any outbreak response measure
could be taken, epidemic engulfed six more
provinces of the country leading to moe than 300
clinical cases!7
The risk of importation is highest for countries
adjacent to endemic countries, but importations
over long distances also occur. Globalization and
international migration pose a risk for re-
introduction of WPV for all countries. Inability to
achieve and / or maintain high routine
immunization (RI) coverage in the absence of
periodic NID, predisposes some countries with
imported WPV to re-establishment of polio
transmission within their borders3,4,7.
2. Vaccine associated paralytic poliomyelitis
(VAPP)
VAPP is one of the few inherent weaknesses
of the OPV. In the face of diminishing burden of
WPV cases every year, we have now reached a
state where burden posed by VAPP has become
much greater than the wild virus itself. Already,
voices of dissent asking for more transparency
on actual burden of VAPP in the country and
demanding compensation for the victims of VAPP
are emanating from different quarters12. Most
experts believe that the risk is lower in India and
put it around 100-200 cases per year13,14.
In recent times, a new variant of VAPP called
imported VAPP is documented in an
unvaccinated US adult, who traveled abroad15.
This highlights the previously unrecognized risk
for paralytic polio among unvaccinated persons
exposed to OPV during travel abroad.
3. Circulating vaccine derived polioviruses
(cVDPV)
This is yet another looming threat posed by
continuous use for OPV and again highlights the
inherent weakness and risk of using live oral
vaccine. Fortunately, in India, there is no instance
Indian Journal of Practical Pediatrics
of cVDPV so far but continued use of OPV
perpetuates this risk at every location. Many
experts believe that even the discontinuation of
OPV may pose a risk for the development of
cVDPV during the 3-5 years period after cessation
of OPV16. World over, seven outbreaks of cVDPV
have been recognized most recent being in
Indonesia. Hence, both VAPP and cVDPV are
ethically incompatible with eradication17.
Reasons behind the delay
When GPEI was launched in 1988, the year
2000 was set as the target year to achieve the
goal of polio eradication and certification of
eradication by 200518. However, with the frequent
set backs suffered in last few years particularly in
developing, third world countries, the first deadline
is already a matter of history19. Strong voices of
dissent questioning the achievements of GPEI so
far and dubbing it as yet another exercise in
mismanaging the health priorities and programs
in developing countries in the era of globalization
have started emanating20.
1. Poor efficacy of OPV in endemic regions
(Vaccine failure)
OPV was the right choice to begin the
massive, synchronized global exercise and it did
deliver goods in restricting the wild poliovirus to
certain limited geographical regions. It has certain
inherent weaknesses like VAPP and cVDPVs.
But, the greatest drawback of OPV is its
unpredictable immune response in a vaccinee.
Even after administration of 10 doses, one can
not be sure whether the vaccinee has developed
adequate immune protection or not. For example,
in India in 2005, 33% of children with confirmed
polio had received 10 or more doses 16 .
Historically, it is believed that control of
poliomyelitis can be achieved by properly
immunizing 80-85 % of the at risk population 21.
In some high-risk districts of western U.P., despite
achieving coverage as high as 96.5 %, OPV failed
40
2006; 8(3) : 226
to break wild virus transmission and 7.25 %
children of a study group failed to show
seroconversion to any of the three sero-subtypes22.
Though it could also be due to over reporting of
the coverage to some extent.
The OPV has geographic variation in
efficacy- high in industrialized nations, low in
Taiwan, and Oman, lower still in many developing
countries23 due to host factors like concomitant
infections, malnutrition, programmatic factors like
cold chain maintenance failures and environmental
factors, requiring substantially more doses to
seroconvert for such an individual5. In the foci of
persistent transmission, the efficacy may be the
lowest. Low vaccine efficacy spells low
effectiveness and low herd effect; all factors that
make the vaccine a poor match to the task of
interrupting the transmission of the most
transmissible among wild poliovirus types namely
type 123. India, Pakistan, Egypt, and to some
extent Nigeria, provide the toughest challenge to
effectiveness of OPV in halting the wild virus
transmission. High population density, sub-optimal
sanitation, concurrent enteroviral infection,
interference among 3 sero-subtypes of Sabin
viruses, sub-optimal practices of vaccine handling,
poor coverage and at times over-reporting of the
coverage which gives a false sense of security
along with tropical climates combine to lead to
failure to curtail the transmission of wild
poliovirus5,19.
Hence, OPV was the right tool to start with
but we all failed to anticipate the current
shortcoming of the vaccine in final phase of the
GPEI, particularly in some most hostile geographic
regions. As a result, neither alternate strategy nor
other options were envisaged to deal with current
imbroglio24. Though, monovalent OPV might
salvage the situation to some extent, it is also not
devoid of some of the most inherent deficiencies
of its precursor. The presumed failure of OPV to
combat ongoing transmission of wild virus in few

pockets of endemic countries like India despite
using it very aggressively in its most potent form
pose the greatest challenge to the ultimate success
of GPEI.
2. Programmatic hiccups
Failure to reach all children below five years
of age in some highly endemic regions, suspension
of all forms of polio activities in Nigeria in 2003-
2004, resistance to OPV among some religious
community in India and Nigeria, poor quality of
SIAs, inadequate engagement and involvement
of the general community, failure launch an
effective, aggressive IEC, lack of co-ordination
amongst enforcing agencies, programmatic fatigue
and inertia are the main factors that halted the
swift progression of the initiative25,26.
3. Peculiar epidemiology of type 1 poliovirus
in endemic regions
The vast difference in the epidemiology and
environmental factors in different parts of the
world provided conducive ground and force for
wild virus transmission. The strategy adopted in
the regions where force of transmission is low did
not work in places with high force of transmission
such as India, Egypt and Nigeria 27. Wild
polioviruses have been eliminated nearly from all
low-income countries with low or moderate force
of transmission with lesser efforts. However, high
density of population, relatively high birth rates
and consequent high density of infants and
toddlers- the most efficient amplifiers and
transmitters of WPV, poverty, low literacy, low
living standards with poor sanitation and hygiene
form a milieu of formidable high force of
transmission in these last remaining endemic
countries23,27. Interventions that worked in other
poor communities and countries may not be
sufficient to overcome such exceedingly high force
transmission. We failed to recognize this
geographic variation in behavior of wild poliovirus,
especially type 1, and are now facing the prospects
41
2006; 8(3) : 227
of losing control over the eradication imitative.
4. Neglect of routine immunization (RI)
Routine immunization (RI) is unarguably the
weakest link and probably is the most neglected
area of the four pronged eradication strategy.
The current strategy has put all the emphasis on
SIAs. It seems the strategist do not have much
faith on the effectiveness of RI and by increasing
the frequency of SIAs, they have indeed left
nothing for the strengthening of RI19. This is
certainly a major setback. Even if transmission is
broken and zero polio status is achieved through
high quality SIAs, it is ultimately RI that will
determine the herd immunity and will thwart
any attempt of importation of the disease in the
community. As the recent episode of importation
of WPV in 21 previously polio free countries
shows, the 8 countries with no sustained WPV
transmission after importation of the virus differed
considerably in RI status from 13 countries where
transmission following importation was
sustained7. According to WHO /UNICEF estimate
for 2003, the median vaccination coverage with 3
dose of OPV (OPV 3) by 12 months of age in the
8 countries without sustained spread was 83%,
compared with a median coverage of 52 % in the
other 13 countries (P = 0.001)7. Hence, the
robust RI would be the greatest deterrent to the
greatest threat to polio free status the importation
of wild viruses! The current status of RI in some
of the highly endemic countries is indeed pitiable25.
5. Conflict, social unrest and accessibility
problem
Conflict among community and presence of
political vacuum in certain war affected countries
like Sudan, Afghanistan, and Angola have already
adversely affected the ongoing eradication
campaign. Afghanistan, Pakistan, Sudan and
Somalia are the few countries where major
security risks have made covering the entire
population for vaccination extremely challenging.
Indian Journal of Practical Pediatrics
Frequent floods in Bihar (India) and fierce
resistance by some religious communities in
northern Nigeria have also made the task of
volunteers more difficult.
6. Lack of foresight and flexibility
The greatest flaw of the current strategy was
almost exclusive and over reliance on OPV to
achieve the goal. The conceivers of the program
failed miserably to even anticipate OPVs limitation
in final stages of polio eradication in some of the
most stubborn regions of the world. Apart from
keeping the option of using monovalent OPV in
final stages and during post eradication phase, they
failed to device an alternate strategy to break wild
virus transmission where OPV was found wanting
and quite unequal to the task. The enforcing
agencies did fail to anticipate the current scenario
in endemic countries where intense, high force
transmission of type 1 WPV almost rendered the
OPV redundant.
How far is the goal?
Undeniably, the whole initiative has made a
remarkable progress in terms of over 90 %
reduction in WPV cases ( from 350,000 in 1998
to 1932 cases in 2005) and an impressive
curtailment in total number of endemic countries
(125 to 4 by 2005). Three WHO regions have
already been declared polio free, WPV type 2
has not been isolated anywhere in the world since
October 1999, WPV type 3 has only very few
clusters confined to few endemic countries
only2,19. But the fact remains that even after 18
years of uninterrupted global efforts; we have still
not been able to accomplish the first task the
interruption of wild virus transmission from half
of the globe!
As we all know that merely making any
country polio free is not sufficient. Certification
is conducted on a regional basis. Each region can
consider certification only when all countries in
42
2006; 8(3) : 228
the area demonstrate the absence of WPV
transmission for at least three consecutive years
in the presence of excellent surveillance. As of
now, none of the remaining three WHO regions
have achieved polio free status even for a single
year. Worse, the recent re- introduction of
type1 WPV into several previously polio free
countries have further compounded the worries
associated with the plan. Some countries like
Indonesia after remaining polio free for 10 years
had to restart all the suspended activities of SIA
from the scratch once again. Hence, a most honest
and dispassionate analysis of the performance of
GPEI would reveal that the proposed eradication
plan is quite a complex issue.
How to move forward?
The first and foremost objective for the year
2006 is to urgently halt the ongoing intense wild
virus transmission in remaining endemic countries
and at the same time, to maintain a high level of
immune coverage in most polio free countries,
particularly those bordering with endemic ones.
Quickly stopping polio outbreaks in previously
polio free countries should top our agenda. The
WHO Advisory Committee on Polio Eradication
(ACPE) recommends that any polio free country
that detects imported WPV should immediately
obtain a risk assessment by an international expert
group and prepare a large scale response plan
(within 72 hours of case confirmation) and conduct
three large scale house-to-house immunization
campaigns using type-specific mOPV, initiating the
first round within 28 days of confirmation of the
case7. If we do not stick to these guidelines, the
world would soon experience more instances of
inter-continental importation and rapid resurgence
of polio worldwide. The only deterrent to prevent
importation of WPV is a robust RI coverage.
Hence, addressing low RI rates in certain polio
free countries should take the top most priority.
However, apart from these established
measures, we must look for certain unconventional

approaches. What they could be? Though ground
implementation of some of them may seem
unfeasible, but the current situation definitely
warrants some serious consideration to these
innovative albeit unconventional options. After all,
desperate situation demands desperate measures
and we all must know the time is fast running
out. We cannot afford to push the deadline beyond
a certain limit.
A. Targeted use of IPV
Use of IPV in post eradication phase is quite
complex- depending upon the will and resources
of an individual country. But what is the use of
IPV in the ongoing, pre eradication phase of GPEI
in some most challenging endemic regions of the
world such as India. We have already exercised
the option of maximizing immune response of
OPV by using monovalent type 1 and type 3 OPV
in endemic states of UP and Bihar. But even that
intervention, it seems, failed to break the deadlock.
What next then? Targeted use of currently
available IPV in local endemic areas, preferably
in combination with DPT may not only boost the
sagging RI state but can also augment OPV in
halting the ongoing intense wild virus transmission.
This move might also take care of circulating
VDPV and VAPP the two inherent weaknesses
of its oral counterpart. The fear of most western
agencies involved with GPEI, whether developing
countries with tropical settings will be able to
achieve good coverage (i.e. more than 90 %) with
IPV is not quite unfounded. However, with a lesser
effort than in some northern states of India (UP
and Bihar), most southern states of the country
(Tamil Nadu and Kerala, particularly) are able to
achieve >95% coverage of third dose of DPT17.
Hence, with good programmatic management
similar results can be achieved in endemic states
also. The DPT- IPV combination in RI along with
OPV supplied through SIAs would greatly enhance
the chances of rapidly breaking WPV transmission
in endemic regions. Indian studies had already
43
2006; 8(3) : 229
shown very high efficacy of IPV and low efficacy
of OPV in tropical settings. On the other hand,
western studies showed complete safety of IPV
but not of OPV17.
B. New polio vaccines for end game and
post eradication phase
The current IPV is made from three wild
poliovirus strains (Mahoney type 1, MEF type 2
and Saukett type 3). The risk of accidental or
intentional release of wild strains from IPV
manufacturing sites would pose a significant risk
to the polio-free world. Hence, ultimately, we
would need to part away with current IPV also to
make the gains of polio eradication permanent.
What would be the next option then? Development
of new vaccine candidates to tackle the biosafety
concerns would be most prudent approach. Why
didnt we look for this option earlier? Why did
we continue to rely heavily only on the two
vaccines developed some 50 years ago despite
knowing their inherent weakness and formidable
challenges ahead. This is indeed a mystery.
Instead, we should have looked for safer, more
efficacious and cheaper polio vaccines. We all
knew well in 1999 that the proposed goal of
eradication would be unachievable in 2000. Yet
no attempt was made device better strategies.
The work on new polio vaccines was started
in mid-1980s where various types of poliovirus
antigens were investigated in depth for their
immunogenicity. They included peptides, proteins
and vector vaccines using vaccinia 28. The
conclusion at the time was that none of these
approaches offered a practical way forward, and
the existence of two highly effective vaccines
made further development in a manufacturing or
marketing sense unlikely. This is believed to
remain the case at present, but it might be of interest
to revisit capsid formation by non-polio expression
systems such as DNA vaccines for post
eradication era. This would be the only vaccine
Indian Journal of Practical Pediatrics
type not associated with risk of poliovirus
infection.
Though DNA polio vaccine appears to be
the most desirable one to use, currently the most
exciting prospect seems to be the development of
IPV from the virus strains used for making Sabin
OPV. The Sabin-IPV made from, live,
attenuated strains of OPV, would have lower
transmissibility. Three manufacturers (Japanese,
Chinese and Indian) of the world are currently
involved in its manufacturing but so far are not
able to develop a licensed product. Even WHO
has recently shown great interest in SabinIPV
and urged acceleration of studies demonstrating
its safety, efficacy, attenuation and possible use
in near future 29 . Potential difference in
immunogenicity and antigenicity between Sabin
and conventional IPV strains need to be
investigated and may necessitate modification in
order to achieve equivalent protection.
In addition to live strains for which there is
clinical experience, there are a number of other
strains designed on molecular biological principles,
which are likely to be suitable for consideration
as new IPV seeds28. Over the past 20 years the
molecular basis of the attenuation of the Sabin
vaccine strains has been studied in detail, and it is
considered possible to exploit this understanding
to create new live attenuated strains.
Points to remember
1. The GPEI despite experiencing frequent
setbacks, delays and new evolving
challenges has made handsome progress
towards achieving its final goal.
2. New emerging threats like importation of
wild virus to polio free countries and
epidemics of circulating VDPVs have
compounded the problems of the initiative.
3. There is urgent need to rapidly halt the
ongoing intense wild virus transmission in
44
2006; 8(3) : 230
endemic countries that call for more
flexibility in approach and to venture in to
some unconventional, innovative
interventions.
4. The program initiators must do a thorough
dispassionate reappraisal of the whole
strategy and should set new targets and
timelines.
References
1. CDC. Progress toward interruption of wild
poliovirus transmission world wide, January
2004- 2005. MMWR 2005; 54: 408-412
2. World Health Organization. Polio eradication
monthly situation report- February 2006.
Available at www.polioeradication.
www.polioeradicationorg/casecount.asp .
Accessed on February 20, 2006.
3. CDC. Resurgence of wild poliovirus type 1
transmission and consequences of
importation- 21countries 2002 2005.
MMWR 2006 ; 55 (06):145-150.
4. Vashishtha VM, Shah RC, Thacker N and John
TJ. Importation: The greatest threat to polio
free countries. Bulletin of Polio Eradication
Committee, Indian Academy of Pediatrics
2005, (December)2: 13-15.
5. World Health Organization. Global Polio
Eradication Initiative Strategic Plan 2004-
2008. Weekly Epidemiol Rec 2004;79:55-57.
6. CDC. Progress towards poliomyelitis
eradication, Nigeria, January 2004-July 2005.
MMWR 2005; 54: 873- 877.
7. World Health Organization. Resurgence of
wild poliovirus type 1 transmission, and effect
of importation into polio free countries, 2002-
2005. Weekly Epidemiol Rec 2006(7), 81:
63-68.
8. National Polio Surveillance Project, India.
Available at http://www npspindia.org
Accessed on February 21, 2006.
9. Conclusions and Recommiutations. Special
Interim Meeting of the India Expert Advisory

Group for Polio Eradication, New Delhi, India,
th
28 July, 2006.
10. John TJ, Shah NK, Thacker M, Vashishtha VM.
Editorial. Polio eradication: Learn from failure
to create success. Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics 2006 (August) Vol 3 (In press).
11. Global polio Eradication Initiative-
Country Profile. Available at http://
www.polioeradication.org/countries.asp
Accessedx on August 19, 2006.
12. Paul Y, Dawson A. Some ethical issues arising
from polio eradication programs in India.
Bioethics 2005; 19 (44): 393-406.
13. John TJ. A developing country perspective on
vaccineassociated paralytic poliomyelitis.
Bull WHO 2004; 82: 53-57.
14. Shah RC, John TJ, Thacker N, and Vashishtha
VM. Vaccine associated paralytic
poliomyelitis (VAPP). Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics, 2005; 2: 6-7.
15. CDC. Imported vaccine associated paralytic
poliomyelitis United States, 2005. MMWR
2006 3; 55(4): 97- 99.
16. John TJ, Shah RC, Shah NK, Thacker M,
Vashishtha VM. Editorial. Bulletin of Polio
Eradication Committee, Indian Academy of
Pediatrics 2005 2 :2-3.
17. John TJ. Will India need inactivated poliovirus
vaccine (IPV) to complete polio eradication?
Indian J Med Res 2005; 122: 365-367.
18. The Global Eradication of Polio- A polio free
world in 2005. Available at http://
www.polioeradication.org/strategies.aso http:/
/wwwpolioeradication Accessed on February
20, 2006.
NEWS AND NOTES
APLS: The Pediatric Emergency Medicine Course
Contact Course Director: Dr. Suresh Gupta, Sir Ganga Ram,Hospital, New Delhi - 110 060.
Phone : 9811426628, 28312656, 28312591
2006; 8(3) : 231
19. Thacker N, Vashishtha VM, and Krishna SA.
Polio eradication: How far we have reached
and where have we gone wrong? Pediatr Today
2005; (8): 320-24.
20. Sathyamala C, Mittal O, Das Gupta R and Priya
R. Polio eradication initiative in India:
Deconstruction the GPEI. Int J Health Ser
2005; 35(2): 361-83.
21. Nightangel O. recommenation for a national
policy onpoliomyelitis vaccination. N Eng J
Med 1977;297:249.
22. Hasas AS, Malik A, Shukla I and Malik MA.
Antibody levels against polioviruses in children
following pulse polio immnization program.
Indian Pediatr 2004;41:1040-1044.
23. John TJ. Polar Spectrum of problems in polio
eradication. Indian J Med Res 2004;120:133-
135.
24. Vashishtha VM. But do we have other option?
Indian J Pediatr 2004;71:183-184.
25. Thacker N. Shendurnikar N. Current status of
polio eradication and future prospects. Indian
J Pediatr 2004;71:241-245.
26. John TJ, Thacker N. Despande JM. Setbacks
in polio eradication in India: Reasons and
Remedies. Indian Pediatr 2003;40:195-203.
27. John TJ. The vicissitudes of global eradication
of polio. Indian J Med Res 2004;120:133-135.
28. World Health Organization. New polio
vaccines for the post-eradication era.
Department of vaccines and Biologicals,
Geneva 2000. Available at at http://
www.who.int/vaccines-documents/ Accessed
on February 24, 2006.
29. World Health Organization. AACPE
recommendations. Weekly Epidemiol Rec
2004;79:401-408.
24-25 March 2007
Email: drguptasuresh@yahoo.co.in
45
Indian Journal of Practical Pediatrics
VACCINES
HEPATITIS VACCINES - CURRENT
CONCEPTS
*Ashish Bavdekar
**Sheila Bhave
Abstract: Hepatitis A is the commonest cause of
acute sporadic hepatitis and acute liver failure
in Indian children. Atypical clinical manifesta-
tions, co-infections and acute infections in adults
are being increasingly reported. Some regions
in the country have shown an epidemiologic shift
of HAV infection from early childhood to
adolescents and adults. HA vaccination has a
definite role in these regions to prevent epidemics
and protect against severe HAV infection in
adulthood. Both the inactivated and live
attenuated HA vaccines are safe, immunogenic
with long-lasting protective efficacy. Hepatitis
B vaccination not only prevents HBV infection
but also associated chronic liver disease and
hepatocellular carcinoma. Many vaccination
schedules have been used, with similar
immunogenicity. Effectiveness of the vaccine in
reducing the burden of hepatitis B is well
demonstrated in countries adopting the universal
immunization program. Hepatitis E vaccine is
undergoing clinical trials while the hepatitis C
vaccine is still in early experimental stage.
Key words: Hepatitis A, B, C, E; Vaccines
Five different viruses appear to target the liver
and produce liver disease as their main
* Consultant Pediatric Gastroenterologist,
Liver & Gastroenterology Unit,
K.E.M. Hospital, Pune.
** Consultant in Pediatric Research,
Department of Pediatrics,
K.E.M. Hospital, Pune.
46
2006; 8(3) : 232
manifestation. Hepatitis A virus (HAV) and
hepatitis E virus (HEV) are non-enveloped RNA
viruses that are spread predominantly by fecal
oral transmission and cause acute hepatitis in
children and adults. Hepatitis B virus (HBV) and
hepatitis C virus (HCV) are enveloped viruses
causing acute as well as chronic hepatitis. Their
route of transmission is usually parenteral though
HBV may also have a horizontal transmission
among young children. Hepatitis D virus (HDV)
is a defective virus that co-infects and requires
HBV for its expression. Vaccines against HAV and
HBV are now routinely available while vaccines
against HEV and HCV are still in various phases
of development. The hepatitis vaccines have two
purposes : to prevent the morbidity and occasional
mortality associated with acute hepatitis virus
infection and to reduce the occurrence of chronic
hepatitis, cirrhosis and hepatocellular carcinoma.
This article briefly reviews the current status of
hepatitis vaccines.
Hepatitis A vaccines
Hepatitis A (HA) is the commonest cause of
acute sporadic hepatitis and acute liver failure in
Indian children. Generally the disease is mild and
self limited. However, recently, atypical
manifestations like significant ascites, edema,
pleural effusions, skin rashes, firm to hard
hepatosplenomegaly, prolonged recovery, severe
anemia and coagulopathy are commonly seen.
Co-infections of HAV with other infections like
HEV, HBV, typhoid fever, dengue fever,
malaria, etc are also increasingly encountered1.
HA vaccines were originally recommended
for high risk groups only. These included travellers

to endemic countries, children with chronic liver
disease, health personnel, persons using clotting
factor concentrates, etc. However nowadays, in
many countries, the vaccine is increasingly added
to vaccination programs in areas of intermediate
endemicity for HAV. In some regions of India,
recent studies have indicated evidence of
epidemiological shift (shift of age of infection from
children to older age groups) of HA infection
especially in the higher socioeconomic groups2.
With continuing economic development and
subsequent improvement in sanitation and hygiene,
more and more areas will show this shift. These
areas are at risk for epidemic outbreaks in children
and adults as was recently reported in Kerala. In
these vulnerable populations, HA vaccination has
a definite role to prevent epidemics and protect
against severe HAV infection in adulthood. The
Indian Academy of Pediatrics (IAP) has
recommended HA vaccine as an additional vaccine
to be offered to children > 1 year of age belonging
to high socio-economic strata.
Humans are the only known reservoir for
hepatitis A virus. Thus, the virus could theoretically
be eradicated if a widespread immunization
program is implemented. Several hepatitis A (HA)
vaccines are available including the formalin-
inactivated vaccines with and without aluminum
hydroxide as an adjuvant, live attenuated vaccine,
and combined hepatitis A and hepatitis B vaccine.
Inactivated vaccines: Currently four inactivated
vaccines are available worldwide. All these
vaccines are safe, well tolerated, highly
immunogenic and licensed for children aged
> 1 year (except in USA where it is licensed for
children > 2 years of age). The vaccine is
administered intramuscularly in the deltoid region.
The previous three-dose immunization regimen
of 0, 1 and 6 months has been replaced by a two-
dose schedule, given at 0 and 612 months. The
adult dose (> 18 years) is generally twice that of
the pediatric dose. Most studies demonstrate a
47
2006; 8(3) : 233
seroconversion rate of 95-100% (defined as an
anti-HAV antibody level of >20 mIU/mL) after
vaccination in both adults and children 3,4. Anti-
HAV antibodies immediately after immunization,
though 10 to 100 fold lower than that following
natural infection are still very high than the
minimum titer required for protection against HA
infection. There is a gradual decline in antibodies
over time and mathematical modelling studies
assuming a constant rate of decline in antibodies,
suggest that antibody may persist for 2030
years 5. Infants under the age of 1 year with
maternal anti-HAV achieve slightly lower
seroconversion rates (93100%) and lower
geometric mean titres. Nevertheless, studies in
such infants reveal a substantial and rapid
(anamnestic) immune response to HAV antigen,
suggesting that protection may be long lasting even
when anti-HAV is no longer detectable6. This
suggests the existence of a robust recall response
and long-lasting immune memory that make
booster immunization of immunocompetent
individuals unnecessary 7 . The antibody
concentration achieved with the HA vaccine is
much greater than the concentrations reached with
protective doses of immune globulin (IG) and the
response is also much more long-lasting.
A toddlers-only universal immunization program
in Israel using inactivated HA vaccine has not only
reduced the annual incidence rate of hepatitis A
from 50.4 per 100,000 to 2.2 per 100,000 but
also demonstrated marked herd protection8.
Reduced immunogenicity: Seroconversion rate
is less in persons with chronic liver disease (93%),
immunocompromised state (88%), HIV infection
(77%), transplant recipients (26%) and elderly
(65%)9.
Adverse reactions: The HA vaccines have an
excellent safety profile. Reported adverse events
in children have been local pain at the injection
site (15-19%), feeding problems (8%), headache
(4%), injection site induration (4%). There were
Indian Journal of Practical Pediatrics 2006; 8(3) : 234

no accounts of elevations in serum transaminases. effects. A 3-dose schedule of 0, 1 and 6 months

Vaccinating already immune persons did not is suggested using the pediatric vaccine for children
increase the risk of adverse events10. between the ages of 1-15 years and the adult
Simultaneous administration with other vaccine after 15 years. Recent studies have looked
vaccines: The inactivated HA vaccine can be into the possibility of using only 2 doses of the
given concurrently with vaccines for diphtheria, pediatric or adult vaccine for better compliance11,12.
polio, tetanus, hepatitis B, typhoid, cholera, While the results of these studies are quite
Japanese encephalitis, rabies, or yellow fever encouraging, more data is needed before the 2-
without adversely affecting immunogenicity or dose schedule can be recommended. Information
safety. It is recommended that the injections be on the duration of antibody response following
given at different sites. The vaccine can be given vaccination with a combined vaccine, and role of
with immune globulin at different sites. booster is not yet clear. This vaccine has a role in
Combined Hepatitis A and B vaccine: Clinical catchup vaccination of children who have missed
trials evaluating a combined HA and hepatitis B hepatitis B vaccination in infancy (Table 1).
vaccine have shown consistently high
seroconversion rates with no appreciable adverse Post-exposure prophylaxis: The efficacy of
hepatitis A vaccine as post exposure prophylaxis
Table 1. Immune prophylaxis for Hepatitis infections
Infection Passive Active Comments
Immunisation Immunisation
Hepatitis A Immunoglobulin Inactivated vaccines IG protection short lasting (3-5 months)
(IG) and expensive. Recommended for
Live attenuated for post-exposure prophylaxis within
vaccine 2 weeks of exposure
Both vaccines safe, immunogenic and
provide long term protection.
Hepatitis B HB Immune Recombinant DNA HBIG indicated for babies of HBsAg
Globulin (HBIG) vaccines +ve mothers and post-exposure
prophylaxis
HB vaccines safe and immunogenic
Indicated for universal immunization
Combined HA and Combined vaccine useful for catch-up
HB vaccine vaccination
Hepatitis D IG ineffective No specific vaccine Prevention of HBV infection by HB
vaccine will prevent HDV infection
Hepatitis C IG ineffective. Vaccine in IG not recommended for post exposure
experimental stages prophylaxis
Hepatitis E Role of IG Phase II, III studies IG from plasma collected in HEV non
unclear ongoing endemic areas not protective. IG from
plasma collected in HEV endemic areas
unknown efficacy

48

in outbreak settings without accompanying
immunoglobulin is still unclear. One small study
has shown a protective efficacy of 79% when
given within 8 days of symptom onset of the index
case while other studies have shown that vaccine
alone may be insufficient 13.
Live Attenuated Vaccines: The use of attenuated
live HA vaccines has been evaluated in both
animals and humans. The attenuated H2 strain
HAV originating from the feces of a 12 year old
child with hepatitis A has undergone extensive field
trials in China and is now available in India. It is a
freeze dried live vaccine licensed for subcutaneous
use in children > 1 year of age. The vaccine
induces not only neutralizing antibody but also
cell mediated immune response. The vaccine is
well tolerated and highly immunogenic.
Seroconversion in subjects 2 months and 10 years
after vaccination was 98.6% and 80.2%
respectively14. There were no major side effects,
and elevations in serum transaminases were not
noted. In regions in China where mass vaccination
programs have been introduced, there has been
over 95% reduction in Hepatitis A related
morbidity and no cases of HA has been reported
since 199914. At KEM Hospital, Pune, a 96%
seroconversion rate was observed in a study of
144 children between the ages of 1-12 years
immunized with a single dose of the live attenuated
hepatitis A vaccine. (unpublished observations).
The vaccine is given as 0.5 ml sub-cutaneoulsy
and only single dose is recommended by the
manufacturers.
Hepatitis B (HB) vaccine
The first HB vaccine was derived from
HBsAg particles of chronic hepatitis B carriers.
Though this vaccine had excellent immunogenicity
and safety, the plasma origin was of concern.
Hence recombinant vaccines produced by cloning
the HBV S gene in yeast cells are now being
49
2006; 8(3) : 235
widely used all over the world. HB vaccines are
available as single antigen formulations or fixed
combinations with other vaccines hepatitis A,
hemophilus influenzae type B, DPT and IPV.
Seroconversion: Protective anti-HBs antibody
levels of at least 10mIU/ml appear in 90% of
healthy adults and 95% of infants and children
after vaccination. Administration of HB vaccine
with other childhood vaccines does not produce
any significant interference in antibody responses
and vaccines made by different manufacturers are
interchangeable. Increasing age, obesity, smoking,
chronic renal failure, renal dialyses, organ
transplant recipients and immunosuppressed
individuals are at risk for reduced response15.
Duration of protection: Anti-HBs levels decrease
over time and 50-80% of vaccinees may have
levels below 10mIU/ml 12 years after
vaccination 16. However there have been no
symptomatic hepatitis B cases among this group.
This is probably due to priming of memory cells,
which are capable of eliciting an anamnestic
response when challenged. Post vaccination testing
1-2 months after the last vaccine dose is not
required except in newborns of HBsAg mothers,
health care workers and individuals with risk
factors for poor response.
Need for booster doses: Booster doses are not
routinely recommended for persons with normal
immune status but may be necessary in the
individuals with risk factors for poor response.
Annual anti-Hbs testing and booster doses when
anti-HBs level drops to below 10mIU/ml may be
considered in this group.
Effectiveness: As long-term follow-up studies are
now available, the beneficial effects of HB vaccine
are now increasingly apparent. In Taiwan, the
prevalence of HBsAg positivity among children
15 -20 years old decreased from 9.8% (born before
universal immunization program) to 0.7% (born
Indian Journal of Practical Pediatrics
after universal immunization program). 12-14%
of babies born to HBeAg positive mothers and
3-4% of the babies born to ani-HBeAg positive
mothers became carriers following vaccination (as
compared to 86-96% and 10-12% without
vaccination respectively). The incidence of
hepatocellular carcinoma per 100,000 also declined
from 0.7 in 1981-86 to 0.36 in 1990-9413.
Safety: The currently licensed HB vaccines are
safe. Mild adverse reactions are reported in 1-3%
and include low grade fever, pain at injection site,
headache, myalgia etc. Estimated anaphylaxis
incidence is 1 per 1.1 million vaccine doses.
Association between HB vaccination and Guillain
Barre syndrome or multiple sclerosis is not proven.
Rarely illnesses like chronic fatigue syndrome,
leucoencephalitis, optic neuritis, transverse
myelitis, rheumatoid arthritis, auto-immune
disorders, type I diabetes, alopecia have been
reported after HB vaccination but no causality
has been demonstrated17.
New vaccines: A commercially available triple
recombinant mixed particle vaccine containing pre-
S1 and pre-S2 regions has been shown to be
immunogenic in nave individuals and previous
non-responders18. A two dose regimen has been
found to be as effective as the three dose one. Its
present role is still unclear. Other newer vaccines
in various stages of development are single dose
controlled microparticle release vaccine, oral
vaccines, vaccines using newer adjuvants like
MF-59, live recombinant vaccines and DNA
vaccines. These vaccines are still in experimental
stages.
Schedule of vaccination: WHO has
recommended that all countries provide universal
HBV immunization programs for infants and
adolescents. They have suggested the following
options for introducing HB vaccine in the
immunization schedule19.
a) In areas of low perinatal transmission (low
HBeAg prevalence) - HB vaccine given at 6,10,14
50
2006; 8(3) : 236
weeks either as single antigen or as a combined
vaccine.
b) In areas of significant perinatal transmission
(high HBeAg prevalence) HB vaccine at birth,
6, and 14 weeks (3 dose schedule) or birth, 6, 10,
and 14 weeks (4 dose schedule).
IAP recommendation: IAP has recommended
two HB vaccine schedules for all babies (except
those born to HBsAg +ve mothers) - birth, 6 and
14 weeks or 6, 10 and 14 weeks.
For babies born to HBsAg positive mothers,
HB vaccine should be initiated from birth onwards,
followed by 2 more doses at 6 weeks and 14
weeks along with HB immunoglobulin (HBIG)
which should be given within 12 hours of birth. If
HBIG is not available, then HB vaccine alone must
be given preferably in a four doses schedule at
birth, 6 weeks, 10 weeks and 12 months.
Interrupted vaccine schedules: An interruption
in the vaccination schedule does not require
restarting the vaccination series or adding extra
doses. The missed doses should be administered
as soon as possible.
Vaccine induced escape mutants: Some infants
get infected with HBV despite an adequate anti-
HBs response to vaccine. These are commonly
due to HBV S gene mutants. These mutants are
detected in less than 5% of infants receiving HB
vaccine and only 10-40% of vaccine failures are
due to HBV S mutants. In Taiwan, prevalence of
HBV S mutants in HBsAg positive children
increased from 7.8% in 1984 to 28% in 199420.
Careful epidemiological surveillance is necessary
to monitor this increasing prevalence of escape
mutants and establish continuing efficacy of the
conventional HB vaccines.
Hepatitis E vaccine
Hepatitis E is a common cause of acute
hepatitis in adults and is now also increasingly

reported in children throughout Asia, Middle East
and North Africa. In India, besides causing regular
water-borne epidemics, HEV accounts for 23-28%
of acute sporadic viral hepatitis in children and
40-53% in adults. It is a water borne disease with
a possibility of zoonotic spread of the virus since
several non-human primates, pigs, cows, sheep
and rodents are susceptible to the infection. The
case fatality rate can be 1 3% in non pregnant
patients and upto 20% among pregnant women.
Once an effective HE vaccine is available, its role
would have to be defined.
The development of attenuated or killed
vaccine is not currently possible due to lack of
self-cultured system for replication of HEV, though
some cell lines have been reported for culturing
and isolating HEV in vitro. Therefore, a nucleic
acid based vaccine or a recombinant protein
vaccine is needed. At present no commercially
prepared vaccine exists. However, several studies
for the development of an effective vaccine against
Hepatitis E are in progress. HEV is a spherical
non enveloped particle having 3 open reading
frames (ORFs). IgG HEV antibody to ORF3
wanes during convalescence, while that to the
ORF2 persists for several years making it a
candidate for a vaccine against HEV. Only one
vaccine has progressed to the stage of clinical trials.
This is the 56ku recombinant vaccine developed
at the NIH, USA. Phase I trials have found it to
be safe and immunogenic in 88 American
volunteers and 44 Nepalese volunteers. Phase II,
Phase III trials are underway in Nepal. Once an
effective HE vaccine is available, the vaccination
strategy would have to be defined.
Hepatitis C vaccine
The development of an effective hepatitis C
vaccine has been slow due to lack of a susceptible
small animal, a high degree of hepatitis C virus
(HCV) genomic diversity and failure to produce
high quantities of HCV in tissue culture. Clinically
51
2006; 8(3) : 237
adequate vaccines against HCV are not yet
available but protection against homologous strains
of the virus has been achieved in animal studies.
Declaration of conflict
The authors have received grant support
from GlaxoSmithKline Biologicals for non-
hepatitis vaccine trials and from Wockhardt Ltd
for a clinical trial of live attenuated hepatitis A
vaccine.
Points to remember
1. Inactivated and live attenuated HA vaccines
are safe and immunogenic
2. HA vaccine should be offered to children
from higher socioeconomic groups, as they
are most likely to benefit from this vaccine
3. Universal Hepatitis B vaccination
programs are effective in reducing
morbidity and burden of Hepatitis B
4. Hepatitis E and C vaccines are still in
various stages of development
References
1. Bavdekar AR, Bhave SA, Pandit AN.
Hepatitis A : treatment and its prevention. In :
Thapa BR, edi, Recent advances in Pediatric
Clinical Gastroenterology. Chandigarh,
Relume Printec, 2001; pp 282-286.
2. Arankalle VA. Hepatitis A vaccsine strategies
and relevance in the present scenario. Indian J
Med Res 2004; 119(5):3-6.
3. Just M, Berger R. Reactogenicity and
immunogenicity of inactivated hepatitis A
vaccines. Vaccine 1992; 10(1) : S110-113.
4. Balcarek KB, Bagley MR, Pass RF, Schiff ER,
Krause DS. Safety and immunogenicity of an
inactivated hepatitis A vaccine in preschool
children. J Infect Dis 1995; 171 (1): S70-72.
5. Van Herckk, Van Damme P. Inactivated hepatitis
A vaccine-induced antibodies: followup and
Indian Journal of Practical Pediatrics
estimates of long-term persistence. J Med
Virol 2001;63:1-7.
6. Dagan R, Amir J, Mijalovsky A, et al.
Immunization against hepatitis A in the first
year of life: priming despite the presence of
maternal antibody. Pediatr Infect Dis J 19,
10451052.
7. Van Damme P, Banatvala J, Fay O, et al.
Hepatitis A booster vaccination: is there a
need?. Lancet 2003; 362:1065-1071.
8. Dagan R. Leventhal A, Anis E, Slater P, Ashur
Y, Shouval D. Incidence of Hepatitis A in Israel
following universal immunization of toddlers.
JAMA 2005;295:202-210.
9. Craig A, Schaffner W. Prevention of
hepatitis A with the hepatitis A vaccine. NEng
/ Jmed 2004;350:76-81.
10. Prevention of hepatitis A through active or
passive immunization: Recommendations of
the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep
1999;48:1-37.
11. Duval B, Gilca V, Boulianne N, Deceuninck G,
Rochette L, De Serres G. Immunogenicity of
two paediatric doses of monovalent hepatitis
B or combined hepatitis A and B vaccine in 8-
10-year-old children. Vaccine. 2005; 23(31):
4082-4087.
12. Kurugol Z, Mutlubas F, Ozacar T. A two-dose
schedule for combined hepatitis A and B
vaccination in children aged 6-15 years.
Vaccine2005;23(22):2876-2880.
NEWS AND NOTES
INDIAN ACADEMY OF PEDIATRICS - CHILDHOOD DISABILITY GROUP
In association with IAP Kerala, Indian Academy of Pediatrics-Childhood Disability Group initiates
Newborn Hearing Screening Programme in 4 Districts of Kerala. Ernakulam, Calicut, Trivandrum
& Kottayam. This initiative is the first of its kind in India.
Dr. Abraham K. Paul,
Chairman,
IAP-Childhood Disability Group.
52
2006; 8(3) : 238
13. Karayiannis P, Main J, Thomas H. Hepatitis
vaccines. Br Med Bull 2004;70:29-49.
14. Zhuang F, Qian W, Mao Z, et al. Persistent
efficacy of live attenuated hepatitis A vaccine
(H2 strain) after a mass vaccination program.
Chin Med J 2005;118(22):1851-1856.
15. Poland G, Jacobsen R. Prevention of
Hepatitis B with the Hepatitis B vaccine. NEng
/ Jmed 2004;351:2832-2838.
16. West DJ, Watson B, Lichtman J, Hesley TM,
Hedberg K. Persistence of immunologic
memory for twelve years in children given
hepatitis B vaccine in infancy. Pediatr Infect
Dis J 1994; 13:745-747.
17. A comprehensive Immunisation strategy to
eliminate transmission of Hepatitis B virus
infection in the United States.
Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR
Recomm Rep 2005;54:1-33.
18. Zuckerman JN, Zuckerman AJ. Recombinant
hepatitis B triple antigen vaccine: Hepacare.
Expert Rev Vaccines 2002;1:141144.
19. WHO. Wkly Epidemiol Rec 2004;79(28):
255263
20. Hsu HY, Chang MH, Liaw SH, Ni YH, Chen
HL. Changes of hepatitis B surface antigen
variants in carrier children before and after
universal vaccination in Taiwan. Hepatology
1999; 30:1312-1317.
Dr. S.S. Kamath,
Secretary,
IAP-Childhood Disability Group.

VACCINES
RABIES VACCINE CURRENT
CONCEPTS
* Tapan Kumar Ghosh
Abstract: Several breakthroughs have taken place
since the invention of rabies vaccination by
Louis Pasteur. Semples neural tissue vaccine
(NTV) has been in use in India for nearly a
century. Modern tissue culture vaccines or
purified avian tissue vaccine have replaced the
NTV. WHO has approved two intramuscular
(Essen protocol and Zagreb protocol) and two
intradermal regimes (Oxoford ID protocol and
Thai Red Cross Society - ID protocol, ie, TRC -
ID protocol). The updated TRC - ID protocol
and KIMS-ID protocol are also suitable for Indian
population. Passive immunization by Human
Rabies Immunoglobulin (HRIG) and Equine
Rabies Immunoglobulin (ERIG), their usage,
advantages, disadvantages and failure of RIG
treatment are also discussed in this article.
Key words: Rabies vaccine, Intramuscular,
Intradermal
Rabies is a disease characterised by acute
viral encephalitis. It is said to be a disease of
antiquity known to mankind from time
immemorial.
The prevention of rabies by vaccination was
started with Louis Pasteurs anti-rabies vaccine
which was the suspension of infected rabbit spinal
cord that had been dried over caustic potash for
different period of time, at least 2 weeks time
* Scientific Coordinator
Institute of Child Health, Kolkata
53
2006; 8(3) : 239
was needed to make it non-infective. Fermi in
1908 introduced a new method in which the
vaccine was treated with carbolic acid. Fermis
method introduced uniformity of vaccine and
simplicity of preparation. In 1911, Sir David
Semple, the then director of Central Research
Institute (CRI ) Kasauli evolved the method
of preparation of dead carbolized vaccine and
since then this Semples Neural Tissue Vaccine
(NTV) has been used for nearly one century in
India.
The original neural tissue vaccine was made
from brain of the adult animal. Serial changes in
rabies vaccines took place after that and the neural
tissue vaccines was then prepared from the brain
of suckling mouse. The idea was to reduce the
content of adult myelin to avoid the incidence of
neuroparalysis. In 1956, the avian tissue vaccine
was also used successfully e.g., duck embryo
vaccine and ultimately the era of modern tissue
culture vaccine started.
WHO Expert Committee on Rabies in its
7th report has recommended abandoning the use
of neural tissue vaccine due to its serious side
effects like development of neuroparalysis
attributed to high content of myelin 1. This
recommendation was given after the availability
of modern tissue culture vaccine for the last four
decades. Following the recent ruling of Supreme
Court of India to phase out the use of NTV and
ultimately stop its use altogether in India from
2005, the production and use of NTV are stopped
and the only option left is to use modern tissue
culture vaccine (MTCV) or purified avian tissue
vaccine.
Indian Journal of Practical Pediatrics
Rabies vaccines Current Concepts
Modern Tissue Culture Vaccine
Vaccination with modern tissue culture
vaccine is the standard of practice in rabies
immunization today and MTCV is available for
2 decades in India. This is the best vaccine as
regards to safety, potency, convenience and has
several advantages over the age old NTV, ie.,
nerve tissue vaccine.
Advantages 2
Modern tissue culture vaccines (MTCV) are
highly potent, more immunogenic and less
reactogenic in comparison to neural tissue vaccine
(NTV) e.g., (i) High titer of antibody production
in shorter period, (ii) Development of detectable
antibodies within 10 days, (iii) Persistence of
antibody for longer time, (iv) Much less allergic
reactions to protein content, (v) Less number of
injections needed, which are spaced and not given
daily, (vi) Longer shelf life, (vii) Almost nil neuro-
paralytic incidence, (viii) Lack of local side effects
of NTV like, local pain, swelling, redness, abscess
formation etc, (ix) Excellent tolerance and safety
profile, (x) Capability of pre-exposure application.
Vaccine strains, production, quality control
and antigenic content Two vaccine strains are
now in use viz. Pitman Moore strain and Flury-
LEP-C25 strain. The Pitman Moore strain is
adapted to human diploid cells and vero cells.
Flury-LEP-C25 strains are adapted to primary
chick embryo cell lines.
The cell lines are infected with vaccine virus
and incubated. After incubation, the cells are tested
for heme-adsorbing viruses as well as other
extraneous agents. For vaccines derived from avian
embryos, their freedom from avian viruses and
adenoviruses is also demonstrated. The harvests
obtained are pooled, homogenized and inactivated,
usually by beta propiolactone (BPL). After
inactivation, purification and concentration, the
54
2006; 8(3) : 240
vaccine is lyophilized and the final product is
subjected to same tests of quality control as are
recommended by WHO for lyophilized neural
tissue vaccines.
Each final dose of tissue culture vaccine must
contain 2.5 IU as determined in a mouse protection
test. Nowadays liquid vaccine namely, liquid
human diploid cell vaccine is also available in India.
Various protocols of modern tissue culture
vaccines
There are various protocols or regimes of using
modern tissue culture vaccine in animal bite cases,
of which WHO has approved 2 intra-muscular
and 2 intradermal regimes.
1. Intramuscular Regimes: Two intramuscular
regimes approved are Essen protocol and Zagreb
protocol.
(1a) Essen protocol : The six dose schedule spread
over a period of three months was recommended
at an International Conference on Rabies, held at
Essen, Germany, and is popularly known as Essen
schedule. Nowadays in place of 6 doses, 5 doses
are recommended i.e. on days 0, 3, 7, 14 and 28.
The dose on day 90 is optional and is only used
in cases of immunodeficiency, extremes of age
and presence of debilitating condition. Day 0
indicates the date of the first injection. The dose
of purified chick embryo cell vaccine (PCECV)
and human diploid vaccine (HDCV) is 1 ml and
in case of purified vero cell vaccine it is 0.5 ml.
Table 1 shows the Essen Protocol for rabies
vaccination.
Table 1. Essen protocol
Day of Vaccination No.of doses
Day 0 1
Day 3 1
Day 7 1
Day 14 1
Day 28 or Day 30 1
Day 90 1

(1b) Zagreb protocol : Another intra-muscular
regime is Zagreb protocol or short IM protocol,
where 2 doses are given at separate sites on day 0
and subse-quently single dose given on day 7 and
day 21, so 4 doses are given in 3 sittings. This is
an equally effective schedule, though not
recommended in countries like India, which are
considered as the hyperendemic for rabies. This
schedule induces early and enhanced immune
response initially but when given along with RIG
leads to poor development of antibodies on long
term3. Table 2 shows the Zagreb schedule of rabies
vaccination.
Table 2. Zagreb protocol
Day of No. of Doses
vaccination
Day 0 2 extensive use of this most cost effective schedule
Day 7 1 Thai Red Cross Society has brought down the
Day 21 1 incidence of rabies death drastically in Thailand
(1c) Pre exposure intramuscular schedule:
In pre-exposure IM schedule 3 doses are
recommended in India. First dose is given on day
0, 2nd on day 7 and 3rd on day 28. The dose used
is the same as used for post-exposure prophylaxis.
Booster dose is indicated at the end of 1st year
and then every 3 years, though it is better to
estimate the antibody titer if possible before giving
the boosters (if titer is less than 0.5 IU/ml, the
booster is indicated). Pre-exposure prophylaxis is
only possible with MTCV. The pre-exposure is
given to high risk groups like (i) veterinarians (ii)
laboratory personnel working with rabies virus,
(iii) medical and paramedical personnel treating
rabies patients, (iv) dog catchers/dog pound
workers, (v) forest staff, (vi) zoo keepers,
(vii) postmen,(viii) policemen, (ix) courier boys,
(x) school children in endemic countries4 etc.
2. Intradermal regimes
Though there are 2 regimes approved by
WHO namely, 8 doses Oxford regime and 2 doses
55
2006; 8(3) : 241
Thai Red Cross (TRC-ID) regime, there are other
protocols too. These two intradermal (ID)
schedules have been found to be equally
immunogenic and effective if given by experienced
hands5. This has been studied and found cost
effective in bringing down the mortality due to
rabies and unfortunately are yet not widely
practiced6,7.
(2a) 2-2-2-0-1-1 (Thai Red Cross Intradermal
Schedule or TRC-ID Schedule): Two ID doses,
one on each deltoid region, are given on day 0,
day 3 and day 7; and one ID dose on any one
site of deltoid on day 28 and day 90. No dose is
given on day 14. One ID dose should be 1/5th
the quantity of IM dose depending on vaccine,
though 0.1 ml of purified chick embryo cell vaccine
is also used successfully in Thailand. With the
in last one decade. We should think of this cost
effective schedule in our country. We should plan
to give training to the personnel to make him/her
a skilled worker in vaccine centers and help our
country to avail of this opportunity of using cell
culture vaccine in animal bite cases at a much
cheaper cost. Table 3 shows TRC-ID schedule.
Recently Drug Controller General of India has
approved this schedule with PVRV or PCEC
vaccines in centers where there are 50 cases of
postexposure cases per day.
(2b) Updated TRC-ID Schedule8: TRC-ID
Schedule is modified by omitting the dose on day
90 and 2 doses are given on day 28 in place of
1 dose. Table 4 shows the updated TRC-ID
Schedule. This schedule is also recommended by
DCGI as above.
(2c) Kempegowda Institute of Medical Sciences
Bangalore, has tried another modified regime
of TRC-ID Schedule Their work is also very
well appreciated by the medical fraternity. This is
Indian Journal of Practical Pediatrics 2006; 8(3) : 242

Table 3. TRC-ID Schedule or 2-2-2-0-1-1 Schedule*

Day of PVRV** PCECV*** No. & Site of
Immunization Injection
Day 0 0.1 ml 0.2 ml 2 : Left and right deltoids
or anterolateral thighs
Day 3 0.1 ml 0.2 ml - do -
Day 7 0.1 ml 0.2 ml - do -
Day 14 None None None
Day 30 0.1 ml 0.2 ml 1 : deltoid
or anterolateral thigh
Day 90 0.1 ml 0.2 ml - do -
* This schedule is also practiced officially in Philippines and Sri Lanka
** Purified Vero Cell Vaccine
*** Purified Chick Embryo Cell Vaccine
Table 4. Updated TRC-ID schedule or Table 5. KIMS Bangalore Modification
2-2-2-0-2-0 schedule of TRC-ID Schedule or 2-2-2-2-2-0
schedule
Day 0 - One ID dose x 2 sites
Day 0 - One ID dose x 2 sites
Day 3 - One ID dose x 2 sites
Day 3 - One ID dose x 2 sites
Day 7 - One ID dose x 2 sites
Day 7 - One ID dose x 2 sites
Day 14 - No dose
Day 14 - One ID dose x 2 sites
Day 28 - One ID dose x 2 sites Day 28 - One ID dose x 2 sites
Day 90 - No dose Day 90 - No dose

an effective schedule for India, a highly endemic
country for Rabies6. In this schedule 2 ID doses
are given on all the days i.e. day 0, day 3, day 7,
day 14 and day 28. Table 5 shows KIMS
Bangalore Modification of TRC-ID Schedule.
(2d). 8-0-4-0-1-1 schedule (Oxford schedule or
Warell and Nicholson schedule)7 : One ID dose
is 0.1 ml each given on 8 sites on day 0. The sites
are deltoids (two), lateral side of thighs (two),
suprascapular regions (two) and lower quadrant
of abdomen on either side (two). No dose is given
on day 3. Then 4 doses are given on day 7, the
sites are deltoids and thighs on either side. No
dose is given on day 14. One dose is given on day
28 and on day 90. Table 6 shows the 8-dose ID
Schedule.
56
(2e) Pre-exposure ID schedule for prophylaxis.
Here 0.1 ml of PCEC is given on day 0, day 7
and day 21/28. So total 3 ID doses are given.
Table 7 shows pre-exposure ID schedule.
The volume per intradermal site is usually
one-fifth of IM dose
(a) 0.1 ml of PVRV (Purified vero cell vaccine,
0.5 ml vial)
(b) 0.2 ml of PCECV (Purified chick embryo cell
vaccine 1 ml vial)
(c) 0.1 ml of PCECV may also be considered for
use by National health authorities as approved by
WHO
Report of multicentric study with ID schedule has
already published in India, approved by National
 2006; 8(3) : 243

Table 6. 8-0-4-0-1-1 Intradermal schedule (Oxford schedule) or Warell and

Nicholson schedule)
Day of PCECV No of Site of injection
Immunization doses
Day 0 0.1 ml 8 Deltoid (2), anterolateral thigh (2),
lower quadrant of abdomen (2),
suprascapular region (2)
Day 3 - NiL -
Day 7 0.1 ml 4 Deltoid (2), anterolateral thigh (2)
Day 14 - Nil -
Day 28 0.1 ml 1 Deltoid (1)
Day 90 0.1 ml 1 Deltoid (1)

Table 7. Pre-exposure ID schedule for prophylaxis

Schedule PVRV (Dose in ml) PDEV/PCEC(Dose in ml)

D0 D7 D 21/28 D0 D7 D 21/28

Intradermal 0.1 0.1 0.1 0.1 0.1 0.1

OR
Intramuscular 0.5 0.5 0.5 1.0 1.0 1.0

Institute of Communicable Disease (NICD), New
Delhi and actively supported by Association for
Prevention and Control of Rabies in India
(APCRI), Bangalore9. It is felt by many that the
implementation of ID schedule is the only
economical, scientific and viable alternative to use
MTCV at all anti-rabies clinics of India and very
recently DCGI has started giving permission to
MCID schedule in a phased manner.
Rabies Immunoglobulin (RIG)
The discussion on anti-rabies vaccination cannot
be complete without mentioning the role of RIG
in prevention of rabies. RIG infiltration is the
passive method of protection, whereas the
vaccination is the active mode of protection. Both
57
are important specially in the category III (WHO)
cases where there is (are) transdermal wound(s).
There are 2 types of rabies immunoglobulin
namely, (i) Human rabies immunoglobulin (HRIG)
and (ii) Equine rabies immunoglobulin (ERIG).
The dose of HRIG is 20 IU/kg of body weight
whereas the dose of ERIG is 40 IU/kg of body
weight. It is to be kept in mind that a skin test
prior to application of ERIG is medicolegally very
important. RIG neutralizes rabies virus on contact.
RIG gives a coating to the virus so that it cannot
enter the nerve ending resulting in reduction or
total obliteration of inoculated virus.
Choice of RIG: Though HRIG represents the
gold standard for passive immunization, the cost
of HRIG is exorbitantly high making it impossible
Indian Journal of Practical Pediatrics
to afford by majority of patients of our country.
Supply of HRIG is also erratic. ERIG is an
acceptable alternative. The crude anti-rabies serum
(ARS) is related with high incidence of
anaphylactic reaction and induction of serum
sickness. Now the crude ARS has been replaced
by purified and pepsin-digested product which is
far safer and can be used with confidence. The
increased production of highly purified equine
immunoglobulin (ERIG) should be promoted to
provide an alternate effective solution to the
problems of supplies of human immunoglobulin
(HRIG) and the cost involved1. One study shows
that the incidence of adverse reaction is as low as
2.4% with anaphylactic reaction of 0.2% 10.
Another study shows 1.7% serum sickness
reaction in a series of 297 cases 11. In Thai
population it was reported by Wilde et al to be as
low as 0.81%6. Presently the purified ERIG
preparation has been available and produced by
Indian manufacturers. CRI, Kasauli also produces
a small quantity ARS which is insufficient for a
vast country like India.
Failure of RIG treatment: Failure occurs if RIG
is not used locally but administered only
systemically. Local infiltration of the wound is
essential in order to neutralize virus before it can
enter the nerve endings. Other causes of RIG
treatment failure are: (i) Insufficient quantity of
RIG used. (ii) Time interval from the time of bite
to RIG administration if it is unusually delayed.
Theoretically as well as practically RIG
administration should start simultaneously with
first dose of vaccine administration but not in same
site. Use of RIG after 7 days of bite or after 3
doses of vaccination may result in failure. (iii)
Same site of injection of RIG and anti-rabies
vaccine (ARV). (iv) When infiltration of some
wounds are not done. It has been experienced
especially in children that quantity of RIG
calculated according to body weight is small and
insufficient in a good number of cases where
wounds are extensive. So, inexperienced person
58
2006; 8(3) : 244
may leave some wounds without infiltration with
RIG. It is better to dilute the RIG 2 to 3 folds
with normal saline in this type of cases so that all
wounds can be covered. (v) RIG is administered
alone without the use of vaccines This is most
unscientific decision. The rationale of use of RIG
is to neutralize the virus immediately as 7 to 14
days time is taken for ARV (MTCV) to achieve
the desired antibody level but RIG has no long
standing effect which vaccines can only achieve.
Points to remember
1. Modern tissue culture vaccines are the only
suitable vaccines for rabies prophylaxis
2. Intradermal (ID) schedules approved by
WHO are found to be equally immuno-
genic and should be adopted in all anti
rabies clinics in our country in view of their
efficacy and cost effectiveness. This will be
introduced in phased manner
3. Local administration of rabies immuno-
globulin (Human or Equine) is indicated
in all cases of transdermal wounds along
with rabies vaccination.
References
1. WHO Experts Committee on Rabies, Seventh
Report. WHO Techn Rep Series 709. Geneva
: WHO, 1994 68-70.
2. Ghosh TK. Rabies Control How to Make
MTCV Cost Effective at Individual and
Community Level. In : Ghosh TK, ed.
Infectious Diseases in Children and Newer
Vaccines, Part 1. Kolkata : IAP Infectious
Diseases Chpater, 2003; 159-165.
3. Dutta AK, Kanwal SK. Rabies and its
prevention. J Assoc Prev Control Rabies India
1999; 1(1): 5-13.
st
4. Background Document and Slide Text. 1
National Workshop for APCRI Training in
Modern WHO approved Rabies Prophylaxis
st
held on 31 March 2001 at National Institute
of Mental Health and Neurosciences.
Bangalore : Association for Prevention and
 2006; 8(3) : 245

Control of Rabies in India. 2001; slide no.35-
36.
5. Madhusudana SN. Recent advances in Rabies.
In : Proceedings of the Conference II on
Rabies Prevention and Management,
Kathmandu. November 20-24, 2003: 17-20.
6. Wilde H, Chomchey P, Prakongsri S,
Punyarathabandhu P. Safety of equine rabies
immunoglobulin. Lancet 1987; 2 : 1285.
7. Warell MJ, Nicholson KG, Sitharasami P,
Udomaskadi D. Economical multiple site
intradermal immunisation with human diploid
cell strain vaccine is effective for post-
exposure rabies prophylaxis. Lancet 1985; 1 :
1059-1062.
8. Ghosh TK. Beginning of the end of the rabies
in India. Bulletin of Infectious Diseases
Chapter of Indian Academic of Pediatrics.
2005; 5 : 1-5.
9. Madhusudana SN, Editor. Peoceedings of
National Seminar on ID Rabies Vaccination
Bangalore 2003, Bangalore , APCRI; 2005.
10. Tripathi KK, Madhusudana SN. Safety of equine
rabies immunoglobulin. Vaccine 1989; 7 : 372-
373.
11. Goswami A. Safety and tolerance of equine
rabies immunoglobulin in the Indian
popu lation. J Assoc Prev Control Rabies India
2000; 1 : 30-34

NEWS AND NOTES

ANNUAL CONVENTION
NATIONAL NEONATOLOGY FORUM
TAMILNADU CHAPTER
4th & 5th November 2006.
Theme : COMPREHENSIVE NEWBORN CARE

Venue : Hotel Green Park, Chennai

Conference Secretariat :
Dr. J. Kumutha, Organising Secretary
22, Temple Street, Alagappa Nagar, Kilpauk, Chennai 600010
Ph-044-26446431 E-mail: githkarthi@yahoo.co.in / Dr_kumutha@yahoo.com
Registration Before
30-09-2006 Spot
Delegate Fees
(Include CME) 750 1,000
PG student 500 1,000
NRP 500 -
Transport Workshop 500 -
Nurse Workshop 250 -
Accompanying Person 600
D.D should be drawn in favour of CHENNAI NEOCON 2006 payable at Vijaya Bank,
Kilpauk, Chennai

59
Indian Journal of Practical Pediatrics 2006; 8(3) : 246

RADIOLOGIST TALKS TO YOU

HEPATOMEGALY AND HEPATIC multiple, found incidentally and do not require

MASSES- 2 any further investigaton2.
*Vijayalakshmi G Sometimes they are large and present a more
**Elavarasu E complex appearance (Fig 2). There are echogenic
**Porkodi areas because of closely packed channels and
***Malathy K fibrosis, cystic areas because of hemorrhage and
***Venkatesan MD lysis of thrombi and bright specks because of
calcification. There may be tubular structures
Primary liver tumors are rare and malignant
representing venous channels, more in the
liver tumors are generally more common than
periphery. These are seen better with Doppler
benign tumors. In neonates and infants one should
though flow may be too slow to give a good
always think of benign tumors like cavernous
Doppler signal. On CT they are seen as low
hemangiomas and hemangioendotheliomas.
attenuated or isodense lesions. On contrast
Among malignant tumors, hepatoblastoma is seen
administration they show peripheral nodular
in children less than five and the extremely rare
enhancement. Later films will show central
hepatocellular carcinoma after ten years of age1.
enhancement. Hemangiomas are hypointense on
Metastases to the liver must also be considered in
T1 weighted images and hyperintense on T2
the differential diagnosis.
images. Inhomogeneity may also be seen as in
Tumors of the liver look so much alike in ultrasound.
imaging that it is often confusing. There are certain The infantile hemangioendothelioma has an
classical findings for each type that are not seen interesting appearance. In ultrasound they are seen
in all cases. However, one easily identifiable lesion
is a cavernous hemangioma when it is seen as a
solid, echogenic, round lesion mostly situated in
the peripheral parts of the liver (Fig.1).
Hemangiomas consist of multiple vascular
channels lined by endothelium.Therefore there are
multiple interfaces reflecting the ultrasound beam
which is why it appears bright. They are often

* Addl.Professor
** Tutor in Radiology
*** Reader
**** Professor
, Department of Radiology,
Chenglepet Medical College Hospital, Chenglepet Fig. 1. Cavernous hemangioma
60

as multiple hypoechoic lesions 3,4,5 (Fig 3).
Bloodflow through the lesion is so much that the
preferential flow into the tumor reduces flow to
the peripheries of the body. The aorta is of normal
or increased caliber proximal to the take-off of
the hepatic artery while distally it appears thin.The
Fig. 2. Complex cavernous hemangioma in
a newborn with Jaundice
Fig. 3. Infantile hemangioendothelioma
61
2006; 8(3) : 247
hepatic artery is also wider6,7. The patient may
present with high-output cardiac failure.On CT
they are seen as hypodense areas in the plain
images (Fig 4). Late films after contrast show
brilliantly enhancing lesions that are so typical of
this lesion8 (Fig 5). MRI shows similar features.
Fig. 4. Infantile hemangioendothelioma CT
plain
Fig. 5. Infantile hemangioendothelioma - CT
contrast
Indian Journal of Practical Pediatrics
Fig. 6. Hepatoblastoma
The hepatoblastoma is a solid tumor (Fig 6)
that may have a heterogenous appearance.
Calcifications may be present in some histological
types. After contrast, in CT, they show patchy
enhancement. Hepatoblastomas may look very
much like a large, complex hemangioma9,10. In
that case only histological diagnosis will give the
answer. However, if fine-needle biopsy yields
only some blood and endothelial cells it is either a
non-diagnostic sample or a case of hemangioma.
Therefore we are left with the same differential
diagnosis. Alphafetoprotein levels may help in these
cases. VMA levels can help in metastatic
neuroblastomas.
62
2006; 8(3) : 248
Thus diagnostic evaluation of liver tumors
needs an integrated approach combining clinical
features, laboratory tests and radiological imaging.
References
1. Weinberg AG, Finegold MJ. Primary hepatic
tumors in childhood. In: Finegold MJ, ed.
Pathology of neoplasia in children and
adolescents. Philadelphia: WB Saunders,
1986;333.
2. Jabra AA, Fishman EK, Taylor GA. Hepatic
masses in infants and children: CT evaluation.
AJR 1992;158:143-149.
3. Siegel MJ. Liver and biliary tract. In Siegel Mj,
ed. Pediatric Sonography. 2nd ed. New York,
Raven Press, 1995;186-187.
 2006; 8(3) : 249

4. Boon LM, Bourrows PE, Paltiel HJ, et al.
Hepatic vascular anomalies in infancy: a
twenty-seven-year experience. J Pediatr
1996;129:346-354.
5. Paltiel HJ, Patriquin HB, Keller MS, et al.
Infantile hepatic hemangioma: doppler US.
Radiology 1992;182:735-742.
6. Abuhamad AZ, Lewis D, Inati MN, et al. The
use of color flow doppler in the diagnosis of
foetal hepatic hemangioma. J ultrasound
Med.4.22,1933.
7. Mejides AA, Adra Am, OSullivan Mj,
Nicholas MC. Prenatal diagnosis and therapy
for foetal hepatic vascular malformation.
Obstet Gynecol 1995;85:85
8. Lucaya J, Enriquez G, Amat L, Gonzalex-
Rivero MA. Computed tomography of infantile
hepatic hemangioendothelioma. AJR
1985;144:821-826.
9. King SJ, Babyn PS,Greenberg ML, et al: Value
of CT in determing the reectbility of
hepatoblastoma before and after
chemotherapy. AJR Am J Roentgenol 1993;
160(4):793-798.
10. Miller J, Greenspan B. Integrated imaging of
hepatic tumours in children. Part I. Malignant
lesions (primary and metastatic). Radiology
1985;145:83-90.

NEWS AND NOTES

COMPED 2006
FIRST NATIONAL CONFERENE OF COMMUNITY PEDIATRICS
(SUBCHAPTER OF IAP)
Date: 11th & 12th November 2006
Organized by: IAP Chhattisgarh State Branch & IAP Raipur Branch
Venue: Hotel Babylon International, VIP Road, Raipur.
Registration Fee Upto 31st Oct. 2006 SPOT
Delegates IAP Rs.1,000/- Rs.1,200/-
Delegates Non-IAP Rs.1,200/- Rs.1,400/-
Postgradyate student Rs. 800/- Rs.1,000/-
Demand draft should be sent in favour of COMPED 2006 payable at Raipur (c.g.)
*Scientific paper on community pediatrics are invited for presentation before 15th October 2006
Contact : Dr. Ashwani Agrawal, Organizing Secretary, C/O Swapnil Nursing Home, Civial Lines,
Raipur (c.g.) 492001. Phone no. : 0771-2424111, 0771-2593093 Mobile no. 94252 08789
E-mail : drakagr_r@yahoo.co.in or annopve@yahoo.com

Karnataka State PEDICON 2006, Karnataka October 7-8, 2006

Contanct : Dr. Nitin Tikare, Organizing Secretary, Dr. Bidaris Ashwini Hospial. B.L.D.E. Road,
Bijapur 586 103, Karnataka.
Ph. : (H) 08352 - 261128. Mo. 09844363382. E-mail : pedicon2006@rediffmail.com

63
Indian Journal of Practical Pediatrics 2006; 8(3) : 250

CASE STUDY

MILROYS DISEASE distension. There was no history of dyspnoea on

exertion, no cyanosis, no redness or warmth over
*Farzana.Beg the swelling. His mother and maternal great
*Ajit Saxena grandmother had similar swelling of their feet.
*Imteyaz Ahmad Khan
*Siraj N Huda On examination: He was lethargic, pale, not
*Faisal Haque dyspnoeic, with no facial dysmorphism and had
bilateral pitting pedal oedema of his feet.(Fig1).
Abstract: Milroys disease is a rare familial System examination was normal.
disorder of the lymphatic vessels characterized
by hypoplasia of the lymphatics, presenting as
congenital lymphoedema. We report a toddler who
presented with disturbing cough and increasing
pallor of a short duration and swelling of both
his feet since birth. On treatment the presenting
symptoms improved but the pedal oedema
persisted.
Key words: Lymphoedema, Milroys disease.
Milroys disease is due to hypoplasia or
aplasia of the lymphatic vessels and constitutes
5-10% of primary lymphoedema. It usually occurs
from birth or may be noted later in life it is more
common in females and presents as bilateral pedal
oedema. Prevention of complications is important Fig. 1. Pedal oedema in mother and child
in the management of Milroys disease and surgery Invesitgations: The complete blood count
plays a very minor role. showed Hb of 6.8Gm/dl, total WBC 16,000 cells/
Case summary: A one year four months old boy cumm with a differential of 73% neutrophils. The
born to consanguineous parents was brought with renal function tests and serum transaminases were
cough and increasing pallor of 8 days duration. normal. Total protein was 5.3Gm/dl with albumin
His parents had noted swelling of his feet since 2.9 Gm/dl. X ray chest showed consolidation of
birth which was non progressive and not the right upper lobe which resolved with
associated with puffiness of face or abdominal antibiotics. Ultrasound of the abdomen was normal.
Colour doppler of the lower limb for both the
* Dept. of Pediatrics & Radiodiagnosis
child and his mother did not identify any
J.N.Medical College. arteriovenous malformation. He was prescribed
A.M.U., Aligarh, Uttar Pradesh. iron supplements and his mother was advised
64

regarding diet. He responded to therapy but the
swelling of his feet persisted.
Discussion: The eponym Milroys disease was
given by Sir William Osler and hereditary
lymphoedema of the legs described by Nonne in
1891. In 1892 Milroy described a 31 years
clergyman who had returned from India with
swelling of his legs. Milroy studied the 250 years
family records of this patient and identified 22
patients in his family. Meige described the same
condition in 1898.
Primary lymphoedema can be of different types
depending on the age of onset. Milroys disease
(Nonne-Milroy Syndrome)usually occurs soon
after birth or within the first year of life. Meige
syndrome is a non congenital familial
lymphoedema which occurs during puberty. It also
involves the feet but is not associated with
intestinal lymphangiectasia. Lymphoedema
praecox is the most common type and constitutes
80% of primary lymphoedema and occurs before
the age of 35years. Lymphoedema tarda occurs
after the age of 35years.
Syndromic Lymphoedema: Several syndromes can
be associated with lymphoedema in children.
They are Turners, Noonans, Klienfelter, Downs,
Amniotic band syndrome and Klippel Trenuay
Weber syndrome and Lymphoedema Distichiasia
Syndrome.
Milroys disease has a predilection for females
and there is usually a positive family history. The
oedema in Milroys disease is described as a
brawny swelling which pits on pressure and is
soft to touch. It is restricted to the dorsum of the
feet. The right leg being involved more than the
left. It may involve the arms, hands, face and
also the intestinal lymphatics. The intestinal
NEWS AND NOTES
RAJ PEDICON 2006 11th & 12th November 2006
Contact : Dr. J.N. Sharma, Email: drsharmajn@rediffmail.com
65
2006; 8(3) : 251
involvement may result in protein losing
enteropathy. Some have associated cystic
hygroma of the neck or pulmonary
lmphangiectasia. The disease is inherited as
autosomal dominant with incomplete penetrance
(about 50%). A tyrosine kinase receptor, specific
for lymphatic vessels has been reported to be
abnormally phosphorylated in patients with
Milroys disease. The gene for this disease,
VEGFR3 Vascular Endothelial Growth Factor
Receptor 3(FLT4), has been mapped to the
telemeric part of chromosome arm 5q in the region
5q34-q35. The complications of Milroys disease
include cellulitis, lymphangitis, bacteremia,
chylothrax, chylous ascites, protein losing
enteropathy and lymphangiosarcoma. The
diagnosis is usually clinical but lymphangiography,
lymphoscintigraphy and MRI are useful
techniques. The management of Milroys disease
is supportive and includes excercises, elastic
stockings, bandages, gentle message, elevated
positioning of legs and pneumatic compression.
Cellulitis has to be treated adequately with
antibiotics. Surgery has a very limited role in the
management of Milroys disease.
Reference
1. Dale RF. The inheritance of primary
lymphoedema. J Med Genet 1985;122:274-
278.
2. Ko Ds, Lerner R, Klose G, Cosimi AB.
Effective treatement of lymphedema of the
extremities. Arch Surg 1998;133:452-458.
3. Mortimer PS, Swollen lower limb -
lymphoedema. Br Med J 2000;320:1527-
1530.
4. Tiwari A, Cheng KS, Buttun M. Diffrential
dignosis invariyable and current treatment of
lowe limb lymphoede. Arch Surg
2003;138:152-161.
Indian Journal of Practical Pediatrics
CASE STUDY
NECROTIZING FASCITIS
*Shrishu R Kamath
*Anjul
*Rajeshwari
**Balaji V
***Suchitra Ranjit
****Radha Rajagopalan
Abstract: A 14 year old child presented with
necrotizing fascitis following a trivial trauma.
The presentation was of toxic shock syndrome
with multiorgan dysfunction. Aggressive early
debridement, targeted antibiotics and supportive
PICU care played a key role in his recovery.
Keywords: Necrotizing fascitis, Multiorgan
dysfunction, Toxic shock syndrome.
Necrotizing fascitis is a potentially life threatening
condition characterized by rapidly advancing local
tissue destruction and systemic toxicity. The onset
is acute with swelling of the skin and subcutaneous
tissues followed by systemic toxicity. Early
debridement and antibiotic therapy help in early
recovery. We present a child with necrotising
fascitis who had a stormy course necessitating a
co-ordinated multi-disciplinary approach to
management.
Case report
A 14 year old adolescent boy was brought
with history of fall in the toilet 14 days earlier,
* Registrar, Peditric Intensive Care Unit
** Surgeon, Department of Vascular Surgery
*** HOD, Pediatric Intensive Care Unit
**** Head of Pediatric Department
Apollo Hospitals, Chennai.
66
2006; 8(3) : 252
following which there was a progressively
increasing swelling of thigh along with yellowish
discoloration of eyes. As the boy developed
decreased urine output he was admitted.
On examination in the Emergency Room, he
was well nourished, had icterus and was toxic.
His vitals were stable and capillary refill time was
2 seconds. He had generalized swelling of the right
thigh which was extending till the upper half of
the calf. This swelling was warm, tense and tender.
There was a small discolored patch of 3 x 2 cms
in the back of the thigh. Physical examination
revealed an enlarged liver 3cm below the right
costal margin without spleno megaly. Other
systems were normal.
A possible diagnosis of cellulitis with hepatic
and renal dysfunction was considered. He was
admitted to the PICU for observation. Over the
next 4 hours there were subtle changes in his vital
parameters. He remained afebrile, oriented and
normotensive but developed progressive
tachycardia and effortless tachypnoea. The heart
rate increased from 90/minute to 130/minute and
respiratory rate went up to 40/minute from a
baseline of 20 breaths per minute. However, he
continued to have a good urine output and
remained well oriented and afebrile. There was
also a progressive increase in the size of the
discolored patch on the back of his thigh along
with the appearance of surrounding blebs. Evolving
toxic shock resulting from necortising fascitis was
considered on account of the presence of skin
necrosis with progressive changes in vital
parameters.
Blood gas analysis revealed significant
metabolic acidosis with compensatory respiratory

Fig. 1. The picture depicts the extent of tissue destruction and debridement being done.
alkalosis. This explained the tachypnoea and
supported the diagnosis of septic shock.
Aggressive fluid resuscitation was initiated and
central line was inserted in the inernal jugular vein
for CVP (Central Venous Pressure) monitoring.
Despite adequate fluid resuscitation his CVP
remained low (4mmHg) suggesting the presence
of capillary leak.
Further fluids were administered, but acidosis
persisted. He developed respiratory distress and
hypotension. He was electively intubated and
ventilated in order to facilitate full fluid
resuscitation and reverse the rapid deterioration
in his vital parameters.
At this time his total counts were
42,000/cmm with predominant polymorphs.
He had thrombocytopenia (Platelet count -
97,000/cmm). His urea was 178mg/dl and
creatinine 1.8 mg/dl. His total bilirubin was
17.3mg/dl and direct bilirubin was 14.4mg/dl
SGPT was 351U/L and SAP was 8031U/L,
GGTP was 351U/L with albumin of 2.3gm/dl and
67
2006; 8(3) : 253
globulin of 3.2gm/dl. His coagulation parameters
were deranged, Prothrombin time was 58 secs
(Control13secs), Activated Partial
Thromboplastin Time was 98secs (Control
30secs). His urine myoglobulin and haemoglobin
were negative. Echo cardiogram was normal.
Doppler of the affected limb was normal. Culture
and ASO titers were non contributory.
Maximal dose antibacterials were initiated
with Piperacillin/Tazobactum and Clindamycin.
Child was taken up for immediate fasciotomy and
wound debridement. Infectious disease
consultation was sought and was advised
intravenous gamma globulin in addition to the
antibiotics. Appropriate blood products were
administered. 48 hours post surgery, fever
appeared for the first time with a further increase
in total white cell count and recurrence of
metabolic acidosis. A Computed Tomography
Scan (CT) of the thigh showed reappearance of
pus pockets with no intra-abdominal extension.
The child was taken up for re-debridement and
following this, rapid and steady improvement in
Indian Journal of Practical Pediatrics
clinical and laboratory parameters allowed weaning
off from ventilation and vasoactive support by
day 4 of his PICU stay. He required prolonged
hospital stay on account of the need for multiple
sittings for skin-grafting.
Discussion
Necrotising Fascitis: Since 1980s there was
marked increase in the recognition and reporting
of necrotising fascitis and associated toxic shock
syndrome. The British tabloids coined the
termFlesh Eating Bacteria to describe invasive
necrotising infections caused by Group A
Streptococcus(GAS). Necrotising soft tissue
infections are potentially life threatening conditions
characterized by rapidly advancing local tissue
distribution and systemic toxicity. Tissue necrosis
differentiates this condition from cellulitis. In
cellulitis, an inflammatory process involves the
subcutaneous tissue but does not destroy it.
Necrotising soft tissue infection presents with early
cutaneous signs. However the extent of cutaneous
signs may be disproportionate to the rapidity and
degree of destruction of subcutaneous tissue.
Streptococcus pyogenes and Staphylococcus
aureus are the most common agents. Occasionally
other gram positive cocci and or rarely Escherichia
coli may be responsible. In patients who are
Table 1. CDC case definition of Necrotising Fascitis
Suspected case
1. Necrosis of tissue with involvement
of the fascia plus
2. Serious systemic disease including
one or more of the following:
a. Death
b. Shock(Syst BP<90mmHg)
c. DIC
2006; 8(3) : 254
immunocompromised or have diabetes mellitus,
a number of fungal or bacterial agents may be
involved. These are Pseudomonas aeruginosa,
Aeromonas hydrophila, Enterobateriaceae,
Legionella spp, the Mucorales, particularly
Rhizopus spp. It may be polymicrobial with a
mixture of anerobic and aerobic bacteria. Infection
may be due to any one single organism or
combinations of organisms such as Clostridium,
E.coli, Klebsiella, Proteus and Aeromonas. In the
absence of toxic shock syndrome, streptococcal
necrotising fascitis is seldom fatal but may be
associated with substantial morbidity.
The most common location of necrotising
fascitis is on the extremities, abdomen and perineal
region. In neonates, the commonest predisposing
factors are omphalitis and balanitis occurring after
circumcision. Predisposing factors are
immunosuppression, extremes of age, diabetes
mellitus, neoplasia or vascular surgery. A healthy
individual may acquire infection by blunt trauma,
abrasions, laceration, hypodermic needle injection
or following a surgical procedure.
Clinical manifestations : The onset of
necrotizing fascitis is abrupt with local swelling,
erythema and tederness resulting from the
destruction of subcutaneous tissues, fascia and
Definite case
1. 1+2and serologic confirmation of group A
streptococcal infection by a 4 fold rise against:
a.Streptolysin O
b.DNAse B
2. 1+2 and histologic confirmation of gram-postive
cocci in a necrotic soft tissue infection.
68

sometimes muscles. Skin changes occur 48 hours
later when ill-defined cutaneous erythema and
edema may be seen. Constitutional signs are
frequently out of proportion to the visible
cutaneous sings. Fluid filled bullae appear and
finally, frank tissue gangrene, ischaemia and
necrosis occur. Vesiculation or bulla, crepitus and
local anaesthesia are ominous and indicative of
advanced disease. Significant systemic toxicity
may accompany necrotising fascitis including
shock, organ failure and death. Rapid progression
to death can occur within hours.
In an extremity, a compartment syndrome
may develop which will manifest as tight edema,
pain on movements and loss of distal sensation
and pulses. This is a surgical emergency. Definitive
diagnosis is made by surgical exploration. Necrotic
fascia and sub cutaneous tissue are gray and offer
minimal resistance to probing. MRI and CT scan
aid in delineating the extent and tissue planes of
involvement, but these procedures should not
delay surgical intervention. During surgery, frozen
section incisional biopsy may help to delineate
margins of involvement.
Treatment : Early supportive care and
debridement by surgery are paramount. All
devitalized tissue has to be removed to freely
bleeding edges and repeat surgery may be required
until no necrotic tissue remains. Antibiotic therapy
should be initiated as soon as possible. Initial
therapy with broad spectrum antibiotics is
NEWS AND NOTES
FIFTH NATIONAL CME IN NEONATOLOGY, NEW DELHI.
February 10-11, 2007
Contact: Dr.Ramesh Agarwal, Assistant Professor,
Department of Pediatrics, All India Institute of Medical Sciences,
New Delhi - 110 029.
Tel.: 011-26593621 Fax : 011-26862663
E-mail : aranag@rediffmail.com
69
2006; 8(3) : 255
necessary. Crystalline penicillin has been
hypothesized to Inoculum effect where by it is
suggested that large inocula reach the stationery
phase of growth sooner than smaller inocula and
pencillin cannot act during the stationery phase.
Use of intravenous gamma globulin is also
effective and is thought to act by decreasing toxin
production.
The greater efficacy of clindamycin may be
multifactiorial: It is not affected by inoculums size
or stage of growth. Clindamycin is a potent
suppressor of toxin synthesis. It facilitates
phagocytosis of organism by inhibiting M-protein
and all enzymes involved in cell wall synthesis
and degradation, longer post antibiotic effect and
suppresion of synsthesis.
Bibliography
1. Bisno AL, Steven DL: Strepcoccal infections
of skin and soft issues. N Engl.J.Med 1996;
334:240
2. Brogan TV, Nizet V, Werldhaisen JH et al:
Group A Streptococcus necrotising fascitis
complicating varicella : A series of ten patients
Pediatr Infect Dis J 1995; 14:588
3. Steven DL: Invasive group A Streptococcal
infections: The past, present and future, Pediatr
Infect Dis J 1994; 13:561
4. Stevens DL: Streptococcal Toxic Shock
Syndrome: Spectrum of disease , pathogenesis
and new concepts in treatment. http://
www.cdc.gov/ncidod/EID/volno3/stevens.htm
Indian Journal of Practical Pediatrics
CASE STUDY
MCKUSICK - KAUFMAN:
HYDROMETROCOLPOS
POLYDACTALY - A RARE SYNDROME
*Sridharan S
**Pradip Vincent
***Ramesh S
Abstract : Discovery of an abdominal mass in a
neonate presents a challenging problem in
diagnosis and treatment. We present a neonate
with a large midline abdominal mass. Clinically
and sonologically it was proven to be
hydrometrocolpos. She also had polydactyly.
Hence a possible diagnosis of McKusick
Kaufman syndrome was made. The pit falls in
diagnosis of McKusick Kaufman syndrome is
highlighted. A single stage abdominoperineal
vaginal pull through for the repair is possible
but necessary steps to prevent vaginal stenosis
which should be followed are also discussed.
Keywords : Hydrometrocolpos, McKusick
Kaufman syndrome, Abdominoperineal vaginal
pull-through.
Case history
A term appropriate for gestational age female
baby with birth weight of 2.8 kg was born by an
emergency LSCS, indication being decreased fetal
movements with meconium stained liquor. The
affected child is the second child born to second
* Senior Consultant Pediatric Surgeon
** Surgical Resident
*** Consultant Pediatric Anaesthesiologist
Kanchi Kamakoti CHILDS Trust Hospital,
Nungambakkam, Chennai.
70
2006; 8(3) : 256
degree consanguineous parents. The mother had
polydactaly. The other sibling, a girl child, is
normal.
The antenatal ultrasound showed
hydrometrocolpos with hydronephrosis of right
kidney with paranephric pseudocyst. Apgar scores
were 7 and 9 at 1 and 5 minutes respectively.
Child was referred within 4 hours of birth with
evidence of large midline abdominal mass. The
baby passed meconium immediately after birth
and was voiding urine well.
Cardiovascular system examination was
normal. Limb examination revealed an extra digit
in right upper limb and left lower limb. Left lower
limb edema was also seen.
Physical examination revealed a distended
tense abdomen with dilated veins over the
abdomen (Fig.1). Palpation revealed a tensely
cystic to firm swelling occupying the umbilical and
suprapubic regions partly extending in to the
epigastric and right and left hypochondria. At the
upper pole of the swelling a firm to hard mass
was palpable whenever the child cried. Bladder
was also palpable as it was pushed forward.
External genitalia showed a single opening
(common urogenital sinus) between the labia.
There was no bulge. Clitoris appeared normal but
separate vaginal and urethral orifices were not
made out. Ano rectum was normal.
Characteristically the mass persisted even after
bladder catheterization.
A neonate with midline abdominal mass with
post axial polydactaly and a urogenital sinus with
absent vagina with a pre op provisional diagnosis
 2006; 8(3) : 257

of hydrometrocolpos the possiblity of The neonate didnot exhibit any problem both
McKusickKaufmann syndrome was thought. during induction and recovery from anesthesia.
Preoperative work up : Hematological The surgical procedure done was a single stage
investigations were normal. Sonogram revealed a abdominoperineal vaginal pull through with
right kidney (5x 2.5 cm) with grade II parenchymal creation of a new vagina at the normal position
change and dilated collecting system with (Figs. 2 and 3).
perinephric collection. Left kidney showed 2 to 3
Per operative findings: (1) A huge 20x 15cm
cortical cysts again with dilated collecting system.
dilated vagina with uterus, thick walled with
Echo cardiogram showed a small patent foramen
mucoid material approximately 150 ml. (2) Distal
ovale. A thorough genital / vaginal examination
atretic vagina (Fig. 4). (3) Normal ovaries and
was also done.
Fallopian tubes and (4) Bladder compressed
Anaesthetic work up : The major problem for anteriorly and a 6 Fr tube passed in to the bladder
anaesthesia for Mckusick Kaufman syndrome are draining clear urine.
the abdominal distension, large abdominal mass
causing circulatory and ventilatory dysfunction
associated congenital heart anomalies and some
times upper air way problems1. Preoperative echo
ruled out any congenital heart defects.

Fig. 2. Shows the bladder infront, uterus

behind and decompressed vagina in between
(stays on the vagina)

Fig. 3. Post surgery shows the bladder

catheterized, opened new vagina and a dilator
Fig. 1. Neonate with distended abdomen in the anus.
71
Indian Journal of Practical Pediatrics 2006; 8(3) : 258

Before After

Fig. 4. Line diagram showing anatomy of perineum before and after surgery

Follow up : A stent was kept in the neovagina

but on the sixth day it slipped out. From second
week child underwent routine vaginal dilatation.
On day 36 child had abdominal distension, hence
a sonoguided decompression of vagina with
cannula along with vaginal dilatation carried out.
Three months after surgery child developed
abdominal distension along with difficulty to void
urine. Sonogram revealed a recurrence of the
swelling. Hence a redo abdominoperineal vaginal
pull through was done (Fig. 5 & 6). This time an
indwelling sialastic tube was kept for more than 6
weeks followed by daily dilatations for 6 months. Fig. 5. Recurrent hydrometrocolpos after the
Child is regularly being followed up and in the vagina stenosed
last follow up underwent removal of the extra
digits.

Discussion
Hydrometrocolpos is a pathological distension
of uterus and vagina with excessive amount of
fluid in presence of distal vaginal outflow
obstruction2. It can be divided into secretory and
urinary type depending on the type of fluid, mucus
or urine3. The urinary type is related to a urogenital
sinus or cloacal anamoly, where as the secretory
type is related to the vaginal obstruction3. Vaginal
obstruction results from disorder of vertical and Fig. 6. Redo abdominoperineal - Vaginal pull
lateral fusion of mullerian ducts4. through

72
 2006; 8(3) : 259

Fig. 7

73
Indian Journal of Practical Pediatrics
Table 1. Classification of vaginal anomalies and treatment2
Type Anomaly
I Low hymenal obstruction
II Mid Plane Transverse membrane /septum
III Distal Vaginal atresia and high obstruction
IV Vaginal atresia with persistence of
Urogenital sinus
V Vaginal atresia with cloacal anomaly
The aim of surgical treatment is distal vaginal
drainage, which can be achieved by a perineal
procedure in most cases. Laparotomy is indicated
in cases of high vaginal atresia, urogenital sinus
or cloacal anomalies which require a pull through
procedure5,6.
Mc Kusick- Kaufmann Syndrome (MKKS)
and Bardet Biedel Syndrome (BBS)
First described by McKusick in 1964 and
1968; Kaufman in 1972 did a more
comprehensive description. It comprises of
hydrometrocolpos, polydactaly and congenital
heart defects and overlaps with Bardet- Biedel
syndrome (BBS) comprising of retinitis
pigmentosa or retinal dystrophy, polydactaly,
nephropathy, obesity, mental retardation, renal
and genital anomalies7.
MKKS is inherited in an autosomal recessive
pattern8. They are caused by the mutations in the
MKKS gene. Locus mapped to 20 p12 close to
the jagged 1 gene8.
So far about 60 cases of MKKS have been
reported7. Hydrometrocolpos is present in 80-95%
of females. Postaxial polydactaly is present in 90%
of cases. Congenital heart defects are seen in only
10% of cases. Mental prognosis in MKKS is
favourable9,10,11.
The similarities of MKKS and BBS indicate
that the MKKS gene products are likely to act in
74
2006; 8(3) : 260
Treatment
Hymenectomy
Abdominoperineal repair
Abdominoperineal vaginal pull-through
Abdominoperineal vaginal pull-through
Abdominoperineal vaginal pull-through
and rectal pull through
the same developmental pathway and to interact
with the proteins involved in the pathogenesis of
BBS7.
There are no phenotypic features in the
neonatal period that may show reliable
differentiation between MKKS and BBS as
hydrometrocolpos and polydactaly are common
to both syndromes7. The consequences of this
are straightforward. As long as genetic tests for
MKKS or BBS are unavailable routinely, genetic
counseling for parents of newborns with
hydrometrocolpos and polydactyly should be much
more cautious, even when congenital heart defect
is present, considering the poor visual prognosis
of BBS and the risk of mental impairment9. A
firm diagnosis of MKKS should be deferred to
5 to 10 years and the possibility of delayed
complications should be discussed accordingly.
Similarly, this clinical overlap in infancy makes it
necessary to establish systematic ophthalmolo-
gical and neurodevelopmental follow up of all
newborns presenting as MKKS10.
Conclusion
Hydrometrocolpos is a rare congenital
anamoly. A proper work up of the type of anamoly
is to be done before surgery. It is possible to do a
single stage abdominoperineal vaginal pull-
through12,13. After this it is advisable to keep a
indwelling sialastic tube to prevent adhesion.
Regular dilatation should be done for maintaining
 2006; 8(3) : 261

the patency of the vagina. As differentiation from
BBS is not possible, genetic counselling and long
term follow up are recommended.
References
1. Tekin I,OK G,Genc A, Tok D. Anesthetic
management in McKusick-Kaufman syndrome.
Paediatr Anaesth 2003; 13:167-170.
2. Gupta D. Hydrometrocolpos. In: New born
nd
surgery, 2 Edn,Ed, Prempuri, Oxford
University press, London 2003; pp. 875-882.
3. Jan HP, Kvist Nina, Nielsen OH.
Hydrometrocolpos current views on
pathogenesis and management. J Urol 1984;
132: 537-540.
4. Anthony S. Vaginal obstruction. Semin in Paed
surg 2000; 9: 128-134.
5. Ramenofsky M, Raffensperger JG. An
abdomino perineal vaginal pull -through for
definitive treatment of hydrometrocolpos.
J Paed Surg 1971 ; 6: 381.
6. Gerald CT, Victor MF. Hydrocolpos causing
urinary obstruction. J Urol 1964 ; 92 : 127
132.
7. David A, Bitoun P, Lacombe D, et al.
Hydrometrocolpos and polydactaly:a common
neonatal presentation of Bardet-Biedel and
McKusick-Kaufman syndromes. J Med Genet
1999;36:599-603.
8. Stone DL, Agarwala R, Schaffer, et al. Genetic
and physical mapping of the McKusick-
Kaufman syndrome. Hum Mol Genet 1998;
7:475-481.
9. Schaap C, de Die- Smulders CE, Kuijten RH,
Fryns J. McKusick Kaufman syndrome : The
diagnostic challenge of abdominal distension
in the neonatal period. Eur J Pediatr 1992 ;
151:583-585.
10. Lurie IW, Wulfsberg EA. The Mckusick-
Kaufman syndrome : Phenotypic variation
observed in familial cases as a clue for the
evaluation of sporadic cases. Genet Couns
1994 ; 5 : 275-281.
11. Chitayat D, Hahm SY, Marion RW. Further
delineation of the McKusick- Kaufman
hydrometrocolpos polydactyly syndrome.
Am J Dis child 1987;141: 1133-1136.
12. Graivier L, McKay D, Katz A. Hydrocolpos,
vaginal atresia and urethro vaginal fistula in a
Neonate : Abdomino perineal vaginal pull
through. J Paed Surg 1977; 12: 605-607.
13. Hendren Hardy. Further experience in
reconstructive surgery for cloacal anomalies.
J Paed Surg 1982; 17: 695-717.

NEWS AND NOTES

NCPID 2006
IX National Conference of Pediatirc Infectious Diseases
Theme : Pediatric infections - Basics and beyond
Date : 14-15 October 2006 Venue : Hotel Green Park, Chennai
Organised by Infectious Diseases Chapter - IAP
Host IAP-Tamil Nadu State Chatpter
in coordination with IAP - Chennai City Branch
Conference Secretariat :
NCPID2006
IX National Conference of Pediatric Infectious Diseases, Ground Floor, F-Block, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. Tamilnadu.
Phone : (O) 044-28191524, 044-42696885 Email : ixncpid2006@yahoo.co.in
75
Indian Journal of Practical Pediatrics
PRACTITIONERS COLUMN
IS THERE A NEED FOR REGULAR
ULTRASOUND IN EVERY INFANT?
*Janani Sankar
*Alka Sophia Rao
**Nammalwar BR
**Vijayakumar M
***Muralinath S
Congenital abnormalities of the renal and
urinary tract of the fetus constitute about
2030% of all fetal abnormalities1. The frequency
of infant mortality due to genito-urinary
malformations is about 10 per 10000 live births1.
The early antenatal diagnosis of these
abnormalities by ultrasonographic examination
and early postnatal intervention improves
considerably the prognosis of children having such
divergences in their renal and urinary tract1. Some
of the defects are even amenable to intrauterine
interventions. The anomalies that are not detected
antenatally get detected during a routine sonogram
done for indications like UTI, PUO and recurrent
abdominal pain during infancy. At times the
pediatrician is in for a surprise when anomalies
like dysplastic kidneys and single kidneys are
identified. There is a strong indication for regular
ultrasound in every infant coming under the review
of pediatrician, as early detection and treatment
reduces the future morbidity related to renal
diseases and dysfunction. We feel that this
approach will help us to reduce the expenditure
* Pediatrician
** Consultant Pediatric Nephrologist
*** Radiologist
Kanchi Kamakoti CHILDS Trust Hospital,
Nungambakkam, Chennai.
76
2006; 8(3) : 262
involved in treating these children at later years
when they present with the end result, the chronic
kidney disease in adulthood.
Our experience and opinion
We had conducted an analysis to find out
the frequency of renal anomalies, detected by
ultrasonogram done for renal and non-renal
indications and to analyse the type of anomalies
and their modes of presentation as well as to assess
the co-relation of the type of anomalies with clinical
presentation.
A total number of 2889 abdominal sonograms
were done between January to December
2001.Out of this 223 (7.7%) children had renal
anomalies. Sixty-eight (30.49%) children were less
than 1 year, 62 (27.8%) were between 1-3 years,
49 (21.9%) between 3- 6 years and 44 (19.7%)
were in more than 6 years age group. The male
to female ratio was 2:1.
Some important observations made in this
study were as follows (Table-1). Failure to thrive
and recurrent vomiting were the symptoms in
50.3% of children with small kidneys. Recurrent
abdominal pain was the presentation in 44.8% of
ectopic kidneys. No specific urinary symptoms
were documented in 15.5% of hydronephrosis,
55.2% of ectopic kidneys and 73.2% of renal
agenesis. No specific urinary symptoms could be
documented in 77.0% of anomalies that were
detected in children more than 6 years of age.
Indications for ultrasonograms by convention
include; 1) follow up of antenatally detected
anomalies 2) in pyrexia of unknown origin, to
locate the site of infection, 3) recurrent abdominal

Table 1. Observations from abnormal ultrasonograms
Renal anomaly Follow-up Recurrent Recurrent
found scan done* vomiting abdominal pain thrive
Bifid Coll. system # - -
Agenesis - -
Ectopic Kidney - -
Small Kidneys - 27.8%
Hydronephrosis 72% - -
* Follow up scan done for antenatally detected anomalies
# Bifid collecting system
pain, 4) in dysmorphic features like ear anomalies
and vertebral anomalies to rule out associated renal
anomalies and 5) in recurrent culture positive
urinary tract infection to assess the renal status.
Not infrequently major or minor renal anomalies
are identified in them.
Discussion
To establish the prevalence of renal
abnormalities in school children an epidemiological
study of 132,686 school children, including 69,903
boys and 62,783 girls, was conducted from March
1987 to May 1988 in the City of Taipei3. Renal
abnormalities were detected in 645 students
(0.5%). There were 256 (39.6%) hydronephrosis,
103 (15.9%) unilateral renal agenesis, 128 (19.8%)
unilateral small kidneys, 90 (13.9%) renal cystic
disorders, 30 (4.6%) ectopic kidneys and 38
(5.8%) other abnormalities. Surgically correctable
lesions were demonstrated in 50 of these children.
In another study by Sheih CP et al, rapid renal
ultrasonography was found to effectively detect
some renal abnormalities initially and then
prevalence could be established with further
investigations3. In the present study renal anomaly
without specific urinary symptoms were found in
7.7% of children and bifid collecting system was
77
2006; 8(3) : 263
Failure to Culture No Specific
positive UTI urinary
symptoms
- - 65.5% 34.5%
- 13% 13.8% 73.2%
44.8% - - 55.2%
- 22.5% - 49.7%
- 12.5% 15.5%
the commonest anomaly seen (42.8%) followed
by small sized kidneys (29.2%), hydronephrosis
(8.7%) and rotational anomalies (9.0%) and others.
(Table-2)
Studies have recommended the routine use
of ultrasound in healthy infants because a
significant number of infants harbor silent urinary
tract abnormalities that can be detected by
ultrasound at a low cost 4. This study supports
our observation that in children more than 6 years
diagnosis of renal anomalies without specific
urinary symptoms was noted in 77% of children.
Every second patient with a solitary kidney
suffers from renal disease. This accumulation of
renal diseases of varying origin makes special care
for these children necessary5. This observation is
very true and it is our duty to protect those with
single kidney from developing infection,
hypertension and end stage renal disease.
Counseling of parents is also important. As renal
anomalies can get missed during routine prenatal
sonogram and early detection of these anomalies
can prevent progression of disease and prevention
of end stage renal disease and considering the easy
availability and non-invasiveness of ultra
sonogram, routine post- natal sonogram should
Indian Journal of Practical Pediatrics
Table 2. Various renal anomalies detected incidentally
Type of anomaly
Bifid collecting system
Small sized kidneys
Hydronephrosis
Rotational anomalies
Ectopic kidney
Renal agenesis (unilateral)
Miscellaneous (Horse-shoe kidney, fused kidneys)
be done as a part of health screening programmes
in children3.
Conclusion
References
From our experience and opinion from
literature we could derive the following conclusions
Renal anomalies may be detected without
specific urinary symptoms in children with
recurrent vomiting, failure to thrive and
recurrent abdominal pain.
Early diagnosis of major anomalies helps in
initiation of treatment and prevention of
complication and end stage renal disease.
Considering the number of anomalies without
specific urinary symptoms identified during
sonogram done for other indications, we feel
postnatal sonograms during infancy should
be routinely advised in the following
situations; family history of renal anomalies,
previous fetal loss/neonatal deaths and
presence of other congenital anomalies.
NEWS AND NOTES
MP PEDINEOCON 06
Venue: Gwalior Date: 2nd & 3rd December 2006
For futher details contact: email: mppedicon06@yahoo.co.in
78
2006; 8(3) : 264
Percentage of children
42.8%
29.2%
8.75%
9%
4.25%
4.5%
1.5%
Its routine need in every infant to reduce
future morbidity and mortality can be obtained
clearly only with multicentric analysis.
1. Todarova M,Buzalov S,Vasilev . Prenatal
Diagnosis of Bilateral Fetal Renal
Polycystosis. Akush ginekol 2000; 39: 53-55
(Medline ref)
2. Gunn TR, Mora JD, Pease P.Antenatal diagnosis
of urinary tract abnormalities by
ultrasonography after 28 weeks gestation:
incidence and outcome. Am J Obstet Gynecol
1995; 172: 479-486.
3. Sheih CP, Liu MB, Hung CS, Yang KH, Chen
WY, Lin CY. Renal abnormalities in
schoolchildren. Pediatrics 1989; 84 (6):1086-
1090.
4. Donovan JM, Ney KG, Maizels M. Urosound.-
In-office ultrasonography for pediatric
urology. Urol Clin North Am 1989; 16(4): 841-
855.
5. Beyer HJ, Hofmann V, Brettschneider D .
Value of ultrasound in the treatment of solitary
kidneys in infancy and childhood. Prog Pediatr
Surg 1989; 23:3-17.
 2006; 8(3) : 265

PICTURE QUIZ

3 year old girl with history of tilting of head to the right and inability to abduct the right eye;
following a short duration of fever

What is the diagnosis, aetiology and prognosis?

Compiled by:
*Ganesh R, **Deenadayalan M, ***Lalitha Janakiraman

*Resident in Pediatrics, **Junior Consultant in Pediatrics,

***Senior Consultant Pediatrician
Kanchi Kamakoti CHILDS Trust Hospital
12-A, Nageswara Road, Nungambakkam, Chennai - 600 034.
Tamilnadu.

Answer on page: 268

79
Indian Journal of Practical Pediatrics
EMERGING EPIDEMICS
CHIKUNGUNYA - IS IT A THREAT?
What is chikungunya fever?
Chikungunya fever is a viral disease
transmitted to humans by the bite of infected
mosquitoes. Chikungunya virus (CHIKV) is a
member of the genus Alphavirus, in the family
Togaviridae. CHIKV was first isolated from the
blood of a febrile patient in Tanzania in 1953,
and has since been identified repeatedly in west,
central and southern Africa and many areas of
Asia, and has been cited as the cause of numerous
human epidemics in those areas since that time.
The virus circulates throughout much of Africa,
with transmission thought to occur mainly
between mosquitoes and monkeys.
What type of illness does
chikungunya virus cause?
CHIKV infection can cause a debilitating
illness, most often characterized by fever,
headache, fatigue, nausea, vomiting, muscle pain,
rash, and joint pain. The term chikungunya is
Swahili for that which bends up.
The incubation period (time from infection
to illness) can be 2-12 days, but is usually 3-7
days. Silent CHIKV infections (infections
without illness) do occur; but how commonly this
happens is not yet known.
Acute chikungunya fever typically lasts a few
days to a couple of weeks, some patients have
prolonged fatigue lasting several weeks.
Additionally, some patients have reported
incapacitating joint pain, or arthritis which may
last for weeks or months. The prolonged joint
pain associated with CHIKV is not typical of
80
2006; 8(3) : 266
dengue. Co-circulation of dengue fever in many
areas may mean that chikungunya fever cases are
sometimes clinically misdiagnosed as dengue
infections, therefore the incidence of chikungunya
fever could be much higher than what has been
previously reported.
No deaths, neuroinvasive cases, or
hemorrhagic cases related to CHIKV infection
have been conclusively documented in the
scientific literature.
CHIKV infection (whether clinical or silent)
is thought to confer life-long immunity.
How do humans become infected
with chikungunya virus
CHIKV is spread by the bite of an infected
mosquito. Mosquitoes become infected when they
feed on a person infected with CHIKV. Monkeys,
and possibly other wild animals, may also serve
as reservoirs of the virus. Infected mosquitoes
can then spread the virus to other humans when
they bite.
Aedes aegypti (the yellow fever mosquito),
a household container breeder and aggressive
daytime biter which is attracted to humans, is the
primary vector of CHIKV to humans. Aedes
albopictus (the Asian tiger mosquito)may also play
a role in human transmission is Asia, and various
forest-dwelling mosquito species in Africa have
been found to be infected with the virus.
How is chikungunya virus infection
treated?
No vaccine or specific antiviral treatment for
chikungunya fever is available. Treatment is
symptomaticrest, fluids, and ibuprofen,
 2006; 8(3) : 267

naproxen, acetaminophen, or paracetamol may
relieve symptoms of fever and aching. Aspirin
should be avoided
Infected persons should be protected from
further mosquito exposure (staying indoors and/
or under a mosquito net during the first few days
of illness) so that they cant contribute to the
transmission cycle.
What can people do to prevent
becoming infected with chikungunya
virus?
The best way to avoid CHIKV infection is
to prevent mosquito bites. There is no vaccine or
preventive drug. Prevention tips are similar to
those for dengue or West Nile virus:
Use insect repellent containing an DEET or
another EPA-registered active ingredient on
exposed skin. Always follow the directions
on the package.
Wear long sleeves and pants (ideally treat
clothes with permethrin or another repellent).
Have secure screens on windows and doors
to keep mosquitoes out.
Get rid of mosquito breeding sites by
emptying standing water from flower pots,
buckets and barrels. Change the water in pet
dishes and replace the water in bird baths
weekly. Drill holes in tire swings so water
drains out. Keep childrens wading pools
empty and on their sides when they arent
being used.
Additionally, a person with chikungunya fever
or dengue should limit their exposure to
mosquito bites in order to avoid further
spreading the infection. The person should
stay indoors or under a mosquito net.
Source : WWW.cdc.gov/travel

NEWS AND NOTES

PHOCON 2006
X NATIONAL PAEDIATRIC HAEMATOLOGY ONCOLOGY CONFERENCE
Date: 16th-18th November 2006
Venue: Christian Medical College, Vellore, Tamil Nadu
Registration Fee Till 15.10.06 SPOT
IAP Member Rs.1,000/- Rs.1,200/-
PG Student* Rs. 800/- Rs. 900/-
Non-IAP Member Rs.1,200/- Rs.1,500/-
Accompanying person Rs. 600/- Rs. 600/-
All payments to be made by Demand Draft, in favour of Phocon 2006 payable at Vellore.
Leni G Mathew Mammen Chandy
Organizing Secretary Chairperson
For further details contact : Leni G Mathew, Organizing Secretary, PHOCON 2006,
Child Health Unit I, Christian Medical College and Hospital, vellore 632 004, Tamil Nadu.
Tel: 91-416-2283350 Fax: 91-416-2232103 eimail: lenimathew@cicvellore.ac.in

81
Indian Journal of Practical Pediatrics 2006; 8(3) : 268

QUESTION AND ANSWER

Q.No.1. A male child 1 year 3 months, 8 kg
attended a clinic (Indian Red Cross Society) for
2nd dose of Hepatitis B vaccine, which is 3 months
after the 1st dose. The mother was requested to
take the first dose again and then 2nd and 3rd dose
after one and 6 month of the first dose. Kindly
let me know what is the Hepatitis B vaccination
schedule suggested for this child?
Dr.Pradyut Mondal
Khoshbagan, Burdwan, West Bengal.
A.No.1. This is a very wrong immunization
practice; all 3 doses of hepatitis B vaccine can be
completed within one year of starting the 1st dose.
So the correct schedule that should have been
followed in this child is to have given the 2nd dose
when the mother reported after 3 months after
the 1st dose and complete the 3rd dose at 4 weeks
(28 days) intervals after the 2nd dose. Being an
aluminium adjuvanted vaccine the completion of
3 doses within 1 year of starting the 1st dose is
equally immunogenic. It has been categorically
proved that the immuogenicity of Hepatitis B
vaccine is 96-98% by whatever schedule the
vaccine is administered. viz birth, 6, 14 weeks,
6,10,14 weeks; 0,1,2 months or 0,1,6 months.
Further no booster doses are necessary as
protective titer is enhanced to more than 10mIU,
when it falls below the protective level due to
anamnestic response.
Prof.Dr.A.Parthasarathy
Retd. Clinical Professor
MMC, Chennai.

PICTURE QUIZ

Answer for the picture quiz

Diagnosis is right lateral rectus palsy

Acquired isolated abducens nerve palsy in children is rare. The aetiology is usually post- viral. Other
less common causes are trauma, tumor and meningitis. This condition is generally benign and
resolves spontaneously within 2 weeks to 2 months. In this child, it was probably post viral and she
recovered completely within 2 months.

82
 2006; 8(3) : 269

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Indian Journal of Practical Pediatrics 2006; 8(3) : 270

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 2006; 8(3) : 271

Indian Journal of
Practical Pediatrics IJPP
Subscription Journal of the
Indian Academy of Pediatrics

JOURNAL COMMITTEE NATIONAL ADVISORY BOARD

Editor-in-Chief President, IAP

Dr. A.Balachandran Dr.Nitin K Shah
Executive Editor
President 2007, IAP
Dr. K.Nedunchelian
Managing Editor Dr.Naveen Thacker
Dr. Malathi Sathiyasekaran Editor, Indian Pediatrics
Associate Editors
Dr. Panna Choudhury
Dr. N.C.Gowrishankar
Dr. P.Ramachandran Members

Dr. C.V.Ravisekar Dr. Arati Deka

Dr. V.Sripathi Dr. B.K.Bhuyan
Dr. S.Thangavelu
Dr. C.Kamaraj
Executive Members
Dr.Kul Bhushan Sharda
Dr. G. Durai Arasan
Dr. Mahesh Kumar Goel
Dr. Janani Sankar
Dr. S.Lakshmi Dr. M.A.Mathew
Dr. V.Lakshmi Dr. Mukesh Kumar Khare
Dr. (Major) K.Nagaraju Dr. Subhash Singh Slathia
Dr. T. Ravikumar Emeritus Editors
Dr. S.Shanthi
Dr. A.Parthasarathy
Dr. So.Shivbalan
Dr. B.R.Nammalwar
Dr. C.Vijayabhaskar
Dr. M.Vijayakumar
Dr. Deepak Ugra
(Ex-officio)

85
Indian Journal of Practical Pediatrics 2006; 8(3) : 272

Indian Academy
of Pediatrics
IAP Team - 2006 Kailash Darshan,
Kennedy Bridge,
Mumbai - 400 007.
President Karnataka
Dr.Nitin K Shah Dr.M.Govindaraj
President-2007 Dr.R.Nisarga
Dr.Naveen Thacker Dr.Santosh T Soans
President-2005 Kerala
Dr.Raju C Shah Dr.Guhan Balraj
Vice President Dr.M.A.Mathew
Dr.VN.Tripathi Dr.T.U.Sukumaran
Secretary General Madhya Pradesh
Dr.Deepak Ugra Dr.Mukesh Kumar Khare
Treasurer Dr.C.P.Bansal
Dr.Rohit C Agrawal Maharashtra
Editor-in-Chief, IP Dr.Anand K Shandilya
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Editor-in-Chief, IJPP Dr.Vijay N Yewale
Dr.A.Balachandran Dr.Yashwant Patil
Joint Secretary Manipur
Dr.Bharat R Agarwal Dr.K.S.H.Chourjit Singh
Members of the Executive Board Orissa
Andhra Pradesh Dr.B.K.Bhuyan
DR K Umamaheswara Rao Punjab
Dr.P.Venkateshwara Rao Dr.Kul Bhushan Sharda
Dr.P.Sudershan Reddy Rajasthan
Assam Dr.Prem Prakash Gupta
Dr.Arati Deka Dr.Ashok Gupta
Bihar Tamilnadu
Dr.Sachidanand Thakur Dr.K.Chandrasekaran
Chhattisgarh Dr.M.P.Jeyapaul
Dr.Pradeep Sihare Dr.K.Nedunchelian
Delhi Uttar Pradesh
Dr.Ajay Gambhir Dr.Mahesh Kumar Goel
Dr.Sunil Gomber Dr.V.N.Tripathi
Gujarat Dr.Vineet K Saxena
Dr.Baldev S Prajapati West Bengal
Dr.Satish V Pandya Dr.Nabendu Choudhuri
Haryana Dr.Sutapa Ganguly
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86
 INDIAN JOURNAL OF IJPP
PRACTICAL PEDIATRICS
IJPP is a quarterly subscription journal of the Indian Academy of Pediatrics
committed to presenting practical pediatric issues and management
updates in a simple and clear manner
Indexed in Excerpta Medica, CABI Publishing.

Vol.8 No.4 OCT.-DEC. 2006

Dr. A. Balachandran Dr. K.Nedunchelian
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 271

TOPIC OF INTEREST - VACCINES

Various immunization practices 272
- Parthasarathy A

Newer vaccines (II) 281

- Dutta AK, Kush Jhunjhunwala

Additional vaccines - Current trends (Typhoid, MMR, Varicella) 292

- Niranjan Shendurnikar, Mukesh Kumar Singh

Passive immune prophylaxis for infections 301

- Baldev S. Prajapati, Rajal Prajapati

Immunization in special situations 309

- Shyam Kukreja, Sandeep Aggarwal

Journal Office: Indian Journal of Practical Pediatrics, Krsna Apartments, Block II, 1A, 50, Halls Road,
Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for ordinary letters: The Editor-in-Chief, Indian Journal of Practical Pediatrics, Post Bag No.524,
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Address for registered/insured/speed post/courier letters/parcels and communication by various
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Plot No. 235, 4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
RADIOLOGIST TALKS TO YOU
The Central nervous system - Anatomical basis of radiology 315
- Vijayalakshmi G, Elavarasu E, Porkodi, Malathy K, Venkatesan MD

PICTURE QUIZ 318

CASE STUDY
Cutis verticis gyrata 319
- Sri Venkateswaran K, Purushothaman, Raveendranath V,
Saradambal N, Sujatha L, Susheela Rajendran
Cavernous sinus thrombosis - A case report 322
- Arunkumar J, Lakshmi S, Kumarasamy K, Ravisekar CV,
Venkataraman P, Vasanthamallika TK
Hereditary Sensory Autonomic Neuropathy type IV -
A very rare condition 325
- Nilesh Jain, Vyas BR, Shalini Jain
IAP TASK FORCE REPORT
Guidelines and Management of enteric fever in children 329
AUTHOR INDEX 341

SUBJECT INDEX 342

NEWS AND NOTES 280,291,300,314,317,321,324

FOR YOUR KIND ATTENTION

* The views expressed by the authors do not necessarily reflect those of the sponsor or publisher.
Although every care has been taken to ensure technical accuracy, no responsibility is accepted for errors
or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are the
responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board

Published and owned by Dr. A. Balachandran, from Krsna Apartments, Block II, 1A,
50, Halls Road, Egmore, Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works,
9, Iyyah Street, Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.

2
 EDITORS DESK
Greetings from the Journal Committee of the
IJPP. This issue will cover the remaining topics
on Vaccines. The journal committee once again
thanks Dr. Nitin K Shah for accepting to be the
Guest Editor and formulating the topics. We hope
our readers, both practicing pediatricians and
postgraduates will find these topics useful in day
to day practice.
The topic on Various immunization
practices is contributed by Dr. A. Parthasarathy.
He has discussed in detail, the issues on various
schedules of immunization in special situations.
He has also highlighted certain facts in adolescent
immunization and cleared the common myths.
The article on Newer vaccines is written
by Dr.A.K.Dutta, et al. They have covered certain
newer vaccines which are currently available and
also vaccines under development for the future
such as rotavirus, malaria and HIV vaccines.
Additional vaccines - current trends by
Dr.Niranjan Shendurnikar, et al. narrates those
vaccines not covered under National Immunization
Schedule but recommended by IAP. They have
summarized the pertinent issues with the additional
vaccines which are of clinical relevance and
patient-doctor concern to optimize vaccine
acceptance and cost effectiveness.
Kindly note the address of new premises ;
Krsna Apartments, Block II, 1A,
50, Halls Road, Egmore, Chennai - 600 008
WISH YOU
A HAPPY AND PROSPEROUS
NEW YEAR - 2007
3
Passive immune prophylaxis is used as post
exposure prophylaxis. In this article Dr.Baldev S
Prajapati, et al. mention the advantages and
disadvantages of human and animal products of
immunoglobulins, the various preparations
available, indications, doses etc.
Immunization in special situations by Dr.
Shyam Kukreja and Dr. Sandeep Aggarwal covers
some clinical circumstances which need
modifications of existing immunization practices.
How to tackle the situations like outbreaks,
adolescence, patients with malignancy,
immunotherapy and HIV infections are clarified
in this review.
We thank Dr. Vijayalakshmi, et al for their
contribution to the Radiologist talks to you
column. They have commenced from this issue
the other imaging modalities like CT and MRI.
To begin with the anatomical basis of radiology
of central nervous system is highlighted in this
issue.
We are happy to publish the Guidelines and
management of enteric fever in children which
is being brought under IAP - Presidents Action
Plan 2006.
We thank all the contributors for case study
and picture quiz columns in this issue.
 VACCINES II
THE VARIOUS IMMUNIZATION
PRACTICES
* Parthasarathy A
Abstract: Issues in various schedules of
immunization like Expanded Programme on
Immunization (EPI) and National Immunization
Schedule are discussed. Immunization in special
clinical circumstances like preterm, schedule for
lapsed immunization, rationale of scheduling
individual vaccines, spacing of multiple doses
of an antigen and current concepts of
combination vaccines are also covered. Certain
myths and facts in pediatric and adolescent
immunization are highlighted.
Key words: Immunization schedules, Special
Clinical Circumstances, Myths, Facts
The World Health Organization periodically
issues guidelines for best global immunization
practices. Various professional bodies also keep
updating the immunization practices with
reference to their individual countries. Centre for
Disease Control and Prevention, Atlanta, USA
issues guidelines every year updating the current
recommendations. In India since 1985, the Indian
Academy of Pediatrics is publishing Guide Book
on Immunization which is updated every 2/3 years.
However, controversies still exist among members
of the various professional bodies on issues like
* Sr. Clinical Professor of Pediatrics (Retd.),
Madras Medical College and
Deputy Superintendant,
Institute of Child Health and Hospital for Children
Chennai 600 008.
4
the various schedules for individual vaccines, use
of combination vaccines, simulta-neous
administration of multiple vaccines etc.
I. The various immunization
schedules
The Rationale: The purpose of administering a
vaccine is to offer optimal protection to the
vaccinee. For obtaining the optimal protection,
proper scheduling is mandatory based on
immunological responses. Among the live
vaccines BCG needs only a single dose. Others
like OPV, MMR and Varicella require a minimum
of 3/2/2 doses respectively for life long immunity
in a primary and repeat dose schedule since these
vaccines have no booster effect. Measles, MMR
and Varicella vaccines once thought to be highly
immunogenic in a single dose schedule are now
found to be immunogenic only when a repeat dose
is given. Hence the emerging concept of 2 doses
for MMR and Varicella vaccines and 3 or more
doses for OPV. On the other hand inactivated
subunit vaccines always need to be administered
in a prime boost schedule with the exception of
Hepatitis B vaccine which does not need booster
dose because of its capability of eliciting
anamnestic response following viral exposure.
Generally 3 primary doses are recommended for
inactivated vaccines and for vaccines containing
toxoid / subunit components followed by boosters.
However, Hib vaccine, Pneumococcal vaccine,
etc need either 3/2/1 primary dose(s) depending
upon the age of immunization followed by 1 or 2
boosters, since they act by the mechanism of
natural boosting.
 For certain vaccines like the DTP/DT/TT
etc the dose is the same i.e 0.5 ml for all ages.
For Hepatitis B vaccine, the dose is 0.5 ml and
1 ml respectively for children upto 10 years and
above 10 years. For Varicella vaccine a single dose
of 0.5 ml upto 12 years and 2 doses for those
above 13 years. Hepatitis A is administered in
0 (prime) and 6 months (boost) schedule with
0.5ml/1ml of pediatric or adult formulation. The
dose is 0.25ml/0.5ml for vaccines like Influenza
for children 6 months to 3 years and above 3
years respectively. Hence the schedules also vary
for these vaccines at different settings.1,2
The EPI Schedule
The schedule recommended for the
Expanded Program on Immunization(EPI) by
World Health Organization may be modified by
the ministries of Health in individual countries
based on local recommendations. This is the basis
of the National Immunization Schedule 1985
(Table 1) now in practice in India and the IAP
Immunization Time Table 2004 (Table 2) which
includes certain additional vaccines as well as
additional doses for routine vaccines. However it
should be clearly understood that, when additional
vaccines are desirable, routine vaccines are
mandatory.1,2
The vaccines administered in the National
Immunization Schedule (which once introduced
cannot be withdrawn and should be given free of
cost to all beneficiaries) should be
epidemiologically relevant, immunologically
appropriate, technically sound, economically
viable and socio culturally acceptable. Logistic

Table 1. National immunization schedule 1985 3,4

Age Vaccines
Birth BCG, OPV-0 (for institutional deliveries)
6 weeks DTP1, OPV1 (BCG, if not given at birth)
10 weeks DTP2, OPV2
14 weeks DTP3, OPV3
9 months Measles
16-24 months DTP, OPV
5-6 years DT*
10 years TT*
16 years TT
For pregnant women
Early in pregnancy TT1 (if not immunized early in childhood) or booster if
already fully immunized
One month after TT1 TT2**
NOTE
* A second dose of DT or TT vaccine should be given at an interval of one month if there is no clear
history or documented evidence of previous immunization with DTP.
** A second dose of TT vaccine should be given at an interval of one month if there is no clear history or
documented evidence of previous immunization with DTP, DT or TT vaccines. (Source: National Child
Survival and Safe Motherhood program Module, Ministry of Health and Family Welfare, Govt. of India
New Delhi ; 1994)

5
Table 2. IAP Immunization time table 2004 6
Vaccine Age recommended
1. BCG From birth to 2 weeks
2. OPV At birth; 6, 10 & 14 weeks; 15-18 months; 5 years
3. DTPwc/DTPa 6, 10 & 14 weeks; 15-18 months; 5 years
4. Hepatitis B Birth, 6 & 14 weeks or Birth, 1 & 6 months or 6,10 & 14 weeks.
5. Hib 6, 10 & 14 weeks; 15-18 months
6. Measles 9 months+
7. MMR 15-18 months
8. Typhoid 2 years+ (Revaccination 3-4 years)
9. Td 10 & 16 years
10. 2 doses of TT Pregnant women
Newer Vaccines
1. Varicella Above 1 year
2. Hepatitis A Above 1 year

Note:
1. The IAP endorses the continued use of whole cell pertussis vaccine because of its proven efficacy and
safety. Acellular pertussis vaccine may undoubtedly have fewer side-effects (like fever, local reactions
at injection site and irritability), but this minor advantage does not offset the inordinate costs involved
in the routine use of this vaccine.
2. With the marked decline of paralytic polio cases in our country, inactivated polio vaccine (IPV) should
replace OPV in a phased manner.
3. If the mother is known to be HBs Ag negative, HB vaccine can be given along with DTP at 6, 10, 14
weeks. If the mothers HBs Ag status is not known, it is advisable to start vaccination soon after birth to
prevent perinatal transmission of the disease. If the mother is HBsAg positive (and especially HBeAg
positive), the baby should be given Hepatitis B Immune Globulin (HBIG) within 24 hours of birth, along
with HB vaccine.
4. Combination vaccines can be used to decrease the number of injections being given to the baby and to
decrease the number of clinic visits. Under no circumstances, however, should combination vaccines
be viewed as being more effective than vaccines given separately. The manufacturers instructions
should be followed strictly whenever mixing vaccines in the same syringe prior to injection.
5. At present, the only typhoid vaccine available in our country is the Vi Polysaccharide Vaccine.
Revaccination may be carried out every 3-4 years.
6. Under special circumstances (eg. Epidemics), measles vaccine may be given earlier than
9 months followed by MMR at 12-15 months.
7. MMR, Varicella and Hepatitis A vaccines can be given after one year of age at any time.
8. During pregnancy, the interval between the two doses of TT/Td should be at least one month.

6
considerations have to be taken into account before
scheduling these vaccines. Though the Indian
Academy of Pediatrics recommends, 3 doses of
Hepatitis B vaccine in 3 different schedules viz
birth, 6 and 14 weeks; Birth, 1 month and
6 months; or 6, 10 and 14 weeks; (since the
vaccine is immunogenic in all these schedules),
the Govt. of India has chosen to introduce
Hepatitis B vaccine in 6,10 and 14 weeks schedule
only, due to logistic considerations. However in
private practice, members of IAP practice the
IAP immunization time table. In Government
health facilities only the National Immunization
Schedule is followed.
II. Immunization in special
circumstances 3,4,5,7
1. Immunization in preterm infants
In general, all vaccines may be administered
as per schedule according to the chronological
age irrespective of birth weight or period of
gestation. Very low birth weight babies can
be given immunizations after initial
stabilization.
2. Children receiving corticosteroids
Children receiving oral corticosteroids in high
doses (eg. Prednisolone 1-2 mg/kg/day) for
more than 14 days should not receive live
virus vaccines until steroids have been
discontinued for at least one month. Killed
vaccines are safe in such situations. Patients
Table 3. Vaccination schedule for a non immunized child 3,4,5
Age Less than 5 years
First visit BCG, OPV, DTP, HB
2nd visit OPV, DTP, HB
(1 month later)
3rd visit OPV, DTP, HB, Measles or
(1 month later) MMR, Typhoid
1 year later OPV, DTP
Every 3 years Typhoid booster
7
on topical or inhaled steroid therapy should
not be denied their age appropriate vaccines.
3. Children awaiting splenectomy
Children with loss of splenic function either
with congenital asplenia or after splenectomy
are at high risk of serious infections with
encapsulated organisms. If surgical
splenectomy is being planned, immunization
with Pneumococcal, Hib and Meningococcal
vaccines should be initiated at least 2 weeks
prior to splenectomy.
4. The schedule for lapsed immunization
For children who have missed the routine
immunization during infancy or children who
report late for immunizations, the schedule
suggested is given in Table 3.
5. Adolescent immunization
schedule 3,4,5
Adolescent immunization is also mandatory
for those children who have not been adequately
immunized already and for those adolescents
who leave abroad for education or employment
(Table 4).
Thus it may be seen from the above
discussion, that the various schedules are very
much needed for infant, childhood and adolescent
routine immunization and immunization under
special circumstances. However, consensus
should be the mainstay of these schedules rather
More than 5 years
TT/Td, HB
TT/Td, HB
HB, MMR, Typhoid
-
Typhoid booster
Table 4. Adolescent immunization schedule 6,10,11
Vaccine Age
1. Tetanus diphtheria toxoid
Boosters at 10 and 16 years
2. Rubella vaccine (or) 1 dose to girls at 12-13 years of age, if MMR was not given earlier (or)
MMR vaccine 1 dose at 12-13 years of age, if not given earlier
3. Hepatitis B vaccine 3 doses at 0,1 and 6 months, if not given earlier
4. Typhoid vaccine Vi-polysaccharide vaccine every 3 years
5. Varicella vaccine* 1 dose upto 13 years and 2 doses (at 4-8 weeks interval)
after 13 years of age (if not given earlier)
6. Hepatitis A vaccine* 2 doses - 0 and 6 months(if not given earlier)
* Mandatory for adolescents going abroad or staying in hostels.

than raising unnecessary controversies and
confusing doctors especially when the practice of
immunization has become an integral part of day
to day practice.
It should also be noted that in these days of
easy internet access parents go through so many
web sites on immunization including the
controversial sites and hence the practicing
pediatric physicians have to update their
knowledge keeping abreast of the current concepts
and latest recommendations.
IV. Rationale of scheduling
individual vaccines 3,4,5,8,9
a. BCG: BCG vaccine elicits Cell mediated
immunity (CMI). Maternal CMI is not
transferred to the fetus. Therefore BCG can
be given at birth.
b. OPV: OPV is given by mouth; it establishes
local infection in a proportion of children.
Maternal antibody in the infants circulation
is a very weak inhibitory factor; hence OPV
also can be given at birth.
c. Hepatitis B: Hepatitis B surface antigen is an
excellent immunogen overcoming to a large
extent, the inhibiting effect of maternal
antibody; hence that too can be given at birth.
The HB birth dose along with HBIG is
mandatory for babies born to HBsAg positive
mother followed by 2 more doses at 6 and
14 weeks. Babies born to HBsAg negative
mothers can receive the vaccine either at
6, 10, 14 weeks schedule or at birth, 1 and 6
month schedule. The vaccine is highly
immunogenic in whichever schedule that is
followed. No doubt the third dose given at
6 months produces highest geometric mean
titer (GMT) and GMT is directly proportion-
ate to long term protection. However in view
of the anamnestic response by which HBsAg
acts, natural boosting occurs on virus
exposure even when the vaccine is given at
a minimum of 4 weeks interval thus ensuring
long term protection (Fig.1). In countries
where universal HB immunization is practiced
HB vaccine is advocated either at 4, 6, 8
weeks interval only, comprising of a total of
3 doses. No booster doses are recommended.
Immunogenicity at different schedules is
comparable as mentioned below :
0, 1, and 6 months 96 98%
0, 1, and 2 months 96%
0, 6, and 14 weeks 95 96%
6, 10, and 14 weeks 97 %
2, 4, and 6 months 99%

8

Fig. 1. Anamnestic response following HB
vaccination administered at 4 weeks interval 8,9
Note: The required protective value is 10 mIU.When
given at a minimum of 4 weeks interval the antibody
response elicited is >100 mIU.When the antibody
level declines below the protective level over a period
of time, even a transient infection automatically
elevates the antibody level to well above the
protective titer due to anamnestic response. The upper
curve denotes the anamnestic response when some
protective antibodies are still present and the lower
curve denotes the anamnestic response when the
antibody titre falls below the protective level.
d. DTaP / DTwP / Hib vaccines :
These vaccines can be given earliest at
6 weeks of age since they are capable of eliciting
optimum immune response evoking protective
titres
e. Measles vaccine:
Live measles vaccine may be completely
inhibited in the presence of detectable maternal
antibodies upto 9 months in the infants circulation.
Therefore measles vaccine is given after a delay
of 9 months from birth, followed by MMR after
12 months.
f. MMR and Varicella vaccines :
These vaccines can be given earliest at
12 months of age. They can be given together or
if given separately, should be administered at
4 weeks mandatory interval.
9
V. Combination vaccines -Current
concepts 10,11
1. Combination vaccines have become the
order of the day in developed countries and in
developing countries like India, the concept is
picking up. For instance in India, today, we can
adopt a 3-4-7 strategy with the available
combination vaccines especially for a baby born
to HBsAg negative mother. We need to administer
only 3 vaccine formulations viz BCG at birth,
combined DTP-HB-Hib at 6, 10 and 14 weeks
along with oral polio vaccine at birth, 6, 10 and
14 weeks before the baby reaches 4 months of
age and thus prevent 7 diseases viz tuberculosis,
poliomyelitis, diphtheria, pertussis, tetanus,
hepatitis B and Hib infection.
Current status of new combination vaccines
Already developed DTPw + Hib
DTPw + Hepatitis B
DTPw + Hib + Hep B
DTPa + IPV
DTPa + Hib
DTPa + Hib +
Hep B + IPV
Hepatitis A + Hepatitis B
MMR + Varicella
Under development DTPa + Hib + IPV +
Hep B + Hep A
Available for DTPw + Hib
use in India DTPw + Hep B
DTPw + Hib +
Hepatitis B
Hepatitis A + Hepatitis B
2. The immunogenicity of individual vaccine
components is excellent even when given in
combination formulation12,13. Fig.2 depicts the
individual antigen immunogencity.
It could be seen from the above illustration
that all the vaccine components elicit excellent
 Diptheria(>0.01 IU/ml)
Tetanus (>0.1 IU/ml)
Pertussis (>3.92 EU/ml) - AF Antifimbrial
Pertussis (>2.24 EU/ml) - AP Antipertactin
Hib (>0.15 g/ml)
Hib (> 1.00 g/ml)
Hepatitis B (>10 IU/ml)
Fig.2. Immunogenicity of individual antigens
immune response when given in combination
formulation.
In India two brands of DTwP-HB-Hib
combination vaccine formulations are available viz.
(1) lyophilized formulation and (2) fully liquid
formulation. Similarly there are two brands of
DTwP-Hib combination vaccine formulations viz.
(1) lyophilized formulation and (2) fully liquid
formulation. The lyophilized Hib component in
pellet form is mixed extraneously using the
recommended DTPw formulation as a diluent.
These are studies to show that administering
DTPw and Hib in combination results in reduced
mean PRP antibody levels compared to giving
the same components separately. However, even
in those studies with statistically significant
reduction, antibody levels were still high and 90%
of children (typically 95%) developed greater than
1 mcg/ml of antibody to PRP-T / CRM 197
component of Hib. Plotkin in his review has
described that, this reduced immunogenicity of
Hib when given in combination with DTPw
appears to be of no clinical importance.
Recent data shows that addition of Hib
component to either the DTPw / DTPw HB
lyophilized / liquid formulations does not affect
the safety and immunogenicity of either the
PRP-T / CRM197 Hib component.
10
100%
100%
97%
81%
100%
90%
100%
VI. Spacing of multiple doses of same
antigen 5
4 weeks interval is mandatory for spacing
multiple doses of same antigen. Recommended
age of initiation and maintaining interval between
multiple doses of the same antigen provide optimal
protection. Though recommended minimum
interval of 4 weeks (28 days) is mandatory,
vaccine doses administered less than 4 days before,
can also be counted as a valid dose. Rabies vaccine
is an exception and should be given in 0, 3, 7, 14
and 28 days schedule.
It is therefore mandatory that the
recommended schedules are followed to obtain
optimum immunogenicity. It is always advisable
to refer to the manufactures recommendations
especially before administering newer vaccines.
Points to remember
1. EPI Schedule is the sheet anchor of
childhood immunization.
2. Modifications as needed may be adapted
as per local government / professional body
recommendations.
3. Different schedules have to be followed
under special clinical circumstances.
VII. Myths and facts 12,13
The following myths and facts need to be emphasized on the basis of available evidence.
S.No. Myth
1. Too many vaccines might overload
the immune system
2. Combination vaccines may be less
effective than vaccines administrated
separately
3. Thimerosal used as preservative in
multi dose vaccine formulations is
neurotoxic
4. Aluminium salts used as adjuvants in Since the discovery of DTPw combination
certain vaccines may be harmful to
the child
4. The fear compounded about the doubtful
immunogenicity of individual antigens in
combination formulations, is not true.
5. Recommended interval of atleast 4 weeks
between multiple doses of same antigen is
mandatory.
6. Simultaneous administration of multiple
antigens does not suppress the immune
system.
7. Various myths and vaccination scares are
not true.
Fact
The immune system can simultaneously respond
to over 10 million antigens at any one time
Natural infections present more antigens
(2)
eg Hib-50 or more , Hep B-4 or more
Whole cell Pertussis vaccine contains over
3000 antigens, yet no overload
The DTPw-HB-Hib combination formulation
has
- excellent immunological response
- superior safety and less reactogenicity
The DTPa-HB-Hib combination formulation has
enhanced safety and lowered the reactogenicity
With 2.5 mcg for each vaccine administration,
Thimerosal which is ethyl mercury, does not
produce any neurotoxicity as once feared
formulation in 1943, DTPw-HB and DTPw-HB
Hib in 1998, Alum salts have been successfully
used as adjuvants without any significant
adverse effect
References
1. American Academy of Pediatrics. Scheduling
Immunization. In: Pickering LK, (Ed), 2000
Red Book: Report of the Committee on
th
Infectious Diseases. 25 Edn, Elk Grove
Village IL, American Academy of Pediatrics;
2000: pp54-79.
2. American Academy of Pediatrics. Hepatitis A.
In: Pickering LK, (Ed),. 2000 Red Book:
Report of the Committee on Infectious
th
Diseases. 25 Edn, Elk Grove Village IL,
American Academy of Pediatrics; 2000:
pp282-283.
11
3. American Academy of Pediatrics. Hepatitis B.
In: Pickering LK, (Ed),. 2000 Red Book:
Report of the Committee on Infectious
th
Diseases. 25 Edn. Elk Grove Village IL,
American Academy of Pediatrics; 2000:
pp294-300.
4. American Academy of Pediatrics. Immunizing
agents. In: Pickering LK, (Ed), 2000 Red
Book; Report of the Committee on Infectious
th
Diseases, 25 Edn. Elk Grove Village IL,
American Academy of Pediatrics; 2000;p9.
5. Immunization Special Circumstances, IAP
nd
Guide Book on Immunization, 2 Edn:
Parthasarathy A, Dutta AK, Bhave S (Eds), IAP
Publication, Mumbai 2001: 14, 17, 47-49.
6. Adolescent Immnuzation Schedule, IAP Guide
Book on Immunization. Dubey AP, Surjith
Singh: (Eds). Indian Academy of Pediatrics,
Mumbai 2004;8: pp37-42.
7. Immunization in Special clinical circum-
stances. Innunization in Clinical Practice :
Naveen Thacker, Nitin K Shah, (Eds) Jaypee
Bros. Medical Publishers, New Delhi,
2004;pp10-11.
8. Claire-Anne, Siegrist. Understanding immune
response to Vaccine: Immunization in
childhood. Annales Nestle 2000; 58:75-81.
9. Global Program for Vaccines and
Immunization. Expanded Program on
Immunization Policy on Hepatitis B
Immunization schedule. WHO GPV/GEN/20.
10. American Academy of Pediatrics. Hepatitis A.
In: Pickering LK (Ed): 2000 Red Book: Report
of the Committee on Infections Diseases.
th
25 Edn, Elk Grove Village IL, Americal
Academy of Pediatrics, 2000; pp280-282.
11. American Academy of Pediatrics. Varicella
infection, Recommendations for Immunization
In: Pickering LK (Ed), 2000 Red Book.: Report
of the Committee in Infectious Diseases.
th
25 Edn, Elk Grove Village IL, American
Academy of Pediatrics, 2000: pp634-638.
12. Francis Andre. In Proceedings on
Combination Vaccines: Glaxo SmithKline
publication 2001.
13. Parthasarathy A. Combination Vaccines. The
choice ahead in Pediatric Index. Kumar A,
Mohan M, Mohan H (Eds) Meditech
Publishers and Distributors, New Delhi 2001;
1:3;13-18.

NEWS AND NOTES

COMGAN
SECOND INTERNATIONAL PEDIATRIC NEPHROLOGY TRAINING COURSE
All India Institute of Medical Sciences, New Delhi
9-11, March 2007
Day 1 : Targeted towards specialists, those interested in nephrology, PG students
Day 2, 3 : Intended for specialists, pediatricians, PG students
Registration Fee Till 15-01-2007 Thereafter
Days 1-3 Rs. 1,500 Rs. 2,000
Days 2, 3 Rs. 1,000 Rs. 1,500
Postgraduate students : 50% concession
Demand draft in favour of Pediatric Nephrology Training Coure payable at New Delhi
Chairperson : Arvind Bagga Secretary : Pankaj Hari
Department of Pediatarics, All India Institute of Medical Sciences, Ansari Nagar,
New Delhi - 110 029, India. Phone : 011-26593472; 26588700; ext. 4858
E-mail : arvindbagga@hotmail.com, pankajhari@hotmail.com

12
 VACCINES II
NEWER VACCINES - II
* Dutta AK
** Kush Jhunjhunwala
Abstract: This article deals with few vaccines,
which are already available(acellular pertussis
Tdap and rota virus vaccines), and other
vaccines, which are under development (malaria
and HIV vaccines). Multi component acellular
pertussis vaccines are effective and have less
adverse effects than whole cell vaccines. Tdap is
expected to protect the adolescents against
pertussis and gives protection against tetanus
and diphtheria. The usefulness of presently
available rotavirus vaccine can be established
only after the enumeration of serotypes of
rotavirus strain in India. Malaria vaccines
developed to target different stages of malarial
parasite are found to have varied response in
trials. A safe and effective vaccine remains
elusive with regard to HIV vaccine.
Key words: Acellular pertussis vaccine, Tdap,
Rotavirus, Malaria, HIV Vaccines.
The worlds oldest vaccine invented and
perfected by Sir Edward Jenner has become
obsolete after serving the mankind for over a
century and half. It is needless to state that
vaccination is one of the most cost effective
methods of prevention of disease. In spite of the
* Director, Professor and Head of the Department,
** Senior Resident,
Lady Hardinge Medical College and associated
Kalawati Saran Children Hospital,
New Delhi- 110 001.
13
introduction of universal immunization program
in the world followed by EPI program, still
1.8 million deaths occur in the world due to
common vaccine preventable diseases like measles,
tetanus, whooping cough, and diphtheria.
Approximately 7,45,000 deaths occur in the world
due to measles alone. A large number of vaccine
preventable deaths occur in India due to poor
coverage of vaccine in National Immunization
Program. A large number of newer vaccines are
available in the world including India and many
more vaccines are in the process of development.
The present article will deal with few of the
available vaccines and significant ones in the
process of development.
1) Acellular pertussis vaccine
Diphtheria, tetanus and pertussis are still a
major cause of mortality and morbidity in the
world. Although the whole cell pertussis vaccine
has good immunogenicity, there is a fear of serious
adverse reactions associated with it in the form of
encephalopathy, persistent screaming episodes,
convulsions and hyperpyrexia.
Better understanding of the biology of
B.pertussis and the isolation of components that
appear to be important in the pathogenesis of
disease led to the development of purified
component, known as acellular pertussis vaccine,
in Japan in 1981. The encouraging results of the
Japanese experience stimulated thorough efforts
in developed world to develop other acellular
pertussis vaccines.1, 2, 3
Today, in the world almost a dozen
formulations of acellular pertussis vaccines have
been evaluated for the efficacy and safety and
are being extensively used. These vaccines vary
from one another with respect to their source,
number of components, quantity of each
component, method of purification, method of
toxin inactivation, incorporation of adjuvant and
excipients.
At present there is only one acellular pertussis
containing DTaP available in India. The acellular
pertussis with DT formulation contains pertussis
toxins, viz. pertactin and filamentous
hemagglutinin.
Many large scale acellular pertussis vaccine
efficacy trials have been conducted in various parts
of the world and the results have shown that the
vaccine is safer than the whole cell vaccine in
terms of common as well as serious adverse
reactions.
The efficacy of the whole cell pertussis
vaccine is in the range of 85-95% and that of the
acellular vaccine ranges from 75-90%.1 Whole
cell pertussis vaccine is very effective and
inexpensive. The choice of vaccine depends on
balancing considerations of relative efficacy,
adverse effects and most important is the cost.
However for second booster dose and especially
if it is delayed due to some reasons, acellular
pertussis vaccine would be more safe in terms of
serious adverse reactions.
Doses and Schedule
Three primary doses beginning at 6 weeks
as per the national schedule of the country can be
used safely. In USA 2-4-6 months schedule and
in some countries 2-3-4 months or 3-5-7 months
schedule are in use. The duration of immunity
with the entire schedule using acellular pertussis
vaccine has been found to be equal or more than
that of whole cell pertussis vaccine. Following
3 doses primary schedule, the immunity lasts for
2-4 years, and with two more booster doses, at
14
18-24 months and 5 years, the immunity would
last longer up to 10-15 years. There is evidence
to show that herd immunity is produced using
acellular pertussis vaccine.
Safety and adverse events
Acellular pertussis vaccine has been found
to reduce both the common adverse events e.g.
fever, pain, irritability as well as the uncommon
adverse events e.g. seizures, shock like episodes
by two third compared to the whole cell vaccine.
It has been observed that with latter doses of
acellular pertussis vaccine the rate of adverse
reaction remains less than that seen with the whole
cell vaccine. Acellular pertussis vaccine in reduced
dose has the advantage of use in adults as an
essential tool for control of pertussis.1, 4
Cochrane Review
Six efficacy trials and 45 safety trials were
included. Acellular pertussis vaccines with three
or more pertussis antigens were more effective
than those with one or two antigens. They were
also more effective than one type of whole cell
pertussis vaccine, but less effective than two other
types of whole cell vaccines. Differences in trial
design precluded pooling of the efficacy data and
results should be interpreted with caution. Most
systemic and local adverse events were
significantly less common with acellular than with
whole cell pertussis vaccines.
Conclusions
Multi-component acellular pertussis vaccines
are effective and show less adverse effects than
whole cell pertussis vaccines. However in countries
where cost is a concern, whole cell pertussis
vaccine can be safely used taking into considertion
the risk, benefit of the disease versus adverse
reaction to whole cell vaccine.5
2) Tdap vaccine
Tdap is a formulation for use in adolescents
and contains reduced content of diphtheria toxoid
and acellular pertussis; and normal content of
tetanus toxoid. Pertussis, an acute, infectious
illness, remains endemic in major part of the world
despite routine childhood pertussis vaccination for
more than half a century and high coverage levels
in children for more than a decade.
Recent estimates from the WHO suggest that
in 2002 about 18,351,000 cases of pertussis
occurred worldwide, the vast majority of which
were in developing countries, and that about
294,000 patients died from this disease. It is further
estimated that in 2002 global vaccination against
pertussis averted more than 37 million cases and
587,000 deaths.6 According to a Central Bureau
of Health Intelligence (CBHI) study, the number
of reported cases of pertussis in India has increased
recently, by 50 percent from 1997 to 2003.
A primary reason for the continued
circulation of Bordetella pertussis is that immunity
to pertussis wanes approximately 5 - 10 years after
completion of childhood pertussis vaccination,
leaving adolescents and adults susceptible to
pertussis.7
In 2004, there were more than 25,000 cases
of pertussis in the United States. More than 8,000
of these cases were among adolescents 11-18
years of age. Up to two in 100 adolescents with
pertussis are hospitalized or have complications.7
The spectrum of disease caused by
B.pertussis in adolescents ranges from mild illness
with cough to classic pertussis; infection also can
be asymptomatic.
During the year 2005, two products
containing reduced contents of diphtheria, acellular
pertussis; and normal content of tetanus toxoid
(Tdap) for use in adolescents (and 1 product for
use in adults) were licensed in the United States.
In pre-licensure studies, Tdap administered as a
single booster dose to adolescents was shown to
be safe and effective against tetanus, diphtheria,
15
and pertussis. 7 Currently pediatric DTaP is
routinely advocated for children aged <7 years,
pediatric diphtheria and tetanus toxoids vaccine
(DT) for children aged <7 years with
contraindications or precautions for pertussis
components, and adult tetanus and diphtheria
toxoids vaccine (Td) routinely for persons aged
>7 years. The formulation of choice for
vaccination of persons aged >7 years has been
Td rather than pediatric DT, as the lower
diphtheria toxoid antigen content of Td induces
an adequate immune response and lower rates of
adverse reactions in adults than the pediatric DT.7
In India, since children usually get DT at the age
of five years, and as the incidence of pertussis is
rising alarmingly in the age group of 5-15 years,
Tdap has been recommended for a lower age
group as compared to that in US. Thus, in India
Tdap has been registered for use in children over
the age of 4 years, who have already received
their primary DTP doses in the first and second
year of life. Currently, there is a globally-approved
acellular pertussis boosting vaccine for all age
groups available in India, in the form of Tdap.
Composition of vaccine
Each dose of Tdap contains aluminum
hydroxide (<0.39 mg aluminum) as the adjuvant,
4.5 mg NaCl, <100 g residual formaldehyde and
<100 g polysorbate 80 (Tween 80) per 0.5mL
dose. Tdap contains no thiomerosal or other
preservative. Tdap is available in two
presentations: a pre-filled disposable syringe
without a needle and a single dose vial. The
pertussis antigen composition of the adolescent
and adult Tdap formulations is similar to pediatric
DTaP, but some of the pertussis antigens are
reduced in quantity.6,7
Dosage and administration
The dose of Tdap is 0.5 mL, administered
intramuscularly (IM), preferably into the deltoid
muscle.
Safety
The primary safety study, conducted in the
United States, was a randomized, observer-
blinded, controlled study in which 3,080
adolescents aged 1018 years received a single
dose of Tdap. No immediate events (within 30
minutes of vaccination) were reported.
Adverse effects:
Mild
Pain and redness or swelling
Mild fever/ headache/ tiredness/ nausea,
vomiting diarrhea.
Other mild problems reported include chills,
body aches, sore joints, rash and swollen
lymph nodes.
Moderate to severe
Severe pain at the injection site / severe
redness or swelling / fever more than 102F
A severe allergic reaction could occur after
any vaccine. These are estimated to occur
less than one in a million doses.
Specific recommendations to reduce pertussis
morbidity in adolescents and maintain the standard
of care for tetanus and diphtheria protection in
adolescents aged 11 to 18 years are as follows:
Adolescents should receive a single dose of
Tdap instead of tetanus and diphtheria toxoids
vaccine (Td) for booster immunization
against tetanus, diphtheria, and pertussis if
they have completed the recommended
childhood diphtheria and tetanus toxoids and
whole cell pertussis vaccine (DTP)/diphtheria
and tetanus toxoids and acellular pertussis
vaccine (DTaP) vaccination series and have
not received Td or Tdap. The recommended
age for Tdap vaccination is 11 to 12 years.
Those adolescents, who received Td, but not
Tdap, should receive a single dose of Tdap
16
to confer protection against pertussis,
provided they have completed the
recommended childhood DTP/DTaP
vaccination series. To reduce the risk for local
and systemic reactions after Tdap
vaccination, there should be an interval of at
least 5 years between Td and Tdap.8,9
Contraindications
For use of Tdap or Td are a history of serious
allergic reaction (i.e. anaphylaxis) to any
component of the vaccine; and history of
encephalopathy of undetermined cause within
7 days of administration of a vaccine with pertussis
components. Adolescents with the latter
contraindication should receive Td instead of
Tdap.
Simultaneous vaccination with Tdap and
other vaccines
If two or more vaccines are indicated, they
should be administered during the same visit (i.e.,
simultaneous vaccination). Each vaccine should
be administered using a separate syringe at a
different anatomic site.
Can pediatric DTaP be used in adolescents
or can adolescent Tdap be used in the
primary series in children?
No. The capital and lowercase abbreviation letters
denote relatively larger and smaller content of
antigens. Tdap would be expected to have inferior
immunogenicity of diphtheria and pertussis
components in young children, and DTaP would
be expected to have increased reactogenicity in
adolescents. The primary objective of vaccinating
adolescents with Tdap is to protect the vaccinated
adolescents against pertussis while maintaining the
standard of care for protection against tetanus and
diphtheria. A secondary objective of adolescent
Tdap vaccination is to reduce the reservoir of
pertussis within the population at large and
potentially reduce the incidence of pertussis in
other age groups, including infants who have the
highest risk for complications from pertussis. The
extent to which the secondary objective can be
achieved through adolescent vaccination is
unknown.
3) Rotavirus Vaccine
Rotavirus kills approximately half a million
children in the developing countries of the world
and accounts for about one third of hospitalization
for childhood diarrhea throughout the world.10
The first rotavirus vaccine made from
human-rhesus reassortant strains was introduced
in USA but soon suffered a serious setback due
to the possible causal relationship with
development of intussusception following
vaccination.10
At present there are two available rotavirus
vaccines in the world. The first one is the mono-
valent vaccine derived from the most common
human rotavirus strain G1P(8), that has been
attenuated. The mono-valent vaccine strain
replicates well in the gut , is shed by more then
50 % of patients receiving the vaccine after the
first dose and like natural rotavirus infection
provides cross protection against most of the other
serotypes.
This vaccine is given in two doses starting
at 6 weeks of age at an interval of 1-2 months.
The protective efficacy of the vaccine against wild
type of G1P(8) strain induced severe rotavirus
diarrhea is 90%. The efficacy of the vaccine
against strain sharing only P(8) antigen {(G3P (8),
G4P (8) and G9P (8)} is 87.3%. Type G2P (4)
rotavirus which does not share either the G or the
P antigen with the vaccine strain was detected in
less number of cases and against it the vaccine
showed efficacy of 41.0%.10,11
The incidence of severe gastroenteritis of any
etiology that requires rehydration according to
17
WHO plan B or C was 30.9/1000 infant years in
the vaccine group as compared with 51.7 per 1000
infant years in the placebo group for an overall
rate reduction of 40.0 percent among vaccine
recipient. Similarly the rate of hospitalization for
diarrhea of any cause was significantly reduced
by 42.0% in the vaccine group.
The second vaccine is a penta-valent vaccine
based on a bovine strain, WC3 that contains five
human bovine reassortant viruses. The bovine
virus grows less well in the human intestine so
that aggregate titer required to immunize a child
is greater. The bovine vaccine strains are
infrequently shed in the stools. Three oral doses
are required at an interval of one month. The
efficacy of this vaccine is similar to human mono-
valent strain. Both the vaccines are safe and no
causal relationship with intussusception has been
observed in large trials.10
Conclusion : Current evidence shows that rhesus
rotavirus vaccine (particularly RRV-TV) and the
human rotavirus 89-12 are efficacious in
preventing diarrhea caused by rotavirus and all-
cause diarrhea. Bovine rotavirus vaccine were also
efficacious, but safety data are not available. Trials
of new rotavirus vaccines will hopefully improve
the evidence base. Randomised controlled trials
should be performed simultaneously in high,
12
middle and low income countries.
The rotavirus surveillance network in India
is now trying to establish the epidemiology of
rotavirus disease in India. The data would be of
immense help to identify the serogroups involved
and whether the available rotavirus vaccine would
be beneficial in Indian subcontinent or not.
4) Malaria Vaccine
Malaria continues to claim an estimated 2 to
3 million lives annually and is known to account
for untold morbidity in approximately 300 to 500
million people infected annually. Approximately
2.48 million cases are reported annually from
South Asia of which 75% cases are contributed
by India alone.12
At-risk groups include those in whom
immunity has not yet developed (travellers, young
children in endemic areas, etc.) and those in whom
immunity has diminished (pregnant women, and
people from endemic areas who have ceased to
be routinely exposed to infection). Malaria is often
cited as a substantial impediment to economic and
social development in endemic regions.
Malaria is considered a re-emerging disease,
due largely to the spread of drug-resistant parasite
strains, decay of health-care infrastructure and
difficulties in implementing and maintaining vector
control programs in many developing countries.
Historically, vaccines have been one of the
most cost-effective and easily administered means
of controlling infectious diseases, yet no licensed
vaccine exists for malaria. Accumulating basic and
clinical research suggest that effective vaccines
for malaria can be developed and could
significantly reduce morbidity and mortality, and
potentially reduce the spread of infection.
The idea that a vaccine against malaria is feasible
is supported by the following findings:
Immunity can be acquired as a result of
natural exposure.
Most of the severe disease in endemic area
occurs in young children before they have
developed immunity.
Passive transfer of purified immunoglobulin
from immune people has been shown to be
protective.
A pre-erythrocytic vaccine would protect against
the infectious form injected by a mosquito
(sporozoite) and/or inhibit parasite development
in the liver. An erythrocytic or blood stage vaccine
would inhibit parasite multiplication in the red cells,
thus preventing (or diminishing) severe disease
18
during the blood infection. A sexual stage vaccine
does not protect the person being vaccinated, but
instead interrupts the cycle of transmission by
inhibiting the further development of parasites once
they, along with antibodies produced in response
to the vaccine, are ingested by the mosquito.13
A pre-erythrocytic vaccine would ideally not
only prevent sporozoites from invading
hepatocytes but also induce cytotoxic cell mediated
immunity against any infected hepatocytes. The
lead candidate among the tried vaccine is the RTS
recombinant protein vaccine, targeting the
circumsporozoite antigen that is expressed on both
sporozoites and the infected hepatocytes. This
antigen is fused with the hepatitis B surface
antigen and expressed as a recombinant protein
in yeast and used with a powerful adjuvant AS02.
Though the vaccine is safe and immunogenic, the
protective efficacy is only 30-60%. This RTS,
S/ASO2 pre-erythrocytic vaccine holds out hope
of achieving sterilizing immunity and is eminently
suited for immunization of travelers.14,15
DNA vaccine and prime-boost approaches
Perhaps the most viable multi-component
attack on malaria is offered by DNA vaccines,
which can be genetically tailored to induce both
cell-mediated and humoral immune responses.
Multi-component DNA vaccines offer the best
prospects for protection against malaria because
they can be tailored to include a variety of
numbers, types, and arrangements of epitopes (the
sites within a molecule to which a specific antibody
binds). DNA vaccines, unlike conventional
vaccines, have high immunogenicity, unlike multi-
component synthetic peptide vaccines like
SPF-66. DNA vaccines are also cost-effective.
SPF-66 was a vaccine designed to contain
sequences from three blood stage antigens,
combined with the tetra-peptide repeats of the
circumsporozoite protein. Unfortunately in large
phase III trials this vaccine lacked significant
efficacy. Vaccine directed at antigens of the
merozoites important for the red blood cells
invasion include those against the apical membrane
antigens(AMAI) and merozoite surface antigens
(MSP1, MSP2). These have been shown to be
highly effective in animal models, but are poorly
immunogenic in humans, while high antibody titers
are required to prevent invasion.
Transmission blocking or so-called altruistic
vaccines rely on preventing fertilization of the
sexual stage of the parasite in the gut of the
mosquito vector. Two candidate antigens under
development are Pfs28 and Pfs25 containing
sexual stage (ookinete) antigens expressed by
P.falciparum and P. vivax, respectively.
Recombinant vaccines
Through a collaborative program between
investigators at Oxford University and SB Bio
(SmithKline) detailed characterization of the
cellular immune response to the RTS,S/SBAS2
vaccine is underway. Planned clinical trials include
prime-boost studies of RTS, S boosted with a
recombinant modified vaccinia virus Ankara
encoding the CS protein.13
Two P. falciparum candidate vaccines are
under investigation. One, an ~41 kd protein called
FALVAC-1. It has been expressed in a baculovirus
expression system in collaboration with National
Institute of Immunology, New Delhi, India.
A second candidate, FALVAC-2, is under
development. CDC has entered into a
Collaborative Research and Development
Agreement (CRADA) with the Bharat Biotech,
International Limited (BBIL), Hyderabad, India,
for production of GMP-grade candidate vaccine
antigens.
Genomic and proteomic approaches
In 1996, a collaborative International effort
was undertaken to sequence the complete genome
of P. falciparum. The most promising development
19
in the field is publication of the genomes of Homo
sapiens, Plasmodium falciparum and Anopheles
gambiae - the three corners of the fatal triangle of
African malaria. This would certainly open up
immense possibilities. Use of sophisticated
procedures like micro arrays, gene analyses and
proteomics will throw up a large number of vaccine
candidates. It is now estimated that essentially all
of the parasites approximately 6000 genes are
available in existing databases. Thus, the malaria
community and vaccine developers have access
to virtually all of the genes encoding the antigens
and proteins expressed by this organism.13
Cochrane review
Four types of malaria vaccines, SPF-66 and
MSP/RESA vaccines (against the asexual stages
of the Plasmodium parasite) and CS-NANP and
RTS, S vaccines (against the sporozoite stages),
have been tested in randomized controlled trials
in endemic areas
Eighteen efficacy trials involving 10,971
participants were included. There were ten trials
of SPF-66 vaccine, four trials of CS-NANP
vaccines, two trials of RTS,S vaccine, and two of
MSP/RESA vaccine. Results with SPf66 in
reducing new malaria infections (P. falciparum)
were heterogeneous: it was not effective in four
African trials (Peto odds ratio (OR) 0.96, 95%
confidence interval (CI) 0.81 to 1.14), but in five
trials outside Africa the number of first attacks
was reduced (Peto OR 0.77, 95% CI 0.67 to
0.88). Trials to date have not indicated any serious
adverse events with SPf66 vaccine.
In three trials of CS-NANP vaccines, there
was no evidence for protection by these vaccines
against P. falciparum malaria (Peto OR 1.12, 95%
CI 0.64 to 1.93).
In a small trial in non-immune adults in the
USA, RTS,S gave strong protection against
experimental infection with P. falciparum. In a
trial in an endemic area of the Gambia in semi-
immune people, there was a reduction in clinical
malaria episodes in the second year of follow up,
corresponding to a vaccine efficacy of
66% (CI 14% to 85%).
In a trial in Papua New Guinea, MSP/RESA
had no protective effect against episodes of clinical
malaria. There was evidence of an effect on
parasite density, but this differed according to
whether the participants had been pretreated with
sulfadoxine/pyrimethamine or not. The prevalence
of infections with the parasite subtype of MSP2
in the vaccine was reduced compared with the
other subtype (Peto OR 0.35, CI 0.23 to 0.53).
Conclusion: There is no evidence for protection
by SPf66 vaccines against P. falciparum in Africa.
There is a modest reduction in attacks of
P.falciparum malaria following vaccination with
SPf66 in other regions. Further research with
SPf66 vaccines in South America or with new
formulations of SPf66 may be justified. There
was not enough evidence to evaluate the use of
CS-NANP vaccines.
The RTS,S vaccine showed promising result,
as did the MSP/RESA vaccine, but it should
include the other main allelic form of MSP2. The
MSP/RESA trial demonstrated that chemotherapy
during a vaccine trial may reduce vaccine efficacy,
and trials should consider very carefully whether
this practice is justified.16,17
5) HIV Vaccine
The HIV-1 pandemic has grown to become
one of the greatest infectious disease threats to
human health and social stability that the world
has ever encountered. Nearly 40 million persons
are living with HIV-1 infection and more than
21 million people have already died from HIV-
induced disease. Regarding the status of AIDS in
India, since the first report of the HIV infection
20
among sex workers in Chennai in 1986, India has
the second largest number of people living with
HIV/AIDS in the world, with an adult population
prevalence of approximately 5.13 millions. Though
HIV infection in India is concentrated among poor,
marginalized groups, HIV is spreading quickly into
the general population. Approximately 90 percent
of reported AIDS cases occur in sexually active
and economically productive individuals aged
15 to 44 years. HIV infection among women and
children is on the rise. The reported doubling time
of HIV epidemic in India is nearly two years.18
HAART allows the stabilisation of the
patients symptoms and viremia, but they do not
cure the patient of HIV, nor of the symptoms of
AIDS. High levels of HIV-1, viremia often
HAART resistant, return once treatment is
stopped. Moreover, it would take more than the
lifetime of an individual to be cleared from HIV
infection using HAART. Antivirals are also too
expensive for developing countries, which have
the highest rates of HIV-infection. Only a vaccine
will be able to halt the pandemic. This would
possibly cost less, thus being affordable for
developing countries, and would not require daily
treatments. However, after over 20 years of
research, HIV-1 remains a difficult target for a
vaccine.19
Current Strategies for an HIV Vaccine
Traditional
Immunization with live attenuated viruses
Possible limitations In vivo mutation may
render vaccine pathogenic, no animal
model for pathogenicity.
Immunization with inactivated viruses with
adjuvant
Possible limitations - Brief duration of
immunity, absence of cytotoxic
T lymphocytes
Newer approaches
Immunization with recombinant HIV protein
with adjuvant
Possible limitations -Brief duration of
immunity, absence of cytotoxic T cells,
restricted number of isolates recognized
Immunization with synthetic HIV peptides
with adjuvents
Possible limitations -Restricted number of
immunogenic epitopes
Combined approaches (e.g. recombinant
vaccinia virus and recombinant protein)
Possible limitations -No consistent protection
in the animal model
Intramuscular inoculation of the virus agent
Possible limitations -Little experience with the
approach
Use of vaccine for immune potentiation in
HIV infected patients
Possible limitations -No evidence of
effectiveness
The classical vaccination approaches that
have been successful in the control of various viral
diseases by priming the adaptive immunity to
recognize the viral envelope proteins have failed
in the case of HIV-1, as the epitopes of the viral
envelope are too variable. Furthermore, the
functionally important epitopes of the gp120
protein are masked by glycosylation, trimerisation
and receptor-induced conformational changes
making it difficult to block with neutralising
antibodies.Thus the vaccine failed to protect
because the circulating HIV strain hides its epitopes
in a variety of ways that genetically engineered
gp120 proteins do not mimic successfully. In
February 2003, VaxGen announced that their
AIDSVAX vaccine was a failure in North America
as there was not a statistically significant reduction
of HIV infection within the study population. In
November 2003, it also failed clinical trials in
Thailand for the same reason.20, 21
21
Based on the observation that in the initial
part of the infection, T cells are involved in the
identification and killing of HIV infected cells,
various vaccine are underway that stimulate
T cells responses. Methods attempted include
recombinant proteins, synthetic peptides,
recombinant viral vectors, recombinant bacterial
vectors, recombinant particles, DNA vaccines to
induce production of a specific antigen, and whole-
killed and live-attenuated HIV, however, initial
results cast doubts about the vaccine
immunogenicity. Another vacine now in the early
stage of a proof of concept, or phase 2B trial,
contain replication-defective adenovirus type 5
that transmit the HIV genes gag, pol, and nef
(which codes for internal HIV protein and may
stimulate cellular immunity), this vaccine looks
far more promising.20, 21
Other novel approaches will soon be tested
in nonhuman-primate models of AIDS, among
them the direct intramuscular inoculation of viral
genes. Such an immunization procedure generates
potent antibody and cell-mediated immune
responses and protects against challenge with live
influenza virus.
Clinical trials for the HIV vaccines
A total of 17 vaccine candidates are in phase
I trials and four in phase I/II. There is only one in
phase III (the NIH/Department of Defenses
ALVAC vCP 1521 canary pox vector/AIDSVAX
prime-boost vaccine trial now under way in
Thailand). ALVAC-HIV: a genetically
engineered HIV vaccine composed of a live,
weakened canary pox virus (ALVAC) into
which parts of genes for non-infectious
components of HIV have been inserted. When
ALVAC infects a human cell, the inserted HIV
genes direct the cell to make HIV proteins. These
proteins are packaged into HIV-like particles that
bud from the cell membrane. These particles are
not infectious but fool the immune system into
mounting an immune response to HIV. ALVAC
can infect but not grow in human cells, an important
safety feature.
Up to May 2003 over 60 phase I/II trials of
candidate vaccines have been conducted
worldwide. Most initial approaches focused on
the HIV envelope protein. At least thirteen
different gp120 and gp160 envelope candidates
have been evaluated, in the US predominantly
through the AIDS Vaccine Evaluation Group.
Overall, they have been safe and immunogenic
in diverse populations, have induced neutra-
lizing antibody in nearly 100% recipients, but
rarely induced CD8+ cytotoxic T lymphocytes
(CTL). 19,20
On January 26, 2005, a large phase IIb clinical
trial of a novel HIV vaccine has begun enrolling
volunteers at sites in North America, South
America, the Caribbean and Australia. The
organizers are seeking 1,500 participants. The trial
is co-funded by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the
National Institutes of Health (NIH), and the
pharmaceutical company Merck & Co. Inc. In
previous smaller trials, this vaccine was found to
be safe and to induce cellular immune responses
against HIV in more than half of volunteers.
NIAID and Merck expect the trial be
completed in four-and-a-half years, with results
anticipated in 2010.19
Novel approaches, including modified
vaccinia Ankara (MVA), adeno-associated virus,
Venezuelan Equine Encephalitis (VEE) replicons,
and codon-optimized DNA have proven to be
strong inducers of CTL in macaque models, and
have provided at least partial protection in some
models. Most of these approaches are, or will
soon, enter clinical studies.19,20,22
In India, Pune-based National AIDS
Research Institute (NARI) is set to begin the
phase 1 trial that involves administration of
22
Modified Vaccinia Ankara (MVA) HIV-1 subtype
C vaccine for the first time to humans in India.
The tests in the western city of Pune will involve
30 HIV-free volunteers between 18 and 45 of
both sexes.
Due to an enormous amount of pre-clinical
work over the last several years, many other
vaccines are being studied and include important
concepts worth watching. These include the
Venezuelan equine encephalitis virus vectors
(encoding gag from clade C), the heat-killed
recombinant Saccharomyces cerevisiae
(expressing gag from Clade B), the IL-2/Ig cytokine
adjuvanted DNA of the VRC in collaboration with
Harvard, the IL-12 cytokine adjuvanted Gag
subtype B vaccine of Wyeth and the DNA prime/
MVA boost strategy being developed by Harriet
Robinson at Emory. But as in 1984, still a safe
and effective preventive vaccine remains elusive.
Points to remember
Acellular pertussis and Tdap vaccines have
definite role as newer vaccines.
With regard to rotavirus, malaria & HIV
vaccines an ideal vaccine is yet to be
developed.
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S5.
12. Kundu R, Ganguly N, Ghosh TK, Choudhury P,
Shah RC. Diagnosis and management of malaria
in children: recommendations and IAP plan of
NEWS AND NOTES
XIV INTERNATIONAL CONFERENCE OF
THE INDIAN ASSOCIATION OF PALLIATIVE CARE
Date : 10th to 12th February 2007
Registration fees : Rs. 2,000.
Contact :
Dr. Sajid S. Qureshi, Pediataric Surgical Oncologist, Tata Memorial Hospital, Mumbai.
E-mail : sajidshafique@rediffmail.com; Tel No. 24177276 / 7000
23
action, Indian Pediatr 2005;42(11):1101-
1114.
13. Raghunath D. Malarial Vaccine:Are we
anywhere close? JPGM 2004;50: 51-54.
14. Read Andrew. Quoted in Malaria - from Infants
to Genomics to Vaccines, by Long CA,
Hoffman SL. Science 2002; 297:345-347.
15. Richie TL, Saul A. Progress and challenges for
malaria vaccines. Nature 2002; 415:694-701
16. Karen Fleming Michael. Steady progress;
Malaria vaccines show progress thanks to
Armys efforts, assessed at dc military.com
17. Graves P, Gelband H. Vaccines for preventing
malaria. The Cochrane Database of Systematic
Reviews 2003, Issue 1. Art. No.: CD000129.
DOI: 10.1002/1465 1858.CD000129
18. Norman L. Letvin. Vaccines against Human
Immunodeficiency Virus Progress and
Prospects. N Engl J Med 1993;329:1400-
1405.
19. HIV vaccine: from Wikipedia, the free
encyclopedia; http://en.wikipedia.org
20. Steinbrook R., Drazen JM. AIDS - Will the
Next 20 Years Be Different? N Engl J Med
2001;344:1781-1782.
21. Cohen Jon. The search for an AIDS vaccine and
on effective global response shots in the dark:
The Wayward search for an AIDS vaccine. N
Engl J Med 2001;344:1801-1802.
22. HIV vaccine: National institute of allergy and
infectious disease ( NIAID), assessed at :http:/
/www.niaid.nih.gov/information/search.htm.
 VACCINES II
ADDITIONAL VACCINES - CURRENT
TRENDS
* Niranjan Shendurnikar
** Mukesh Kumar Singh
Abstract : Additional vaccines (vaccines not
covered under National Immunization Schedule
but recommended by IAP) like Typhoid, MMR
and varicella vaccines are covered in this article.
In developing countries, Vi polysaccharide and
Ty 21a typhoid vaccines are equally effective.
Another option for less than 2 years old children
is Vi-conjugate vaccine. Reviving whole cell
typhoid vaccine manufacture could be considered
in view of its cost effectiveness, usefulness even
in infants and toddlers and possibility of reducing
the side effects by excluding paratyphoid bacilli
and administering it intradermally. Indian
Academy of Pediatrics recommends M/MMR
vaccine strategy with measles vaccine at
9 months of age and MMR at 15 months of age.
The varicella vaccine is effective in preventing
all forms of varicella infection.
Keywords : Typhoid, MMR, Varicella Vaccines.
Typhoid Vaccines
Need for typhoid vaccines
Besides sanitation, immunization is an
additional effective tool for the prevention of
typhoid fever. With the global emergence of multi-
* Associate Professor
** Assistant Professor
Department of Pediatrics
Medical College, Baroda 390001
24
drug resistance and of strains with reduced
susceptibility to fluoroquinolones, prevention is
of paramount importance.1 Immunization is useful
for prevention of typhoid in travellers from
developed countries to typhoid-endemic countries,
in preventing and controlling epidemics, and for
children in endemic settings aged 2 to19 years.2
Vaccine availability
The old parenteral whole-cell typhoid-
paratyphoid A and B (TAB) vaccine was effective
against typhoid and paratyphoid fevers but has
been largely discontinued because of frequent
side-effects and the cumbersome manufacturing
process.3,4 Currently, two vaccines for typhoid
fever, one based on Vi polysaccharide and the
other oral one based on whole-cell live attenuated
bacteria, are licensed. There is no licensed vaccine
for paratyphoid fever. The liquid formulation of
the live oral vaccine for younger children is
currently marketed in only a few countries.1 The
live oral Ty21a vaccine in the capsule formulation
is also no longer available in India.
Whole-cell typhoid vaccine and vaccine efficacy
In a meta-analysis of randomized controlled
trials evaluating the efficacy of the various typhoid
vaccines, the three-year cumulative efficacy was
73% (95% confidence interval 65% to 80%) for
two doses of whole cell vaccines (based on seven
trials); 51% (35% to 63%) for three doses of
Ty21a vaccine (four trials); and 55% (30% to
71%) for one dose of Vi vaccine (one trial). For
whole cell and Ty21a vaccines, regimens of fewer
doses were less effective. Efficacy was shown to
be significant for five years for whole cell vaccines,
four years for Ty21a vaccine, and two years for
Vi vaccine. After vaccination, fever occurred in
15.7% (11.5% to 21.2%) of whole cell vaccine
recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine
recipients, and 1.1% (0.1% to 12.3%) of
Vi vaccine recipients. This meta-analysis
concluded that whole-cell vaccines are more
effective than the Ty21a and Vi vaccines, but are
more frequently associated with adverse effects.
Whether the added efficacy of the whole cell
vaccines outweighs their toxicity will depend on
the setting in which immunization is used.3
The acetone-killed whole-cell vaccine was
reported to have a protective efficacy of 79 88%
in various studies. The Vi and oral typhoid vaccines
are safe but the protective efficacy is much less
(between 50 70%) compared to the effective
vaccines available for other diseases.5
Whole cell vaccines
The whole-cell vaccine is quite inexpensive
and it is effective even in infants and toddlers. Its
side-effects can be decreased if the vaccine
contains only S.typhi (and not paratyphoid bacilli
too) and if it is administered by the intradermal
route (as recommended for revaccinations) rather
than subcutaneously. The adverse effects of the
whole-cell vaccine are no worse than the local or
systemic reactions to DTP vaccine, are not serious,
and are short-lived and well-tolerated. Reviving
the manufacture of the whole-cell vaccine could
be considered.4
Vi polysaccharide vaccine
This is the only typhoid vaccine available
widely in India currently. This vaccine is licensed
for use in individuals older than two years and is
given in a single subcutaneous or intramuscular
dose. The vaccine is moderately effective for
about three years after vaccination. Revaccination
is recommended every three years. However, 58%
25
of participants in a field trial in South Africa still
had protective levels of antibodies ten years after
vaccination.6 This vaccine has shown about 70%
protective efficacy in a population vaccinated
before or during an outbreak in China.7
Ty21a vaccine
This live oral vaccine in enteric-coated or
liquid formulation is approved for use in individuals
six years of age and older. Three doses are
recommended each given two days apart.1 The
oral typhoid vaccine is recommended as four initial
doses in the USA and only three in Europe -
a potential point of confusion. Antimicrobials
should be avoided for seven days before or after
vaccination.
The oral vaccine is moderately effective for
up to about three years after vaccination.
Revaccination is recommended every three years
in endemic areas and every five years for travellers
to developing countries. Travellers to typhoid-
endemic areas such as South Asia need to be
vaccinated even if they plan to stay for less than
two weeks. Herd immunity was shown during field
trials in Chile.1
In a study to determine the acceptability of
oral typhoid vaccine among Thai children, the
rates of successfully being able to swallow all three
capsules (one capsule every other day) were
84.4%, 94.9%, and 100% in the age groups
4-6 years, 7-9 years, and 10-12 years
respectively.8
Choosing a typhoid vaccine
The effectiveness of both the vaccines in
developing countries is similar. Ty21a has the
advantage that it is given orally and therefore might
be easier for immunizing groups of children, as in
schools. The Ty21a vaccine, especially the enteric-
coated capsule formulation, is not licensed for use
in 25 year-old children. Vi vaccine has a relative
advantage that it can be used for these preschool
children, in settings where typhoid fever is
common in this age-group. The vaccine, however,
is not licensed for use in children younger than
two years.1
Adverse events
Post-marketing surveillance in the U.S. for
licensed typhoid fever vaccines from the Vaccine
Adverse Effects Reporting System (VAERS) from
1990 to 2002 revealed that unexpected frequently
reported symptoms included dizziness and pruritus
for Vi polysaccharide vaccine and fatigue and
myalgia for Ty21a. Gastroenteritis for Ty21a and
abdominal pain after Vi vaccine were previously
recognized events. Occasional nonfatal anaphylaxis
was reported after both vaccines. VAERS reports
do not indicate any unexpected serious side effects
that compromise use of these vaccines as
prophylaxis for travellers.9
Vi-conjugate vaccine
Unlike polysaccharide vaccines, conjugate
vaccines can be effective in children younger than
two years and elicit immunologic memory.
Vietnamese children between the ages of two and
five years given Vi-conjugate vaccine had 91.1%
protection against typhoid 27 months after
vaccination, with geometric mean titers of 7.61
ELISA units for those vaccinated at age two to
three years. 10 The efficacy of this conjugate
vaccine persisted after 46 months of vaccination;
over the entire period, the protection was 89%
(95% CI: 76%97%).11 As yet, it has not been
tested in infants. This vaccine could be used for
children younger than two years and be
incorporated into the Expanded Program on
Immunization (EPI) schedules in the future.
Combination vaccines
In a multicenter study to evaluate the first
combined vaccine against typhoid fever and
hepatitis A in healthy subjects aged 15-50 years,
26
more than 95% of the subjects were positive for
anti-Vi antibodies and more than 86% were
positive for anti-HAV antibodies as early as
14 days after immunization. The combined
vaccine offers more convenience and rapid
seroconversion for travellers.12 Clinical studies in
healthy adults have also documented the safety
and immunogenicity of concomitant administration
of an inactivated hepatitis A vaccine and either a
typhoid fever (Vi) vaccine or a combination of Vi
and yellow fever vaccines.13
MMR Vaccine
Is a second dose necessary?
Research over the merits of two doses of
MMR vaccine versus a single dose is not new. In
Finland, a two-dose MMR vaccination program
was begun in 1982. The program with high
coverage (9798%) has eliminated these three
diseases from Finland. In a study following the
kinetics of measles virus antibodies in MMR-
vaccinated cohorts, the primary dose induced
99.4% seroconversion for measles with a geo-
metric mean haemagglutination inhibition(HI)
antibody titer (GMT) of 1/269 (219). After
12 years, 80% of the original children remained
available for sampling. The 12-year follow-up
samples showed a measles seropositivity rate of
100% as assayed with the HI test with a mean
HI antibody titer of 1/39 (54). The authors
postulated that vaccination-induced measles virus
antibodies decline in the absence of natural
booster infections.14
It is important to follow how long the
protection achieved by the present vaccine
programs will last after elimination of indigenous
measles.14 It must be borne in mind that at any
given time, the epidemiology will vary among
countries and the situation in developing countries
cannot be extrapolated from that in the developed
countries.
 Even in the industrialized countries, two
doses of the trivalent MMR vaccine are currently
advocated. The MMR triple (i.e. combined)
vaccine is used in over 90 countries worldwide
and no country recommends immunization for
measles, mumps and rubella in separate
vaccinations.15 The first dose of MMR vaccine
is given routinely at 12-15 months. The second
dose is usually given between three and five years
of age during the school immunization booster
program. Two doses of MMR are required in
order to ensure that all children receive the
vaccination as some may miss it when they are
12-15 months old for a variety of reasons. It is
also important as it confers immunity on those
who did not respond to the first vaccination, which
can be as many as 5-10% (primary vaccine
failure).15,16 The majority of individuals who fail
to respond to the first dose of MMR respond to a
second dose. For children who did receive and
responded to the first vaccination, the second
simply boosts their antibodies to measles, mumps
and rubella just as they start attending school and
increasing social contact with other children.15
During a 1998-99 outbreak of mumps among
children of a religious community in North East
London, a case-control study was conducted to
assess the effectiveness of the mumps component
of the MMR vaccine. Two doses of vaccine were
more effective (88% (95% CI: 6296%)) than a
single dose (64% (95% CI: 4078%)). The authors
concluded that the two-dose vaccination program
remains the best method for controlling mumps
infection in the community.17
Measles and mumps, but not rubella,
outbreaks have been reported amongst populations
highly vaccinated with a single dose of MMR
vaccine. Repeated experience has shown that a
two-dose regime of measles vaccine is required
to eliminate measles. A study paper reported the
effect of the first and second MMR doses on
specific antibody levels in a variety of
populations.18
27
Two to four years after receiving a first dose
of MMR vaccine at age 1218 months, it was
found that a large proportion of pre-school children
had measles (19.5%) and mumps (23.4%) IgG
antibody below the putative level of protection.
Only a small proportion (4.6%) had rubella
antibody below the putative protective level.
A total of 41% had negative or equivocal levels to
one or more antigens. The proportion who had
measles antibody negative (but not rubella or
mumps) was significantly higher in children
vaccinated at 12 months of age than at 1317
months. After a second dose of MMR, the
proportion who were negative to one or more
antigens dropped to <4%. Examination of National
serosurveillance data found that following an MR
vaccine campaign in cohorts that previously
received MMR, both measles and rubella antibody
levels were initially boosted but declined to pre-
vaccination levels within 3 years. This study
supports the policy of administering a second dose
of MMR vaccine to all children. However,
continued monitoring of long-term population
protection will be required and this study suggests
that in highly vaccinated populations, total measles
(and rubella) IgG antibody levels may not be an
accurate reflection of protection. Further studies
including qualitative measures, such as avidity, in
different populations are merited and may
contribute to the understanding of MMR
population protection.18
MMR being a combination vaccine, the
question of a single dose versus two doses can be
addressed only in the context of each of the three
diseases separately. Measles vaccine is known to
have lower seroconversion rate when administered
before 12 months of age, hence a two-dose
measles vaccine schedule (with MMR vaccine at
15 18 months) should be the best approach.
Efficacy of a single dose of mumps vaccine is
around 95%.19 However, in the Indian scenario,
where MMR vaccine or mumps vaccine is not
part of the National Immunization Program
currently, coverage with even a single dose of
mumps vaccine is negligible. It is too far-fetched
to debate over the issue of a second dose.
However there exists the possibility of eradication
of mumps with two doses of mumps vaccine.16
A single dose of rubella vaccine (RA 27/3 strain)
provides seroconversion in more than 95%
children with vaccine efficacy of about 90% for
lifelong protection. The Indian Academy of
Pediatrics recommends M/MMR vaccine strategy
with measles vaccine at 9 months of age to be
followed by MMR vaccine at 15- 18 months.19
As of now, MMR is not included in EPI and
parents must bear the expense for their childs
immunization.
Mumps vaccine virus strain and aseptic
meningitis
The live attenuated mumps virus component
in MMR vaccine could be one of the several strains;
these different strains (Urabe, Leningrad-Zagreb
and Jeryl-Lynn used in India at some time or the
other) have good immunogenicity, though it is
claimed that side-effects are least with the Jeryl-
Lynn strain, particularly in reference to aseptic
meningitis. There is an association between the
Urabe strain of mumps vaccine and aseptic
meningitis.16 Studies have estimated the incidence
of aseptic meningitis to be 49-100, 20-30 and 1.0
per 100,000 doses for the Urabe, L-Zagreb and
Jeryl-Lynn strains respectively20 i.e. it is negligible
for all strains. Moreover, this is a benign disease
with complete recovery even if untreated. A recent
study done in Egypt covering more than 100,000
children being given MMR with the L-Zagreb
mumps virus strain showed that there was not a
single case of aseptic meningitis on prospective
follow-up. All MMR vaccines are considered as
equally safe and immunogenic by IAP.
MMR vaccine scares
Epidemiologic studies do not support a
causative link between MMR vaccine and autism,
28
Inflammatory Bowel Disease and Guillian-Barre
Syndrome.16 From multiple population-based
studies and extensive review committee reports,
it has been summarized that neither immunization
nor thimerosal exposure has been conclusively
linked to autism.
Contested reports associating the MMR
vaccine with autism had resulted in diminished
confidence and public acceptance of the vaccine
in the UK. In a postal survey of parental attitudes,
both MMR-accepting and refusing parents were
supportive of immunization, yet the high level of
concern about the safety of the vaccine expressed
even by parents who had immunized their children
is worrying in its implications for public confidence
and trust in health care.
The weight of evidence lies in favor of triple
MMR vaccination and a 95% uptake of this
vaccine would confer immunity that would protect
not only the immunized child but also those too
young to be immunized and those in utero.15
Varicella Vaccine
Effectiveness of the vaccine and duration of
protection
Varicella vaccine is effective in preventing
any form of the disease in 90-95% of vaccinees
whereas protection against moderate to severe
disease is provided to >95% of vaccinees. The
seroconversion rate in children aged 112 years
was 95% after a single dose. After 13 years of
age, seroconversion rates were 7882% after the
first dose and 99% after two doses. The immunity
to varicella lasts for at least 1020 years.
Secondary vaccine failure may result from waning
vaccine-induced immunity over the years.
Exposure to natural infection in the community
will continue to provide a boosting effect.5
The six-year cumulative varicella antibody
persistence rate was 99.5% (95% CI: 98.9%-
100.0%) in a manufacturer-funded study of
healthy children aged between 1 to 12 years given
the Oka varicella vaccine. The annual
breakthrough rate through seven years ranged
from 0.2% to 2.3% per year; the estimated
cumulative event rate was 6.5%. Comparison of
the observed average annual breakthrough rate
with the age-adjusted expected annual incidence
rate of varicella in unvaccinated children
corresponded to an estimated vaccine efficacy of
93.8% to 94.6%. Eighty vaccinated children were
exposed to varicella in the household, resulting in
8 (10%) cases of infection. When compared with
the historical attack rate of 86.8% in unvaccinated
susceptible persons exposed to varicella in the
household, this yields an estimated vaccine
efficacy of 88.5% (95% CI: 80.9%, 96.1%).
Varicella cases in vaccinated children generally
were mild.21
Results from a study indicate that the
effectiveness of the varicella vaccine used in actual
clinical practice (as against in a clinical trial) is
excellent, at least in the short term. Against
moderately severe and severe disease, the vaccine
was 97 % effective (95% CI - 93 to 99%). Virtually
all the vaccinated children in whom chickenpox
subsequently developed (all of whom were
infected with wild-type virus) had very mild
disease.22 These findings are consistent with those
of a study by the Center for Disease Control and
Prevention that show a marked decline in the
incidence of chickenpox in areas where the vaccine
is widely used, as well as with reports of the
effectiveness of the vaccine after outbreaks in day-
care centers.
Breakthrough varicella
Live attenuated varicella vaccine (Oka strain)
was approved for administration to healthy children
in the United States in 1995. Over the past
10 years, varicella vaccine has been given to
millions of U.S. children, usually at ages between
12 and 18 months. The main unanticipated
observation has been a growing number of
29
outbreaks of varicella among immunized children
(breakthrough varicella). The most cited risk
factors for breakthrough varicella include the
following: (i) 3 to 5-year interval since
immunization and (ii) immunization at the
youngest ages, especially 12 months. Explanations
for breakthrough varicella include a lessened
immune response among the youngest recipients
of the vaccine. Another possibility is genetic
variation among circulating VZV strains.
Breakthrough disease among vaccine recipients
appears to be more common in the United States
than in Japan.23
A study documented an outbreak of varicella
among largely immunized 4-year-olds at a day-
care centre in New Hampshire. Moderately severe
varicella spread from the index case to 15 others,
indicating that the vaccine was only 44% effective
in this outbreak. Children who had been vaccinated
three years or more before the outbreak were at
greater risk for vaccine failure than those
vaccinated more recently.24 There are still not
enough data to recommend a second dose of
varicella vaccine for younger children. However
this may become the reality after more experience
is gained as happened in case of MMR.
Varicella vaccine: Other issues
Rates of herpes zoster are much lower
(2.4 cases per 1,00,000 population) in vaccinees
than in those who develop zoster following
wild virus infection (68 cases per 1,00,000
population).5
For post-exposure prophylaxis, susceptible
immunocompetent children and household
contacts can be given varicella vaccine within
2-3 days of the appearance of the rash in the index
case.19
In a randomized, double-blind, placebo-
controlled study, it was concluded that varicella
vaccine may not be effective in preventing varicella
when administered after household exposure,
although it is highly effective in ameliorating the
disease in those who acquire it under these
circumstances. The risk of developing moderate
to severe disease was eight times greater in the
placebo group (RR = 8), indicating an 80%
protective effect against moderate/severe
disease.25
Varicella vaccine administered in a two-dose
regimen was generally well-tolerated and highly
immunogenic in US and Canadian children
(12 months to <18 years) with nephrotic
syndrome, including those on low-dose, alternate-
day prednisolone.
A study at the Johns Hopkins Childrens
Center, Baltimore to determine whether the
vaccine was immunogenic in children with chronic
renal insufficiency identified fifty such children
with no detectable varicella zoster virus antibody.
Each child was given two doses of vaccine 48
weeks apart, rather than the typical one dose, and
subsequent rates of seroconversion were
measured. During three years of follow-up all
children (including 16 who received kidney
transplants later) retained a concentration of
antibodies considered to be protective against
chicken pox.
The Centers for Disease Control and
Prevention recommends varicella immunization
for those HIV-1-infected children without clinical
or laboratory evidence of clinically significant
immune suppression.
Combination vaccines and newer vaccines
A new MMRV combination vaccine was
studied in 480 children aged 1223 months. The
response rate to the first dose was 96% for
measles, 99% for mumps, 95.1% for rubella, and
91.2% for varicella. The response rate after the
second dose was 98.6% for measles, 100% for
mumps, 94.8% for rubella, and 99.2% for
30
varicella. These results compared favorably with
the licensed MMR and varicella vaccines. The
combined vaccine was well-tolerated with the only
exception being a slight increase in measles-like
rash after the initial dose.26
The gelatin content in the varicella vaccine
may be associated with hypersensitivity reactions.
A new gelatin-free varicella vaccine tested in
Japanese studies has been reported to be safe,
with similar immunogenicity to the earlier gelatin-
containing vaccine.27
Summary
Universal coverage with efficacious vaccines
is still a distant dream in most developing countries
today. Theoretically, however, science is equipped
with the means to prevent, control and eventually
even eradicate certain infectious diseases. In the
future, widespread coverage with vaccines is likely
to present newer challenges to the scientific and
medical communities due to the changes it brings
about in the epidemiology of infectious diseases.
In summary, these pertinent issues with the
additional vaccines are of clinical relevance and
patient-doctor concern to optimize vaccine
acceptance and cost-effectiveness.
Points to remember
The efficacy of the available typhoid
vaccines is reported to be similar in
developing countries.
The two-dose vaccination program remains
the best method for controlling measles and
mumps infection in the community, using
MMR as a part of national schedule.
Varicella vaccine is effective in preventing
any form of the disease in 90-95% of
vaccinees, whereas protection against
moderate to severe disease is more than
95% of vaccinees.
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Childhood vaccination against varicella:
Persistence of antibody, duration of protection,
and vaccine efficacy. J Pediatr 2001;139: 297-
304.
22. Vazquez M, LaRussa PS, Gershon AA,
Steinberg SP, Freudigman K, Shapiro ED. The
Effectiveness of the Varicella Vaccine in
Clinical Practice. N Engl J Med 2001;
344:955-960.
23. Grose C. Varicella vaccination of children in
the United States: Assessment after the first
decade 19952005. J Clini Virol 2005; 33:
89-95.
NEWS AND NOTES
24. Galil K, Lee B, Strine T, et al. Outbreak of
varicella at a day-care center despite
vaccination. N Engl J Med 2002; 347: 1909
1915.
25. Mora M, Harelb L, Kahanc E, Amirb J.
Efficacy of postexposure immunization with
live attenuated varicella vaccine in the
household settinga pilot study. Vaccine
2004; 23: 325-328.
26. Kerr C. Good response rate for MMRV
vaccine. The Lancet Infectious Diseases 2003;
3: 748
27. Ozakia T, Nishimuraa N, Mutoa T, et al. Safety
and immunogenicity of gelatin-free varicella
vaccine in epidemiological and serological
studies in Japan. Vaccine 2005; 23: 1205-
1208.

SYMPOSIUM ON DIAGNOSIS AND TREATMENT OF

GASTROINTESTINAL INFECTIONS
Chandigarh, January 13-14, 2007
Enquiries to : Dr. Chetana Vaishnavi, Department of Gastroenterology, P.G.I.M.E.R.,
Chandigarh.
Email : vaishnav@rediffmail.com; evaishnavi@sify.com

PALS PROVIDER COURSE

New Delhi, January 20-21, 2007
Enquiries to : Dr. Suresh Gupta, Department of Pediatrics, Sir Ganga Ram Hospital,
New Delhi 110 060.
Email : drguptasuresh@yahoo.co.in

ICPP 3
INTERNATIONAL COURSE ON PEDIATRIC PULMONOLOGY
April 12-14, 2007
Hotel Royal Riviera, Saint-lean Cap-Ferrat
Information :
ICPP Secretariat, 27, Rue Massena 06000 Nice, France
Tel. +33(0)497038597 Fax: +33(0)497038598 E-mail : cipp@cipp-meeting.com

32
 VACCINES II
PASSIVE IMMUNE PROPHYLAXIS
FOR INFECTIONS
* Baldev S. Prajapati
** Rajal Prajapati
Abstract : Passive immune prophylaxis is used
mainly as post exposure prophylaxis. Advantages
and disadvantages of human and animal products
of immunoglobulins are discussed. Preparations
available, indications, dose, etc. of immuno-
globulins against various diseases are dealt with.
Keywords : Passive immune prophylaxis,
Indications, Disease specific immunoglobulins
Preformed antibodies as a therapeutic tool is
used for immediate protection against certain
infections. They are used either to prevent or to
treat the infectious diseases. Use of preformed
antibodies to prevent the infection is called passive
immunoprophylaxis and its use to treat the
infection is called passive immunotherapy. Passive
immunoprophylaxis is used in a susceptible
individual mainly as post exposure prophylaxis.
Animal derived hyperimmune globulins are
mainly of equine origin and is available in the form
of antitoxins. Animal derived products are known
for their serious side effects. Human derived
preparations are safer and used as prophylaxis for
measles, rubella, hepatitis-A, hepatitis-B, varicella,
tetanus, rabies etc. Respiratory syncytial viral
immunoglobulin (RSV-IVIG) is recently
* Associate Professor
** Associate Professor
Sheth L G General Hospital
Smt. NHL Municipal Medical College, Ahmedabad
33
introduced for prevention of RSV infection
especially in high risk patients like preterm babies
and those who are suffering from broncho-
pulmonary dysplasia.
Preparations (Table 1)
There are two sources of immuno-
globulin preparations available for human
administration and they are human and animal
derived products. Animal derived hyperimmune
globulins, generally of equine origin are available
in the form of sera. Due to their known serious
reactions and availability of safer human
immunoglobulin preparations, the animal derived
antisera or antitoxins are now in less use. Products
derived from human plasma include human
immune serum globulin (ISG). Intravenous
immunogloblin IVIG and specific hyperimmune
ISG.
Human immune serum globulin (ISG)
Human immune serum globulin is derived
by alcohol fractionation of pooled human plasma.
It contains 95% IgG (in 16.5% solution), with
trace quantities of IgM and IgA. A plasma pool of
more than 1000 donors provides a wide diversity
of antibodies in each lot. Plasma pool needs to be
screened for a variety of viruses to minimize the
potential for transmission of infections. The utility
of ISG is limited due to several reasons. It must
be given by deep IM route. It is painful. The
maximum volume that can be given per site is
1 to 3 ml in a small child and 5 ml in a large child
or an adult, with a maximum total volume of
20 ml. Peak antibodies are not attained till
Table 1. Available preparations for passive immunoprophylaxis
Human Normal Immunoglobulin
10% and 16.5% preparations for IM use in 1 ml and 2 ml ampoules.
Bharglob, Globunal, Gamafine, Gammalin, Sii Gama globulin.
Intravenous Immunoglobulin IVIG and specific hyperimmune Ig G
Intraglobin
5 ml (250 mg), 10 ml (500 mg), 20 ml (1gms), ampoules.
50 ml (2.5 gms), 100 ml (5 gms),200 ml (10 gms) in infusion bottles.
Pentaglobin :
5 ml, 10 ml, 20 ml ampoules.
5 ml, 100 ml infusion bottles.
Sandoglobulin : 1gms, 3 gms and 6 gms vials.
Gamma IV : 0.5gms, 2.5 gms and 5 gms infusion bottles.
Hepatitis B Immunoglobulin
Hepabig, Hepaglob
0.5 ml (100 IU),
1 ml (200 IU) vials for IM use.
Hepatect 2 ml ampoule (100 IU) for IV use.
Varicella Zoster Immunoglobulin.
Varitect 5 ml, 20 ml, 50 ml.
VZIG 125 units per vial.
Rabies Immunoglobulin
Human Rabies Immunoglobulin (HRIG)
Berirab 300 IU (2 ml)
750 IU (5 ml)
Imogam 300IU (2 ml)
Equine Rabies Immunoglobulin (ERIG)
Imorab 1000 IU (5 ml vial)
Tetanus Human Immunoglobulin
Tetglob 250 IU, 500 IU, 1000 IU in vials
Immunotetan 250 IU, 500 IU
Tetnal 250 IU
Sii TIG 250 units for IM and IV
Tetanus Antitoxin
Tetanus antitoxin Haffkine 1500 IU (1 ml)
10,000 IU (3.4 ml)
20,000 IU (5 ml)
Tetanus Antitoxin B.C. 1500 IU (1 ml)
Anti-TET 10,000 IU (3.3 ml)
Tetanus antitoxin Bengal Immunity
750 IU, 5000 IU, 10,000 IU, 20,000 IU, 50,000 IU
RSV-IVIG
Respi Gam 50 mg/ml.
Anti Rh D Immunoglobulin Rhiggal, Rhesogram, sii Anti D,Masteram-P, Vinobulin. 100 ug, 250 ug,
300 ug, 350 ug, 2ml vial for IM.
34
2 to 3 days and are limited by the injected volume.
Serum IgG half life is approximately 4 weeks.1
The WHO has laid down definite standards
for its preparation. It should contain at least
90 percent intact IgG, it should be as free as
possible from IgG aggregates, all IgG sub classes
should be present, there should be a low IgA
concentration, the level of antibody against at least
two bacterial species and two viruses should be
ascertained etc.2
Live vaccines should not be given for
12 weeks after an injection of ISG and if a live
vaccine has already been given, ISG should be
deferred for 2 weeks.2
Intravenous immunoglobulin (IVIG)
Large plasma pools from more than 1000
donors (in some cases more than 15,000 donors)
are fractionated as for ISG and then further
processed by a variety of techniques such as
polyethylene glycol fractionation, ion exchange,
chromatography, ultrafiltration, exposure to low
pH and others to make IVIG suitable for
IV administration. Products vary in their sources
of plasma pools and processing methods. While
each lot must contain a minimal antibody titre to
certain marker organisms (measles, polio and
tetanus) antibody titres to other bacterial and viral
pathogens vary greatly between preparations and
lots. In addition to it, processing steps may alter
functional capabilities of IgG or change relative
distribution of immunoglobulin subclasses, changes
not reflected in proposed antibody titres.
Therefore, IVIG should not be considered as a
uniform generic product. Different preparations
are packed as liquid or lyophilized formulations
and in different total IgG concentrations, from
5% to 10%.1
Specific hyperimmune human
immunoglobulin
The specific hyperimmune human immuno-
globulin should contain atleast five times the
35
antibody potential of the standard preparation per
unit volume. These preparations are made from
the plasma of patients who have recently recovered
from an infection or are obtained from individuals
who have been purposefully immunized against
the specific infection under consideration.
Therefore, they have a high antibody concentration
against a specific organism and provide immediate
protection.2
Specific hyperimmune human immuno-
globulin is administered by intramuscular injection.
These preparations suitable for intravenous
administration have also become available.3 The
IM injections are painful. Peak blood levels are
reached in 2 days after IM injection. The half life
is 20-35 days.2
Adverse reactions are local as well as
systemic. Pain and sterile abscess like reactions
are relatively common especially when large
volumes are injected by IM route. Systemic
reactions may be immediate or late. Immediate
reactions occur during or within minutes of
administration and they are anaphylactic in type.
Late reactions may occur within hours or days,
are usually less severe and include urticaria,
arthralgia, pyrexia etc.2
Animal derived antisera or antitoxins
Originally passive immunization was achieved
by administration of antisera or antitoxins prepared
from animals such as horses. These preparations
have high incidence of serious reactions like
anaphylaxis and serum sickness. Due to their
serious complications and availability of safer
human immunoglobulin preparations, the current
trend is unfavouring their regular use. Still these
preparations are mainstay of passive immunization
against diphtheria, gas gangrene, and snake bite
etc.2
Indications for passive immunoprophylaxis
Measles: Passive immunization with
immunoglobulin is effective for prevention and
attenuation of measles within 6 days of exposure.4
Susceptible household and hospital contacts who
are less than 12 months of age and pregnant
women should receive immunoglobulin in a dose
of 0.25 ml/kg (maximum 15 ml) IM as soon as
possible after exposure, but within 5 days.
Immunocompromised persons should receive
immunoglobulin 0.5 ml/kg IM regardless of
immunization status. Infants less than 6 months
of age born to non immune mothers should receive
immunoglobulin. Infants less than 6 months of
age born to immune mothers are considered
protected by maternal antibodies. Measles vaccine
should be deferred following administration of
immunoglobulin, depending on the dose and
duration of therapy.5
Rubella : The susceptible pregnant women
exposed to rubella in early pregnancy for whom
abortion is not an option, immunoglobulin should
be administered in the dose of 0.55 ml/kg which
reduces the attack rate but does not eliminate the
risk of fetal infection. The use of IVIG may be an
alternative but not studied in details.6
Hepatitis A: Indications for IM administration of
ISG include preexposure and postexposure
prophylaxis (Table-2). IVIG is likely to be effective
against hepatitis A infection, but appropriate dose,
efficacy and duration of protection have not been
defined. ISG is recommended for preexposure
prophylaxis for all susceptible travellers to
countries where HAV is endemic. For individuals
age 2 and older, HAV immunization is preferred
if the interval before departure is more than
1 month after first dose. ISG as post exposure
prophylaxis is indicated in household and sexual
contacts of HAV cases, newborn infants of HAV
infected mothers, child care centre staff,
employees, children and their household contacts
during an outbreak and outbreaks in institutions
and hospitals. The use of ISG more than 2 weeks
after exposure is not indicated. ISG is not
recommended routinely in sporadic non-
household exposure e.g. protection of hospital staff
or school mates.6

Table 2. ISG Prophylaxis for HAV7

Age Exposure
Pre-exposure Prophylaxis (Travellers to Endemic areas)
< 2 years Expected < 3 months
Expected 3-5 months
Expected long term
> 2 yeas Expected < 3 months
Expected 3-5 months
Expected long term
Post-Exposure prophylaxis
> 2 years < 2 weeks since exposure
> 2 weeks since exposure
All ages < 2 weeks since exposure
> 2 weeks since exposure
Dose
0.02 ml/kg
0.06 ml/kg
0.06 ml/kg at departure and every
5 months thereafter.
HAV vaccine or ISG 0.02 ml/kg
HAV vaccine or ISG 0.06 ml/kg
HAV vaccine
ISG 0.02 ml/kg and HAV vaccine
HAV vaccine
ISG 0.02 ml/kg + HAV vaccine
No prophylaxis

36
Hepatitis B: Prophylactic treatment can
effectively prevent infection after exposure to
HBV. It is indicated in the following situations.
Perinatal exposure of an infant born to a
HBsAg-positive mother.
Inadvertent percutaneous or permucosal
exposure to blood.
Sexual exposure to a HBsAg-positive person.
Exposure of an infant less than 12 months of
age to a primary care giver who has acute
hepatitis B.
The mainstay of postexposure immuno-
prophylaxis is hepatitis B vaccination, but in some
settings passive immunization with HBIG provides
increased protection. HBIG is prepared from
plasma known to contain a high titre of antibodies
and provides temporary protection for 3 to 6
months in certain postexposure settings. The
standard dose of HBIG for postexposure
prophylaxis of infants born to HBsAg positive
mother is 0.5 ml while in all other situations it is
0.06 ml/kg. For prevention of perinatal
transmission, hepatitis B vaccination and one dose
of HBIG given concurrently but at separate sites
using separate syringes, administered within 12
to 24 hours after birth, is highly effective in
prevention of both acute and chronic HBV
infection.7,8,9,10
Varicella-Zoster: Varicella-zoster immunoglobulin
(VZIG), prepared from high titre immune human
serum, reduces the attack rate of varicella when
it is given just after exposure (Table-3). Break
through infections occur, but the extent of
exanthem and risk of varicella pneumonia are
diminished. VZIG given after the appearance of
varicella rash does not alter the disease process.
The dosage is 1 vial (125 U)/10 kg body weight
(maximum 5 vials) given intramuscularly. VZIG
should be given to susceptible high risk individuals
within 96 hours and if possible within 48 hours
after close contact to a person with varicella or
herpes zoster. VZIG prophylaxis is recommended
for immunocompromised children and newborn
infants exposed to maternal varicella. VZIG should
be given to infants born to mothers with onset of
varicella 5 days or less before delivery or within
2 days after delivery. VZIG is not indicated for
healthy, full term infants exposed postnatally,
including those whose mothers rash developed
more than 48 hours after delivery.10.11.12

Table 3. Use of Varicella-Zoster Immunoglobulin (VZIG) for prophylaxis 10

Individuals at risk :
Immunocompromised children with no history of varicella.
Pregnant women with no history of varicella and no antibodies to varicella zoster.
Infants born to mothers who develops varicella 5 days before or 2 days after delivery.
Criterias of close exposure :
Varicella
House-hold contact, close in-door contacts like schoolmates, playmates etc.
Hospital contact, newborn exposure to maternal varicella.
Herpes Zoster
Intimate, direct contact with infected individual.
Administration of VZIG :
VZIG must be given within 96 hours and possibly with 48 hours after exposure.
Dose : 1 vial (125 units)/10 kg body weight (maximum 5 vials) by IM injection.

37
 The administration of VZIG administration
does not eliminate the possibility of disease in high
risk patients. The incidence of varicella despite
VZIG prophylaxis is significantly higher after
household exposures. VIZG to immuno-
compromised children lowered the risk of severe
varicella significantly, but 11% of these children
still developed pneumonia. Because passive
antibody titres of VZIG decline by
2 weeks in some patients and by 4 weeks in most
patients, a second dose should be given if a new
exposure occurs more than two weeks later. VZIG
does not reduce the risk of VZV reactivation in
high risk population or alter the clinical course of
herpes zoster when given after the onset of
symptoms.12
Rabies: Once rabies develops, it is almost
invariably fatal in humans, and prevention is the
only option. With the availability of safe and
effective modern tissue culture vaccines and
immunoglobulins, the prevention of rabies is
almost assured.
Rabies immunoglobulins (RIGs) are special
neutralizing antibodies that immediately neutralize
virus on contact. RIGs give a coating to the virus
so that it can not enter the nerve endings resulting
in reduction or total obliteration of inoculated virus.
Replication of virus is also prevented by RIG.
Administration of RIGs as part of routine post
exposure prophylaxis is intended to provide a
passive source of antibodies before endogenous
development of antibodies by the vaccine.
Pregnancy and lactation are not contraindication.
The need for RIG appears to be on the rise,
because of the ubiquity of human exposure to
rabies virus from uncontrolled canine sources in
developing countries.10,12,13
Indications for use of RIGs13
All category III bites as per WHO
classification.
38
Licks on mucous membrane by wild or pet
animals.
Category II and III bites in immunologically
compromised patients such as AIDS,
varicella, patients on long term steroid therapy,
patients on chemotherapy, radiation therapy
etc.
Before wound suturing for local infiltration.
Those with past history of complete post
exposure prophylaxis using modern tissue
culture vaccines do not need to be given RIG
irrespective of the class of bites.
Human rabies immunoglobulin (HRIG).10,13: It is
a freeze dried preparation containing IgG
immunoglobulins obtained from plasma or serum
of donors immunized against rabies and contains
specific antibodies neutralizing the rabies virus.
Though HRIG represents the gold standard for
passive immunoprophylaxis, its cost is exorbitantly
high. Its supply is also erratic. Advantages of
HRIG include purity, presence of minimal or no
foreign protein and absence of immediate
hypersensitivity reaction. Disadvantages of HRIG
include cost, chances of transmission of potential
plasma borne infections, erratic supply,
development of some rare side effects like angio
edema, nephrotic syndrome and anaphylactic
shock etc. Patients sensitive to other human
immunoglobulins products may be sensitive to
HRIG also. The dose of HRIG is 20 units/kg body
weight to a maximum of 2000 units.
Equine rabies immunoglobulin (ERIG).10,13: It is
produced by immunizing horses with low dose of
rabies vaccines. The modern automated
ultrafiltration technology saves the time and makes
it safer. Easy availability and low cost are its
advantages. Due to presence of foreign protein,
there are chances of immediate hypersensitivity
reaction. It is the main disadvantage of this
product. It is given in dose of 40 units/kg body
weight with maximum of 4000 units.
 Administration of RIGs : As much as
anatomically feasible the RIG should be infiltrated
through, into and around the wound. The
remaining portion of the calculated amount of
RIG, if any, is to be injected in the deltoid region
in older children and adults or anterolateral aspect
of thigh in newborns, infants and young children.
It should be given at a site different from the one
where the vaccine is administered. For injecting
RIG and vaccine separate syringes should be used.
If the administration of RIG is delayed, it can be
administered up to the seventh day after the first
dose of vaccine. Caution is needed while injecting
RIG in certain tissues like finger pulp as excess of
fluid can result in increased compartment pressure
leading to necrosis. For small children calculated
dosage of RIG may be insufficient to infiltrate all
the wounds. In this situation, RIG should be diluted
with sterile normal saline 2 to 3 fold to permit
thorough effective infiltration of all the wounds.
In case of ERIG skin sensitivity testing is essential,
but not required for HRIG.12,13
Tetanus: Tetanus prevention consists of
postexposure administration of vaccine and
antitoxin following a tetanus-prone injury. Need
is determined by type of injury and history of
immunization. Although wounds with major tissue
injury are most tetanus prone, any type of wound,
if contaminated, can lead to tetanus. Tetanus
toxoid vaccine is given immediately if history of
tetanus immunization is not available, is unsure,
or 60 months have elapsed since previous booster
dose. Simultaneous passive immunoprophylaxis
is also indicated in these circumstances.10,14
Two types of preparations are available for
this purpose, Tetanus Human Immunoglobulin
(TIG) and Tetanus Antitoxin (Anti tetanus serum
ATS). TIG is a freeze-dried preparation containing
immunoglobulin mainly IgG obtained from plasma
or serum from immunized human donors. It is
more efficacious, longer acting and safer than
39
equine antitoxin (ATS). The half life of TIG is
4 weeks and significant blood levels are maintained
upto 14 weeks. As a prophylactic, TIG is given in
dose of 250 to 500 IU by IM route. It does not
cause serum sickness like reactions. If TIG is not
available, the use of IVIG may be considered.
ATS is another preparation used for this
purpose. The standard dose is 1500 IU, injected
subcutaneously after negative skin sensitivity test.
It gives protection for about 7 to 10 days. Being a
foreign protein, ATS is rapidly excreted from the
body and there may be very little antibody at the
end of two weeks. It may not cover tetanus
incubation period in all cases. Therefore, it is less
reliable and not favored for routine use.
The infants born to the mothers who have
not previously received 2 doses of tetanus toxoid
are exposed to the risk of neonatal tetanus. They
can be protected by 250 IU of TIG or 750 IU of
ATS, if given within 6 hours of birth.
RSVIVIG: Administration of respiratory syncytial
viral IV immunoglobulin (RS-IVIG) is
recommended in dose of 750 mg/kg for protecting
high risk children against serious complications
from RSV disease. Immunoprophylaxis reduces
the frequency and total days of hospitalization for
RSV infection in high risk infants. These agents
are administered monthly from beginning
(October-December) to end (March-May) of RSV
season. Another IM preparation is also available
and given in dose of 15 mg/kg. Candidates for
immunoprophylaxis include children with lung
diseases like bronchopulmonary dysplasia and
premature babies to be discharged from hospital
during RSV season.15,16
Points to remember
Passive immunoprophylaxis has vital role
in prevention of certain infections in
susceptible individuals, used mainly as post
exposure prophylaxis.

Animal derived products are known for
serious reactions. Human derived
preparations are safer and are commonly
used now-a-days.
Various immunoglobulins are used as
passive prophylaxis for susceptible
individuals against measles, rubella,
hepatitis-A, hepatitis-B, varicella, tetanus,
rabies, RSV, etc. Certain preparations are
recently introduced for clinical use and
some are expected in the near future.
References
1. Fischer GW. Prevention of infectious
diseases. In: Long SS, Pickering LK, Prober
CG (Eds), Principles and Practice of Pediatric
st
Infectious Diseases, 1 Edn. New York,
Churchill Livingstone 1997; pp44-49.
2. Immunoglobulins. In: Parks Textbook of
th
Preventive and Social Medicine, 18 Edn. (Ed)
Park K. Jabalpur. M/s. Banarasidas Bhanot
2005; pp97-98.
3. Cohn JE, Strong LE, Hughes Jr. Wl, Mulford
DJ, et al. Introduction and research objectives,
Bull WHO. 1982;60(1):43-47.
4. Subbarao EK, Andrews-Mann L, Amin S, et al.
Postexposure prophylaxis for measles in a
neonatal intensive care unit. J Pediatr 1990;
117: 782-785.
5. Maldonado YA. Rubeola virus (Measles and
subacute sclerosing panencephalitis). In: Long
SS, Pickering LK, Prober CG (Eds) Principles
st
and Practice of Infectious Diseases, 1 Edn,
New York, Churchill Livingstone, 1997;
pp1251-1262.
6. Maldonado Y. Ruibella. In: Behrman RE,
Kleigman RM, Jenson HB, Eds, Nelson
th
Textbook of Pediatrics, 16 Edn, New Delhi,
Harcourt (India) Private Limited, 2000; pp951-
954.
7. Snyder JD, Pickering LK. Viral Hepatitis In:
Behrman RE, Kliegman RM, Jenson HB.
40
th
(Eds), Nelson textbook of Pediatrics, 16 Edn.
New Delhi, Harcourt (India) Private Limited,
2000;pp768-776.
8. Mahoney FJ, Hepatitis B Virus. In: Long SS,
Pickering LK, Prober CG, Eds, Principles and
Practice of Pediatric Infectious Diseases,
st
1 Edn, New York, Churchill Livingstone.
1997; pp1193-1202.
9. Parthas Immunization digest. Parthasarathy A,
st
Lokeshwar MR, Shah NK, 1 Edn, New Delhi,
Jaypee Brothers, 2005; pp41-42.
10. Dubey AP, Singh S (Eds) IAP Guide Book on
rd
Immunization (3 Edn) 2005;pp20-21.
11. Arvin AM: Varicella-Zoster Virus In: Long SS,
Pickering LK, Prober CG, Eds, Principles and
st
Practice of Infectious Diseases, 1 Edn, New
York, Churchill Livingstone 1997; pp1144-
1154.
12. Centres for Diseases Control and Prevention:
Varicella Zoster Immunoglobulin for the
prevention of Chicken Pox: recommendations
of the immunization practices advisory
committee. Ann Intern Med 1984; 100: 859-
865.
13. Ghosh TK. Prevention of Rabies by vaccination
and immunoglobulin therapy: Some
controversies and solutions In: Ghosh TK,
Kalra A, (Eds), Infectious diseases In Children
and newer vaccines. Part-II Agra, 2003: pp171-
176.
14. Prajapati BS. Prajapati RB. Rabies
Immunoglobulins in Practice. Bulletin of
Infectious Diseases Chapter of IAP.
15. Rathore MH: Clostridium Tetani. In: Long SS,
Pickering LK, Prober CG, Eds, Principles and
Practice of Pediatric Infectious Diseases,
st
1 Edn, New York, Churchill Livingstone 1997;
pp1081-1084.
16. McIntosh K: Respiratory syncytial virus In:
Behrman RE, Kleigman RM, Jenson HB (Eds),
th
Nelson Textbook of Pediatrics, 16 Edn, New
Delhi, Harcourt (India) Pvt. Ltd. 2000; pp991-
993.
 VACCINES II

IMMUNIZATION IN SPECIAL recommending a vaccine. In this chapter

SITUATIONS vaccination in children in the following special
situations are being discussed:
* Shyam Kukreja
** Sandeep Aggarwal 1. Patients with HIV infection
2. Patients with maligancy
Abstract : In some clinical circumstances there
arises a need to modify the already existing 3. Patients on steroids
immunization practices. How to go about in 4. Patients on immunoglobulins
situations like disease outbreaks, adolescence, 5. During disease outbreak
patients with HIV infection, malignancy and
6. Adolescents
patients on steroid therapy/immunoglobulin are
discussed in this article. 7. Travellers
1. Patients with HIV infection
Keywords : Special situation, Immunization
HIV infected patients being immuno-
Immunization is an attempt to replace the
compromised are more susceptible to a wide range
anticipated natural primary (first) contact between
of pathogens thereby necessitating prevention.
the human body and pathogenic organism with a
They are also potentially at risk of getting
safer artificial contact so that the subsequent
disseminated infection following administration of
natural contact between the two takes place in a
live vaccines. In addition to the risk of severe
state of heightened immunity. Immunization forms
complications from live attenuated vaccine in
the backbone of preventive strategies in public
patient with more advanced HIV infection, there
health medicine. Recommendations for
is a risk of activating the immune systems by
immunization practices are based on scientific
vaccination which could potentially increase the
knowledge of vaccine characteristics, principles
viral replication and thereby increase HIV viral
of immunization and epidemiology of specific
load. This theoretical possibility has been
disease. These recommendations become normally
demonstrated in some studies where there was a
applicable to most individuals in the community.
transient increase of HIV RNA concentrations
There are several special clinical circumstances
after immunization with influenza and
that are commonly and uncommonly encountered
pneumococcal vaccines but other studies have
in pediatric practice where some variations from
shown no such increase.1,2 There is no evidence
the norm are to be kept in mind while
to indicate that this transient increase in HIV RNA
load enhances progression of disease. Lastly HIV
* Head, Dept. of Pediatrics,
Max Balaji Hospital, New Delhi infected individuals may develop sub-optimal
** Pediatrician responses to immunization, especially if they have
Max Balaji Hospital, New Delhi immune suppression. Screening to detect HIV
41
infection before initiating routine immunization in
asymptomatic children is not recommended.
Asymptomatic children should be immunized in
accordance with recommended childhood
immunization schedule. Children with
asymptomatic or symptomatic HIV infection
should receive all the killed and conjugate vaccines
and toxoids such as DPT, Hep B and Hib according
to the recommended schedule. Patients with HIV
infection have a high risk of infections with
Hemophilus influenzae type b (Hib) and
pneumococcus. So HIV infected patients should
receive Hib and conjugate pneumococcal vaccines.
Most evidence supports the idea that immunization
with these vaccines should be given early in the
course of HIV infection. Annual immunization
with influenza vaccine is also recommended in
HIV infected children. The use of this vaccine
has been questioned in patients with more
advanced HIV infection because of the risk of
severe disease and likelihood of a poor response
to immunization with influenza vaccine in patients.
Most experts prefer to give influenza vaccine
thinking that benefits do exceed the risk. The
safety of immunization with live attenuated vaccine
is a matter of concern as discussed earlier; hence
it is necessary to weigh the risk and benefits before
deciding to administer the live vaccine to the child.
Measles vaccine should be given to asymptomatic
HIV infected children3 and symptomatic but not
severely immuno-compromised HIV infected
children. Severely immuno-compromised HIV
Patients with CD4 lymphocyte count less than
15% should not receive measles vaccine. Currently
varicella vaccine is recommended for HIV infected
children who have CD4 T lymphocyte count more
than 25% percent (those with no evidence of
immuno-suppression). WHO currently
recommends BCG immunization for all children
in developing countries at high risk for tubercular
infection including HIV infected children. BCG is
given at birth and no HIV infected child is
symptomatic or immuno-deficient at birth. Hence
42
BCG is safe and must be given to all newborns.
However BCG immunization is not recommended
in developed countries with a low risk of
contracting tuberculosis. The most commonly
used live vaccine is oral polio vaccine. Rider and
colleagues reported from Zaire that no serious side
effects were reported in infants with HIV infection
who were given trivalent Sabin vaccine. However,
use of inactivated poliovirus vaccine (IPV) is
generally recommended as this does not carry the
risk for development of paralytic disease.
Table 1 summarizes the recommendations
for immunizing HIV infected children. In general
children with symptomatic HIV infection have
poor immunologic response to vaccine. Hence
when these children are exposed to vaccine
preventable disease, they should be considered
susceptible regardless of the history of
immunization and should receive if indicated,
passive immuno-prophylaxis or chemoprophylaxis.
2. Patients with malignancy
Leukemia is the most common form of
childhood malignancy. Most of these cases occur
before the age of 10 years. Other tumors like
Hodgkins and Non Hodgkins lymphoma occur
more frequently in the age group over 10 years.
Hib and pneumococci are important causes of
infection in patients with hematological
malignancies.4 Patients with Hodgkins disease are
frequently splenectomized as part of their diagnosis
and therapy making these patients particularly
vulnerable to disseminated pneumococcal
infection. Also these patients are at increased risk
of invasive Hib disease.4 Antibody response is
likely to be best when these patients are
immunized at least 2 weeks before splenectomy
or before initiation of chemotherapy. During
chemotherapy, antibody responses to vaccination
are impaired. Immunization is effective if carried
out 3 months after cessation of chemotherapy or
radiation therapy. The immune response to killed
Table 1. Recommendations for immunizing a child with HIV infection
Vaccine WHO ACIP/AAP WHO ACIP/AAP
recommendations recommendations recommendations recommendations
for asymptomatic for asymptomatic for symptomatic for symptomatic
child child child child
BCG Yes (for areas with No No No
High incidence of TB)
DTP/ DTaP Yes Yes Yes Yes
OPV Yes No No No
Measles/ MMR Yes Yes Yes Yes
IPV - Yes - Yes
Hepatitis B Yes Yes Yes Yes
Hib - Yes - Yes
Pneumococcal - Yes - Yes
Influenza - Yes - Yes
Varicella - Consider - Consider
Hepatitis A - Yes - Yes
AAP America Academy of Pediatrics, ACIP Advisory Committee on Immunization Practices,
WHO World Health Organization

vaccines like diphtheria and tetanus toxoid in
children undergoing maintenance chemotherapy
is similar to those of healthy children.5 Oral polio
vaccine can induce paralytic polio and should be
avoided in children undergoing chemotherapy for
cancer. Primary varicella zoster virus (VZV)
infection causes high mortality in children with
malignancy. The available vaccine for protection
is live attenuated VZ vaccine. The vaccine has
been shown to be effective and safe in children
with leukemia who are in remission. The
frequency of side effects from the vaccine is low
and the breakthrough disease can be treated with
acyclovir. The sero-conversion rates are 88% after
one dose and 98% after two doses. The immunity
is stable for more than 5 years. The risk for herpes
zoster after vaccination was lower than in patients
who had natural varicella. Cancer patients who
are infected with measles have a high mortality
rate. Immunization with measles vaccine is
43
contraindicated owing to severe side effects in
cancer patients undergoing chemotherapy.
However it can be given 3 months after cessation
of chemotherapy or before initiating
chemotherapy.
3. Patients on steriod therapy
The degree of immuno-suppression in a child
receiving corticosteroids is influenced not only by
the duration, route and dose of steroids but also
by the underlying disease and other concurrent
therapy the patient is receiving. The vaccines other
than live viral vaccines may safely be given, and
the following guidelines 6 are useful for
administration of live vaccines in recipients of
steroids.
a) Topical therapy or local injection of
corticosteroids: Usually does not result in immuno-
suppression that would contraindicate
administration of live viral vaccines.
b) Physiological maintenance dose of
corticosteroids: Such children can receive live
vaccine.
c) Low or moderate dose of systemic
corticosteroids or an alternate day therapy:
Children receiving less than 2 mg/kg per day of
prednisolone can receive the live viral vaccine
during corticosteroid therapy.
d) High dose of systemic corticosteroids given
daily for less than 14 days: Children receiving less
than 2 mg/kg per day of prednisolone for duration
of less than 14 days can receive live viral vaccine
immediately after discontinuation of therapy. If
there is no urgency it is preferable to delay
immunization until 2 weeks after corticosteroids
have been discontinued.
e) High dose of systemic corticosteroids given daily
or an alternate day for 14 days or more: Children
receiving more than 2 mg/kg per day of
prednisolone should not receive live virus vaccine
until corticosteroids have been discontinued for
at least 1 month.
Children with a disease that by itself is considered
to suppress immune response and who are
receiving corticosteroids: These children should
not be given live vaccines.
4. Immunization of children who recently
received immunoglobulin
Administration of immunoglobulin (IG)
preparation has not been demonstrated to cause
significant inhibition of the immune responses to
inactivated vaccines and toxoids. Concurrent
administration of recommended dose of hepatitisB
immunoglobulin (HBIG), tetanus immunoglobulin
(TIG) or human rabies immune globulin (HRIG)
and the corresponding inactivated vaccine or
toxoid for post exposure prophylaxis does not
impair the efficacy of vaccine and provides
immediate and long term immunity.
44
Live viral vaccine may have demonstrated
reduced immunogenicity when given shortly
before or during few months after receipt of IG.
This has shown to inhibit the response to measles
vaccine.7,8 Measles vaccine should be deferred
for 3 months after Tetanus IG, HRIG, HBIG, IG
administration; for 6-7 months after blood / plasma
administration and 10-11 months after IVIG
administration in the dose of 2gm / kg as in
Kawasaki disease or ITP.6
Immunoglobulin preparation also contains
rubella, mumps and varicella antibodies. High dose
of passively acquired antibodies can inhibit the
response to live rubella vaccination for as long as
3 months.9,10 Administration of rubella vaccine
should be postponed for at least 3 months. The
effect of IG preparation on the response to live
mumps and live varicella vaccine is not studied;
postponement of mumps and varicella vaccines
for 3 months and 5 months respectively is
recommended because of possible interference by
administration of IG.
Immunoglobulin administration should be
delayed for 2 weeks after MMR and 3 weeks
after varicella vaccine for adequate antibody
response to occur.
5. Immunization of adolescents
Adolescence should be considered an
appropriate age for top up immunization as well
as administration of certain vaccines which may
not have been given earlier. Table 2 shows
vaccination schedule for adolescents
6. Vaccination during outbreak
Measles outbreak: During outbreak, monovalent
measles vaccine may be given to infants as young
as 6 months of age. Seroconversion rates are
significantly lower in children immunized before
the age of 9 months. These infants should receive
another dose of measles vaccine or preferably
Table 2. Vaccination schedule for
adolescents 11
Vaccine Age
Tetanus toxoid and Booster at 10 and 16 yrs
diphtheria (dT)
MMR 1 dose if not given earlier
Hepatitis B 3 doses (0, 1, 6 months)
if not given earlier
Typhoid vaccine Vi vaccine given every
3 years (other typhoid
vaccines not available)
Varicella vaccine* 1 dose up to 13 years
2 doses after 13 years
(if not given earlier)
Hepatitis A vaccine* 2 doses, 6 months apart
(if not given earlier)
*If the child has suffered from chicken pox and
Hepatitis A (serological evidence) in the past the
respective vaccine need not be given.
MMR after the age of 1 year. During outbreak,
susceptible children above the age of 1 year should
be given a dose of MMR. If MMR vaccine is not
affordable or not available, then monovalent
measles vaccine may be given.
Meningococcal outbreak: Because secondary
cases can occur several weeks or more after the
onset of disease in index case, meningococcal
vaccine may be offered as a possible adjunct to
chemoprophylaxis when an outbreak is caused by
a sero-group contained in the vaccine.6
Japanese B encephalitis outbreak: Vaccination
is the method of choice for prevention of JE. This
should ideally be used to prevent the outbreak.
Contrary to common belief, this vaccine is not
meant to be used as an outbreak vaccine. In India
after introduction of vaccine in high-risk areas of
Andhra Pradesh, cases of JE decreased from 300
cases in 2002 to 25 in 2003. The inactivated
mouse brain vaccine is troubled by issues regarding
45
its safety, high cost, non-availability in large
quantity and efficacy. The SA 14-14-2 vaccine
produced by China is a live attenuated, cheap and
effective vaccine. The vaccine is likely to be used
in India in endemic areas to prevent outbreaks of
Japanese B encephalitis in recent future.
7. Immunization for travellers 11
The risk of travellers contracting infectious
disease depends on the region/country to be
visited, duration of trip and nature and conditions
of travel. Uniform recommendations are not
possible because the epidemiology of disease differ
in various geographical areas. The physician should
try to update routine immunization and provide
destination specific immunizations. For instance,
vaccines commonly recommended for Indian
travellers include yellow fever vaccine for those
intending to go to destinations in South America
and sub-Saharan Africa (except for infants less
than 9 months and pregnant women) and
meningococcal vaccine for those intending to go
on a Haj pilgrimage. Similarly, visitors coming to
India from Western Europe/North America are
usually advised vaccination against typhoid and
Hepatitis A, especially if the stay is likely to be
prolonged.
Points to remember
All killed vaccines can be given in HIV
infected children, irrespective of the clinical
status. While giving live attenuated
vaccines, it is necessary to weigh the risks
and benefits.
Patients with malignancies should receive
vaccines like pneumococcal, influenzae and
hepatitis B vaccines before starting therapy,
including splenectomy.
Patients on prednisolone in a dose of
2 mg/kg for a period of more than 2 weeks
should be given live vaccines one month
after discontinuation of the steriods.
 Vaccines recommended for adolescents
should be administered.
Immunization for travellers and during out
breaks need the knowledge of local
epidemiology of the VPDs.
References
1. OBrien W, Grovit-Ferbas K, Namazi A, et al.
Human immunodeficiency virus-type 1
replication can be increased in peripheral blood
of seropositive patients after influenza
vaccination. Blood 1995;86:1082-1089.
2. Staprans S, Hamilton B, Follansbee S, et al.
Activation of virus replication after vaccination
of HIV-1 infected individuals. J Exp Med
1995;182:1727-1737.
3. Mclaughlin M, Thomas P, Onorato I et al. Live
virus vaccines in human immunodeficiency
virus infected children: A retrospective survey.
Pediatrics 1988;82:229-233.
4. Feldman S, Gigliotti F, Shenep J, et al. Risk of
Haemophilus influenza type b disease in
children with cancer and response of
immunocompromised leukemia children to a
conjugate vaccine. J Infect Dis 1990;161:926-
931.
5. Van der Does-van den Berg A, Hermans J,
Nagel J and van Steeins G. Immunity to
diphtheria, pertussis, tetanus, and poliomyelitis
NEWS AND NOTES
ANNUAL CONVENTION OF KERALA STATE NNF
FEBRUARY 17-18, 2007
Contact :
Dr. Naveen Jain,
Consultant Neonatologist,
Kerala Institute of Medical Sciences,
Trivandrum.
Mobile : 93878 14568,
E-mail : naveen_19572@hotmail.com
46
in children with acute lymphocytic leukemia
after cessation of chemotherapy. Pediatrics
1981;67:222-229.
6. American Academy of Pediatrics 2003 Red
Book: Report of the committee on infectious
th
disease 26 Edn, Elk Grove Village IL,
American Academy of Pediatrics.
7. Dengler T, Strnad N, Zimmermann R, et al.
Pneumococcal vaccination after heart and liver
transplantation. Immune response in
immunosuppressed patients and in healthy
controls. Dtsch Med Wochenschr 1996;121:
1519-1525.
8. American Academy of Pediatrics. Measles. In
Peter G (ed.) 1997 Red Book: Report of the
th
Committee on Infectious Disease, 24 Edn, Elk
Grove Village IL, American Academy of
Pediatrics, 1997; pp 344-357.
9. Mauch T, Crouch N, Freese D, et al. Antibody
response of pediatric solid organ transplant
recipients to immunization against influenza
virus. J Pediatr 1995;127:957-960.
10. American Academy of Pediatrics. Rubella. In:
Peter G (ed.) 1997 Red Book: Report of the
th
Committee on Infectious Disease, 24 Ed, Elk
Grove Village, IL, American Academy of
Pediatrics, 1997; pp 456-462.
11. IAP Guide Book on immunization IAP
committee on Immunization 2003-2004.
 RADIOLOGIST TALKS TO YOU
THE CENTRAL NERVOUS SYSTEM-
ANATOMICAL BASIS OF
RADIOLOGY
* Vijayalakshmi G
** Elavarasu E
** Porkodi
** Malathy K
*** Venkatesan MD
In this issue we will start the study of the
central nervous system. Ultrasound, CT and MRI
are useful. Let us study the appearances in the
various sections obtained by these imaging
modalities. For this, we will combine the study of
anatomy, physiology and embryology. This kind
of approach will help us understand the various
pathologies of CNS seen in children.
Water forms the major part of the body and
also determines the appearances of body structure
in all types of imaging. The brain is suspended
within a waterbath of CSF. The distribution of
this extracellular fluid varies in the different
anatomical spaces that are enclosed in the cranium,
varying from a thin film in the normal subdural
space to larger collections in the ventricles and
basal cisterns.
As we trace the formation and flow of CSF
we will note the anatomical landmarks that we
see in cranial CT. CSF is formed in the choroid
* Addl.Professor
** Asst. Professor
*** Professor
, Department of Radiology,
Chenglepet Medical College Hospital, Chenglepet
47
plexuses in the ventricles. The triangular,
symmetrical dark grey structures seen on either
side of the midline are the lateral ventricles
(Fig 1). The choroid plexus is easy to note in the
adult and older child as it shows calcification
which appears as a white spot in the posterior
part of the body of the lateral ventricle. From the
lateral ventricle the CSF flows down through the
foramen of Munro into the third ventricle. This is
the small round midline fluid space (Fig 2). It then
passes through the aqueduct of Sylvius which is
very thin and not discernible in CT axial images.
CSF in the fourth ventricle is seen as a midline
round fluid space. The CSF filled central ventricles
are easily identifiable and any change or distortion
in these help in diagnosis.
If you recall embryology, the cranial part of
the neural tube which forms the brain develops
dilatations that are the future ventricles. The
cerebral cortex and the corpus striatum form
from the telencephalon and therefore are related
to the telencephalic vesicles or the lateral
ventricles. So look for these structures on either
side of the lateral ventricles. The corpus striatum
or basal ganglia consist of the medial caudate
nucleus abutting the lateral wall of the lateral
ventricle. The lateral part of the basal ganglia which
is the lenticular nucleus is separated from the
caudate nucleus by the internal capsule (Fig 1).
On either side of the third ventricle are the
thalami or the diencephalic structures. Caudal to
these is the midbrain. The CSF cavity here is the
aqueduct which is not discernible. Therefore look
for the colliculi (Fig.3) on the dorsal aspect that
will help you identify this part. This is shaped like
a double U.
 L
c
l t 3

Fig 1. Section showing lateral (L)ventricles with Fig 2. Section showing slit-like, midline third
cerebrum, caudate nucleus(c) and lentiform ventricle (3) and thalamus (t) on either side.
nucleus (l)

p
m

Fig 3. Section showing midbrain (m). The Fig 4. The fourth ventricle with the pons (p)
colliculi are on the posterior aspect and the and the cerebellum(c ).
cerebral peduncles extend anteriorly.

48
 3 3 L

Fig 5. Dilated third ventricle . Note the dilated Fig 6. All ventricles are dilated. L-temporal
temporal horns on either side. horn of lateral ventricle.

The fourth ventricle is related to the pons
and the medulla oblongata which are the
rhombencephalic structures (Fig.4). The folding
of the neural tube brings the pons to lie anterior
to the fourth ventricle while the medulla is placed
posteriorly. This is an important relation which
will help you to know the site of lesions and
therefore the pathology.
From the fourth ventricle the CSF flows
through the foramina of Magendie and Luschka
into the subarachnoid space . From the
subarachnoid space the fluid is absorbed through
the arachnoid villi into the dural venous sinuses.
The villi consist of projections of fused arachnoid
membrane and endothelium of the sinuses which
act as valves allowing the CSF to flow into the
venous sinuses.
If the flow of CSF down this conduit is
stopped at any point, the proximal part of the
system dilates. Look at the normal size of the
ventricles (in Fig. 1 to 4) See the concave lateral
border in the case of the lateral ventricles. When
the lateral ventricle dilates the outer edge bulges.
The normal third ventricle which is thin and slit
like assumes a round shape (Fig.5) when there is
distal obstruction, as in aqueduct stenosis. When
the fourth ventricle also becomes dilated and
more spherical, we can call it tetraventricular
hydrocephalus (Fig.6). This happens when thick
basal exudates block the outlets of the fourth
ventricle or disturb the flow through the arachnoid
villi.
The central, fluid filled ventricles are readily
identified and aid in knowing the level of the section
and therefore the site of any lesions.

NEWS AND NOTES

APLS : THE PEDIATRIC EMERGENCY MEDICINE COURSE
New Delhi, March 24-25, 2007
Enquiries to : Dr. Suresh Gupta, Department of Pediatrics, Sir Ganga Ram Hospital,
New Delhi 110 060. Email : drguptasuresh@yahoo.co.in

49
 PICTURE QUIZ

11 year old girl has presented with progressive abdominal distension, cachexia, anemia, short stature
with massive splenomegaly and moderate hepatomegaly. Bone marrow aspirate revealed the characteristic
cells, which is diagnostic (shown in the picture). What is the diagnosis?
Compiled by:
*Aditi Devidas Kamble, **Sandeep S. Patil
*Lecturer, **Resident
Department of Pediatrics
Govt. Medical College, Aurangabad-431001.

Answer on page: 328

50
 CASE STUDY
CUTIS VERTICIS GYRATA
*Sri Venkateswaran K
**Purushothaman
***Raveendranath V
**Saradambal N
****Sujatha L
*****Susheela Rajendran
Introduction
Cutis verticis gyrata is a descriptive term to
describe skin lesions with a folded and loose
appearance. It can be primary due to a genetic
defect or secondary to various disorders like
myxedema, pachydermoperiostosis, neuro-
fibromas, naevi etc.1 Associated central nervous
system defects have been described in Cutis
verticis gyrata.2,3 Herewith we are reporting a case
of congenital melanocytic nevus presenting as
Cutis verticis gyrata (CVG) for its morphological
appearance.
Case report
A boy of 12 years presented with an irregular
mass consisting of ridges and furrows on the scalp
present since birth with gradual increase in size.
He had no neurological complaints and there was
no family history. On examination cerebriform,
* Associate Professor, Dept. of Dermatology
** Prof. and Head, Dept. of Plastic Surgery
*** Internee
** Prof. and Head, Dept. of Pathology
**** Tutor, Dept. of Radiodiagnosis
***** Prof. and Head & Medical Superintendent
Dept. of Pediatrics
Vinayaka Missions Medical College, Karaikal
51
non tender, firm, hyperpigmented tumorous
lesion of 12 cm size was present in the occipital
and parietal area of the scalp (Fig.1,2). There was
alopecia over the mass. No similar lesions elsewere
in the body. A clinical diagnosis of Cutis verticis
gyrata was made.
Skull X- ray revealed an intact cranial vault.
CT of the brain and skull showed a soft tissue
swelling in the occipital area of the scalp with a
normal brain study (Fig.3). A diagnosis of
melanocytic nevus presenting as CVG was made.
The mass was surgically excised in toto (Fig.4)
and the skull was covered with split skin graft by
plastic surgeon. Histopathology of the biopsy of
the lesion showed dermal melanocytic nevus cells
(Fig. 5).
Discussion
The importance of congenital melanocytic nevus
presenting as Cutis verticis gyrata is to exlude
neurological abnormalities and prevention of
malignant transformation. Patients with
congenital melanocytic nevi may have associated
leptomeningeal melanocytosis with or without
central nervous system melanomas3. Patients with
large congenital melanocytic nevi in a posterior
axial location are at greater risk for manifesting
with neurocutaneous melanosis4. Nervous system
associations such as cerebral mass5, encephalo-
cele, melanomas, neurologic findings, lipomatosis
have been described.
Giant nevi may have different morphological
appearances. Four children presenting with hard,
ligneous progressively hypopigmented and alopecic
 Fig.1. Cutis verticis gyrata lesion over Fig 3. CT Scan skull showing extracranial
scalp soft tissue shadows

Fig.2. Close up view of lesion in fig 1 Fig.4 Excised specimen

Fig.5. Histopathology showing naevus cells in dermis 40X

52
giant nevi with features suggestive of desmoplasia
have been reported6. Giant Melanocytic Naevus
with progressive sclerodermoid reaction in a
newborn has also been described.7 In our case it
was a cutis verticis gyrata like appearance.
Whether the evolution of this unique
appearance of the lesion in our patient mimicking
the contours of the brain is related to the
embryological origin of the neuroectoderm is not
known . It is well known that in some dermal
naevi there are neuroid changes in the deeper
parts.The differentiation of these neuroid naevi
from solitary neurofibroma may be difficult in
routinely stained sections but distinction may be
possible by immunohistochemistry employing
myelin basic protein which is positive only in
neurofibroma.8 These findings support the belief
that dermal melanocytic nevi are hamartomas of
both melanocytic and neural cells. In the etiology
of melanocytic naevi it is proposed that during
embryogenesis a morphogenic error in the
neuroectoderm results in the dysregulated growth
and distribution of melanoblasts from the neural
crest to the leptomeninges and the integument.9
References
1. Mathur NB, Maria A, Khandpur S, Bala S. Giant
congenital melanocytic nevus with cutis vertis
gyrate.Indian Pediatr 2001;38:553-556
NEWS AND NOTES
NATIONAL TYPE 1 DIABETIC MEET FOR PARENTS OF
DIABETIC CHILDREN OF ALL AGES
Kanpur, UP, January 27-28, 2007
Enquiries to :
Dr. Rashmi Kapoor, Pediatric Intensivist,
Regency Hospital Ltd., A-2, Sarvodaya Nagar, Kanpur, UP.
Phone No. -0512-2236201, 02 Mobile - 9839027449
E-mail : rashmireg@rediffmail.com
53
2. Shermak MA, Perlman EJ, Carson BS,
Dufresne CR.Giant congenital nevocellular
nevus overlying an encephalocele.J Craniofac
Surg 1996;7(5):376-383.
3. Cabrere H, Gomez ML, Garcia S. Lipomatous
melanocytic nevomatosis.J Eur Acad Dermatol
Venerol 2002;16(4):377-379.
4. Martinez-Granero MA, Pascual-Castroviejo I,
Roche Herrere MC, Urgelles Fajardo E.
Neurocutaneous melanosis and congenital
melanocytic nevi.Neurolgia 1997;12(7): 287-
292.
5. Schaffer JV, MC Niff JM, Bolognia JL.
Cerebral mass due to neurocutaneous
Melanosis:eight years later.Pediatr Dermatol
2001;18(5):367-377.
6. Maldonada R, Orozco L. Desmoplastic
hairless hypopigmented nevus:a variant of
congenital melanocytic nevi. Br J Dermatol
2003;148(6) 1253-1255.
7. Pattee SF, Hansen RC, Bangert JL, Joganic EF.
Giant congenital nevus with progressive
sclerodermoid reaction. Pediatr Dermatol
2001;18(4):320-324.
8. Elder D, Elenitsas R. Benign pigmented lesions
and malignant melanoma. In: Levers
th
Histopathology of skin 8 Edn. Lippincott-
Raven, Philadelphia 1997; p 636.
9. Marghoob AA. Congenital melanocytic nevi-
evaluation and management. Dermatol Clin N
Am 2002;20:607-616.
 CASE STUDY
CAVERNOUS SINUS THROMBOSIS
A CASE REPORT
* Arunkumar J
** Lakshmi S
** Kumarasamy K
** Ravisekar CV
** Venkataraman P
*** Vasanthamallika TK
Introduction
Intracranial septic venous thrombosis is very
rare in the post antibiotic era. It may complicate
meningitis, epidural or subdural abscess or spread
from extracranial veins. A review of literature
between 1940 and 1988 has identified only 88
cases. The treatment is controversial and the
outcome is fatal in approximately 30% and nearly
half have chronic neurological sequelae including
oculomotor weakness, blindness, ptosis, proptosis,
hemiparesis and hypopituitarism.1
Case report
A four year old boy presented with history
of furuncle over the bridge of the nose. He also
had swelling in the right periorbital region and low
grade fever. Subsequently, the child became toxic
with increase of swelling, pain and limitation of
movements of both eye balls. He then developed
right sided ptosis, mild proptosis, chemosis of
* Postgraduate
** Asst. Professor
*** Addl. Professor
Institute of Child Health and Hospital for Children,
Chennai - 8.
54
conjunctiva and bilateral lateral rectus palsy
(Fig.1). The pupils and rest of the CNS
examination were normal except for meningeal
signs.
Based on these, a diagnosis of cavernous
sinus thrombosis was made and the child was
investigated. Routine investigations revealed
polymorphonuclear leucocytosis. CSF was
normal and blood, pus and CSF culture were
negative. CT scan showed dilated superior
ophthalmic vein on the right side. Contrast MRI
confirmed the thrombus in the cavernous sinus
(Fig.2).
The child showed remarkable improvement
with antibiotics (vancomycin and ceftriaxone for
three weeks and metronidazole for two weeks)
and steroids (dexamethasone 0.2mg/kg/dose iv
every 8 hours for seven days) and was discharged
with bilateral resolving lateral rectus palsy and
partial ptosis on the right side.
Anticoagulants were not initiated as its role
is controversial and for the fear of spread of
infection as the child had septic foci in the face2.
Discussion
Septic facial lesion remain the most frequent
predisposing infection for intracranial venous
thrombosis, the others being infection of sinuses
and jaw. Staphylococcus aureus is the most
common pathogen isolated in nearly two thirds
followed by pneumococci, H. influenzae and
anaerobes. Gram negative rods and fungi may be
isolated in chronic forms.3

Fig. 1. Clinical picture with bilateral squint
and residual ptosis right eye
The principal symptoms are fever and
periorbital edema initially affecting one eye.
Within 24-48 hours the other eye becomes
involved through spread from intercavernous
sinuses. The classical physical features include
ptosis, proptosis, chemosis, oculomotor palsies and
painful limitation of movements of eyeball.
Depending on the involvement of sixth, third
or fifth cranial nerve and sympathetic plexus there
may be focal deficits. Contralateral hemiparesis
results if internal carotid artery is thrombosed.
The differential diagnosis includes other
causes of periorbital edema: orbital cellulitis,
carotico-cavernous fistula, idiopathic
granulomatous inflammation of the superior orbital
fissure and cavernous sinus (Tolosa Hunt
Syndrome), periarteritis nodosa associated with
cerebral venous sinus thrombosis (Cogans
Syndrome) and tumors. But orbital cellulitis is
the most common mimic and it can be
differentiated by the characteristic bilaterality of
cavernous sinus thrombosis.
CT scan is the diagnostic study of choice.1
Contrast CT will demonstrate irregular filling
defects and convex bulging of the lateral sinus
walls on coronal sections and dilation of superior
ophthalmic vein. MR venography or cerebral
angiography with venous phase studies may be
necessary to confirm the diagnosis.4 Blood or
CSF culture may reveal the offending organism.
The mainstay of therapy is early intravenous
55
administration of antibiotics in high dosage
directed against the most likely pathogens. A
penicillinase resistant penicillin combined with a
third generation cephalosporin is a good empirical
choice. Metronidazole may be added to enhance
anaerobic coverage.
Corticosteroids are universally used in
patients treated non surgically.3,5 This does not
prove that steroids influence the morbidity or
mortality of cavernous sinus thrombosis but their
use as an adjunctive therapy might partially prevent
cranial nerve dysfunction caused by
inflammation.3,6
There are insufficient data regarding the
indication of anticoagulant therapy2 because the
condition is rare. Anticoagulation should be
considered only when there is no evidence of
cortical venous infarction either clinically or on
imaging. Early addition of heparin to the primary
treatment with antibiotics (within seven days of
hospitalization) may reduce the morbidity and
mortality in this disease.1 However there is a
potential danger of hemorrhagic cerebral infarction
and enhance spread of infection.
Cavernous sinus surgical exposure and
drainage is not recommended because of the high
risk of damage to vital nerves.
Fig. 2. MRI showing thrombus in the right
cavernous sinus
 Recent advances in interventional neuro
radiology and endovascular techniques enable the
local delivery of thrombolytic agents to selective
venous channels where thrombosis occur and these
newer techniques will undoubtedly be used with
increasing frequency in the future for the treatment
of cortical venous thrombosis.
References
1. Southwick FS, Swastz MN. Inflamatory
thrombosis of major dural venous sinuses and
cortical veins. In: Wilkins RH, Rengachary SS
(EDs) Neurosurgery, 2nd Edn,Vol III, McGraw-
Hill, USA 1996;PP3307-3308.
2. Bhatia K. Jones NS. Septic cavernous sinus
thrombosis secondary to sinusitis: are
anticoagulants indicated? J Laryngol Otol
2002; 116 (9) : 667 676.
3. Migirov L, Eyal A, Kroneberg J. Treatment of
cavernous sinus thrombosis. I Med Assn J
2002; 4: 468469.
4. Verma A, Solbring MV. Infection of the nervous
system. In: Bradley WG, Daroff RB, Fenichel
GM, Jankovic J (Eds). Neurology in clinical
th
practice, 4 Edn, Vol II, Elsevier, USA. 2004;
pp 1488 1489.
5. Johanson DL, Markle BM, Wiedermann BL,
Hanahan L. Treatment of intracranial
abscesses associated with sinusitis in children
and adolescents. J Pediatr 1988; 113: 15 23.
6. Southwick FS, Richardson EP, Swartz MN.
Septic thrombosis of the dural venous sinuses.
Medicine 1986; 65: 82 106.

NEWS AND NOTES

9th ASIAN AND OCEANIAN CONGRESS OF CHILD NEUROLOGY

Philippines, January 24-27, 2007
Enquiries to :
Secretariat, Philippine Neurological Society,
RM 1006, 10th floor, North Tower, Cathedral Heights Building,
St. Lukes Medical Center, E. Rodriguez St., Quezon City, Philippines.
Email : secretariat@aoccn2007.org and pna@surfshop.net.ph

5th NATIONAL CME IN NEONATOLOGY

New Delhi, February 10-11, 2007
Enquiries to :
Dr. Ramesh Agarwal,
Department of Pediatrics,
All India Institute of Medical Sciences,
New Delhi 110 029.

56
 CASE STUDY
HEREDITARY SENSORY
AUTONOMIC NEUROPATHY TYPE IV-
A VERY RARE CONDITION
* Nilesh Jain
** Vyas BR
*** Shalini Jain
Introduction
Hereditary Sensory Autonomic Neuropathy
(HSAN) is classified into five types according to
natural history, mode of inheritance and
electrophysiological characteristics. HSAN type IV
is a rare autosomal recessive disorder. Very few
cases have been reported in literature. The main
features are insensitivity to pain, anhidrosis, mental
retardation and self-mutilating behaviour, present
since birth1. The diagnosis primarily relies on
history and examination but can be confirmed by
absence of sensory evoked potential and absence
of unmyelinated axons in sural nerve biopsy.
Mutation of Neurotrophic Tyrosine Receptor
Kinase - 1(NTRK-1) causes defect in nerve
growth factor (NGF) signalling, leading to death
of various NGF dependent neurons.2 Recurrent
trauma as well as episodes of fever require medical
treatment.
Case Report
A 3 year old male child presented with history
of generalized convulsions associated with fever,
self inflicted injury with mutilation of lower lip,
* Asst. Professor, Dept. of Pediatrics
** Assoc. Professor, Dept. of Pediatrics
*** Tutor, Dept. of Anaesthesiology
M.P. Shah Medical College,
Guru Gobind Singh Hospital, Jam Nagar, Gujarat.
57
nose, fingers and toes leading to multiple scar
formation, dry skin, mental retardation and near
blindness. There was no history of tingling,
burning, numbness and sensation of pins and
needles. The child was born full term to second
degree consanguineous parents. Antenatal,
intranatal and postnatal periods were uneventful.
The child was able to walk without support but
could neither climb stairs with assistance nor walk
sideways. He was able to speak 8-10 words but
could not form simple sentences. He was toilet
trained and dry during the day. There was history
of repeated biting and scratching of lips, fingers
and nose without sensation of pain during
scratching and injury causing deep ulcer formation,
fibrosis and deformity. He had inadequate sweating
and repeated episodes of unexplained fever and
two such episodes were accompanied by seizures.
There was no similar history in the family.
On examination, he had corneal opacities in
both eyes. The nose was deformed, lower lip was
mutilated and fingers of both hands were
deformed especially index and ring fingers of right
hand with hyper pigmentation. Feet and toes were
also hyper pigmented and had multiple scars. The
skin was rough and dry. Sweating was not
observed in the child. Fungiform papillae were
seen over the tongue. Eyebrows, teeth and nails
were normal.
Blood pressure was normal. No sphincter
disturbances were present. Pain and temperature
sensations were absent all over body, however
touch sense was preserved. Corneal reflex was
present and deep tendon reflexes were sluggish.
There was no cerebellar sign and gait was normal.
 Intradermal injection of 1:10000 histamine
failed to show axon flare.
Study of conduction velocity showed absence
of evoked potential from sensory nerves. The
motor action potential and conduction velocities
were normal. The normal values in children
more than 2 years are 50-70 m/s in arms and 40-
60 m/s in legs as in adults. Sural nerve biopsy
showed absence of unmyelinated axons, decrease
in number of small myelinated axons and normal
distribution of large myelinated axons. Serum uric
acid level was normal.
Discussion
HSAN is a group of hereditary sensory and
autonomic neuropathy, classified by Dyck into
five types (Table 1). Hereditary sensory and
autonomic neuropathy type-IV (HSAN-IV) is a
very rare autosomal recessive disorder. The
frequency of this disease is unknown. HSAN-IV
is also known as congenital insensitivity to pain
with anhidrosis (CIPA, MIM#256800) and Familial
dysautonomia type two. It was first described by
Swanson in 1963.3
The diagnosis is commonly based on clinical,
neuropathological findings and histamine test.
Recently molecular analysis of NTRK-1, the gene
mutated in this disease is available.
Clinical features4 : The constant features (100%)
are anhydrosis, episodes of unexplained fever,
severe mental retardation, insensitivity to pain,
self-mutilating behaviour. The frequent features
include multiple fractures with slow healing skin
infections, bruises, corneal ulcerations, and
aggressive behaviour. Impaired immune response,
proteinuria, renal failure, anemia, hyperkeratosis,
dry skin and early primary teeth loss have also
been reported.
HSAN-IV is caused by mutation of
neurotrophic tyrosine receptor kinase I gene
58
(NTRK 1) located on 1q21-q22 which encodes a
receptor tyrosine kinase (RTK) for the nerve
growth factor (NGF).
Intradermal injection of 1:10000 histamine
fails to show axon flare.
Diagnosis is confirmed by neruropathological
finding showing the absence of unmyelinated
axons, decrease in number of small myelinated
axons and normal distribution of large myelinated
axons. Sweat glands have a normal structure but
are not innervated. Electrophysiological studies
reveal reduction in sensory action potential.
Differential Diagnosis: Familial dysautono-mia,
HSAN III and HSAN IV have many features in
common. However in HSAN III, insensitivity to
pain is not prominent, corneal reflex is absent and
fungiform papillae of the tongue are not seen.
Affected children with ectodermal dysplasia are
anhidrotic because sweat glands are absent. The
nervous system is intact, and sensation to pain is
present.
Another differential diagnosis for self-
mutilation is Lesch Nyhan disease. Affected
children have compulsive self mutilation and
mental retardation but pain and temperature
sensations are present.
Treatmet : No specific therapy is available for
HSAN-IV. However, constant vigilance and
protective milieu to prevent injuries to the skin
and bones are essential. Extraction of teeth has
been performed in some children to prevent
mutilation. An important goal of therapy is to
prevent foot ulcers. Recurrent traumatic
complications, as well as severe episodes of fever
require frequent medical treatment. Fracture must
be suspected whenever bruising or swelling are
identified. Proper and rapid immobilization is
mandatory. It is estimated that about 20% deaths
occur due to hyperthermia or sepsis.
Table 1. Hereditary sensory and autonomic neuropathies. Modified by Dyck
(1994)
Neurons (Axons)
HSAN Onset Inheri- Motor Loci Gene Salient clinical features
tance A- A- C
alpha delta

Type 1 >2 AD + ++ ++ LS 9q22 SPTLC1 Lancinating pain, plantar

decades ulcers. Feet are more
involved than hand

Type 2 Co AR ++ ++ + G Unknown Unkown Infantile hypotonia. Arms

and legs are equally
involved. Touch and
pressure are more affected
than pain and temperature

Type 3 Co AR ++ ++ ++ G 9q31 IKVKAP Feeding difficulties and

poor control of autonomic
function

Type 4 Co AR N + + G 1q21 NTRK1 Absence of pain and tempe-

rature sensation; touch and
vibration are intact in some
cases. Anhidrosis and
mental retardation are
prominent features.

Type 5 Co AR N N/+ N/+ G Unknown Unknown Pain sensation lost

selectively.

Co = Congenital LS = Lumbo sacral G = Generalised

Reference insensitivity to pain with anhidrosis (CIPA), a

1. Fenichel GM. Sensory and autonomic
disturbances. In: Clinical Pediatric Neurology
th
4 Edn. W.B. Saunders Company, Philadelphia
2001;pp 216-218.
2. Indo Y. Molecular basis of congenital
insensitivity to pain with anhidrosis (CIPA):
mutations and polymorphisms in TRDA
(NTRK) gene encoding the receptor tyrosine
kinase for nerve growth factor. Hum Mutat
2001;18:462-471.
3. Swanson AG. Congenital insensitivity to pain
with anhidrosis. Arch neurol 1963; 8:299-306.
4. Toscano E, Delta Casa R, Mardy S, et al.
Multisystem involvement in congenital
59
nerve growth factor receptor (TrkA) related
disorder. Neuropediatrics. 2000;31:39-41.
5. Levi-Montalcini R. the nerve grwoth factor.
Thirty-five years later. EMBO J 1987; 6:1145-
1154.
6. Asaumi K, Nakanishi T, Asahara H, Inoue H,
Takigawa M. Espression of neurotrophins and
their receptors (Trk) during fracture healing.
Bone 2000; 26:625-633.
7. Dyck PJ, Chance P, Lebo R, Camey JA.
Hereditary motor and sensory neuropathies. In:
Dyck PJ, Thomas PK, Griffin JW, Low PA,
Poduslo JF (Eds). Peripheral Neuropathy
Vol 2 WB Saunders, 1993;pp1094-1123.
8. Greco A, Filla R, Tubine B, Romano L, Penso
D, Piertotti MA. A novel NTRK1 Mutation
associated to insensitivity to pain with
anhidrosis. IS J Hum Genet 1999; 64:1207-
1210.
9. Indo Y, Mardy S, Miura Y, et al. Congenital
insensitivity to pain with anhidrosis (CIPA):
novel mutations of the TRKA (NTRK1) gene,
a putative uniparental disomy, and a linkage
of the mutant TRKA and PKLR genesis in a
family with CIPA and pyruvate kinase
deficiency. Hum Mutat 2001;18:308-318.
10. Shatzky S, Moses S, Levy J, et al . Congenital
insensitivity to pain with anhidrosis (CIPA) in
Israli-Bedouins. Genetic heterogeneity, novel
mutations in the TRKA/NFG receptor gene
clinical findings and results of nerve
conduction studies. Am J Med Genet
2000;92:353-360.

PICTURE QUIZ
Answer for the picture quiz : Gauchers Disease
ADVT.

MAHAMAHAM PEDICON - 2007

KUMBAKONAM
XXXII ANNUAL STATE CONFERENCE OF IAP-TAMILNADU STATE CHAPTER
ORGANISED BY IAP-TTKPN DIST. BRANCH
DATE : 10th - 12th OF AUGUST 2007
Org. Chairman Org. Secretary Treasurer Jt. Org. Secretary
Dr. R. Virudha Giri Dr. R. Palanivelu Dr. S. Lakshmi Narayanan Dr. G. Sambasivam
94433 82982 94433 64111 94431 60800 94431 34711
Theme : Childrens Safety and Nutritional Security - Nations Priority
Delegate fee upto 31-03-06 31-05-06 15-07-06 Spot
IAP 1500 2000 2500 3000
Non - IAP 1750 2250 2750 3500
Post Graduate 1250 1500 1750 2000
Accompanying person 1250 1750 2250 2500
The delegate fee as DD / Cheque drawn in favour of Mahamaham Pedicon - 2007 payable at
Kumbakonam, (Please add Rs. 50 for outstation cheques) along with registration form may be
sent to :
Dr. R. Palanivelu, Organising Secretary, 39, Chellam Nagar, Kumbakonam - 612 001.
Phone : 0435 - 2431712 Cell : 94433 64111

60
 IAP TASK FORCE REPORT

GUIDELINES AND MANAGEMENT Diagnosis of Enteric Fever

OF ENTERIC FEVER IN CHILDREN
The correct and rapid diagnosis of enteric
(UNDER IAP ACTION PLAN 2006)
fever is of paramount importance for instituting
Chairperson appropriate therapy and also for avoiding
Dr Nitin K Shah, President, Indian Academy unnecessary therapy.
of Pediatrics Complete Blood Count (CBC)
Writing Committee
For practical purposes the CBC in enteric
Dr Ritabrata Kundu, Professor of Pedaitrics,
fever is unremarkable. The hemoglobin is normal
Institute of Child Health, Kolkata
in the initial stages but drops with progressing
Dr Nupur Ganguly, Assistant Professor of
illness. Severe anemia is unusual and should make
Pedaitrics, Institute of Child Health, Kolkata
one suspect intestinal hemorrhage or hemolysis
Dr Tapan Kr Ghosh, Scientific Coordinator,
or an alternative diagnosis like malaria. The WBC
Institute of Child Health, Kolkata
count is normal in most cases and leukocytosis
Dr Vijay N Yewale, Consultant Pediatrician, makes the diagnosis less probable. Leukopenia
Dhapi, Navi Mumbai perceived to be an important feature of typhoid
Dr Raju C Shah, National President 2005 fever and has been reported in only 20-25%
Dr Nitjn K Shah, National President 2006 cases. 1 The differential count is usually
Recommendation Committee unremarkable except for eosinopenia. Eosinopenia
Dr A Balachandran often absolute may be present in 70-80% cases.2,3
Dr Ajay Kalra Presence of absolute eosinopenia offers a clue to
Dr Anju Aggarwal diagnosis but does not differentiate enteric fever
Dr Ashok Kapse from other acute bacterial or viral infections.
Dr Deepak Ugra Conversely a normal eosino-phil count does make
Dr Nigam P Narain typhoid fever a less likely possibility. Platelet
Dr Nitin K Shah counts are normal to begin with and fall in some
Dr Nupur Ganguly cases by the second week of illness. Overall
Dr Panna Chowdhury prevalence of thrombocytopenia is around 10-
Dr Raju C Shah 15%.4
Dr Ritabrata Kundu
Cultures
Dr Shivananda
Dr Shyam Kukreja Blood Culture :
Dr Tanu Singhal Blood cultures are the gold standard
Dr Tapan Kr Ghosh diagnostic method for diagnosis of enteric fever.5
Dr Vijay N Yewale The sensitivity of blood culture is highest in the
61
first week of the illness and reduces with
advancing illness.6 Overall sensitivity is around
50 % but drops considerably with prior antibiotic
therapy.5 Failure to isolate the organism may be
caused by several factors which includes
inadequate laboratory media, the volume of blood
taken for culture, the presence of antibiotics and
the time of collection. For blood culture it is
essential to inoculate media at the time of drawing
blood.
Salmonella can be easily cultured in most
microbiologic laboratories with use of routine
culture media (Hartleys media, Blood agar and
MacConkey agar). Automated blood culture
systems such as BACTEC certainly enhance the
recovery rate. Sufficient amount of blood should
be collected for culture as the median bacterial
count in the peripheral blood is only 0.3 CFU/ml
(inter quartile range 0.1 to 10; range, 0.1 to 399).7
At least 10 ml of blood in adults and 5ml in
children should be collected. Dilution should be
appropriate in order to adequately neutralize the
bactericidal effect of serum and a ratio of 1:5 to
1:10 of blood to broth is recommended. Clot
cultures, wherein the inhibitory effect of serum is
obviated have not been found to be of superior
sensitivity as compared to blood cultures in several
clinical studies.8-10 In the laboratory, blood culture
bottles should be incubated at 370 C and checked
for turbidity, gas formation and other evidence of
growth after 1, 2, 3 and 7 days. For days 1,2 and
3 only bottles showing signs of positive growth
are cultured on agar plates. On day 7 all bottles
should be sub-cultured before being discarded as
negative.
There are considerable advantages of routine
blood cultures in investigation of suspected enteric
fever. Not only are they 100% specific, but they
also provide information on the antimicrobial
sensitivity of the isolate. This is vital in todays
scenario of multidrug resistance. Moreover
alternative methods for diagnosis particularly
62
serology are rather unsatisfactory as will be
discussed later. Blood cultures may actually turn
out to be cheaper and very cost effective in the
long run, as positive cultures unequivocally
establish the diagnosis of enteric fever and all other
investigations for PUO can be safely deferred.
Bone Marrow Culture :
Salmonella typhi is an intracellular pathogen
in the reticuloendothelial cells of the body including
the bone marrow.5 Studies have revealed that the
median bacteremia in the bone marrow is 9 CFU/
ml (IQR, 1 to 85; range, 0.1 to 1,5805) compared
to 0.3 CFU/ml (IQR, 0.1 to 10; range, 0.1 to
399) in blood. This bone marrow: peripheral blood
ratio which is around 4.8 (IQR, 1 to 27.5) in the
first week of the illness increases to 158 (IQR, 60
to 397) during the third week owing to
disappearance of bacteria from the peripheral
blood.7 The overall sensitivity of bone marrow
cultures ranges from 80 95 % and is good even
in late disease and despite prior antibiotic
therapy.5,11-13
The invasive nature of bone marrow
aspiration deters from its use as a first line
investigation for diagnosis of typhoid fever. It is
however a very useful and valid investigation in
evaluation of PUO wherein the marrow should
be inoculated in the culture bottle at the bedside.
Stool, Urine and Other Cultures :
Stool specimen should be collected in a sterile
wide mouthed container. Specimens should
preferably be processed within 2 hours after
collection. If there is a delay the specimen should
be stored in a refrigerator at 40 C or in a cool box
with freezer packs. The sensitivity of stool culture
depends on the amount of feces cultured, and the
positivity rate increases with the duration of the
illness. Rectal swabs should be avoided as these
are less successful. Stool cultures are positive in
30% of patients with acute enteric fever.5 For the
detection of carriers, several samples should be
examined because of irregular shedding of
salmonella. Urine cultures are not recommended
for diagnosis in view of poor sensitivity.5,14 Other
methods such as duodenal string and skin snip
culture of rose spots have been reported to be
more efficacious than blood cultures but are
mainly of academic importance.14-16
Antimicrobial Sensitivity Testing
The crucial issue here pertains to
fluoroquinolone susceptibility testing.
Fluoroquinolones were introduced in 1989 and
during the past decade there has been a progressive
increase in the MICs of ciprofloxacin in
Salmonella typhi and paratyphi.5 Since the current
MICs are still below the National Committee for
Clinical Laboratory Standards (NCCLS) suscepti-
bility breakpoint, laboratory reports will continue
to report Salmonella typhi/paratyphi as
ciprofloxacin/ofloxacin sensitive.17 However use
of fluoroquinolones in this scenario is associated
with a high incidence of clinical failure.5,17 It has
also been demonstrated that resistance to nalidixic
acid is a surrogate marker for high ciprofloxacin
MICs, predicts fluoroquinolone failure and can
hence be used to guide antibiotic therapy (i.e, if
culture results show resistance to nalidixic acid
irrespective of the results of ciprofloxacin/
ofloxacin sensitivity, quinolones should not be used
or if used high doses should be given).18 Since
MIC testing is not within the scope of most
laboratories, nalidixic acid susceptibility testing is
mandatory to help guide choice of antibiotics.
Serologic Tests
WIDAL test :
This test first described by F Widal in 1896,
detects agglutinating antibodies against the O and
H antigens of Salmonella typhi and H antigens of
paratyphi A and B.6,19 The O antigen is the
somatic antigen of Salmonella typhi and is shared
63
by Salmonella paratyphi A, paratyphi B, other
Salmonella species and other members of the
Enterobacteriaceae family.20 Antibodies against the
O antigen are predominantly IgM, rise early in
the illness and disappear early.20 The H antigens
are flagellar antigens of Salmonella typhi,
paratyphi A and paratyphi B. Antibodies to H
antigens are both IgM and IgG, rise late in the
illness and persist for a longer time.19,20 Usually,
O antibodies appear on day 6-8 and H antibodies
on days 10-12 after the onset of disease. The test
is usually performed on an acute serum (at first
contact with the patient). A convalescent serum
should preferably also be collected so that paired
titrations can be performed.
Conventionally, a positive WIDAL test result
implies demonstration of rising titers in paired
blood samples 10-14 days apart.19 Unfortunately
this criterion is purely of academic interest.
Decisions about antibiotic therapy cannot wait for
results from two samples. Moreover antibiotics
may dampen the immune response and prevent a
rise in titers even in truly infected individuals.
Therapeutic decisions have to be generally based
on results of a single acute sample. In endemic
areas, baseline anti O and anti H antibodies are
present in the population owing to repeated
subclinical infections with Salmonella typhi/
paratyphi, infections with other Enterobacteria-
ceae and other tropical diseases such as dengue
and malaria.19-21 These antibody titers vary with
age, socio economic strata, urban or rural areas
and prior immunization with the TAB vaccine.
Establishing appropriate cut offs for distinguishing
acute from past infections is thus important for
the population where the test is applied. In one
study from Central India, anti O and anti H titer
of more than 1: 80 was seen in 14% and 8%
respectively of a study sample of 1200 healthy
blood donors. 22
While interpreting the results of the WIDAL
test, both H and O antibodies have to be taken
into account. There is controversy about the
predictive value of O and H antibodies for
diagnosis of enteric fever. Certain authorities claim
that O antibodies have superior specificity and
positive predictive value (PPV) because these
antibodies decline early after an acute infection.23
Other studies report a poorer positive predictive
value of O antibodies probably due to rise of these
antibodies in other salmonella species, gram-
negative infections, in unrelated infection and
following TAB vaccination 21. For practical
purpose and for optimal result this test should be
done after 5-7 days of fever by tube method and
level of both H and O antibodies of 1 in 160
dialution (four fold rise) should be taken as cut
off value for diagnosis. H anitbodies once positive
can remain positive for a long time.
The WIDAL test as a diagnostic modality
has suboptimal sensitivity and specificity.19-21 It
can be negative in up to 30% of culture proven
cases of typhoid fever. Sub optimal sensitivity
results from negativity in early infection, prior
antibiotic therapy and failure to mount an immune
response by certain individuals.19 Poor specificity,
an even greater problem and is a consequence of
preexisting baseline antibodies in endemic areas,
cross reactivity with other Gram-negative
infections and non-typhoidal salmonella,
anamnestic reactions in unrelated infections and
prior TAB or oral typhoid vaccination. The purity
and standardization of antigens used for the
WIDAL test is a major problem and often results
in poor specificity and poor reproducibility of test
results.19 The slide WIDAL test should also be
discouraged owing to high rate of false positives.20
Nowithstanding these problems, the WIDAL
test may be the only test available in certain
resource poor set ups for diagnosis of enteric. In
Vietnam, using a cutoff of >1/200 for the O
agglutinin or >1/100 for H agglutinin test
performed on acute-phase serum the WIDAL test
could correctly diagnose 74% of blood culture
64
positive typhoid fever, however 14% results would
be false positive and 10% false negative.21 Hence,
it is important to realize the limitations of the
WIDAL test and interpret the results carefully in
light of endemic titers so that both over diagnosis
and under diagnosis of typhoid fever and the
resulting consequences are avoided.24
Other Serologic Tests
In view of the limitations of the WIDAL test
and need for a cheap and rapid diagnostic method,
several attempts to develop alternative serologic
tests have been made. These include rapid dipstick
assays, dot enzyme immunoassays and
agglutination inhibition tests.25-27
Enzyme Immunoassay (EIA) test or
Typhidot? test A dot enzyme immunoassay that
detects IgG and IgM antibodies against a 50 KD
Outer Membrane Protein distinct from the somatic
(O), flagellar (H) or capsular (Vi) antigen of
Salmonella typhi is commercially available as
Typhidot.27 The sensitivity and specificity of this
test has been reported to vary from 70%-100%
and 43% - 90% respectively.28-33 This dot EIA
test offers simplicity, speed, early diagnosis and
high negative and positive predictive values. The
detection of IgM reveals acute typhoid in the early
phase of infection, while the detection of both
IgG and IgM suggests acute typhoid in the middle
phase of infection. In areas of high endemicity
where the rate of typhoid transmission is high the
detection of specific IgG increase. Since IgG can
persist for more than 2 years after typhoid
infection34 the detection of specific IgG can not
differentiate between acute and convalescent
cases. Further more, false positive results
attributable to previous infection may occur. On
the other hand IgG positivity may also occur in
the event of current reinfection. In cases of
reinfection there is a secondary immune response
with a significant boosting of IgG over IgM, such
that the later can not be detected and its effect
masked. A possible strategy for solving this
problem is to enable the detection of IgM by
ensuring that it is unmasked 35. The original
Typhidot test was modified by inactivating the
total IgG in the serum samples. Studies with
modified test, Typhidot M, have shown that
inactivation of IgG removes competitive binding
and allows the access of the antigen to the specific
IgM when it is present.
The Typhidot M that detects only IgM
antibodies of Salmonella typhi has been reported
to be slightly more specific in a couple of
studies.26,33
IDL Tubex test The Tubex test is easy to
perform and takes approximately 2 minutes
time36. The test is based on detecting antibodies
to a single antigen in S. typhi only. The 09 antigen
used in this test is very specific found in only sero
group D salmonellae. A positive result always
suggest a salmonellae infection but not which
group D salmonella is responsible. Infection by
other serotypes like S. paratyphi A give negative
result. This test detects IgM antibodies but not
IgG which is further helpful in the diagnosis of
current infections.
IgM dipstick test26 The test is based on the
binding of S. typhi specific IgM antibodies to S.
typhi lipopolysaccharide (LPS) antigen and the
staining of the bound antibodies by an antihuman
IgM antibody conjugated to colloidal dye particles.
This test will be useful in places where culture
facilities are not available as it can be performed
without formal training and in the absence of
specialized equipments. One should keep in mind
that specific antibodies appear a week after the
onset of symptoms so the sensitivity of this test
increases with time.
Antigen detection tests Enzyme
immunoassays, counterimmune electro-phoresis
and co-agglutination tests to detect serum or
urinary somatic/flagellar/Vi antigens of Salmonella
typhi have been evaluated.37-40 Sensitivity of
65
Vi antigen has been found to be superior to
somatic and flagellar antigen and has been
reported as ranging from 50% to 100% in different
studies.37-40 Similarly specificity estimates have
been reported to vary from 25% to 90%.37-40 The
suboptimal and variable sensitivity and specificity
estimates, inability to detect Salmonella paratyphi
infection and Vi antigen negative strains of S typhi
are serious limitations of the Vi antigen detection
tests.
Molecular Methods
The limitations of cultures and serologic tests
advocate for development of alternative diagnostic
strategies. PCR as a diagnostic modality for
typhoid fever was first evaluated in 1993 when
Song et al successfully amplified the flagellin gene
of S typhi in all cases of culture proven typhoid
fever and from none of the healthy controls.41
Moreover some patients with culture negative
typhoid fever were PCR positive suggesting that
PCR diagnosis of typhoid may have superior
sensitivity than cultures. Over the next 10 years a
handful of studies have reported PCR methods
targeting the flagellin gene, somatic gene, Vi
antigen gene, 5S-23S spacer region of the
ribosomal RNA gene, invA gene and hilA gene
of Salmonella typhi for diagnosis of typhoid
fever.42-50 These studies have reported excellent
sensitivity and specificity when compared to
positive (blood culture proven) and healthy
controls. The turnaround time for diagnosis has
been less than 24 hours.
These reports should be viewed within the
context of certain limitations. Clinical utility of PCR
tests has been inadequately evaluated.
Performance of the test in individuals with febrile
illnesses other than typhoid, in those with past
history of typhoid, carriers of S typhi, and those
vaccinated with typhoid vaccine is not known.
Patients with a clinical diagnosis of typhoid fever
who are culture negative but PCR positive may
in fact be false positives. Comparison of PCR to
bone marrow cultures as a gold standard may be
a superior way of evaluating the sensitivity and
specificity of these tests, but has not been done.
The tests claim to detect as few as 10 organisms,
but it should be remembered that in typhoid the
median bacteremia is 0.3 CFU/ml of blood.7 Using
small volumes of blood for DNA extraction may
significantly lower the sensitivity of these tests.
The cost and requirement for sophisticated
instruments is also a potential drawback of
molecular methods.
Conclusion
The complete blood count is the logical first
investigation. Presence of a normal or low
leukocyte count with eosinopenia points to possible
enteric. It also helps in evaluation of alternative
diagnoses such as malaria, dengue and other
bacteremias. Blood cultures remain the most
effective investigations for diagnosis of enteric till
date. They should be sent early in the course of
the illness and prior to starting antibiotic therapy.
Susceptibility testing for nalidixic acid should be
routinely done for all isolates to aid choice of
antibiotics. Bone marrow culture is a highly
sensitive diagnostic test even in late stages of the
illness and with prior antibiotic therapy. It should
be performed in all patients with prolonged pyrexia
if routine investigations have failed to establish a
diagnosis. The WIDAL test has several limitations
and should be requested for in the second week
of the illness and its results interpreted with caution.
Data on baseline titers in the local population
should be generated by appropriate studies to help
in determining appropriate cut offs for the WIDAL.
The modified WIDAL test, Typhidot, Tubex and
Vi antigen tests need to be evaluated further before
their routine use can be recommended. Molecular
methods are still experimental.
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37. Rao PS, Prasad SV, Arunkumar G, Shivananda
PG. Salmonella typhi Vi antigen co-
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38. Sharma M, Datta U, Roy P, Verma S, Sehgal S.
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44. Chaudhry R, Laxmi BV, Nisar N, Ray K, Kumar
D. Standardisation of polymerase chain
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Diagnosis of Enteric Fever
1. Contrary to the popular belief leukopenia
perceived as an important diagnostic feature of
typhoid fever is reported only in limited cases.
2. Blood culture is the gold standard for
diagnosis of typhoid fever. Blood culture can turn
out to be cheaper and cost effective in the long
run as positive culture unequivocally establishes
the diagnosis and also gives the sensitivity pattern,
thereby helping in the choice of antibiotics.
3. Since MIC is not within the scope of most
laboratories nalidixic acid sensitivity is a surrogate
marker of fluoroquinolone sensitivity and nalidixic
acid susceptibility testing is mandatory to help to
guide the choice of antibiotics.
4. Sensitivity of marrow culture is 80 95
% even in late disease and prior to antibiotic
therapy. Marrow should be inoculated in the
culture bottle at bed side.
5. Widal is the most widely used test in the
diagnosis of typhoid fever in our country. It has
poor sensitivity due to its negativity in early
infection, prior antibiotic therapy may influence it
and certain individual fail to mount an immune
response to the disease. It should be done after 5-
7 days of fever by tube method and level of 1 in
160 for both H and O antibodies are usually taken
as diagnostic.
6. Widal test also has poor specificity due
to preexisting base line antibodies in endemic areas.
Cross reactivity with other Gram negative
infection and nontyphoidal salmonella, prior
typhoid vaccination and anamnestic reaction in
unrelated infection. Data on base line titers of O
and H antibodies should be generated in
determining the appropriate cut of for Widal test.
7. Slide Widal test should be discouraged
due to high rate of false positivity.
8. It is important to realize the limitations of
the Widal test and interpret the results carefully
69
in light of endemic titers so that both overdiagnosis
and underdiagnosis of enteric and the resulting
consequences are avoided.
9. Typhoid test detects IgG and IgM against
outer membrane protein of Salmonella typhi. As
IgG can persist over a long time it is difficult to
distinguish between acute infection and
convalescent cases.
10.This test has been improved in modified
typhidot M test which detects only IgM antibodies.
11. Other serological tests IDL tubex and
IgM dipstick test detects only IgM antibodies to
different S typhi antigens.
12.Molecular methods like PCR are still in
experimental stage not used in day to day practice.
13.The modified Widal test, Typhidot,
Tubex and Vi antigen tests need to be evaluated
further before their routine use can be
recommended.
Treatment of Enteric Fever
The timely appropriate management of typhoid
fever, can considerably reduce both morbidity and
mortality. General supportive measures like use
of antipyretics, maintenance of hydration,
appropriate nutrition and prompt recognition and
treatment of complications are extremely important
for a favorable outcome. The child should
continue to have normal diet and no food should
be restricted.
In areas of endemic disease 90% or more of
typhoid cases can be managed at home with
proper oral antibiotics and good nursing care1.
Close medical follow up is necessary to look for
development of complications or failure to respond
to therapy.
Patients with persistent vomiting, inability to
take oral feed, severe diarrhea and abdominal
distension usually require parenteral antibiotic
therapy preferably in a hospital.
Antimicrobial Therapy
Since 1990s Salmonella typhi has developed
resistance simultaneously to all the drugs used in
first line treatment (chloramphenicol,
cotrimoxazole and ampicillin) and are known as
Multi Drug Resistant typhoid fever (MDRTF).
There are some reports of re-emergence of fully
susceptible strain to first line drugs2. But these
reports are few and unless antibiotic sensitivity
testing shows the organisms to be fully susceptible
to first line drugs they are not advocated for
empirical therapy in typhoid.
Fluoroquinolones are widely regarded as the
most effective drug for the treatment of typhoid
fever3. But unfortunately some strains of S. typhi
have shown reduced susceptibility to
fluoroquinolones 4,5. On routine disc testing with
the recommended break points, organisms
showing suspectibility to fluoroquino-lones shows
poor clinical response to actual treatment. These
organisms when tested by disc testing with
nalidixic acid shows resistance to it. So in other
words resistance to nalidixic acid is a surrogate
marker which predicts fluoroquinolones failure and
can be used to guide antibiotic therapy. The
resistance to fluoroquino-lones may be total or
partial. The nalidixic acid resistant S typhi
(NARST) is a marker of reduced susceptibility to
fluoroquinolones.
With the development of fluoroquinolones
resistance third generation cephalosporins were
used in treatment but sporadic reports of resistance
to these antibiotics also followed 6.
Recently azithromycin are being used as an
alternative agent for treatment of uncomplicated
typhoid fever 7.
Aztreonam and imipenem are also potential
third line drugs which are used recently3.
There is now considerable amount of
evidence from the long term use of fluroquinolones
in children that neither they cause bone or joint
toxicity nor impairment of growth.
70
Ciprofloxacin, ofloxacin, perfloxacin and
fleroxacin are common fluoroquinolones proved
to be affective and used in adults. In children the
first two are only used in our country and there is
no evidence of superiority of any particular
fluroquinolones. Norfloxacin and nalidixic acid
do not achieve adequate blood concentration after
oral administration and should not be used.
Fluoroquinolones have the advantage of lower
rates of stool carriage than the first line drugs8.
However, fluoroquinolones are not approved by
Drug Controller General of India to be used under
18 years of age unless the child is resistant to all
other recommended antibiotics and is suffering
from life threatening infection.
Of the third generation cephalosporins oral
cefixime has been widely used in children9,10,11.
Amongst the third generation cepha-losporins in
injectable form ceftriaxone, cefotaxime and
cefoperazone are used of which ceftriaxone is most
convenient.
Fluoroquinolones like ofloxacin or
ciprofloxacin are used in a dose of 15mg per kg
of body weight per day to a maximum of 20mg/
kg/day.
Of the oral third generation cephalosporins,
oral cefixime is used in a dose of 15-20 mg per kg
per day in two divided doses. Parenteral third
generation cephalosprins include ceftriaxone 50-
75mg per kg per day in one or two doses;
cefotaxime40 80 mg per kg per day in two or
three doses and cefoperazone 50-100 mg per kg
per day in two doses.
Azithromycin is used in a dose of 10mg per
kg given once daily for 14 days.
Fluoroquinolones are the most effective drug
for treatment of typhoid fever. For nalidixic acid
sensitive S. typhi (NASST) 7 days course are
highly effective. Though shorter courses are
advocated but they should be reserved for
containment of epidemics. For nalidixic acid
resistant S. typhi (NARST) 10-14 days course For complicated typhoid the choice of drug
with maximal permitted dosage is recommended. is parenteral third generation cephalosporin eg,
Courses shorter than seven days are not ceftriaxone. In sever life threatening infection
satisfactory. fluoroquinolones may be used as a last resort.
Aztreonam and imepenem may also be used.
In case of uncomplicated typhoid oral third
generation cephalosporine eg, cefixime should be Combination therapy though practiced all
the drug of choice as emperic therapy. If by over needs substantiation with adequate data from
5 days there is no clinical improvement and the studies.
culture report is inconclusive add a second line
Below (Tables 1, 2) are given various
drug eg, azithromycine or any other drug effective
antibiotics in the management of both complicated
against S typhi depanding up on the sensitivity
and uncomplicated typhoid with different
pattern of the area.
sensitivity patterns.
Table 1. Treatment of Uncomplicated Typhoid
SUSCEPTIBILITY FIRST LINE ORAL DRUG SECOND LINE ORAL DRUG
Antibiotic Daily Dose Days Antibiotic Daily Dose Days
(mg/kg) (mg/kg)

Fully Sensitive 3rd Gen. 15-20 14 Chloramphenicol 50- 75 14-21

Cephalosporin Amoxicillin 75-100 14
e.g.Cefixime TMP-SMX 8 TMP
40 SMX 14
Multidrug Resistant 3rd Gen. 15-20 14 Azithromycin 10-20 14
Cephalosporine
e.g.Cefixime
Table 2. Treatment of severe Typhoid

SUSCEPTIBILITY FIRST LINE PARENTERAL SECOND LINE PARENTERAL

DRUG DRUG
Antibiotic Daily Dose Days Antibiotic Daily Dose Days
(mg/kg) (mg/kg)
Fully Sensitive Ceftriaxone 50-75 14 Chloramphenicol 100 14-21
or Ampicillin 100 14
Cefotoxime TMP-SMX 8 TMP
40 SMX 14
Multidrug Resistant Ceftriaxone 50-75 14 Aztreonam 50-100 14
or
Cefotoxime
Imepenem are potential second line drug and fluoroquinolones can be used in life threating infection
resistant to other recommended antibiotics.
71
The Antibiotic Therapy of Typhoid Fever
Multidrug resistamt typhoid cases, resistant
to 1st line drugs, namely chloramohenicol,
co-trimoxazole and ampicillin are reported
since 1990. They need to be treated with 2nd
line drugs like 3rd generation cephalospotins.
Most of the typhoid cases can be managed
at home with oral antibiotics and good nursing
care.
For severe cases with persistent vomiting,
inability to take oral feeds, severe diarrhea,
abdominal distensions parenteral antibiotic,
will be needed preferably in a hospital.
Though some strain have shown reemergence
of sensitivity to first line drugs still it is too
early for their recommendation in emperic
therapy.
The nalidixic acid resistant S. typhi (NARST)
is a marker of reduced susceptibility to
fluoroquinolones.
Third generation cephalosporin, both oral and
injectables are recommended first line
treatment. Of the oral 3rd generation
cephalosporins, cefixime and cefpodoxime
proxelil are used commonly and of parenteral
preparation ceflriaxone, cefotaxime, and
cefoperazone are used, of which ceftriaxone
is most convenient. Oral 3rd generation
cephalosporin is to be used in higher dose in
typhoid fever.
Azithromycin is used as an alternative agent
in treatment of uncomplicated typhoid fever.
Aztreonam and Imepenem are potential
second line drugs
For life threatening infection resistant to all
other recommended antiobiotics
fluoquinolones may be used.
72
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Mukesh kumar singh (292)
Muralinath S (262)
Nammalwar BR (262)
Natarajan B. (85,176)
Naveen Thacker (221)
Nilesh Jain (325)
Niranjan shendurnikar (292)
Nitin K Shah (197)
Pangrikar AG (178)
Sujatha L (319)
Porkodi (246, 316)
Pradip Vincent (256)
Pramod Sharma (99)
Purushothaman (319)
Radha Rajagopalan (252)
Raghupathy P. (123)
Rajal Prajapati (301)
Rajeshwari (252)
Raju C Shah (190)
Ramakrishnan TV (43)
Ramalingam A (85,176)
Ramesh S (256)
73
Rana K S (181)
Randeep Singh (99)
Rashmi Kapoor (27)
Raveendranath V (319)
Ravisekar CV (322)
Renu P Kurup (61)
Sandeep Aggarwal (309)
Santosh T Soans (35)
Saradambal N (319)
Sathyaprakash.M (92)
Shalini Jain (325)
Sheila Bhave (232)
Shivbalan So (79,160)
Shrishu R Kamath (51,252)
Shyam Kukreja (309)
Siraj N Huda (250)
Sood A (181)
Sridharan S (256)
Sri Venkateswaran K (319)
Subba Rao SD (16)
Subramanyam L (160)
Suchitra Ranjit (51,252)
Susheela Rajendran (319)
Sunit Singhi (6)
Tapan Kumar Ghosh (239)
Vasanthamallika TK (322)
Venkatesan MD (246, 316)
Venkataraman P (322)
Vijayakumar M (262)
Vijayalakshmi G (85,176,246, 315)
Vijayasekaran D. (160)
Vipin M. Vashishtha (220)
Vyas BR (325)
 SUBJECT INDEX

Abdominal epilepsy (178) Immunization : Special situations (309)

Acquired velopalatopharyngeal palsy (181) Klippel Trenaunay Syndrome (87)
Acute asthma (116) Mckusick Kaufman Syndrome (256)
Acute poisoning (146) Medico legal issues (155)
Acute stridor (27) Milroys Disease (250)
Additional vaccines (292) Mixed Connective Tissue Disease (92)
Adverse events following Immunization (208) Necrotizing fascitis (252)
Approach : Respiratory distress (110) Newer Vaccines (197,281)
Avian Influenza (Bird flu) (95) Nutrition (167)
Cardio Pulmonary Resuscitation (16) Passive immune prophylaxis (301)
Cardiogenic shock (61) Pediatric Emergency Room (6)
Cavernous sinus thrombosis (322) Pediatric Pulmonary Function Test (160)
Chikungunya (266) Picture Quiz (99,265,318)
Cholelithiasis (79) Polio eradication (220)
Critical care Transport (74) Rabies Vaccines (239)
Cutis verticis gyrata (319) Radiology :
Dengue hemorrhagic fever, shock Acute abdomen (85)
syndromes (51) Hepatomegaly and hepatic masses (176,246)
Endocrine emergencies (123) Central Nervous System (315)
Enteric Fever - Guidelines Management (330) Scorpion sting (134)
EPI/IAP Immunization Schedule (190) Snake bite (139)
Hepatitis vaccines Current concepts (232) Status epilepticus (35)
Hereditary sensory autonomic neuropathy (325) Trauma: Resuscitation (43)
Immunization practices (272) Ultrasound (262)

74
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 Indian Journal of
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77
 Indian Academy
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