Indian Journal for

the Practising Doctor

Executive Editor Editor-in-Chief

Bashir Gaash, MD, PhD, DCH Muzaffar Ahmad, MD, FACP, FIMSA

Medical Quiz: Diagnostic dilemma

Childhood Infections: Fever in childhood
Immunization: Cold chain maintenance
Student’s page: B cell development
Endemic Disease: Viral hepatitis
Surgical emergency: Reduction of rectal prolapse
Global threat: Influenza
Drug update: Cefixime in UTI
Pregnancy: Rh incompatibility
Rural surgery: Operating room etiquette
Heart Disease: Rheumatic Fever
Parent/patient education: Febrile child, asthma, osteoarthritis, cervical cancer
Haematology : Diagnosis of anaemia
Foods we take: Tea
A leaf from the history of Medicine: Joseph Lister
Hazardous waste: Healthcare waste – A Consideration
Special supplement: Drug Use in Hepatic Impairment

Vol I No. 4 (January 2005)

Published from: REGIONAL INSTITUTE OF HEALTH & FAMILY WELFARE, KASHMIR

 Indian J for Practising Doctor, Vol: 4

INDIAN JOURNAL OF
THE PRACTISING DOCTOR

(A bimonthly journal for doctors working in

peripheries)

Editor-in-Chief Executive Editor

Dr Muzaffar Ahmad, MD, FACP, FIMSA Dr Bashir Gaash, MD, PhD, DCH.
Director Health Services, Kashmir. Principal, Regional Institute of
Health & Family Welfare, Kashmir.

Editorial Assistance:
Dr Rehana Kausar, MD, Dipl H&FW
Dr Manzoor Kadri, MBBS, PG Dipl HIV/AIDS
Dr Rohini Bhan, MBBS, PG Dipl RCH
Dr Farooq Fazilli, MD
Dr Rubina Shaheen, MD
Dr Shabnam Bashir, MBBS

Managing Editor:
Neelam Bashir, BCA, G.Tech

Editorial correspondence: P. O. Box: 673 (GPO), Srinagar, Kashmir

[Phones: 951954-255042; Email: gaashb-10@yahoo.co.in]

0194-2422987

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 Indian J for Practising Doctor, Vol: 4

Contents:

• Medical Quiz IVI

• Diagnosis of Anaemia: role of CBC & PBF, 7 (Neha Dahiya)
• Torch Test – Need for Use as a Screening Test, 13 (Naveen Thapliyal, Getta Jain, &
Godavari Pandey)
• Torch Test: Test & Inference, 1??8 (S M Kadri)
• Patient education: Anaemia, 12; Influenza 25; Asthma, 62; Cervical Cancer 83;
Osteoarthritis 85.
• Influenza – A Reminder, 18 (Bashir Gaash)
• Cold Chain Maintenance, 27 (Rubina Shaheen)
• Operating Room Etiquette, 34 (W.H.O.)
• Pregnancy: Rh Incompatibility, 39 (Rehana Kausar)
• Fever in Children, 43 (Farooq Fazilli)
• Rheumatic Fever, 52 (Shabnam Bashir)
• Foods We Take: Tea (Neelam Bashir)
• Viral Hepatitis, 78. (Rohini Bhan & Arvind Bhan)
• Immunity: B-Lymphocyte Development, 79, (Gazala Shakoor)
• Role of Cefixime in Paedriatic UTI, ?? (Srividya Rao)
• A Leaf From the History Of Medicine: Joseph Lister, 90 (RIHFW)
• Waste From Health care activities, 91 (Muzaffar Ahmad)
• Reduction of Rectal Prolapse, 95 (Shabnam Bashir)
• Special Supplement: Drug use in Hepatic Impairment, 97 (WHO guidelines)

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 Indian J for Practising Doctor, Vol: 4

Editorial

The first two issues of the IJPD met an expectedly warm response. The doctors practicing
in the field as well as medical students, both, have enthusiastically welcomed the issue. This has
encouraged all those involved in the publication of the journal.
The journal, as promised, carries articles of direct relevance to the practising doctor.
Anaemia is a common nutritional disorder particularly rampant in the developing world.
Classification & typing is generally based on the results of complete blood count and peripheral
blood smear. These parameters are easy to do and are within the reach of practitioners even in
the remote areas of the country. One article has been put to highlight the role of CBC 7 PBF in
diagnosis of anemia.
Pregnancy is a special occasion, where the mother’s condition directly affects the child.
The so-called TORCH infections are generally mild in the mother but can prove disastrous to the
ofetus & the neonate. Accordingly the fetus may abort or the neonate may get congenital
anomalies, rashes and CNS calcifications. Rh incompatibility between the mother and her foetus
is an important cause of mortality among the neonate, and at the same time is so easy to prevent.
One article on this not so infrequent condition has also been included. Als.
Cold chain maintenance is an area which is so crucial to the potency of vaccines yet is so
easily overlooked. We have discussed this important aspect of immunization is detail.
Influenza is a tricky infectio: it is one of the oldest scourges of mankind which runs the
danger of attaining pandemic proportions every few years. Why despite all efforts to curb its
epidemicity influenza virus still continues to baffle mankind has been fully dealt with. Viral
hepatitis is a common infection across the world, and new viruses are emerging with passage of
time. Some recent information on this hepatotrophic virus has been shared here.
Urinary tract infection in children is a common infection. Infants and younger children
require aggressive therapy because they are prone to get pyelonephritis with renal scarring.
Traditionally, patients of this tender age have been treated intravenously, but cefexime – a 3rd
generation oral cephalosporin - has made treatment very convenient and cheaper. The role of
cefexime in the treatment of urinary tract infection is discussed by our collague from Andhra.
Fever in children is one of the commonest symptoms, and may sometimes try the wits of any
doctor. Management of paedriatic fever is dealt in with reference to use of antipyretics.
Foods we use are not only nutritionally important sometimes have benefits which only
recently have been explored and documented. Our favourite beverage, tea, has been found to
contain antioxidats and ingredients which could prevent atherosclerosis, heart disease and even
cancers.
In a series of essays on establishing and maintaining surgical facilities in remote areas,
we are carrying an article on surgery room etiquette. A surgical emergency, reduction of rectal
prolapse also has been included.
A special supplement on drug use in hepatic impairment has been given as the annexure.

January 2005.

(Executive Editor)

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 Indian J for Practising Doctor, Vol: 4

Contributors:

Neha Dahiya, DNB (Path), is Consultant Pathologist, & Director, K G Lab Services, Coimbatore,
Tamil Nadu.

Srividya Rao, MD, DCH, is a paedriatician from Guntur (Andhra Pradesh), currently working with
the Ministry of Health, Islamic Repu
blic of Iran. She is stationed at Turbat-e- Hyderiya, Khorasan.

Naveen Thapliyal, MD. is Assistant Professor, Pathology, STMFH & Medical College, Haldwani,
Uttaranchal.

Geeta Jain, MD, is Assistant Professor, & Godavari Pandey, MD, Resident, Deptt of Obstetrics &
Gynaecology, STMF & Medical College, Haldwani, Uttaranchal.

Rehana Kausar, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate
from SK Institute of Medical Sciences, Soura, Srinagar. Before joining RIHFW she has had a stint
in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Manzoor A Kadri: Trainer at the Regional Institute of Health, Kashmir, was a teacher at the
Government Medical College, Srinagar (Department of Microbiology) before joining us.

Farooq Fazilli, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate
from the SK Institute of Medical Scinces, Soura, Srinagar. Before joining the RIHFW, the doctor
worked in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Rubina Shaheen, MD: Faculty member, Regional Institute of Health, Kashmir, is a postgraduate
in Microbiology. She taught at the SKIMS before her new appointment.

Gazala Shakoor, MD, is a private practitioner working in Srinagar.

Rohini Bhan is a trainer at the Regional Institute of Health, Kashmir.

Shabnam Bashir is a medical graduate from the Government Medical College, Srinagar.

Bashir Gaash; an International Fellow in Tropical Diseases, is a postgraduate in Social &

Preventive Medicine and Health Administration, and currently is the Principal, Regional Institute of
Health, Kashmir.

Muzaffar Ahmad; MD in general Medicine, has a Fellowship in Emergency Medicine from USA,
and currently is the Director Health Services, Kashmir.

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 Indian J for Practising Doctor, Vol: 4

Diagnostic dilemmas
Medical Quiz: III
A 10-year old boy presented with a history of lethargy and abnormal behaviour at school. He is
taking iron tablets for iron-deficiency anaemia, which was diagnosed by his doctor. The boy is the only
child in the family; they live in a 3-bedroomed old house. He is withdrawn and does not want to talk. He has
been described as a ‘violent child’ by his mother on several occasions in the last 3 months, and has been
expelled from a school club because of his behaviour. His best friends had left him because of his
argumentative nature. Sometimes he complains of headache, with fuzzy vision. His eyes were checked twice
by optometrist for refraction errors without detection of any abnormalities. The child has once threatened to
jump out from the window of his room where he passes most of his time. The child has started losing
weight. He wakes up at nights shouting and complaining of headache, which requires analgesics. The boy
looks withdrawn and makes no eye contact. He hates the school and does not want to go there.
All aspects of the systemic examination are normal. All cranial nerves are intact but he does not
like to have a light shone into his eyes. A fundus examination shows papilloedema but no other abnormality.
His BP is 120/75 mm, heart rate 70, and respiratory rate 20. X-ray abdomen suggested the presence of
ureteral stones and a calcified lesion in the bladder. His lab findings showed:

Hb 8.7 g/dl MCV 45fl

MCHC 25g/dl
Platelets 3.57 laks
Blood sugar 4.5 mmol/l
Urine shows Proteinuria & phosphaturia

After admission, he had a cranial MRI, which turned to be normal. After mid-night he started to
have generalized tonic-clonic seizures for 5 minutes, which stopped after rectal administration of diazepam.
There were no more seizures and an EEG was carried out which showed no epileptiform activity. His
behaviour fluctuated and a decision was made to treat him as having encephalitis.
1) At this juncture which single test should be carried out?
Abdominal ultrasound Barium swallow
Urine toxicology IVP
Cystoscopy Lumbar puncture
Ferritin level Lead level
Ammonia level Mantoux test

2) Which other two investigations should be carried out to reach at the diagnosis?
Blood film
Urinary copper level
Long-bone x-ray
Abdominal CT
CSF for HSB-PCR
Repeat EEG
3) What is the diagnosis?
The patient was treated and after 6 weeks another blood test was taken which showed that
he still had the same problem, even though there had been some improvement in his
behaviour and he had started to attend the school in the last 2 weeks.

4) What should the management plan be?

ƒ Admit to hospital until he finishes the course of treatment
ƒ Refer to the psychiatrist
ƒ Inform the social services/child protection team/police?
ƒ Start treatment again with strict supervision by the community care team.

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 Indian J for Practising Doctor, Vol: 4

………………………….. (Answers on pg 18)

Diagnosis of Anaemia: There are many types of anemia.

Primarily they can be classified into
Role of CBC & Peripheral 1) Anemia because of blood loss
Blood Smear 2) Anemia because of impaired red cell
production
3) Anemia due to increased destruction
of RBC (haemolytic anaemia)
Neha Dahiya*
_________________________________ Various steps for diagnosing
anaemia are:
Anaemia is less than normal 1) Clinical signs / symptoms
2) Physical Examination
number of red blood cells, measured as a
3) Laboratory investigations
decrease in the haemoglobin content of
the red blood cells. Anaemia leads to a
decrease in the oxygen carrying capacity
of blood.

Fig 1: CBC - Parameters considered while establishing & typifying anaemia:

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 Indian J for Practising Doctor, Vol: 4

Here focus is on the investigations useful - In some instances of aplastic

in diagnosing and classifying anaemia.
The most basic of all the tests asked for
is “CBC” – a Complete Blood Count,
which gives information regarding
presence or absence of anaemia and also
helps to classify the type of anaemia to
some extent. The CBC has to be seen in
conjunction with a peripheral blood
smear examination. The automated CBC
encompasses a number of parameters,
which throw light on the aetiology of
anaemia. A CBC on a haematology cell
counter with 5 part differential gives at
least 24 parameters as seen in Fig 1.
anemia
- Myxoedema
In all cases the red cell precursors in the
marrow are normal in morphology.
2) Moderate increase in the MCV:
[MCV >105 and <110 fl]
- Liver disease
3) Marked increase in the MCV:
[MCV > 110 fl]
- Megaloblastic due to the lack of
vitamin B-12 or folic acid.

Table 1 The red cell distribution width - “RDW”-

RBC Total red blood cell count assesses the variation in volume of red
HGB Haemoglobin blood cells. This is equivalent to the
microscopic assessment of anisocytosis –
HCT / PCV Haematocrit / Packed cell
volume
variation in cell size
Red Blood Cell Indices:
Increased RDW indicates the presence of
MCV Mean corpuscular volume more than one population of red blood
MCH Mean corpuscular cells.
haemoglobin
MCHC Mean corpuscular The RDW expressed as CV
haemoglobin conc (coefficient of variation) has been found
RDW Red cell distribution width
to be of some value in the distinction
The red blood cell indices help in morphological between:
classification of anemia and aid in further
1) Iron deficiency anemia (RDW
investigational studies.
usually increased) and
The macrocytic anaemias can be thalassaemia trait (RDW usually
further divided according to MCV: normal).
2) Megaloblastic anemia (RDW
1) Slight increase in MCV: often increased) and other causes
[MCV >100 but <105 fl] of macrocytosis (RDW usually
- Due to the presence of normal)
reticulocytes

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 Indian J for Practising Doctor, Vol: 4

Table 2: MORPHOLOGICAL CLASSIFICATION OF ANAEMIA

ANAEMIA CRITERIA DISEASE TYPE

CLASSIFICATION
Normocytic normochromic MCV: 76 to 98 fl ƒ Recent Bleeding
anaemia MCHC: 32 – 36% ƒ Haemolysis
ƒ Marrow
On Blood smear: replacememt
Normocytosis, Normochromia, Slight ƒ Marrow
Anisocytosis and Poikilocytosis (ie Depression
variation in size and shape of RBC
respectively)

Macrocytic anaemia With MCV > 98 fl Pernicious anemia

"Megaloblastic" Marrow MCHC > 36%
On Blood smear:
Macrocytosis, Anisocytosis,
Poikilocytosis (Teardrop)

Macrocytic Without MCV > 98 fl Liver Disease

"Megaloblastic" Marrow MCHC > 32 - 36%
On Blood smear:
Macrocytosis, Target Cells

MCV: < 76 fl ƒ Iron deficiency

MCHC: 32 – 36% if sub-classified as anemia
simple
MCHC < 30%, if sub-classified as ƒ Repeated
Microcytic Hypochromic pregnancy
"Hypochromic"
Anaemia
On Blood Smear: ƒ Thalassemia
Microcytosis, Hypochromia,
ƒ Chronic Blood
Anisocytosis, Poikilocytosis
loss
ƒ Vit. B 6
deficiency

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Indian J for Practising Doctor, Vol: 4

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 Indian J for Practising Doctor; Vol I; No. 4

Increased RDW indicates presence of Whenever a patient presents with

more than one population of red blood
cells.
The RDW expressed as CV (coefficient
of variation) has been found to be of
some value in the distinction between:
1) Iron deficiency anemia (RDW usually
increased) and thalassaemia trait (RDW
usually normal).
2) Megaloblastic anemia (RDW often
increased) and other causes of
macrocytosis (RDW usually normal)
CBC provides all this
information. On peripheral blood smear
one can confirm the same findings eg
one can see the presence of microcytes
(small RBCs) / macrocytes (large RBCs)
/ schistocytes (fragmented RBC).
Thus, CBC and PBF
examination have a decisive role in
diagnosis and classification of anaemia.
Another investigation, which is of
importance, is the “Reticulocyte Count”.
Reticulocyte count reflects
erythropoietic activity of the bone
marrow and corresponds to the finding of
polychromasia on a blood film. The
normal range is 0.5 to 1.5% of the red
cell population studied. Disease states
with increased Reticulocyte counts are:
1. Hemolytic Anaemias
2. After acute hemorrhage
3. Pernicious Anaemia or iron
deficiency anaemia after treatment
complaints of fatigue, weakness, mild
dyspnoea on exertion, simple
haemoglobin estimation is done and if
found to be decreased the patient is
labelled as having anaemia. It is always
advisable to do a CBC along with a
peripheral smear, and sometimes a bone
marrow examination.
It must be remembered that
anaemia could be the result of a benign
problem as deficiency of dietary iron or
could be a feature of an underlying
serious disease.We illustrate our point
with two examples:
A 25 year female presented with
easy fatigability, and low grade fever off
and on. Haemoglobin was found to be
8.5 gm/dl and she was labelled as
having anaemia, and started on
haematinics. This continued for two
months without any significant
improvement. Finally she was referred
to KG Hospital (Dept of Medicine),
where the consultant asked for a CBC
and peripheral smear. Her Hb was low
with normal MCV indicating normocytic
anaemia. Her total WBC count was
15,000/μl and platelets were mildly
decreased to 98,000/μl. The peripheral
blood smear revealed occasional blasts
suggestive of leukaemia and the bone
marrow confirmed diagnosis of acute
myeloid leukaemia. Her anemaia was due
to marrow replacement by leukemic blasts.

Disease states with decreased In another case, a 60 year old

reticulocyte counts are: male was diagnosed to have anaemia
and tuberculous parotitis and was on
1. Aplastic Anaemia put on ATT , but there was no response
2. Iron Deficiency Anaemia before to the treatment. Patient developed
treatment swelling of legs with reduced appetite,
3. Pernicious anaemia before treatment nausea and vomiting and was found to
have renal failure. At this stage, the
patient was referred to the neprology

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 Indian J for Practising Doctor; Vol I; No. 4

department of the hospital. The only
positive findings were Hb 7.7gms%,
urea and creatinine were 86 mg and 3.2
mg respectively and the ESR was
120mm/hr. Peripheral smear was
showing a normocytic normochromic
anaemia. No cause for renal failure
could be identified. Hence a bone
marrow was done. This revealed
multiple myeloma. A renal biopsy was
done which showed interstitial infiltrate
of myeloma cells in the kidney. Again the
anemia was due to marrow replacement by
myeloma.
These two cases amply illustrate
the fact that a low Hb does indicate
anaemia, but for a final diagnosis as to
the underlying cause of anemia a panel
of investigations is needed.
The protocol followed in K. G
Hospital, clinics & laboratory, is – CBC,
peripheral smear, reticulocyte count and
bone marrow aspiration. It helps to arrive
at the correct diagnosis as early as
possible.

There is a tendency among the practitioners in peripheral areas to be content with

Hb estimation for diagnosis of anaemia and to put the patient on iron. Anaemia is a
disease of multiple causation and its scientific management requires an exact
classification which can be done only after a complete study of blood.
Fortunately, simple and economical tests are available for diagnosis, classification
and typing of anemia. Hb estimation merely detects the presence and severity of
anaemia. However, further tests are required to classify anaemia for appropriate
management. In any case of anaemia, therefore, it is not wise to begin treatment without
a CBC & PBF.
Nutritional anaemias may be from the deficiency a mononutrient (as iron) or a
combination of deficiencies ie iron, other minerals, B12 & folic acid. In the developing
world, at least two of them – iron & folic acid – are generally deficient in diet.
Pregnancy anaemia is multifactorial, including hypervolemia, need for the feotus,
& iron deficiency. It needs to be seen in that context.
In case of children, both preschool age & school age, presence of anaemia may be
due to nutritional deficiency generally exacerbated by roundworm or hookworm
infestation. Unless the child is rid of the underlying infections, he will not be benefited by
nutritional supplementation and therapeutic iron.
In smaller children, especially with pica, chronic lead poisoning may mimic iron-
deficiency anaemia which is refractory to treatment.
Very important causes of anaemia as chronic blood loss should always be borne
in mind: loss of blood may be gross and evident as in excessive menstrual loss or
incipient and overlooked as microscopic haematuria or blood in stools.
In older patient, possibility of a malignancy should never be forgotten. Anaemia
may also present as a prominent feature of connective tissue disorder or hypothyroidism.

 
 

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 Indian J for Practising Doctor; Vol I; No. 4

 
Patient Education  
Anaemia

Anaemia (Greek, “bloodlessness”) is a blood condition involving an abnormal

reduction in the number of red blood cells (erythrocytes) or in their haemoglobin content.
Red blood cells are the means by which oxygen is carried to the various parts of the body.
People who are anaemic develop symptoms caused by the inadequate delivery of oxygen
to their body tissues. The condition is far more common in women and children than in
men. Pregnant mothers and preschool children are especially prone to get anaemia. There
are three primary causes: (1) reduced production of red blood cells, which may result from
deficiency in nutrients or hormones, or from disease or other conditions; (2) excessive
destruction of red blood cells, often a hereditary problem; and (3) excessive blood loss,
such as that caused by gastrointestinal ulcers, heavy menstrual periods, or overdose of
aspirin. The most usual symptoms of anaemia are pallor, shortness of breath, low vitality,
dizziness, and digestive disorders.

The most common type of anaemia is iron-deficiency anaemia, which occurs when
the body’s need for iron increases, as during certain periods of childhood (during the first
5 years of life; again during adolescence) and in pregnancy, or when there is insufficient
iron in the diet. Pernicious anaemia, a chronic ailment that mostly affects people over 40,
is a result of vitamin B12 deficiency. Rather than a diet deficient in the vitamin, this is
usually caused by intestinal malabsorption, resulting in decreased B12 uptake. Sickle-cell
anaemia is the result of a hereditary defect in the synthesis of haemoglobin. Aplastic
anaemia occurs when there is severe reduction in red blood corpuscles, and when the bone
marrow is unable to regenerate them. Ionizing radiation is one possible cause.

Past treatment of the condition has included removal of the spleen, repeated
transfusions of blood, and a diet featuring beef or calf’s liver. Transfusions are still used in
cases of acute blood loss; iron supplements for iron-deficiency anaemia and injections of
vitamin B12 for pernicious anaemia are often effective. Synthetically manufactured
erythropoietin (normally produced by the human kidney) is now used to stimulate the
production and growth of red blood cells. Other therapy focuses on curing the underlying
causes of the nutritional or hormonal deficiency. There may be deficiency of folic acid
(which is derived from green leafy vegetables) which can cause anaemia which can be
diagnodsed from examination of blood and blood film. Blood transfusions and,
increasingly, bone marrow transplants, are necessary forms of treatment for aplastic
anaemia patients.

Balanced diet containing the required amounts of iron, folic acid and B-12
should be taken by the vulnerable population to prevent development of anaemia.

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 Indian J for Practising Doctor; Vol I; No. 4
TORCH TEST: NEED FOR
USE AS SCREENING TEST
Naveen Thapliyal*, Geeta Jain**,
Godavari Pandey***
_______________________________
Definition
The ‘TORCH’ test is a group of
antibody titre tests, which measures the
presence of antibodies against a specific
group of infectious diseases and their
level of concentration in the blood.
TORCH, an acronym for a special group
of infections, may be acquired by a
woman during pregnancy with disastrous
consequences for the infant. All are
grouped together because they can cause
a cluster of symptomatic birth defects in
newborns, collectively called the
TORCH syndrome.
"TORCH" group of infections includes
1. Toxoplasma infection, also called
toxoplasmosis.
2. Other infections, such as hepatitis B,
syphilis, and varicella-herpes zoster.
3. Rubella, the virus that causes German measles
4. Cytomegalovirus, or CMV, and.
5. Herpes simplex virus, the cause of genital
herpes
TORCH infections can affect any
human; children, men, and non-pregnant
women may also catch these infections.
However, their importance lies in the fact
that they can be they can be transmitted
to the fetus while it is in the womb.
When a mother is exposed during the
first 5 months of pregnancy, serious fetal
complications may occur. (Table)
_________________________________
* Assistant Professor, Pathology, ** Assistant
Professor, Obstetric & Gynaecology, *** Senior
Resident, Obstetric & Gynaecology, Dr.S.T.M. F.H.
& Medical College, Haldwani (UTTARANCHAL)
Table: Complications of TORCH
Infections During Pregnancy
_________________________________
¾ Miscarriage .
¾ Small-for-gestational-age, or SGA.
¾ Congenital heart disease (heart defects
the child is born with)
¾ Cataract (clouding of the lens of the eye),
blindness, or significant visual
impairment.
¾ Hearing impairment, including
deafness.
¾ Microcephaly (Small head size).
¾ Mental retardation or other learning,
behavioral, or emotional problems.
¾ Low blood counts (anemia).
¾ Liver or spleen enlargement.
¾ Pneumonia.
¾ Skin rash - usually reddish-purple or
brown.
¾ Involvement of the central nervous
system (encephalitis, calcium deposits in
the brain tissue, and seizures).
¾ Jaundice.
¾ In addition to these symptoms, each of
the TORCH infections has its own
characteristic differentiating symptom
cluster in newborns.
_______________________________________
Brief Description:
Toxoplasmosis:
Toxoplasmosis is caused by
Toxoplasma gondii, a parasite that the
mother can acquire from handling
infected cats, drinking un-pasteurized
milk, or eating contaminated meat. The
infection is carried transplacentally, and
may cause infection of the eyes or central
nervous system. The organism can
invade brain or muscle tissue and form
tissue cysts. Contracted early in
pregnancy, toxoplasmosis is more likely
to cause a miscarriage or serious birth
defects However, the later in pregnancy
the mother is infected, the higher the
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 Indian J for Practising Doctor; Vol I; No. 4
probability that the fetus will be infected.
The incidence of toxoplasmosis in
newborns is 1 in 1,000 live births.
Syphilis
Syphilis is caused by a spirochete
(spiral- or coil-shaped bacterium),
Treponema pallidum. It is transmitted in
the adult population by sexual
intercourse. About 2-5% of children born
to mothers diagnosed with syphilis will
have the disease at birth. Syphilis was
added to the TORCH panel because of a
rapid increase in reported cases since
1990. Syphilis can cause early delivery,
miscarriage, or stillbirth. The mortality
rate in infants infected with syphilis is
about 54%. With widely available
antibiotic treatment, Syphilis is now
taking a back seat among the sexually-
transmitted infections.
Rubella :
Rubella is a virus that has a
seasonal pattern, with epidemics most
likely in the spring. Between 0.1-2% of
newborns will be infected with rubella.
Birth defects are most likely (85%) in
infants infected during the first eight
weeks of pregnancy. Infants born with
rubella may already show signs of heart
disease, retarded growth, hearing loss,
blood disorders, vision problems, or
pneumonia. They may also develop
problems later in childhood, including
autism, hearing loss, brain syndromes,
immune system disorders, or thyroid
disease.
Cytomegalovirus (CMV):
Cytomegalovirus belongs to the
herpesvirus group of viruses. It can be
transmitted through body secretions, as
well as by sexual contact; some
newborns acquire CMV through the
mother's breast milk. In adults, it
produces symptoms resembling those of
infectious mononucleosis. About 1-2.2%
of newborns are infected with CMV. Of
this group, 10% will have measurable
symptoms. The mortality rate for these
symptomatic newborns is 20-30%.
Surviving infants with CMV may suffer
from hearing problems (15%) or mental
retardation (30%). Newborns that acquire
CMV during the birth process or shortly
after birth may develop pneumonia,
hepatitis, or various blood disorders.
Herpes simplex virus (HSV):
Herpesvirus infections are among
the most common viral infections in
man. They are spread by oral, as well as
genital, contact. Estimatedly, between 1
in 1,000 and 1 in 5,000 infants are born
with HSV infections. About 80% of
these infections are acquired during the
birth process itself; the virus enters the
infant through its eyes, skin, mouth, and
upper respiratory tract. Of the infants
born with HSV infection, about 20% will
have localized infections of the eyes,
mouth, or skin and about 50% will
develop disease spread throughout the
body (disseminated) within 9-11 days
after birth. Disseminated herpes
infections attack the liver and adrenal
glands, as well as other body organs.
Without treatment, the mortality rate is
80%. Even with antiviral medication, the
mortality rate is still 15-20%, with 40-
55% of the survivors having long-term
damage to the central nervous system. It
is critical for the doctor to diagnose HSV
infection in the newborn as soon as
possible, for effective treatment.
Who is a candidate for the test?
Any pregnant woman who has
bad obestetric history or has been
exposed to the above infections is a
candidate for screening.
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 Indian J for Practising Doctor; Vol I; No. 4
How is the test performed?
A blood test measuring antibody-
titers is used to detect antibodies to any
the suspected TORCH organism. An
antibody is a special protein made by the
immune system that helps fight
infections. The body makes specific
antibodies in response to specific
infections. These antibodies are made in
large amounts when an infection occurs.
When the initial sample of blood is taken
shortly after exposure, the body may not
have had enough time to start making
antibodies yet. However, a woman can
have antibodies to the infection in her
blood because of an old infection or from
a vaccine. A second sample of blood is
usually taken 10 to 21 days later to see if
blood antibody levels or titers against the
infection are rising. This generally
means that a new infection, instead of an
________________________________________________________________________
• TOxoplasmosis is a parasitic infection
TORCH Test
Manzoor Kadri
________________________________
TORCH is an acronym for a
group of infectious diseases that, while
infecting the pregnant women, may
cause birth defects in their newborns.
The test is a screen for the presence of
any of the antibodies to these infections.
Confirmation of an active infection may
require more specific tests.
The following tests make up
the TORCH panel:
old one, is present. If an old infection is
the cause of antibodies in the blood, the
level of antibodies will not rise with the
second blood sample, as it does with a
new infection. This is important, because
old infections usually do not result in
harm to the fetus, except in the case of
herpes. Only infections that are newly
caught during the early part of
pregnancy usually put the fetus at risk.
What do the test results mean?
A "negative" test means that the
woman does not seem to have a new
TORCH infection. A positive test means
that high or increasing levels of
antibodies were detected. This generally
means that the mother has caught a new
TORCH infection.
that can be passed from mother to baby
through the placenta during pregnancy.
An infection with Toxoplasma gondii can
cause eye and central nervous system
infections as well as brain and muscle
cysts. If acquired during the pregnancy,
it may result in a miscarriage or cause
birth defects, though this depends on
the time during the pregnancy in which
the infection was acquired by the
mother. Toxoplasmosis is acquired by
ingesting the parasite when handling
the excrement of infected cats, drinking
unpasteurized goat’s milk, and, most
commonly, by eating contaminated
meat.
• Rubella is the virus that causes
German measles. If contracted early in
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 Indian J for Practising Doctor; Vol I; No. 4
the pregnancy, the infant may develop
heart disease, retarded growth,
hearing loss, blood disorders, vision
problems, or pneumonia. Problems
that may develop during childhood
include autism, brain problems,
immune disorders, or thyroid disease.
• Cytomegalovirus (CMV) is another
viral infection that the mother may
have acquired. More than half of all
American adults have been infected
with CMV at some point in their life
and, in most cases, it does not cause
severe illness. It may pass to the fetus
during the birth process but can also
infect newborns through breast milk.
Infected infants may have severe
problems, such as hearing loss, mental
retardation, pneumonia, hepatitis, or
blood disorders.
• Herpes simplex virus (HSV) is a
common viral infection. The two most
common infections with HSV are “cold
sores” affecting the lips and genital
herpes. Both of these infections can
recur. HSV is most commonly
acquired through oral or genital
contact. Newborns who contract the
virus usually do so during travel
through the birth canal of a woman
who has a genital HSV infection. The
virus may spread throughout the
newborn’s body, attacking vital
organs. Treatment with specific
antiviral medication should begin as
soon as possible in the infected
newborn. Even if treated, surviving
babies may have permanent damage to
the central nervous system.
TORCH test is performed to
screen for these infectious diseases that
can cause birth defects in newborns and
illness in adults. The test is indicated
when the mother becomes ill while
pregnant or if a baby is born with
congenital abnormalities suspected to be
caused by an infection with one of the
diseases
Blood Collection
The TORCH panel requires a
sample of the infant's blood. Samples
from infants are usually obtained by the
heel-stick procedure when only a small
quantity of blood is needed. The baby's
foot is wrapped in a warm cloth for five
minutes, to make the blood flow more
easily. The foot is then wiped with an
alcohol swab and a lancet is used to stick
the baby's heel on one side. It is
important to avoid the centre of the heel,
in order to prevent an inflammation of
the bone. No special preparation, other
than sterile technique, is required. The
only complications associated with the
test are those resulting from the heel-
stick technique itself (ie scarring,
infection of the bone, cellulitis, small
lumpy calcium deposits) and the
possibility of inaccurate test results.
Results:
Normal. The normal result
denotes normal levels of IgM in the
infant's blood. IgM is a specific class of
antibodies that seeks out virus particles.
In contrast to adults, IgM is the most
common type of immunoglobulin in
newborn children. It is, therefore, the
most useful indicator of the presence of a
TORCH infection.
Abnormal results. The abnormal
(positive) finding would be high levels of
IgM antibody. The test can be refined
further for antibodies specific to given
disease agents. The TORCH screen,
however, can produce both false-positive
and false-negative findings. Doctors can
measure IgM levels in the infant's
cerebrospinal fluid, as well as in the
blood, if they want to confirm the
TORCH results.
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 Indian J for Practising Doctor; Vol I; No. 4
Usual Concerns of the mother
If I have a positive antibody test, does that
mean I am infected?
A positive IgG antibody test is usually a sign
of past-exposure to the TORCH agent and is
not a marker for current active infection.
Detection of IgM antibody is more difficult,
and false negative and false positive results
may occur. Any positive results should be
confirmed with additional specific tests before
the diagnosis is considered valid. If the doctor
suspects that you or your newborn may have
one of these infections, even though the
results were negative, other tests for the
suspected infection should be done.
To make the diagnosis of an
active infection with one of the TORCH
agents, more specific confirmatory tests
may be required. In a baby, cerebrospinal
fluid testing (requiring a lumbar puncture
or “spinal tap”) is often used to confirm
toxoplasmosis, herpes and rubella; urine
may be cultured for cytomegalovirus;
and skin lesions may be scraped and
cultured for herpes simplex virus.
Making the diagnosis of toxoplasmosis
in the pregnant woman or the baby may
require additional blood samples, which
are sent to a reference laboratory that
specializes in such tests.
***************************************
Answers to Medical Quiz: 4
► affected environment is very helpful.
(from page 6)
1) Lead level 2) Blood film; long-bone x-ray 3)
Lead poisoning 4) Start treatment again with
strict supervision by the community care team.
Chronic lead poisoning can occur
after chewing or sucking pain from old
windows or doors. Lead from burning
batteries, lead shots for fishing, and old
water pipes pose a similar risk. Children
from southeast Asia may get lead poisoning
from using surma or kajal – eye make up
prepared from lead. Affected children may
have pica or a compulsive eating disorder.
Children working as papier mache workers
in Kashmir, who have a habit of mending
their brushes with lips, run the risk of getting
lead poisoning as the base of most paints is
lead oxide. Patients are usually anaemic, are
usually diagnosed as having iron-deficiency
anaemia, but fail to respond to iron-therapy.
Shortly, other clinical features are
superimposed on anaemia. They have
obstipation, abdominal pain, headache, and
behavioural problems, along with a
deteriorating school performance.
When poisoning is severe, the child
can have convulsions, irritability, loss of
consciousness, which may lead to coma and
death.
The lead level can be measured; the
blood film shows hypochromic, microcytic
red cells, and basophilic stippling. Gums
may show lead lines. The long-bones show
lead-lines which affect mainly their ends.
Lead flakes which are radiopaque may be
seen on abdominal x-ray.
Lead poisoning is one of the causes
of increased intracranial pressure, and thus
papilloedema is common.
Removal of the child from the
Chelating agents (D-penicillamine in
mild cases; Ethylene-diamine-tetra-acetic
acid or EDTA, in severe cases) are used.
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 Indian J for Practising Doctor; Vol I; No. 4
Influenza: A Reminder
Bashir Gaash
________________________________
Influenza has been known since
antiquity, at least since 437 BC. The two
faintly remembered epidemics of history
could have been the ‘English Sweat’ of
1485 and 1551. Nevertheless, the first
pandemic which brought the deadly virus
to the world stage was the ‘Spanish’ or
‘swine’ influenza of 1918.
Influenza outbreaks occur
frequently in all parts of the world
including the developed ones. In the UK,
for example, increased number of cases
occur each winter with an annual
mortality of 3000-4000.
Influenza, known since 400 BC, is one of
the last great uncontrolled ‘plagues’ of
mankind. It will continue to strike
mankind off and on because of the
inherent survival techniques of the virus
The virus: Influenza virus has 3
different strains, A, B & C, which differ
in their ribonucleo-protein moieties. The
virus produces 11 different proteins - 3
are surface proteins, while internal
proteins are needed for varied functions
including keeping the virus alive and
virulent. The type A virus has a capacity
to undergo consistent genetic changes of
their nucleic acids, resulting in annual
phenotypic modifications and changes in
their surface antigens. Alterations in
antigenic structure help the virus to
dodge the body’s natural and artificially-
induced immune defences. Four of the
internal proteins make up the polymerase
enzyme system (functionally
transcriptase complex) which triggers
replication of virus in the infected host
cells.
The virus consists of a central core
(nucleocapsid) containing internal proteins and
the viral RNA. The major structural protein,
matrix protein (M1), integral to the nucleocapsid
is responsible for virion integrity. Glycoproteins,
which are needed for entering the host cell,
project as ‘spikes’ through the lipid envelope.
Mature virus is spherical, measuring
some 90-120 nm in diameter.
Growth & Replication: The replication
cycle of the virus begins when it attaches
to specific receptors on epithelial cells
lining the respiratory passages. These
specific receptors are the terminal sialic
(neuraminic) acid residues on the
oligosaccharide side-chains of the
susceptible cells. The virus enters the
cell and gets uncoated so that the viral
nucleocapsid (containing RNA and
enzymes) is released in to the host cell
cytoplasm. Once the nucleocapsid
reaches the nucleus, the viral RNA and
enzymes direct the formation of mRNA
for manufacture of progeny RNA. The
RNA matures into nucleocapsid followed
by assembly and thus formation of new
virus which leave the cell and infect
other susceptible cells.
Epidemiologic and clinical behaviour:
despite similar morphology, the 3 strains
show different epidemiologic and
clinical patterns.
Type A is associated with most of
the widespread epidemics and is the only
one to produce occasional pandemics.
Clinically also the infection is severe
with an increased predisposition to
secondary bacterial infections. The major
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 Indian J for Practising Doctor; Vol I; No. 4
2 surface proteins, Haemaglutinin (HA)
and neuraminidase (NA) undergo subtle,
minor changes in structure almost
annually, because of point mutations in
viral RNA genes coding for them. (This
is because of the absence of a proof-
reading mechanism to correct mistakes
arising during replication of viral nucleic
acid). This annual variability of the type
A virus surface protein, the antigenic
drift, is a major reason for their success
to evade human immune system, and
causing frequent outbreaks and
epidemics.
Antigenic drift, which is an
ongoing process, is greater for the HA
antigen, and leads to distinct alterations
in the reactivity of the surface proteins
every 2-3 years. These mutations can be
detected in the laboratory. These
antigenic changes are responsible for the
reduced capacity of pre-existing
antibodies to previously experienced
influenza virus. The failure of
neutralization by existent antibodies
helps in quicker and wider uptake and
dissemination of virus in the body.
Type B generally causes milder
illness, but spectrum is broader, from
common-cold like illness to typical
severe influenza. Type B infection is
commoner and more symptomatic in
children than adults; infection in adults is
milder or asymptomatic. The number of
patients requiring hospitalization is 1/4th
of that with the type A. The mutation rate
is lower than that in type A, therefore
antigenic variability is less.
The type C virus is either
asymptomatic or causes only mild,
common-cold like mild symptoms (‘the
touch of flu’).
Animal Reservoir: Many animals and
birds function as hosts to type A viruses
which bear genetically similar but
antigenetically different versions of
surface haemaglutinin and neuraminidase
antigens. Wild avian species are primary
extra-human reservoirs of type A virus.
When humans are infected with these
novel viruses, a localized outbreak may
herald a global pandemic. This is
because the new surface antigens are not
recognized by the human immune
defence system, thus the virus meets no
resistance to spread at all.
Type A is far more dangerous because of the
antigenic drift, extra-human reservoir,
potential for pandemics, propensity to cause
severe illness, and ability to predispose to
secondary bacterial pneumonia. The lower
mutation rate and lack of mammalian or
avian reservoir for the type B makes it a
lesser clinical and epidemiologic problem.
Infectivity: The incubation period of
type A influenza is 3 days and of type B
virus 4 days. Virus replication in the
respiratory tract in adults peaks 48 hours
after infection. Newly formed ‘progeny’
virions are shed in nasal secretions and
saliva from 1-7 days after infection.
Children start shedding the virus earlier,
ie from the first day, and much longer, ie
upto 13 days after infection. The main
transmitters of influenza are preschoolers
and school-going children.
Antigenic Shift: Emergence, in the type
A virus, of an HA protein that is novel to
the population results in a large epidemic
or pandemic. In the 20th century 5 such
pandemics have occurred. The deadliest
of these, the ‘Spanish (Swine)’ influenza,
lead to 20 million deaths, particularly
among young adults. The last occurred in
1977 with reappearance of the HA
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 Indian J for Practising Doctor; Vol I; No. 4

Influenza elicits strong immune response, yet it continues to occur regularly in the
population. This virus causes epidemics of ‘flu’ annually and pandemics at frequent
intervals. This is because influenza virus is not only a human virus but has a complex
relationship that includes replication in several hosts. Thus influenza A virus infects not
only humans but also pigs, birds, horses, mink, and some aquatic mammals such as seals
and whales.

At least 14 subtypes of haemagglutinin (H) protein are present in viruses that

infect birds; 3 of these can infect human. Similarly there are 9 neuraminidase (N) surface
antigens. Viruses that cause worldwide infections (pandemics) can be classified according
to their H & N types. Each pandemic is characterized by a new combination (from
recombination/reassortment):

The 1918 pandemic was H1N1

The 1957 ‘Asian Flu’ was H2N2
The 1968 ‘Hong Kong Flu’ was H1Ni, and the 1977 flu was, again, H1N1.

These dramatic shifts of H & N serotypes result from the exchange of genome
segments by mammalian and avian influenza viruses. Although it is presumed that
viruses of one species (as birds) are not efficient at infecting another species (humans),
there is evidence of direct infection of human beings by an avian strain (H5N1) in 1997.
Since no man will have immunity against such a novel virus, large epidemics, even,
pandemics can potentially occur. The only consolation is that such alien viruses are
incapable of efficient spread in human beings, and the man proves the dead-end host.
There is no man-to-man transmission in such viruses.

Pigs provide very good hosts to both human and avian viruses – the lining of their
throats contains receptors for both types of viruses. Thus, pigs act as non-selective hosts
for mixed infections of both human and avian types, and thus a good medium for
reassortment of H & N of different species. This gives rise to new viruses which can lead
to reinfection of human population.

Because of the dense human population in southeast Asia, large number of people
come in daily contact with domesticated pigs, ducks, fowl, & geese. There is
epidemiological evidence that the 1957 and 1968 pandemics originated in China, and that
human N & H serotypes are circulating in wild-fowl population. The intermixing of large
numbers of human beings, migratory birds, and domesticated swine & birds provide a
continually expanding opportunity for recombinations and reassortments of different
influenza viruses and thus emergence of newer viruses.

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 Indian J for Practising Doctor; Vol I; No. 4
antigen similar to those of the 1918 and
1933-34 pandemics.
Curiously all these sudden major
changes occurred in China. Most of them
arose from genetic re-assortment of
surface antigens between human and
mammalian/avian strains. Generally, one
sub-type of type A infects only a
particular species, but when cross-
species transmission occurs, genetic re-
assortment takes place between the
transmitted subtype and type A virus in
the recipient host. A new virus subtype is
formed with surface proteins from either
parent subtype. This virus has the
capability to infect the 3rd host, the
human being. The 1957 ‘Asian’
influenza virus obtained 2 genes coding
for its HA & NA surface proteins and
one gene coding for its internal proteins
from an avian subtype. The remaining 5
genes were derived from the pre-existing
strain in circulation since 1933-34
pandemic.
15 different haemagglutinin (HA)
proteins [H1 to H15] and 9 different
neuraminidase (NA) proteins [N1 to N9]
are found in influenza strains infecting
different hosts including man. However,
only 3 of the former (H1, H2, & H3)
hade been encountered in all type A
strains which had caused epidemics
among humans till 1997, when the first
evidence of direct infection of man from
a virus with non-human HA antigen (H5
avian) appeared in Hong Kong. In 1999,
H9 avian got transmitted to humans, who
proved to be ‘dead-end’ hosts.
Since the pandemic of 1977
(Russian flu), 2 type A viruses have been
circulating among humans: H1N1
(Russian) and H3N2 (Hong Kong).
During the last 30 years, though avian
viruses have infected human beings, they
have not been able to lead to any major
outbreaks. This is because these viruses
could establish among human beings and
thus there was no man-to-man
transmission.
Immunity: Infection elicits both
humoral and cellular immune response.
Antibodies are protective whether
systemic (in serum) or local (at various
mucosal surfaces as nose and other areas
of the respiratory tract). Humoral
response could be life-long but for the
antigenic drift shown by the virus which
leads to waning of protection over time.
Virus-specific CMI (through cytolytic T-
cells) leads to destruction of virus-laden
cells in the respiratory tract and thus
helps in recovery from infection. The
cell-mediated immunity is more
specific, less amenable to antigenic drift,
highly effective but does not take effect
till 2-3 days after the initial infection,
and is short-lived (lasts for only a few
weeks).
Protection from the virus is mainly through
humoral response; role of the CMI in early
stages is minimal. However, cellular
responses take over later and play more
dominant part in limiting the already
established infection and in eliminating the
virus. Elimination of infection is
accomplished by destruction the virus-laden,
infected cells. Regeneration of the destroyed
mucosa occurs 7-10 days after the start of
infection.
Transmission: Influenza virus is
transmitted from person-to-person
through droplets (in nasal secretions and
saliva during sneezing & coughing) as
well as during the normal daily contact
among humans. Thus fomites are also
important in spread of infection.
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 Indian J for Practising Doctor; Vol I; No. 4
Pathogenesis: The virus may infect
whole respiratory tract from nose down
to lungs. Droplets are usually <2 mm,
land in the lower respiratory tract, attach
to the epithelium and initiate infection.
Absence or gross deficiency of the type-
specific surface antibody (IgA) facilitates
establishment of infection.
The establishment of infection
depends on:
• Various non-specific and virus-
specific host factors: Susceptibility
of the local mucosal columnar cells
makes adherence of virus easier.
Muco-ciliary mechanisms get rid of
large quantity of virus in non-
smokers. Antibodies to type B can
not protect from type A infection.
Similarly, previously acquired
antibodies to either type may not
afford any protection to subsequent
infection.
• Viral factors as quantity of virus
inhaled: Larger viral dose
overwhelms the local defences.
• The intrinsic virulence of the virus,
which in turn depends on the type
and subtype and changes with
antigenic drift and shift.
Within 5-6 hours of establishment of
infection, progeny viruses are
released to enter other susceptible
cells. Lytic replication of the virus
leads to almost total destruction of
the ciliated epithelial cells of the
respiratory tract.
Infection in the nasopharynx
leads to a loss of ciliated epithelium –
an important nonspecific respiratory
defence - in nasopharynx and
trachea, which paves way for
secondary bacterial infection
(streptococcal, staphylococcal, H
influenza) in the lower respiratory
tract. Fatal pneumonia may ensue in
the elderly.
Bronchoscopy shows de-ciliated,
oedematous, and acutely inflamed
bronchi, trachea and larynx. This
results in desquamation of cells.
Local defences & recovery:
1) The virus triggers the interferon
release very effectively which
coincides with onset of symptoms,
levels peaking some 24 hours later.
Interferon plays an important role in
reducing replication of virus and in
limiting spread of virus in the
respiratory tract.
The systemic features of malaise,
aching pain in back and joints, and
fever are associated with release of
various pro-inflammatory cytokines
including interferon, interleulkin-6
and tumour necrosis factor-α.
2) Other nonspecific host factors are
soluble factors, such as lung
surfactants, sialylglycoproteins and
alveolar macrophages take up the
virus ands thus prevent it from
attaching to and invading the
susceptible epithelial cells.
3) In the first (primary) infection,
locally elicited antibody response is
important. IgA is secreted locally;
IgG is derived from the transudate
spilling into the respiratory tract
secretions from the bloodstream as a
result of inflammation. Both these
prevent the virus from attaching to
the epithelium or entering the cell, by
blocking the activities of
haemagglutinin proteins. In 80%
cases, a primary serum IgG response
is seen, which again has to reach the
respiratory mucosa for neutralizing
the virus.
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 Indian J for Practising Doctor; Vol I; No. 4
Immunologic memory of the
local IgA which is specific for the
haemagglutinin and neuraminidase
proteins of virus could ward off all
subsequent infections, provided there
were no antigenic drift or shift. Same
applies to the serum antibody, mainly
IgG.
. by:
Clinical presentation
In temperate areas, infections
usually occur in winter with a threat of
outbreaks from December till March.
However, cases occur throughout the
year. In the UK, a weekly incidence of
influenza-like illnesses greater than
400/100,000 population is considered to
constitute an infectious rate of epidemic
proportions.
In adults, influenza is an acute
infection. with an incubation period of 2-
3 days. Usual presentation, after an
incubation period of 2-3 days, is an
abrupt onset of rhinitis, sore-throat, non-
productive cough, with fever (38°-40°C),
malaise, headache, chills and myalgia.
Clinical picture is of pharyngitis and
tracheo-bronchitis. Infection is more
severe in smokers. Majority of cases are
typical; a minority may be asymptomatic
(sub-clinical) or present as simple
rihinitis and sore throat.
When uncomplicated, the acute
episode lasts for 3-7 days, though
weakness may last another week.
In children and adolescents,
influenza is slightly milder and of a
shorter duration. Subclinical and minor
infection is commoner in younger
children. However, there could be severe
presentations with high fever and febrile
convulsions.
Children may exhibit more lower
respiratory tract involvement presenting
as croup or pneumonia. There may be
extrapulmonary manifestations as
vomiting, abdominal pain and myositis.
Complications
In some cases influenza may be complicated
1) Myositis: This is commoner in type B
infection, and in children recovering from
the illness but may occur during acute phase
with direct viral invasion of muscle. It begins
with acute pain and tenderness in
gastrocnemius and soleus muscles leading to
extremely painful walking. There is a
transient elevation of serum creatine
phosphokinase. Very rarely heart muscle
may be involved with tachy-dysrhythmias,
and elevation of cardiac enzymes. Patients
may suffer myoglobinuria and renal failure.
The majority recover within 3-4 days.
2) Reye’s syndrome: It occurs particularly in
paedriatic influenza patients receiving
aspirin. There is acute encephalopathy with
cerebral oedema, with fatty degeneration of
the liver. The cerebrospinal fluid is normal
except for its raised pressure. Liver function
tests are abnormal.
3) Pneumonia: Involvement of lung occurs
usually in those at high-risk of getting
influenza as the elderly, and those with
COPD and other cardiopulmonary diseases.
However, in some pandemics (as the 1957
Asian pandemic) 1/4th of all healthy persons
got it. The virus replicates in the alveolar
epithelial cells. The patient becomes
overwhelmingly toxaemic and exhibits a
rapid respiratory rate, tachycardia, cyanosis,
high fever and hypothension. Chest x-ray
shows patchy consolidation in two or more
lobes; cavitation or pleural effusion implies
bacterial super-infection. Pathological
picture is shared by many viruses invading
lower respiratory tract: thus, there is
interstitial pneumonitis with severe
hyperaemia and broadening of the alveolar
walls together and mononuclear cell
infiltration. The patient may die within 1-4
days. Such severe presentation is usual with
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 Indian J for Practising Doctor; Vol I; No. 4

type A infection. The survivors begin
improving some 5-15 days after the start of
pneumonia. Usually there are no sequelae.
4) Secondary bacterial infections:
Superinfection with pneumococcus, staph
areus and H influenza is common. This is
probably because the viral neuraminidase-1
induces apoptosis (programmed cell death)
in the invaded epithelial cells and leucocytes,
which in turn permits bacterial overgrowth.
There is already existent colonization with
bacteria in cystic fibrosis and occasionally in
COPD, excessive smoking and
environmental pollution. Mortality is greatly
increased with bacterial superinfection.
Diagnosis is mainly clinical and difficult
in absence of an outbreak. During an
epidemic an adult with a diffuse
interstitial pneumonia is likely to be
suffering from influenza virus
pneumonia.
Influenza in special categories:
1) Pregnancy & influenza: There is no
definitive proof of congenital anomalies or
haemotoligical malignancies with influenza.
However, in a pandemic caused by a novel
virus, pregnant women may contract fatal
disease in 2nd or 3rd trimester. It was
observed in both the 1918 and 1957
pandemics.
2) At risk groups: These include the elderly
(75 yr or above, the debilitated, persons with
COPD (including asthma and bronchitis),
diabetrics, ischaemic heart disease, or renal
disease, immuno-compromised persons, and
residents of closed institutions where attack
rate is very high. The majority of at-risk
persons have some degree of immune-
compromise. For example, the elderly
suffering from thymus involution resulting in
T-cell insufficiency. Mortality rate among
the elderly with one or more risk-factors
attributable to influenza among the elderly is
0.8% as compared to 0.02% in those under
65. In obstructive and occupational
respiratory diseases, and among smokers,
local epithelial defences (mucociliary
clearance) are weakened. Influenza
exacerbates asthma in children. Congenital
disorders (cystic fibrosis), organ transplants,
and HIV infection increase risk of death
among young adults.
In ischaemic heart disease, hypoxia and
myocarditis both increase the mortality. HIV
impairs T-cell response which in normal
individuals helps in getting rid of virus.
Elderly diabetics have a 6-fold increased risk
of requiring hospitalization for ketoacidosis ,
with adverse outcome. The increased risk
among them is related to their cardiovascular
complications and deranged metabolic
control. ************

Further reading:
Bender BS, Small PA. Influenza: pathogenesis & host defences. Semin Respir Inf 1992; 7:38-45
Bush RM, Bender CA, Subbarao K. Predicting the evolution of human influenza A. Science 1999;
286:1921-25
Couch, RB. Influenza: prospects for control. Amm Intern Med 2000; 133: 992-8
Das P. Flu experts feel countries are unprepared for a future pandemic. Lancet 2001; 357: 1419.
De Jong JC, Rimmelzwaan GF, Fouchier RAM. Influenza virus: A master of metamorphosis. J Infect 2000;
40:218-28
Ellis J, Joseph C, Zambon M. Fifty years of influenza surveillance. Commun Dis Public Health 1999; 2: 81-
2
Nguyen-Van-Tam JS. Epidemiology of influenza. In: Nicholson KG, Webster RG (ed)> Textbook of
nfluenza. Oxford: Blackwell, 1998.
Olviera EC, Marik PE, Colice G. Influenza Pneumonia: a descriptive study. Chest 2001; 119:1717.
Webster RG. Immunity to influenza in the elderly. Vaccine 2000; 18:1686-9
Potter CW. A history of influenza. J Appl Microbiol 2001; 91:572-9
Simonsen L. The global impact of influenza on morbidity and mortality. Vaccine 1999; 17 Suppl 1

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 Indian J for Practising Doctor; Vol I; No. 4
Patient Education
Influenza
Influenza is an acute, infectious,
contagious disease of the respiratory
tract, especially the trachea, colloquially
called flu or, less often, grippe. The
symptoms of a simple attack include dry
cough, sore throat, nasal obstruction and
discharge, and burning of the eyes; more
complex cases are characterized by chill,
sudden onset of fever, headache, aching
of muscles and joints, and occasional
gastrointestinal symptoms. In
uncomplicated cases, symptoms fade and
temperature drops to normal in a few
days; the risk of death increases if the
disease is accompanied or followed by
viral or bacterial pneumonia.
Since the 16th century, at least 31
influenza pandemics (very widespread
epidemics) have been described. The
most destructive epidemic of modern
times, that of 1918, is estimated to have
caused 40 million deaths.
The three types of causative
virus, known as A, B, and C, were
isolated in 1933, 1940, and 1950,
respectively; the first two are responsible
for disease epidemics. In 1941 it was
shown that influenza could be controlled
by a vaccine containing virus. The
problem of immunization is complicated,
because the different types are
antigenically unrelated and so do not
induce cross-immunity. It is also
complicated because immunity to a
specific virus persists for less than a year
and because these viruses exhibit the
unique quality of periodically mutating
to negate any immunity people may
develop. The problem has been met by
creating polyvalent vaccines: vaccine
against type B is combined with vaccines
against the subtypes of type A as they
evolve. This has required a worldwide
surveillance system to detect altered
virus forms as soon as they arise, so that
adequate stocks of vaccine can be
prepared in time. Because it would be
prohibitively expensive to prepare
vaccine for the entire population each
time the virus mutated, vaccine was for a
long time administered only to those
most susceptible to developing
pneumonia when they contract influenza.
The different antigenic types of
influenza virus appear in cycles; for
instance, the variant appearing in the
1978-1979 season was identical to the
virus that was widespread during the
early 1950s. Some evidence exists that
pandemics occurring 60 to 70 years apart
are caused by the same form of virus.
Based on this theory, public health
officials expected in 1976 that the same
virus that caused the 1918 pandemic
would reappear. When this form of the
organism (known colloquially as swine
flu) was isolated from army recruits in
Fort Dix, New Jersey, United States,
vaccine against it was prepared, and
mass inoculation was carried out in the
United States. No outbreak, however, of
that form of influenza occurred.
The drug amantadine
hydrochloride, which is taken orally, is
effective in preventing influenza caused
by influenza A virus, and also
moderately effective in treating influenza
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 Indian J for Practising Doctor; Vol I; No. 4
A after symptoms have appeared.
Amantadine is used as an adjunct to
immunization for high-risk patients, but
immunization is still considered the most
effective way to combat the disease.
Human infection with avian influenza A
(H5N1) viruses were identified in Hong
Kong in 1997. As of January 1998, a
total of 16 cases and three suspected
cases of this new type of influenza had
been confirmed. Individuals with high
levels of exposure to infected poultry or
direct exposure to the virus in the
laboratory, or health-care workers, are
thought to be at most risk.
Since the 1918 pandemic there
have been two other pandemics, in 1957
and 1968, each of which also killed
millions around the world. Medical
experts now believe it is a question of
when and not if another flu pandemic
causes infection on a global scale and
maybe affects millions of people.
Potentially the situation is worse now
because of the explosion of international
travel in recent decades. However,
improved communications and the
World Health Organization's monitoring
work mean that a deadly strain could be
isolated more quickly, allowing doctors
more time to formulate a vaccination.
Finally, antibiotics, while ineffective
against viruses, would be crucial for
tackling infections that many victims
would develop as a result of influenza.
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 Indian J for Practising Doctor; Vol I; No. 4

Cold Chain Maintenance will avoid artificial shortages created by

accumulation of large balance stocks at
places where the programme is not
functioning effectively.
Rubina Shaheen
_____________________________ Range Vaccines

A vaccine must have two Most sensitive BCG(after reconstitution)

characteristics, one is safety and other is OPV
Measles
potency. The potency of a vaccine is Hepatitis B
maintained by cold chain. The cold chain DPT
is a system of storing and transporting DT
the vaccines at recommended
temperatures from the point of Least sensitive BCG(before
reconstitution)
manufacture to the point of use. The TT(Tetanus toxoid)
essential elements of the cold chain are: Vaccine Vaccines that can be
• Personnel to organize and manage damaged by frozen without harm
vaccine distribution. freezing
• Equipment for storage and DPT BCG(before
transport of vaccine. DT reconstitution)
• Transport facilities TT OPV
• Maintenance of equipment and Hepatitis B Measles(before
reconstitution)
• Monitoring.

Why to maintain the cold chain? Storage temperature:

Maintenance of cold chain
system is important because the
vaccines lose their potency if exposed
to adverse temperatures. The tables
below show the sensitivity of different
vaccines to heat and freezing.
All vaccines are to be retained at
temperatures between +2 to +8 0C. A
break in the cold chain is indicated if
temperature rises above +80C or falls
below +20C in case of ILR & other
refrigerators.

Monitoring of Cold Chain: Potency tests

Monitoring of cold chain
regularly is important if you expect it to
function effectively and efficiently. The
things you will need to monitor are:
• Availability of equipment
working
• Supplies
• Storage temperature
• Potency tests
Supplies:
Arrange supplies according to
demand and utilization so that there is a
regular and smooth flow of vaccines. It
Vaccines produced by production
unit are tested for potency before these
are released in the market. However,
there is no guarantee that this vaccine
&its will remain potent till it is administered
to the child; that dependents on a
competent cold chain. To actually
monitor vaccine potency in the field, one
has to send a random sample of oral
polio vaccines lifted from field to
laboratory for testing potency. This
activity is, in addition, and independent
of production-testing.

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 Indian J for Practising Doctor; Vol I; No. 4
The concentration of live attenuated
polio virus shall constitute the parameter
to measure potency. The titration is
performed on HEp-2 Cincinnati cells
with passage level of <350.
Cases where potency of vaccine
from field needs to be checked
• When you suspect break in the cold
chain
• To monitor the efficiency of storage
in the field.
• As a part of evaluation of
vaccination e.g.; sero-conversion
studies.
Testing facilities are available at the:
• Central Research Institute, Kasauli
(H.P).
• National Institute of Communicable
Diseases, Delhi,
• Enterovirus Research Centre,
Bombay,
• School of Tropical Medicine,
Calcutta.
• S. K. Institute of Medical Sciences
Soura, Srinagar, Kashmir.
OPV has been selected as
“indicator” of cold chain as this vaccine
is more heat-labile than other vaccines
and is easier to test.
Collection of OPV sample for potency
testing
• Select a used or unused vial of
OPV. The used vial must have at
least 2ml of vaccine.
• Affix an adhesive label on the
bottom of the vial name of the
Primary Health Centre and date of
collection.
• Ensure that manufacturer’s label is
intact.
• Place the labeled vial of OPV in a
polythene bag and affix second
label indicating the name of the
Primary Health Centre on the
polythene bag.
• Roll the polythene bag around the
sample and secure it by a rubber
band.
• Place the polythene bag containing
the sample in vaccine carriers
containing enough ice packs.
The samples so collected should
be rushed to the headquarters in vaccine
carrier observing cold chain, known as
the reverse cold chain. If delay is
anticipated in transmitting the sample for
testing, such samples should be kept in a
deep freezer/ILR till they are sent to the
testing laboratory.
General guidelines for testing OPV
sample
• Total number of samples to be
collected from the state in a year is
prescribed. Roughly the number of
samples to be collected is the same
as the number of PHCs in the state.
• Out of the total number of samples,
30 percent should be from out-reach
session PHCs, 15 percent from
district headquarters and 5 percent
from walk- in coolers.
• For samples collected from out-reach
sessions and PHCs, care sold be
taken not to take more than one
sample from one area/ institution in
a year.
• The team formed to collect samples
should plan their visits in advance
and also be responsible for
maintenance of the reverse cold
chain.
• The storage point for vaccines
should be codified; so that
relationship between samples and
storage points can be easily
established.
• Te samples collected should be
rushed to headquarters in a vaccine
carrier observing cold chain (reverse
cold chain.) and kept in the deep
freezer until they are sent for testing
in the laboratory.
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 Indian J for Practising Doctor; Vol I; No. 4
• The VVM status of the sample
should be recorded at the time of
collection of sample and the time of
receipt of vaccine in laboratory.
Cold chain equipments:
There are equipments of different
capacity for storage of vaccines at
different levels as under:
Walk-in-freezers:
These are used for bulk storage of
OPV, measles vaccines and also to
prepare frozen ice-packs at state stores.
They maintain a temperature around
minus 20°C. They are available in sizes
of 16.5 Cu. Mt. and 32 Cu. Mt. These are
provided with two identical cooling units
and a standby generator sets. Bulk
quantities of ice packs are also made and
stored in the walk-in-freezers.
Walk-in-coolers:
These are used for bulk storage of
vaccines at State and Regional stores.
They maintain a temperature of +2°C to
+8°C. They are available in sizes of 16.5
Cu. Mt. and 32 Cu. Mt, and are used for
storage of large quantities of vaccines at
state and regional level. This is provided
with two identical cooling units and
standby generator sets with automatic
start and stop facilities. They are also
provided with temperature recorder and
alarm systems. Walk-in-coolers are
established at regional levels, which
store vaccines for about 4-5 districts.
Both, walk-in collers & walk-in-freezers
store three months of requirement of
vaccines + 25% buffer stock for the
districts they cater.
Deep freezers:
Deep freezers supplied under
immunization programme have a top
opening lid. The cabinet temperature is
maintained between -18° to -20°C. This
is used for storing of OPV and measles
vaccine and also for freezing ice packs.
In case of power failure, it can maintain
the cabinet temperature for 18 to 26
hours, if not opened. These are available
in two models, having a capacity of 300
litres and 140 litres. The chest freezers
are provided with special insulation,
which helps in maintaining inside
temperature, in case of electricity failure,
for much longer time. The 140 litre-chest
freezer can store 65000 doses of
vaccines.
The 300 litre capacity freezer at
district headquarters are to supplied for :
• Storage of OPV& measles
vaccines
• Preparations of ice packs.
The 140 litre capacity freezer at PHC
headquarters are to be supplied for:
• Storage of OPV& measles
vaccines.
• Preparations of ice packs.
The diluents should not be kept in
deep freezers. These should be stored at
a temperature between +2° to +8°C and
should be transported along with the
concerned vaccine.
Preparation of Ice Packs:
• Fill the ice pack with water up to the
mark and close the cap tightly.
• Prepare ice-pack by keeping the
water-filled container in freezer or in
the freezer compartment of
refrigerator so that water freezes.
• Do not add salt to the water in the
ice pack while placing in the freezer,
it will lower the temperature to
subzero level which is not
recommended for DPT, DT, TT and
BCG.
• Shake it and invert to check that it is
not leaking
• Place the ice packs on one side in the
freezer initially, placing 16-24 packs,
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 Indian J for Practising Doctor; Vol I; No. 4
and change to another on the next
day.
• For emergency requirement a PHC
should have 50-60 frozen ice packs
at a given time.
Ice Lined Refrigerators:
These type of refrigerators are
top-opening because they can hold the
cold air inside better than a refrigerator
with a front-opening. An ILR can keep
vaccine safe with as little as 8 hours
continuous electricity supply in a 24 hour
period. It is available in two sizes
• ILR-MK 300 of 300 litre capacity and
• ILR-MK 140 of 140 litre capacity.
The MK-300 is supplied to
district headquarters and MK 140 is
supplied to PHC headquarters.
Inside the ILR, there is a lining of
water-containers fitted all around the
walls and held in place by frame. While
the refrigerator is in operation, water in
containers freezes and when the
electricity supply fails, then the ice lining
keeps the inside temperature of the
refrigerator at a safe level for vaccines.
In such a situation the temperature
remains within safe limits in ILR for
much longer than in deep freezers.
ILR has got two sections- the top
and the bottom. The bottom of the
refrigerator is the coldest place.
Therefore, DPT, DT TT and BCG
vaccines should not be kept directly on
the floor of the refrigerator as they can
freeze and get damaged. The top section
of the ILR maintains the temperature of
+2° to +8°C. BCG, DPT, DT, and TT
vaccines are kept in this section in the
baskets provided with the refrigerator.
Conventional Refrigerators:
• This is to be used in case of
breakdown of ILR.
• Temperature in the ordinary
chamber remains between 4 & 10
degrees. In the ice chamber the
temperature fluctuates between 0-
4 degrees centigrade. Overall
speaking, the temperature in an
ordinary refrigerator ranges from
+2 to +8°C.
• Measles and polio vaccines are kept
on the top shelf below the freezer.
• Vaccines should not be frozen or
thawed repeatedly as this will
decrease their potency.
• DPT, DT, TT, BCG and diluents are
kept in the middle shelf.
• Water bottles with coloured water
(to serve as buffer in case of
electricity failure) are kept at the
bottom shelf and door.
Installation of the equipment:
No electric cold chain equipment
should be installed without a voltage
stabilizer. Before installation, one should
get familiar with various features of
Automatic Voltage Stabilizer.
Vaccine Transportation Equipments
Cold boxes
Cold boxes are mainly used for
transportation of large quantities of
vaccines. They can also be used to store
vaccines for transfer up to five days.
These are of two sizes 5 litres and 20
litres with requisite number of ice packs.
The 5 litre cold box can transport about
1500 doses of vaccines; the 20 litre
boxes have enough space to transport
about 6000 doses of vaccines. The ‘hold
over time’ is more than 90 hrs for 5 L
and six days for 20L cold box. We may
store vaccine in cold boxes in case of
breakdown of ILR. The vials of DPT, DT
and TT vaccines should not be placed in
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 Indian J for Practising Doctor; Vol I; No. 4
direct contact with frozen ice packs and
should be surrounded by OPV vials.
How to keep cold boxes in good
condition when not in use
• Clean and dry after use
• Examine inside and outside
surface after every use for cracks.
• Check that the rubber seal around
the lid is not broken; if broken,
replace immediately.
• Adjust the tension on the latches
so that the lid closes tightly
• Lubricate hinges and locks
routinely.
Vaccine Carriers
Vaccine carriers are used for
carrying small quantities of vaccines (16-
20 vials) to the sub-centers or villages by
health workers. The vaccine carriers are
made of insulated material, the quality of
which determines the cold-life of the
carrier. These are containers with thick
walls and lids of material which does not
allow heat to pass through it easily.
Fully frozen ice packs are used to
keep vaccines cold in the carrier. The
vials of DPT, DT and TT vaccines
should not be placed in direct contact
with the frozen packs. Do not leave the
lid open and do not expose the carrier to
the sun. Vaccines can be kept in the
carrier for 48 hrs.
If more than one vaccine carrier
is being carried, keep the whole range of
the vaccines required for the day in the
carrier so that only one carrier is opened
at a time. Keep the vaccine carrier in
good condition when not in use.
Storage temperature:
To measure the temperature
during storage/transport, different types
of thermometers are used.
• Dial thermometers
Dial thermometers have been
provided to record the temperature in the
ILRs / Freezers. One dial thermometer
should be kept in every unit. A staff
member should be made responsible for
recording the temperature. The
temperature record should be used to
monitor and control the temperature and
to take follow up action as required.
• Alcohol stem thermometers
Alcohol thermometers are much
sensitive and accurate than dial
thermometers. They can record
temperatures from -50°C to +50°C
and can be used for ILRs and deep
freezers.
Recording and monitoring of
storage temperature
The temperature in the ILR must
be monitored twice daily (morning and
evening). This is done in order to:
• Be sure that vaccines were not
exposed to temperature above +80
Celsius.
• Check that the equipment is
working properly.
• We must be careful and ensure
that the temperature in the ILR
does not rise above +8°C. Also
one must check that the
temperature does not fall below
-20°C as it damages the T series
(tetanus-containing) of
vaccines.
• Vaccines are damaged by heat
whether they are exposed to a lot
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 Indian J for Practising Doctor; Vol I; No. 4

STABILITY OF VACCINES AT VARIOUS TEMPERATURES

Vaccines Storage temperature in 0C

0-8 22-25 35-37 Over 37

Tetanus and Stable for 3-7 years Stable for months Stable for at least 6 Stable for 2
diphtheria weeks weeks at 450C,
toxoid as loss of potency
monovalent after few ours at
vaccines or 60 to 650C
components
of vaccines
Pertussis Safe storage for 18-24 Stability varies. Some vaccines Stability varies. At 450c about
vaccine month although with stable for two weeks. Some vaccines loss 10% loss of
continuous slow 50% of potency after potency per day,
decrease of potency one week storage. rapid loss in
potency at 500C
Freeze-dried Stable for one year Stability varies. 20-30% loss of Stability varies. 20% Unstable. 50%
BCG vaccine viability after 3 month storage loss of viability after loss after 30
3-14 month storage minute exposure
to 700C
Reconstituted Reconstituted BCG vaccine should not be used beyond one working session (5-6 hours). This
BCG vaccine recommendation has two bases (1) concern over the risk of contamination, as BCG contains no
bacteriostatic agents, and (2) concern over the loss of potency.
Freeze-dried Stable for two years Retains satisfactory Retains satisfactory 50% loss of
Measles potency for one potency for at least potency after 2-
vaccine month one week. 3 day exposure
to 410c; 80%
loss in potency
after one day
exposure.
Reconstituted Unstable-should be used in one Unstable-50% loss Very unstable; titer Inactivation
measles working session after one hour. 70% may be below within one hour
vaccine loss after 3 hours acceptable level after
OPV Stable for 6-12 months Unstable, 50% loss Very unstable loss of Very unstable.
after 20 days. Some satisfactory titers At 410c 50%
vaccines may retain after 1-3 days loss after one
satisfactory titers for day. At 500c
1-2 weeks loss of
satisfactory
titers after 1-3
hours.
Inactivated Stable for 1-4 years Decline of D-antigen Loss of D-antigen for Precise data
polio vaccine content for type 1 type1 after 20 days lacking
after 20 days in some vaccines but
no significant loss
after 4 weeks in
others

of heat in a short time or a small • A break in the cold chain is

amount of heat over a long indicated if temperature rises
period. above +8°C or falls below +2°C
• Maintaining the cold chain in the ILR; and above -18°C in
demands constant vigilance. the Deep Freezer.

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 Indian J for Practising Doctor; Vol I; No. 4

Shake test:
The “shake test” is a test to Supply of vaccines:
determine if a vaccine was frozen or not A health administrator’s major
at any time. Freezing can damage DPT, responsibility is to provide vaccines to
DT, tetanus toxoid (T-series of vaccines), health centres in time. Before making
typhoid and hepatitis vaccines. We can supplies, we must check the following
find out if any of these was frozen or not • Requirements of the PHC
by performing this test. (session wise)
• Utilization during the previous
Vaccines never frozen months. We can get this
• Smooth and cloudy. information from monthly
• It is clear with no sediment monitoring report
• Find out balance in hand.
Vaccines frozen • Arrange supplies according to
• Vaccines frozen contain granules,
demand & utilization.
and sediments are fond settled at the
bottom.

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 Indian J for Practising Doctor; Vol I; No. 4

Operating Room Etiquette

(Reproduced from “Surgical Care at the District Hospital”, WHO, Geneva, 2003)

{This section is reproduced for the benefit of doctors and paramedics working in the District &
sub-district hospitals of India, particularly J & K State]

__________________________________________________________________________________

The operating theatre is a room enter the operating room,

specifically for use by the anaesthesia
and surgical teams and must not be used
for other purposes. A treatment room has
equipment similar to an operating
theatre, but on a smaller scale. Both
rooms require:
ƒ Goods lighting and ventilation
ƒ Dedicated equipment for
procedures
ƒ Equipment top monitor patients,
as required for the procedure
ƒ Drugs and other consumables,
such as sutures, for routine and
emergency use.
Ensure that procedures are
established for the correct use of the
operating room and that all staff are
trained to follow them:
ƒ Keep all doors to the
operating room closed,
except as needed for passage
of equipment, personnel and
the patient.
ƒ Store some sutures and extra
instruments in the operating
room to decrease the need for
people to enter and leave the
operating room during a
case.
ƒ Keep to a minimum the
number of people allowed to
especially after an operation
has started.
ƒ Keep the operating room
uncluttered and easy to clean.
ƒ Between cases, clean and
disinfect the table and
instrument surfaces.
ƒ At the end of each day, clean
the operating room: start at
the top and continue to the
floor, including all furniture,
overhead equipment and
lights; use a liquid
disinfectant at a dilution
recommended by the
manufacturer.
ƒ Sterilize all surgical
instruments and supplies
after use and store them
protected and ready for the
next use.
ƒ Leave the operating room
ready for use in case of an
emergency.
Sponge & Instrument Counts
It is essential to keep track of the
materials being used in the operating
room and during any complicated
procedure in order to avoid inadvertent
disposal or the potentially disastrous loss
of sponges and instruments in the wound.

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 Indian J for Practising Doctor; Vol I; No. 4
It is standard practice to count
supplies (instruments, needles, &
sponges):
ƒ Before beginning a case
ƒ Before final closure
ƒ On completing the procedure
The aim is to ensure that
materials are not left behind or lost. Pay
special attention to small items and
sponges.
Create and make copies of a
standard list of equipment for use as a
checklist to check equipment as it is set
up for the case and then as counts are
completed during the case. Include space
for suture material and other
consumables added during the case.
When trays are created with the
instruments for a specific case, such as a
Caesarean section, also make a checklist
of the instruments included in that tray
for future reference.
Scrubbing & Gowning
Before each operation, all members of
the surgical team – that is, those will
touch the sterile surgical field, surgical
instruments or the wound – should scrub
their hands and arms to the elbows.
Scrubbing can not completely sterilize
the skin, but will decrease the bacterial
load and risk of wound contamination
from the hands.
Each hospital should develop a
written procedure for scrubbing that
specifies the length and type of scrub to
be undertaken. It is usual that the first
scrub of the day is longer (minimum 5
minutes) than any subsequent scrub
between consecutive clean operations
(minimum 3 minutes).
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 Indian J for Practising Doctor; Vol I; No. 4

When scrubbing:
1. Remove all jewellery and trim the nails
2. Use soap, a brush (on the nails and finger tips) and running water to clean
thoroughly around and underneath the nails.
3. Scrub your hands and arms up to elbows
4. After scrubbing, hold up your arms to allow water to drip off your elbows
5. Turn off the tap with your elbow.

After scrubbing your hands:

1. Dry them with a sterile towel and make sure the towel does not become
contaminated.
2. Hold your hands and forearms away from your body and higher than your elbows
until you put on a sterile gown and sterile gloves.

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 Indian J for Practising Doctor; Vol I; No. 4
Surgical gloves prevent transmission of
HIV through contact with blood, but
there is always the possibility of
accidental injury and of a glove being
punctured. Promptly change a glove
punctured during an operation and rinse
your hand with antiseptic or re-scrub if
the glove has leaked during the
puncture. Patient safety is of primary
concern; do not compromise it. Change
your gloves only when it is safe for the
patient.
Skin Preparation:
The patient should bathe the night
before an elective operation. Hair in the
operative site should not be removed
unless it will interfere with the surgical
procedure. Shaving can damage the skin
so clipping is better if hair removal is
required; it should be done in the
operating room.
Just before the operation, wash
the operation site and the area
surrounding it with soap and water.
Prepare the skin with antiseptic solution,
starting in the centre and moving to the
periphery. This area should be large
enough to include the entire incision and
adjacent working area, so that you can
manoeuvre during the operation without
touching the unprepared skin.
Chlorhexidine gluconate and iodine are
preferable to alcohol and are less
irritating to the skin. The solution should
remain wet on the skin for at least two
minutes.
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 Indian J for Practising Doctor; Vol I; No. 4
Draping:
Scrub, gown and glove before covering
the patient with sterile drapes. Leave
uncovered only the operative field and
those areas necessary for the
maintenance of anaethesia. Secure the
drapes with towel clips at each corner.
Draping exposes the area of the
operative field and provides a sterile
field for the operating staff to work. This
is designed to maximize surgical
exposure and limit potential for
Pregnancy in the Rh-
contamination. There are many
approaches to draping, some of which
depend on the kind of drapes being used.
Do not place drapes until you are
gowned and gloved, so as to maintain the
sterility of drapes. It is important to
secure good exposure and a large sterile
area. When laying out the drapes, the
edges and folds (which hang below the
operating table) are considered to be
non-sterile.
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 Indian J for Practising Doctor; Vol I; No. 4
negative woman
Rehana Kausar
________________________________
Isoimmunization (maternal
blood-group immunization), a disease of
genetic predisposition, has been a focus
of concern for obstetricians for centuries.
Fifty years ago, Landsteiner and Weiner
first described their classic experiment in
which monkey red-cell antiserum was
mixed with blood samples from a
selected human population. Levine and
colleagues subsequently demonstrated
that the immune response in an Rh
negative woman was the primary cause
of hemolytic disease in the newborn. The
identification of the rhesus antigen and
its description in these classic works are
the cornerstone of modern immuno-
hematology. The pregnant woman and
her caregiver now have the ability to
both avoid and treat this historically
difficult problem.
The incidence of Rh negativety in
Caucasian population is 15% to 16%. In
India the incidence is about 5-8%.
Rh system
A) D antigen: The Rh complex consists
of three pairs of antigenic determinants
(Dd, Cc, Ee). The presence of D antigen
determines that the individual is Rh +ve.
The Rh +ve individual will be found to
be homozygous for D (i.eDD)
approximately 45% of the time. This
results from having inherited the D
containing set of alleles from both
partners. The remainder of Rh +ve
individuals will be heterozygous for the
D locus. A homozygous partner (DD) of
a Rh-ve woman will produce only Rh
positive offspring; a heterozygous
partner will produce either Rh +ve or Rh
-ve offspring. Rh iso-immunization can
occur only in that pregnancy in which a
Rh+ve foetus resides, and only that
foetus or subsequent Rh +ve foetuses
will be affected by the maternally
produced Rh antibody.
B) Atypical antibodies: Antibodies
directed against the c and E , and less
commonly against e and C are also
associated with hemolytic disease of the
newborn. These are called atypical
antibodies. A number of other red cell
antigens that are not part of the Rh
antigen complex are capable of
stimulating isoimmunization as well.
Because of the efficacy with which Rh
immune globulin prophylaxis prevents
Rh isoimmunization, hemolytic disease
caused by these antigens has become
relatively more important.
Etiology: Blood group isoimmunization
will occur from one of two pathogenic
mechanisms: incompatible blood
transfusion or foeto-maternal
hemorrhage.
Although the risk of Rh
incompatibility depends on the dose, a
small inoculum of 50-70 ml of Rh +
blood is needed to produce
immunization. The secondary response
will require as little as 0.1 ml of red cells.
Although the mother could be theoretically
immunized if enough erythrocytes enter the
foetal circulation to elicit an immune response,
isoimmunization is rare due to the following
reasons:
1) Varying rate of occurrence of
various red cell antigens.
2) Their variable antigenicity.
3) Insufficient transfer of antigen or
antibody.
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4) Variability of the maternal immune
response to the antigen.
5) Protection from isoimmunization by
ABO incompatibility of foetus and
mother. This confers some protection
against D-isoimmunization because foetal
red cells entering the mother usually are
rapidly destroyed before they can
elicit an immune response viz there is
only a 2 % chance of D isoimmunization
in all women by 6 months postpartum.
RISK FACTORS
• 2% of women are at risk of becoming Rh
immunized after having spontaneous or
therapeutic abortions. The risk grows by
2.5 fold after 20 weeks. A blood sample
should be taken from every woman at
her first antenatal visit for Rh blood
grouping and antibody screening.
• Paternal antigen status: The Rh –ve
gravida’s partner should be evaluated for
ABO and Rh status. If the father is also
Rh –ve the conceptus will be Rh-
negative and the mother is not at risk for
Rh immunization. As extramarital
pregnancies do occur, the patient should
be made aware of the potential for
catastrophic events should a father be
demonstrated antigen positive.
• Trauma to the abdomen poses a special
risk of immunization to the Rh negative
woman. The K-B test can detect the
amount of bleeding. Abruptio placentae
causing third trimester vaginal bleeding
and increased uterine irritability is
associated with transplacental bleeding
and should be evaluated with K-B test.
The appropriate amount of RhIG should
be given.
MANIFESTATIONS OF THE HEMOLYTIC
DISEASE
The haemolytic disease of newborn may
manifest as
1. HYDROPS FETALIS
2. ICTERUS GRAVIS NEONATORUM
3. CONGENITAL ANEMIA OF THE
NEWBORN
Kleihauer-Betke (KB) test: The principle is
that foetal erythrocytes contain hemoglobin
F, which is more resistant to acid dissolution
than hemoglobin A. After exposure to acid,
only foetal hemoglobin remains. Fetal red
cells can then be identified by uptake of a
special stain and quantified on a peripheral
smear. The presence of D-positive fetal red
cells in maternal blood can also be
determined by the rosette test which is more
sensitive than the Kleihaeur –Betke test.
Hydrops foetalis: This is the most serious
form of Rh hemolytic disease. Excessive
destruction of the foetal red cells leads to
severe anemia, tissue anoxemia and
metabolic acidosis. These have got adverse
effects on the foetal heart and brain and on
the placenta. Hyperplasia of the placenta
occurs in an effort to increase oxygen
delivery o the foetus but due to ongoing
hemolysis the foetal red cells are
progressively diminished. Damage to foetal
liver causes hypo-proteinemia leading to
generalized edema (hydrops fetalis), ascites,
and hydrothorax. Foetal death occurs due to
cardiac failure.
Diagnostic features of hydrops :
ƒ Polyhydramnios
ƒ Straight X ray abdomen shows
‘Buddha ‘position of the foetus with a
halo, around the head due to
oedematous scalp.
ƒ At birth, the baby is pale, oedematous,
with an enlarged abdomen due to
ascites.
ƒ Placenta is large, oedematous and
pale. The placental weight is
increased.
Icterus gravis neonatorum: This entity is
due to a lesser degree of foetal hemolysis.
The baby is not jaundiced at birth but
develops it within 24 hours of birth. If the
serum bilirubin level crosses 20mg/dl, the
bilirubin crosses the blood–brain barrier
causing staining and damage to the basal
nuclei and producing kernicterus.
Congenital anemia of the newborn: This is
the mildest form of the disease where the
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hemolysis is going on slowly. Although
anemia develops slowly within first few
weeks of life, jaundice is not usually present.
The destruction of red cells continues up to 6
weeks, after which the antibodies are not
available for hemolysis.
MANAGEMENT:
) Antibody screening: At the first prenatal
visit, the patient’s blood group and Rh
type should be determined, and antibody
screening performed. Maternal antibodies
are identified by indirect Coomb’s test
and neonatal antibodies are evaluated by
direct Coomb’s test. The absorbed
antibodies act as hemolysins, leading to
an accelerated rate of red cell destruction.
If the patient is Rh negative, screening is
performed again at 28 weeks gestation. If
antibody is detected, it is identified and
the titre measured Severe hemolytic
disease of the newborn rarely occurs if
the antibody titer is below 1:16. Patients
whose antibody titre is less than this level
can be managed expectantly. Patients
with antibody titre more than 1:16 ie the
critical titre, indicates the possibility of
severe hemolytic disease. The patient is
no longer a candidate for RhIG. Now an
evaluation for presence of the
Erythroblastosis fetalis must be
undertaken.
When the maternal antibody titre exceeds
the critical level, further evaluation is done
by spectrophotometric analysis of the
amniotic fluid
Today the Rh–immunized
pregnancy may be evaluated by five
complimentary modalities:
• Measurement of antibody titers
• Amniotic fluid (AF) DNA Rh typing
• AF deviation in optical density at 450
nm Eq
• Cordocentesis
• Sonography
Amniotic fluid analysis: If the patient’s
antibody titre is just at the critical level and
the patient has not had a baby with
erythroblastosis, the initial amniocentesis
can be done at 28 to 29 weeks’ gestation. If
the titre or history suggests that the
erythroblastosis foetalis may be more severe,
then the amniocentesis may have to be done
as early as 18 weeks gestation. In this way
the course of management can be decided.
The amount of bilirubin in the amniotic fluid
correlates roughly with the degree of
hemolysis and thus indirectly predicts the
severity of foetal anemia. Since the
concentration of bilirubin is so low, its
concentration is measured by a continuously-
recording spectrophotometer and is
demonstrable as a change in absorbance at
450nm, referred to as ∆OD450 on a graph
originated by Liley in 1961. In the presence
of bilirubin there is a deviation bulge
peaking at 450nm wave length. The greater
the bulge, the more severe is the affection of
the baby. For any given gestational age, the
height of the deviation bulge at 450 nm falls
within one of the three zones when plotted in
Liley’s chart.
Interpretation
) If it falls in zone I (low zone) the
fetus is not affected.
) If it falls in zone II (mid zone) the
fetus may require premature
termination beyond 34 weeks. In
lower zone 2, the expected Hb
concentration is between 11.0 and
13.9 g/dl, whereas in upper zone 2
,the anticipated Hb is 8.0 to 10.9
g/dl and without therapy death
within 7 to 10 days is expected.
Repeat samples are taken at 1 to 2
week intervals to see the trend of
samples. Pregnancies in the line
showing a rise towards zone 3
require immediate evaluation.
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 Indian J for Practising Doctor; Vol I; No. 4
) If it falls in zone III (high zone) the
foetus is severely affected and
death is imminent. If the
pregnancy is beyond 34 weeks,
termination is done forthwith. If
pregnancy is less than 34 weeks,
intrauterine transfusion is done
and repeated till such period when
termination can be done safely.
DELIVERY: Vaginal delivery at or near
term is the goal of management. The
pregnancy is usually closely monitored
with tests of foetal well-being performed.
Gestational age is the most important
consideration in choosing which
treatment to pursue. With careful
monitoring and transfusions, when
appropriate, very preterm delivery can be
prevented. Labour can be initiated as
soon as pulmonary maturity is
documented.
EXCHANGE TRANSFUSION IN THE
NEWBORN:
Cord blood analysis is carried
immediately for any pregnancy in the D-
negative mother. Cord blood is tested
for blood grouping and Rh typing of the
baby. If the baby is Rh negative, then no
further treatment is needed. Cord blood
hemoglobin concentration and Direct
Coomb’s test are of considerable
importance when the infant is Rh
positive. If the infant is overtly anaemic
exchange transfusion is done
immediately. Type O, D-negative red
blood cells, recently collected are used.
For infants who are not overtly anaemic,
the need for exchange transfusion is
determined by the rate of increase in
bilirubin concentration, the maturity of
infant, and the presence of other
complications.
______________________________________________________________________________________
PREVENTION
Anti D immunoglobulin is a 7S immune
globulin G extracted by cold alcohol
fractionation from plasma containing
high-titer D –antibody. Each dose
provides not less than 300μg of D-
antibody. It is given to D-negative, non-
sensitized mothers to prevent the hazards
of sensitization.
Anti-D: Anti D globulin is
provided to D-negative mothers after
miscarriage, abortion, evacuation of a
molar pregnancy or ectopic pregnancy. It
is also administered when there is a
large foeto-maternal bleed like placental
abruption, intrauterine manipulation,
placenta previa. There is need for extra
Rh D immune globulin in these patients.
A dose of 300μ will neutralize about 15
ml of red cells or 30 ml of foetal blood.
A Kleihauer–Betke or rosette test is done
on all such women to know the accurate
amount of anti-D required.
ANTENATAL ADMINISTRATION OF Anti
D: With the concept that feto-maternal
hemorrhage occurs throughout
pregnancy ,some centers advocate use of
anti-D during pregnancy.300 μg of anti
D are administered at 28 weeks and
again at 34 weeks and the routine dose
after delivery.Subsequently it was seen
that a single dose given antenatally at 28
weeks is as effective as two doses
antepartum.
43

Fever in childhood
Farooq Fazilli
_____________________________
Fever is defined as an elevation
of body temperature in response to any
pathological stimulus. American college
of Emergency Physicians has published a
clinical policy on febrile illness in
children that chooses a rectal temperature
of ≥38◦c (100.4◦F) as the most widely
used definition of fever.
Fevers are a sign that the body is
fighting an infection. The main reason to
treat the child is to make him or her feel
better. When the child is achy and fussy,
he/she may need some medicine
In normal circumstances, the
temperature of deep tissues of the body
(‘core temperature’) is kept at a very
even level by a range of automatic
adjustments. Increase in temperature
increases the amount of blood flowing
through the skin by opening up the tiny
capillary blood vessels. This radiates
away excess heat and sweating can
further enhance this. Having too cold
temperature causes shut down of skin
blood vessels and conserves heat within
the internal organs. If necessary more
heat can be generated by shivering. Fever
is part of the body's defense mechanism
against pyrogens. The body tries to
create extra heat so that the foreign
organism cannot survive. Increasing the
temperature helps the body to fight
illness. Thus, fever is an adaptive
response and should be treated only in
selected circumstances. Actions to
reduce a fever can help make someone
feel more comfortable but it is not
possible, or desirable, to aim to
normalize the temperature while
someone is fighting off an infection.
Heat production associated with fever
increases the oxygen consumption,
carbon dioxide production, and cardiac
output. Thus, fever may exacerbate
cardiac insufficiency in children with
heart disease, chronic anemia, pulmonary
insufficiency and metabolic instability.
It must be remembered that the
part of human brain that controls body
temperature is not fully developed in
children. This means that a child’s
temperature may rise and fall very
quickly and the child is sensitive to the
temperature of his or her surroundings.
One of the simplest and most
effective ways to help a child with a
fever feel more comfortable is to take off
some of the child's clothes so that heat
can escape from their body more easily.
What is a normal temperature?
A normal temperature is about
98.6°F when taken orally (by mouth).
Temperatures taken rectally (by rectum)
usually run 1° higher than those taken
orally. Rectal temperatures are the
closest to 'core' temperature and are
about 0.5ºC (2ºF) higher than readings
taken from the mouth or ear. So a
normal temperature is about 99.6°F when
taken rectally. Many doctors define a
fever as an oral temperature above
99.4°F or a rectal temperature above
100.4°F.
How to take child's temperature?
A body temperature reading can be
taken from the mouth, armpit, ear, skin surface or
the rectum. The most accurate way to take the
 Indian J for Practising Doctor; Vol I; No. 4
temperature of a child is orally or rectally with a
mercury or digital thermometer. In a child
younger than 4 years, take the temperature
rectally. In an older child, take it orally. Although
a rectal temperature reading is the most accurate
and is quite often used in hospitals it is not
necessary to be so precise when taking
temperature readings at home. Rectal
temperature reading is therefore not
recommended for home use.
ƒ A mercury thermometer should show a
temperature lower than 98.6°F before
taking a temperature. This can be done
by running cool water over the tapered
end to lower the reading. Some
thermometers must be shaken to lower
the reading.
ƒ Don't bundle the baby or child up too
tightly before taking the temperature.
ƒ Never leave the child alone while taking
his or her temperature.
ƒ Be sure to use the right thermometer.
Rectal thermometers are thicker than
oral thermometers.
ƒ While taking the child's temperature
rectally, coat the tip of the
thermometer with petroleum jelly ie
vaseline) and insert it half an inch into
the rectum. Hold the thermometer still
for 2 minutes. Never let go off the
thermometer.
ƒ While taking the child’s temperature
orally, place the end of the
thermometer under the tongue and
leave it there for 2 minutes. Don't let
the child bite on the thermometer. It
may injure his mouth or release the
toxic mercury into his the GIT.
ƒ After using the thermometer, wash it in
cool, soapy
We can take reading:
♦ From the child’s mouth
♦Temperature
Under the armreadings from the
♦ In the ear
armpit are not very reliable and are about
0.5ºC lower than mouth temperature.
Thermometer strips that are placed on
the child's forehead are popular but give
just a rough indication. Most of the time,
the exact level of a child’s temperature is
not particularly important, unless it is
very high (39ºC or over). In practical
terms the temperature reading will be
enough to give an indication of whether a
fever is present.
Ear temperature
If affordable, an ear thermometer is a very
quick method and will give a read-out in seconds. Ear
thermometers rely on measuring infrared (heat)
radiation from the eardrum.
Other types of thermometer (such as the
probe type) are not suitable for taking ear readings and
must never be placed within the ear canal. Some ear
thermometers are adjustable so they can be made
suitable for adults or children.
ƒ To get a reliable temperature measurement
from the ear, the thermometer must be used
exactly as directed.
ƒ Read the instructions carefully before you
start.
ƒ Especially with small children, ear
thermometers require a steady hand to find
the right spot.
ƒ The ear canal has a natural curve, so to
ensure that the thermometer is pointing
towards the eardrum it may be necessary to
pull the top part of the child's ear gently
upwards during the reading.
ƒ If the child has been lying with his head on a
warm pillow, or has just come inside out of
the cold, you will need to wait 10 to 15
minutes before the ear can provide an
accurate measurement of body temperature.
Short duration fevers
Most cases of short duration
fevers (less than two weeks) are because
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of infections due to viruses, bacteria, or
protozoa. Many of these patients recover
completely even before a precise
diagnosis is made or treatment is given.
Short duration fevers may be
present with or without localizing
manifestations. Malaise, headache,
nausea, vomiting and loss of appetite are
the nonspecific symptoms associated
with most infective fevers in childhood.
Some common infections causing short
duration fevers are considered below:
♦ Respiratory system: Common cold,
pharyngitis, acute otitis media,
mastoiditis and pneumonia are the
usual acute respiratory illnesses.
These are often viral in etiology.
Significantly, in viral infections a
number of mucosal surfaces are
involved simultaneously or in quick
succession. In bacterial infections,
the inflammatory process is usually
localized; regional lymph nodes are
often involved. The rate of spread of
infection is slower in bacterial
infections. Throat should always be
examined to exclude follicular
tonsillitis and diphtheria; other
important area to be examined is ear,
where acute suppurative otitis media
is a common cause of fever among
children.
♦ Urinary tract infection: Infections
of urinary tract are equally common
in infancy among both sexes. After
infancy, girls are more prone to
develop such infections. Signs &
symptoms may, however, be
minimal or absent. The fever may be
high and intermittent, at times
associated with chills. Urine
analysis should be done for the
diagnosis of unexplained fever
especially in girls.
♦ Meningitis: Marked irritability with
photophobia and headache, vomiting
and neck stiffness should arouse the
suspicion of meningo-encephalitis.
The child may have neurological
signs, convulsions, apathy, stupor,
and coma apart from high grade
fever. The diagnosis needs lumbar
puncture for the examination of
cerebrospinal fluid. Meningitis and
septicemia in first 4-6 months of life
usually have atypical presentation.
♦ Exanthematous disorders: Careful
search is required for detection of
exanthema or enanthem in all cases
of fever.
♦ Pyogenic infections: A meticulous
search should be made for the foci
of infection in liver, perinephric and
sub-diaphragmatic regions, bones
and joints. Long bones should be
palpated for any tenderness and even
X-ray may be sometimes required.
♦ Malaria: It should always be
considered in the differential
diagnosis of any short term-fever in
endemic area. Although fever in
malaria is classically intermittent
and relapsing, it may present in an
atypical manner especially in
children in endemic areas.
♦ Typhoid fever: Typhoid fever is
endemic in most tropical and
subtropical countries with poor
standards of sanitation and personal
hygiene. Classical picture of enteric
fever may not be present in some
cases. Mild splenomegaly may be
present.
♦ Other cause: Heat hyperpyrexia,
dehydration, fever, allergy to drugs
(drug fever), thrombo-embolic
phenomena and hemolytic crisis are
other less common causes of short-
term fever among children
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♦ Heat hyperpyrexia: This is not an
unusual cause of fever in tropical
countries where ambient
temperatures may go as high as
45°C. Heat hyperpyrexia may occur
even without direct exposure of the
child to sunlight. The predisposing
factors include high temperature and
humidity in the environment,
unsuitable clothing, dehydration,
and debilitating illnesses as malaria,
pneumonia, measles and renal
disorders. Invariably heat
hyperpyrexia is associated with
cessation of sweating. The onset of
high fever may be sudden. The
rectal temperatures may exceed 42-
43°C. The skin appears dry and hot
(without sweating); tachycardia and
tachypnea are present. Loss of
consciousness occurs early. The
patient may develop peripheral
circulatory failure and hemorrhages.
Headache, faintness, abdominal
discomfort and delirium are usually
present. The liver and kidney failure
may complicate heat hyperpyrexia.
Prolonged fever (more than two weeks)
Long duration of fever among
children is a difficult diagnostic problem
and requires utmost clinical judgment
and skill. Some causes of prolonged
fever among children are given below:
Symptoms of Fever in Children
Signs and symptoms of fever may
be obvious or subtle. The younger the
child, the more subtle the symptoms are.
The infant may be irritable, fussy,
lethargic, quiet, feel warm or hot, not feed
normally, cry, breathe rapidly, or exhibits
changes in sleeping or eating habits.
Common causes of the prolonged fever.
Relatively common causes
1 Infections
2 Connective tissue disorders e.g.
rheumatoid arthritis and systemic
lupus erythematosus etc.
3 Neoplastic disorders e.g. lymphoma,
Hodgkin disease, leukemia etc.
Less common causes
1 Immune deficiency disorders
2 Hematological disorders e.g.
spherocytosis, agranulocytosis, and
hemolytic anemia.
3 Neurological disorders e.g. familial
dysautonomia, hypothalamic and
third ventricular lesions.
4 Genetic disorders e.g. anhidrotic
ectodermal dysplasia.
5 Miscellaneous causes e.g. drug
fever, periodic fever.
6 Metabolic e.g. thyrotoxicosis,
diabetes insipidus.
A verbal child may complain of
feeling hot or cold, body aches, headache,
or have difficulty sleeping or sleep more
Evaluation of fevers
Before starting to investigate it is
essential to document fever and observe the
type of fever. The onset, type and character
of fever and the course of illness should be
clinically evaluated to arrive at possible
diagnosis. In general, a single isolated fever
spike is not associated with an infectious
disease (in infusion of blood & blood
products, some drugs, some procedures, and
other manipulations); temperature in excess
of 41ºC are most often associated with a non
infectious cause. ( e.g. central fever resulting
from central nervous system dysfunction
involving hypothalamus, malignant
hyperthermia, malignant neuroleptic
syndrome, drug fever, or heat stroke.)
Temperatures that are lower than normal
(<36ºC) can be associated with
overwhelming sepsis but are more
commonly related to cold exposure,
hypothyroidism, or overuse of antipyretics.
Fever with chills and rigors suggest malaria,
urinary tract infection, and abscess or
nosocomial infection. Hodgkin disease has
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 Indian J for Practising Doctor; Vol I; No. 4
typical Pel-Ebstein type of fever (3-10 days
cycle of febrile and afebrile periods).
Intermittent fever is an exaggerated
circadian rhythm that includes a period of
normal temperatures on most days;
extremely wide fluctuations may be termed
septic or hectic fever. Sustained fever is
persistent and does not vary by more than
0.5ºC per 24 hours. Remittent fever is
persistent and varies by more than 0.5ºc
/24hr. Relapsing fever is characterized by
febrile periods that are separated by intervals
of normal temperature; tertian fever occurs
on the 1st and 3rd days (e.g. vivax malaria).
And Quartan fever occurs on 1st and 4th
days (e.g. in plasmodium malaria). A
biphasic fever indicates a single illness with
two distinctive periods of fever over one or
more weeks (camel back fever pattern e.g. in
poliomyelitis, Leptospirosis, dengue fever,
yellow fever, tick fever, African
hemorrhagic fevers). Periodic fever is used
narrowly to describe fever syndromes with a
regular periodicity (e. g. cyclic neutropenia,
periodic fever, apthous stomatitis, etc.)
The relationship between the
patient’s pulse rate and temperature can be
informative. Relative tachycardia, when
pulse rate is elevated out of proportion to the
temperature, is usually due to non-infectious
causes in which a toxin is released to cause
the fever. Relative bradycardia
(temperature-pulse dissociation), when the
pulse rate remains low in the presence of
fever, suggests typhoid fever, brucellosis,
Leptospirosis, or drug fever. There can also
be some conduction defects associated with
the fever. Administration of antimicrobial
agents can result in very rapid elimination of
bacteria, if tissue injury has been active, the
inflammatory response and fever can
continue for days after all microbes have
been eradicated.
Fever without focus
Fever is a common manifestation
of infectious disease but is not predictive
of severity. Viral fevers are usually
benign in normal hosts and respond well
to the supportive therapy. Other
infections like; sepsis, meningitis,
pneumonia, osteoarthritis, pyelonephritis
if untreated may have significant
morbidity and mortality.
Fever without localizing signs or
symptoms usually of acute onset and
present for less than one week is a
common diagnostic dilemma. Young
infants demonstrate limited signs of
infection, often making it difficult to
distinguish clinically between serious
bacterial infections and self limiting viral
illness.
Infants younger than 3 months
An infectious agent usually viral
is identified in 70% of infants younger
than 3 months of age with fever. The
remainder has usually undiagnosed self
limited viral infection. However fever in
an infant younger than 3 mo of age
should be taken in the category of
serious illness like bacteremia. Serious
bacterial infections are present in 10-
15% of previously healthy term infants
presenting with rectal temperatures of
38ºC or greater. These infections include
sepsis, meningitis, urinary tract infection,
enteritis, and osteomyelitis and
supparative arthritis. Bacteremia is
present in 5% of febrile infants younger
than 3 mo of age. Organisms responsible
for bacteremia include B streptococcus
and Listeria monocytogens (late onset
neonatal sepsis and meningitis) and
community acquired pathogens including
Salmonella (enteritis), Eschericia Coli
(Urinary tract infection), Neisseria
meningitides, streptococcus pneumonia,
and Hemophilus influenzae type B (sepsis
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 Indian J for Practising Doctor; Vol I; No. 4
and meningitis) and staphylococcus
aureus (osteoarticular infection).
Pyelonephritis is more common in
uncircumcised infant boys, neonates and
infants with urinary tract anomalies, and
young girls.
Other bacterial diseases in this
age group include Otitis media,
pneumonia, omphalitis, mastitis, and
other skin and soft tissue infections.
Viral pathogens can be identified
in 40-60% of febrile illnesses younger
than 3 months of age. In contrast to
bacterial infections which have no
seasonal pattern, viral diseases have
definitive seasonal pattern. Respiratory
syncytial virus and viral influenza-A
virus infections are more common during
the winters, whereas enterovirus
infections usually occur in the summer
and fall.
The approach to the febrile infant
younger than 3 mo should be on
emergency lines and the infant need to be
hospitalized. Careful history and physical
examination should be done. The child is
treated as sick child and evaluated
accordingly.
Children 3 mo -3 years of age.
Approximately 30% of febrile
children 3mo-3yrs of age have no
localizing signs of infection. Occult
bacteremia (bacteremia without an
apparent infection) due to S.
pneumoniae, N. meningitides, and
salmonella occurs in approximately
1.5% of relatively well-appearing
children between 3-36 mo of age with
fever. The increased incidence of
bacteremia among young children may
be due to maturational immune
deficiency in the production of opsonic
IgG antibodies to the polysaccharide
antigens present on encapsulated
bacteria. S. pneumoniae accounts for
90% of cases of occult bacteremia, with
N. meningitidis and salmonella
accounting for most of the remaining
positive cultures.
Common bacterial infections
among children 3-36 mo of age that have
localizing signs include otitis media,
upper respiratory tract infection,
pneumonia, enteritis, urinary tract
infection, osteomyelitis and meningitis.
In this age group, bacteremia is present
in 11% of febrile children with
pneumonia and 1.5% of febrile children
with otitis media or pharyngitis.
Without treatment occult
bacteremia may subside spontaneously
with sequelae, may persist or may lead to
localized infections, such as meningitis,
pneumonia, cellulites, or suppurative
arthritis.`
Fever with petechiae: Independent of
age, fever with petechiae, with or
without, localizing signs indicates high
risk for life-threatening bacterial
infections such as bacteremia, sepsis, and
meningitis. From 8%-20% of patients
with fever and petechiae have a serious
bacterial infection, and 7%-10% have
meningococcal sepsis or meningitis. H.
influenzae type B disease can also be
present with fever and petechiae. All
such children need to be hospitalized for
appropriate evaluation.
Hyperpyrexia (temperature > 41ºC) is
uncommon. Infants and children with
hyperpyrexia should be carefully
evaluated as for all children withy fever.
49
 Indian J for Practising Doctor; Vol I; No. 4
Treatment:
Fever and infection in children
are not synonymous; antimicrobial
agents should, therefore, not be used as
antipyretics and empirical trails of
medication should be avoided.
Hospitalization may be required for
radiographic and laboratory studies that
are un-available or impractical in an
ambulatory setting. After a complete
evaluation antipyretics may be indicated
to control fever and latter on appropriate
antimicrobial therapy may be given to
the child when the evaluation has been
completed.
Fever with temperatures less than
39º C in healthy children usually does
not require treatment. As temperatures
become higher, patients tend to become
more uncomfortable and administration
of antipyretics often makes the patient
feel better. Other than providing
symptomatic relief antipyretics do not
change the course of the infectious
disease. Hyperpyrexia (>41º C) indicates
greater risk of sever infection,
hypothalamic disorders, or CNS
hemorrhage, and should always be
treated with antipyretics.
Aspirin, acetaminophen and
ibuprofen are inhibitors of hypothalamic
cyclo-oxigenase, thus inhibiting PGE2
synthesis. These all drugs are equally
effective antipyretics. Aspirin has been
associated with Reye syndrome in
children and adolescents, its use is not
recommended for the treatment of fever.
Acetaminophen 10-15 mg/kg orally
every 4 hours is not associated with
significant adverse affects, however
prolonged use may be associated with
renal injury and massive overdose may
be hepatotoxic. Ibuprofen, 5-10 mg /kg
orally every 6-8 hours may cause
dyspepsia, GI bleed, reduced renal blood
flow, and rarely aseptic meningitis, or
aplastic anemia.
Tepid sponge bathing in
lukewarm water (not alcohol) is another
recommended method for lowering the
temperatures in children because of
infection or heat stroke.
_________________________________
The pathogens causing human
disease have adapted to thrive optimally
at 37°C ie the normal body temperature.
Fever is body’s response to all
microorganisms which aim to enter the
body’s natural incubator to thrive and
multiply. Our body, in its own fight,
aims to deprive the microorganisms of
the optimal temperature by raising its
temperature above the normal.
Thus, it is not prudent to lower
the body’s raised temperature just for the
sake of bringing it down. Body may be
helped to dissipate heat by evaporation
by lukewarm sponging or bath.
Antipyretics, which reduce body’s
temperature, should be employed only
when the child is very restless, the
temperature exceeds 104°F, or when
there is previous history of febrile
convulsions in the child.
Practitioners should desist from
prescribing antipyretics when the patient
is comfortable.
When prescribed therapeutic dose
should be given at the required intervals,
for example 325 mg (or 650 mg)
paracetamol at 4 hourly intervals, or 200
mg (400 mg) ibuprofen 6-8 hourly. (Ed)
50
 Parent Education
(For the parent of a febrile child)

Tips on giving medicine

• Don't give more than 5 doses in 1 day.

• Don't give a baby younger than 4 months old medicine unless doctor tells to do so.

• Read labels carefully. Make sure you are giving the child, right amount of medicine.

• If using drops, fill the dropper to the line.

• For liquid elixir, use a liquid measuring device to make sure to give the right dose.

Other ways to help the child feel better

• Give the child plenty to drink to prevent dehydration (not enough fluid in the body) and
help the body cool itself.

• Keep the child still and quiet.

• Keep the room temperature at about 70°F to 74°F.

• Dress the child in light cotton pajamas so that body heat can escape.

• If the child is chilled, put on an extra blanket but remove it when the chills stop

Bath helps to lower child's fever

Used together, acetaminophen and a lukewarm bath may help lower a fever. Give
the acetaminophen before the bath. If the bath is given alone, the child may start
shivering as his or her body tries to raise its temperature again. This may make child feel
worse. Don't use alcohol or cold water for baths.

Need for consultation

If the child has any of the warning signs listed in the box below,
Under 1 month old. If the baby's temperature goes over 100.5°F rectally, even if he or she
doesn't seem sick, such babies need evaluation. Babies this young can get very sick very
quickly.

One to 3 months old. If the baby has a temperature of 100.5°F (even if the baby doesn't
seem sick) or a temperature of 99.5°F that has lasted more than 24 hours.

Three months and older. If the child has a fever of 101.4°F, watch how he or she acts. If
the fever rises or lasts for more than 3 days & the children 3 months to 2 years of age, if
the temperature is 102°F, the child may seem to feel fine.

Need of consultation: if the child
has any of these warning signs
• Changes in behavior
• Constant vomiting or diarrhea
• The young child is less than 3 months
old, who runs a high fever.
• The child cries and cries, without being
able to comfort them, and doesn't wake
up easily.

• Dry mouth • The child has a temperature over 38ºC

(101.3ºF) for more than three days.
• Earache or pulling at ears

• Fever comes and goes over several days • The child has just had an operation.

• High-pitched crying
• The child doesn't seem to be getting
• Irritable better.

• Not hungry If the child experiences any of the following

symptoms with a fever, they should be evaluated;
• Pale
• Stiff neck.
• Seizures

• Severe headache • Affected by bright light.

• Skin rash
• Hallucinations.
• Sore or swollen joints
• Red rash or blue/purple dots or patches.
• Sore throat

• Stiff neck • Trouble breathing.

• Stomach pain
• Cramps.
• Swelling of the soft spot on the head
• Continued vomiting or diarrhea.
• Unresponsive or limp

• Wheezing or problems breathing • Continued tonsillitis.

• Whimpering
• Pain when urinating, or urinating more
Critical fever than usual.

Look at the child and see • Other illnesses.

♦ Whether they look exhausted or ill?
♦ Are they behaving differently?
♦ If the answer is yes, evaluation is necessary.
The Indian Journal of Practising Doctor is
distributed to all hospitals of the Kashmir
Province. Individuals can get their copies against
a payment of Rs 150/- per copy. However, the
undergraduate medical students may get a
subsidized subscription at the discretion of the
editors.
 Indian J for Practising Doctor; Vol I; No. 4

Rheumatic Fever about infectious diseases, lack of

awareness about need for getting mild
infections like sore throat being getting
Shabnam Bashir treated, or non-availability of medical
_______________________________ facilities.
Cardiovascular diseases are very Of 12 million people currently
important cause of morbidity and affected by rheumatic fever and
mortality across the world. In the year rheumatic heart disease, 2/3rd are
2002, these diseases accounted for 16.7 children between 5 and 15 years of age.
million deaths globally. There are around 3 lakh deaths each
year, with 2 million people requiring
Rheumatic fever is one of the repeated hospitalization and one million
cardiovascular diseases especially likely to require surgery in the next 5 to
common in the developing world. It 20 years.
usually follows an untreated beta-
hemolytic streptococcal throat infection India, Pakistan, Bangladesh, China, &
in children. It can affect many parts of Indonesia top the list with the highest
the body, and may result in rheumatic number of deaths from rheumatic fever
heart disease, in which the valves are & rheumatic heart disease. Ignorance
permanently damaged, and which may about rheumatic fever & rheumatic heart
progress to heart failure, atrial fibrillation disease is widespread in these countries.
and embolic stroke.
Early treatment of streptococcal
No of cases in 5-14 yr olds (reported in
2003)
sore throat can preclude the development
of rheumatic fever. Regular long-term
S.No Region No of penicillin treatment can prevent
deaths rheumatic fever becoming rheumatic
1 Sub-Saharan Africa 1,008,207 heart disease, and can halt disease
2 South-Central Asia 7,34,786 progression in people whose heart valves
3 China 1,76,576 are already damaged by the disease. If
4 Eastern Mediterranean 1,53,679 treated 75% of people with rheumatic
& North Africa fever recover completely. In many
5 Latin America 1,36,971 developing countries, lack of awareness
6 Other parts of Asia 1,01,822 of these measures, coupled with shortage
7 Eastern Europe 40,366 of money and resources, are important
8 Pacific 7,744 barriers to the control of the disease.
9 Developed countries 33,330

Nowadays, rheumatic fever

mostly affects children in developing
countries, especially where poverty is
widespread. Up to 1% of all school
children in Africa, Asia, the Eastern
Mediterranean region and Latin America
show signs of disease. This has to do
with overcrowding, lack of awareness

53
 Indian J for Practising Doctor; Vol I; No. 4
Patient Education:
Rheumatic Fever
____________________
Rheumatic Fever, once common
acute inflammatory disease,
characterized by fever and pain,
tenderness, redness, and swelling of the
joints. Rheumatic fever can cause
inflammation of the heart and damage to
the heart valves (endocarditis). First
attacks usually occur from the age of 7 to
12 or 14; recurrent attacks can occur
throughout adult life. The mortality from
the acute attack is low, and most cases
subside spontaneously. Often, however,
inflammation of the heart leads to
scarring and deformity, causing the
valves to malfunction. This strain on the
heart muscle causes rheumatic heart
disease, which can cause death in middle
or later life.
Acute rheumatic fever is a
complication of streptococcal infection,
such as strep throat, scarlet fever, or
erysipelas. It sometimes develops after
infections so mild as to pass unnoticed.
Rheumatic fever begins either
insidiously or abruptly after a latent
period of two to six weeks following the
streptococcal infection. Aside from
fever, malaise, and migratory arthritis,
patients may develop nodules under the
skin, skin rashes, abdominal pain,
pleurisy, and chorea. The most serious
aspect of the disease, however, is the
involvement of the heart.
Treatment involves the use of
penicillin to eradicate streptococci that
may still be present, bed rest, and
administration of salicylates or
corticosteroids. It may take many weeks
or months before the attack runs its
course. Rheumatic fever has become
relatively rare, probably due at least in
part to the widespread use of antibiotics.
Endocarditis implies infection
and inflammation of the membrane
lining the inner surface of the heart,
including the heart valves. The two
major forms of the disease are the acute
type, which appears suddenly and can be
fatal within a few days, and the subacute
type, which develops slowly and may
cause death within months.
Subacute bacterial endocarditis
usually results in fever, toxaemia, and
lesions of the heart valves; particles
dislodged from these lesions often cause
embolism. Infection of the heart valves
and lining, or endocardium, may come
from primary infections of the teeth,
tonsils, and sinuses. The disease is
characterized by the formation of
bacterial or fungal growths on the valves
and endocardium. It has its greatest
incidence in people between the ages of
30 and 50 years. Antibiotic therapy,
when used in large doses for extended
periods, is effective in curing the
bacterial infection of subacute bacterial
endocarditis, but damage done to the
heart by the bacteria cannot be repaired.
Routine use of penicillin and other
antibiotics during dental surgery and to
treat primary bacterial infections has
decreased the incidence of endocarditis.
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 Indian J for Practising Doctor; Vol I; No. 4
Management of Rheumatic Fever
Treatment of patients with acute
rheumatic fever is geberally directed
toward decreasing acute inflammation,
decreasing fever & toxicity, controlling
cardiac failure, preventing episodes of
acute rheumatic fever after significant
streptococcal upper respiratory tract
infections, and preventing rheumatic
heart disease.
The mainstay of treatment are
salicylates and corticosteroids. However,
neither of these drugs can prevent or
modify the development of rheumatic
heart disease. Patients clinically
diagnosed with acute rheumatic fever
who have not received antibiotic therapy
for a recent episode of Group A-beta
hemolytic streptococci pharyngitis
should receive a 10-day course of
penicuillin.
Primary prevention of acute
rheumatic fever depends on accurate
diagnosis of a antecedent streptococcal
infection as well as adequate therapy.
Penicillin given orally for 10 days or
intramusclularly one time has been
shown effective in prevention of
rheumatic fever. In penicillin-allergic
patients, although erythromycin is
considered the drug of choice, it has not
been shown to prevent acute rheumatic
fever.
Then there are patients who may
develop acute rheumatic fever despite
receiving adequate therapy for Group A
beta-hemolytic streptococci pharyngitis.
Various reasons for this ominous
situation could be:
• Poor patient compliance (this is a
problem with both oral &
injectable penicillin)
• A shorter latency period
• Currently recommended therapies
for Group A beta-haemolytic
streptococci pharyngitis have
becomes inadequate for
prevention of acute rheumatic
fever. This is the biggest worry
currently.
Approximately 1/3rd of patients
who develop acute rheumatic fever have
streptrococcal infections which are either
subclinical or too mild to be brought to
medical attention. As a result they
receive no antimicrobial therapy for their
infection. Recent studies show that up to
75% of patients with acute rheumatic
fever either have no history of a
preceding streptococcal infection or have
an infection that was so mild they did not
seek medical treatment. This fact
complicates prevention of acute
rheumatic fever
Patients who develop acute
rheumatic fever require continuous
prophylaxis to prevent intercurrent and
recurrent streptococcal infections and
recurrent episodes of acute rheumatic
fever. The preferred regimen consists of
pencillin G benzathine (1.2 million units,
IM every 4 weeks). The recurrence rate
with this regimen is reported to be 0.4
cases/100 patient yearsof observation.
Alternative therapies include oral
penicillin (250 mg, twice a day) or oral
sulfadiazine. Both these regimens are
considered less effective than
intramuscular benzathine penicillin,
primarily because of non-compliance by
patients. Patients who are allergic to
penicillin can be can be treated with
erythromycin (250 mg twice daily).
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 Indian J for Practising Doctor; Vol I; No. 4
Duration of prophylaxis is
controversial. Previously investigators
recommended lifelong prophylaxis.
However, fortunately, the risk of
recurrences of acute rheumatic fever
decreases with patient’s age and the
number of years since the last attack. In
general, it is recommended that
prophylaxis continue until patients are in
their early twenties and at least 5 years
have passed since the most recent
episode of acute rheumatic fever.
The American Heart Association
Committee on Rheumatic Fever &
Endocarditis recommends that patients
who have rheumatic fever without
carditis should receive prophylaxis until
the age of 21 or until at least 5 years
have passed since their last attack.
Patients who had rheumatic fever with
carditis but no valvular disease should
receive prophylaxis until adulthood and
until at least 10 years have passed since
their last attack of acute rheumatic fever.
Patients with valvular disease should
receive prophylaxis until age 40 and until
at least 10 years had passed since their
last attack.
Patients with residual valvular
rheumatic disease must receive antibiotic
prophylaxis whenever they undergo a
surgical or dental procedure, thart may
have a potential of evoking bactermia.
This is necessary to prevent occurrence
of bacterial endocarditis.
_________________________________
Further Reading:
Bisno AL. streptococcus pyogenes. In:
Mandell, Bennett, Ed. Principles & practice
of infectious diseases. 4th ed, New York:
Churchill Livingstone, 1995; 1786-1810.
Congeni BL. The resurgence of acute
rheumatic fever in the United States. Pediatr
Ann 1992; 21:816-20
Dajani AS. Current status of non-suppurative
complications of group A streptococci.
Pediatr Infec Dis J 1991; 10:S25-7
Dajani A, Taubert K (Committee on
Rheumatic fever, endocarditis, and Kawasaki
disease). Treatment of acute streptococcal
pharyngitis and prevention of rheumatic
fever: a statement for health professionals.
Pediatrics 1995;96:758-64.
Denny FW, Wannmaker LW, Brink WR.
Prevention of rheumatic fever. Treatment of
preceding streptococcal infection. J Am Med
assoc 1950;143:151-53
Mackay J & Mensah GA. Rheumatic fever
and rheumatic heart disease. In: The Atlas of
Heart Disease & Stroke. World Health
Organization & Centre for Disease Control
& Prevention, Georgia; 2004; pg 20-21
Gerber MA, Markowitz M. Streptococcal
pharyngitis: clearing up the controversies.
Contemp Pedriat 1992:118-31
Klein JO. Management of streptococcal
pharyngitis. Pediat Infec Dis J; 1994;13:572-
73
Pitetti RD, Stevens DP. Streptococcus
pyogenes. In: Yu VL, Merigan TC, Barrier
SL. Antimicrobial therapy & vaccines.1999;
Williams & Wilkins; pg 448-9
Shulmann ST. Evaluation of penicilins,
cephalosporins, and macrolides for therapy
of streptococcal pharyngitis. Pediatrics 1996;
97:S955-9
56
 Indian J for Practising Doctor; Vol I; No. 4
Neelam Bashir
_______________________________
Tea, which is culturally and
economically the most significant non-
alcoholic beverage of the world, is a
drink from the buds & leaves of the
Camellia sinensis plant.
I HISTORY
Tea-drinking is first said to have
been recorded in China, c. 2737 BC, when the
Chinese emperor Shen Nung, while touring
his empire, sat beneath a tree and ordered
his servant to boil some water for drinking.
A leaf from the tree fell into the water, and
Shen Nung tried the brew and liked it. The
tree was the Camellia sinensis, now known as
the tea plant. By the time of the Tang
Dynasty (618-907) tea was China’s national
drink. Buddhist monks are reputed to have
spread the tea-drinking habit throughout the
Orient. They cultivated tea gardens in the
grounds of monasteries and Chinese royal
palaces. In the 8th century BC, they took tea
to Japan, pioneering tea cultivation there and
developing the Japanese tea ceremony. The
Persian merchant Hajji Muhammad brought
the first knowledge of tea to Europe. He told
the Venetian author Giambattista Ramusio
of his travels in Cathay (China) and how tea
was made and drunk by the locals, and also
those in Persia and the country of the
Franks. Jesuit missionaries, travelling on the
Portuguese ships that pioneered the sea
routes to the Orient in the 16th century,
initially brought the tea-drinking habit back
to Europe. Dutch sailors opened up their
own trade routes with the Orient in the late
16th century. By 1619, Holland was trading
in tea with its European neighbours,
including Scandinavia and Britain. The first
British ships did not reach China until 1637.
By 1644 the British established themselves in
Amoy port, which became their principal
base in China for about a century. European
contact, through the British & Dutch East
India companies made tea an essential world
commodity.
In 1657 the first recorded sale of tea
in England appeared when Thomas Garway,
tobacconist and coffee-shopkeeper, served
and sold tea in Garraways Coffee House,
Exchange Alley, London. Other coffee
houses were quick to follow suit. Tea-
drinking in the coffee houses, the forerunner
of the gentlemen’s clubs, became the vogue.
In 1662 the Portuguese Infanta, Catherine of
Braganza, arrived in England to marry
Charles II. Chests of tea formed part of her
dowry and it was she who introduced tea-
drinking “in the home”.
In the 17th century tea was
expensive, partly because it was still a
relatively rare commodity, but mainly
because of the imposition of duties and taxes
on tea and other beverages. In 1773 the East
India Company gained the monopoly for
British trading with China as well as India,
plus the import rights in the colonies. For
most of the 18th century the high cost of tea
in Britain led to smuggling, adulteration of
tea leaves, and a thriving black market. By
1834 the reduction in the tax on tea and the
end of the East India Company’s monopoly
opened the way to free trade, and the
foundations of Britain’s shipbuilding
industry were laid with the advent of the tea
clipper. Tea, now much more accessibly
priced, replaced ale and gin as the drink of
the masses. More crockery and pottery were
needed to cope with the demand for tea-
drinking, helping the growth of the British
pottery industry.
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 Indian J for Practising Doctor; Vol I; No. 4
CHARACTERISTICS OF THE
II FAMILY
The tea family, with 250
species placed in 20 genera, is primarily
tropical and subtropical in distribution,
centred in south-eastern Asia, with few
temperate members. Most members are
evergreen trees with broad, simple, resin-
containing leaves, although a few climbers
and herbs occur. The flowers usually have
four or five free, or unfused, sepals (outer
floral whorls) and four or five petals (inner
floral whorls) and are radially symmetrical.
The numerous stamens (male floral organs)
are fused either into a ring, as in the plants
of the Camellia or tea genus, or into distinct
bundles. When the stamens are united into a
ring, the petals are often joined to the ring, as
in the plants of the tea genus. The ovary
(female floral organ) is superior—that is, the
sepals, petals, and stamens are produced
from its base.
III THE TEA PLANT
The plant Camellia sinensis is
considered the most important plant in the
Camellia genus, particularly from a
commercial point of view. It is indigenous to
both China (Camellia sinensis sinensis) and
India (Camellia sinensis assamica), hence the
use of the tea trade terms “China jat” or
“Indian jat” to distinguish the origin of the
original tea bushes on some of the older tea
estates. Today, these two jats are considered
the main varieties, of which there are many
hybrids. In its wild state, the tea plant grows
as a tree, reaching some 98 ft in height.
Cultivated tea is grown as a bush, about 3 ft
high, with continuous vegetative growth.
Leaves of the tea bush are, generally,
serrated, shiny, and pointed. The China jat,
classed as an erectophile (leaf angle less than
50 degrees), has a small leaf that is normally
darker in colour than the larger, broader,
and lighter green leaf of the Indian jat,
classed as a planophile (leaf angle less than
70 degrees).
Teas belong to the family Theaceae of
the order Theales. The genus to which
tea belongs is Camellia. The tea plant is
classified as Camellia sinensis.
IV GROWING THE TEA PLANT
Tea varies in flavour and
characteristics according to the type of soil,
altitude, and climatic conditions of the area
in which it is grown. Processing methods
also affect the flavour and characteristics, as
does the blending of different teas from
different areas.
Today, tea is grown on small-
holdings or estates. In smallholding tea
areas, cooperatives are formed to build a tea-
processing factory central to a group of
smallholders. The larger tea estate is a self-
contained unit, often covering hundreds of
hectares, housing its own factory, tea-
growing area, and even staff houses.
Under modern cultivation the tea
bushes are maintained at waist height for
ease of plucking, and are grown from
cuttings or clones, which are carefully
nurtured in nursery beds, and trained to
grow in a fan-shape until ready for planting
out. Young bushes are planted about 5 ft
apart in rows approximately 3 ft apart. This
allows easy access to the bushes for both
pluckers and gardeners. In the higher
altitudes these rows follow the contours of
the hills or mountainsides to avoid soil
erosion. On some of the higher estates and
smallholdings terraces are built, again to
avoid soil erosion.
While coming to maturity, the
shape-training of tea plants continues, so
that after three to five years, the mature
bushes have a flat top, known as a plucking
plateau. Before the first plucking, the bushes
are severely pruned, known as “lung”
pruning. The mature tea bushes are plucked
mostly by hand every 7 to 14 days. Altitude
and climatic conditions of the growing
region are the two deciding factors with
regard to this regrowth period. A tea plant
grown at sea level will replace itself more
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 Indian J for Practising Doctor; Vol I; No. 4
quickly than one grown at a higher altitude,
where the air is often cooler. Only the top
‘two leaves and a bud’ are plucked from the
sprigs on the plucking plateau. Yields range
from 700 to 1800 kg per acre.
V TEA MANUFACTURE
Some 30-35 kg of plucked leaf
makes some 7.5-9 kg of black tea, which
is the type of tea that has the major share
of the market in terms of production,
sales, and consumption.
There are five stages in the tea-
making process. Withering is the first
stage, in which the plucked leaf is spread
on vast trays or racks, and left to wither
in air temperatures of 25-30° C for a
period of 10-16 hours, depending on the
wetness of the leaf. As the leaf moisture
evaporates the leaves become flaccid. In
the next stage, the withered leaf is
broken by machine, releasing the natural
leaf juices. During the fermentation
stage, the broken leaf is spread on trays
or put in troughs. On contact with the air,
the released enzymes (from the leaf
juices) oxidize. The leaf is turned from
time to time until each tray or trough is
full of a rusty-brown coloured leaf.
Drying, often called firing, is the next
stage. The fermented leaf is fed slowly
through a warm air chamber, which
extracts the moisture, emerging as a dark
brown dried leaf, known as black tea.
During the final stage, known as sorting,
the black tea is fed into a machine fitted
with a series of sieves and outlets. This
sorts the grades into chests before its
onward journey to auctions, traders, or
blenders. In China, tea is sometimes
allowed to absorb the scent from various
flowers; jasmine is a particular favourite.
There are two main grades—pekoe
and broken pekoe. Each grade is subdivided
into further categories as the leaf particles
decline in size. Fannings and dust grades are
the two smallest particles. Other terms are
used to describe the colour and content of
the black tea leaf.
1. Black tea dominates the international
market. Grades of black tea conform to
guidelines that emerged from the British tea
industry in 19th-century India & Ceylon
(now Sri Lanka). Whole leaves produce the
best flavour and are classified by the size
and the ways in which they are rolled.
Leaves that have been broken conform to
some of these qualities; the small pieces of
leaves (debris from the processing of whole
& broken leaves) are called ‘dust’ and even
smaller ones are termed ‘fannings’. These go
into teabags & brick tea. Black teas from
India are collectively called Darjeeling teas.
Keemum is a black tea from northern China.
Lapsang Souchongs is a large-leafed black
tea scented with pinewood smoke.
2. Green tea: The teas drunk in China &
Japan are mostly green. In its preparation
fermentation stage is excluded, and the
enzymes are destroyed by steam or pan
heating before the leaves are rolled and
fired. In North Africa, too, green tea is
preferred. Since the classic word
‘fermentation’ customarily applied to the
oxidation process is correlated with the
formation of alcohol, it was misunderstood
by Muslims and thus this stage of tea
preparation in Muslim countries was
omitted. The size of the leaves determines
the grade of a green tea. Gunpowder, a
green tea, consists of the tight, small
balls of younger leaves. It is withered
then dried, steamed, rolled, and further
dried, so that when brewed in hot water
the complete leaf often unfurls.
3. Oolong tea, semi-fermented, stands
between green & black tea; although it is
fermented, this is done only for 30 minutes
after rolling. For other teas, it lasts for 1-2
hours. Oolongs generally come from
Taiwan.
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 Indian J for Practising Doctor; Vol I; No. 4
Before the tea is shipped, factory
tea-tasters sample the finished make to
ensure no mistakes have been made
during manufacture. These tasters also
send samples of the make to their
brokers, agents, and buyers. At the end
of each make the factory is washed
thoroughly to ensure that the completed
make does not contaminate the next.
VII MAJOR TEA PRODUCERS
Today’s major tea producers are
India, China, Sri Lanka, Indonesia,
Kenya, Malawi, Zimbabwe, Papua New
Guinea, Bangladesh, Mauritius, the
Democratic Republic of the Congo, and
Cameroon. Tea is also grown in South
America, Japan, Australasia, Eastern
Europe, and the Middle and Far East, but
mainly for domestic consumption. Some
teas are seasonal, others are not,
depending on the altitude, proximity to
the equator, and climatic conditions of
the producer region. Yield per hectare
also depends on these factors, plus good
husbandry by the producer. The harvest
weight of plucked leaves from an estate
in East Africa or Assam can fluctuate
between 1,600 and 6,000 kg per hectare,
but is less in high-grown regions, such as
Darjeeling (700 kg). Tea plays an
important role in the producer countries’
economies as a foreign-exchange earner.
Sri Lanka is the world’s largest
tea exporter, accounting for 21% of the
world tea exports. Teas from Sri Lanka
retain the country’s old name “Ceylon”.
Scotsman James Taylor is reputed to
have planted the first tea estate at
Loolecondera in Kandy, and today is
known as the “father of tea” by the
islanders. Ceylon teas have been arriving
for sale in the London auction since
1876. Today, Sri Lanka has more than
200,000 hectares under tea cultivation,
and, because of its geographical position,
tea can be plucked throughout the year.
The western and eastern sides of the
island are divided roughly by the central
mountain system, and because of the
natural climatic conditions of the region,
the western side’s plucking season
alternates with that of the eastern side.
Ceylon teas span the complete spectrum
of low, medium, and high-grown teas,
which are drunk as speciality teas and
used for blending purposes.
Although tea was widely used in
neighbouring China, it had not spread to
India till European colonization. The
preferred beverages of India, instead,
were milk & buttermilk. The first
account of tea being eaten and drunk was
given by a Dutch seafarer as late as 1598.
Tea cultivation was begun by the British
in the 19th Century.
India, a major tea producer, with
more than 400,000 hectares under tea
cultivation, produces approximately 30
per cent of the world’s tea, and accounts
for 14 per cent of the world tea exports.
Indian teas are seasonal, with plucking
undertaken from March through to
October. They range from the low-grown
indigenous Assam, discovered around
1832 by the Bruce Brothers, to the high-
grown teas of Darjeeling, which were
originally planted from seeds and
seedlings imported from China.
India is currently the leading producer of tea in
the world with a yield of 715,000 tons annually.
However, since Indians average half a cup daily
on a per capita basis, 70% of the produce is
consumed locally. Tea in India is generally spiced
& served with milk. As a cup of tea with sugar &
milk may contain up to 40 calories, this is also a
source of quick energy. In India, a skilled worker
using hand shears harvests between 60-100 kg of
tea per day; the machine can raise the yield to
1000-2000kg but is used for low-grade teas
meant for teabags.
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China is the second largest tea
producer and exporter after India and Sri
Lanka respectively. It retains the
majority of its tea produce for home
consumption, exporting about a quarter
of its annual tea yield, which accounts
for 18 per cent of the world tea exports.
In the United Kingdom tea accounts
for about 42 per cent of the total drinks
market. There is an average consumption of
150,000 tonnes yearly, which is more than
North America and Europe combined. New
Zealand and Australia also consume large
amounts. As a nation, the United Kingdom
imports about 16 per cent of the producer
countries’ tea exports.
Tea is an aromatic stimulant,
containing various polyphenols, essential
oils, and the alkaloids caffeine and
theobromine. The concentration of
caffeine in tea ranges from 2.5 to 4.5 per
cent, as contrasted to an average
concentration of about 1.5 per cent in
coffee.
How to make good tea
Get fine tea (whole or bagged). Arrange
clean, cold water, that has no taste of its
own. For green tea, bring the water to a
simmer; for black or Oolong, it must be at a
rolling boil. Warm the vessel in which the
tea is to be brewed by pouring boiling water
into and out of it, and add about 3 gm of tea
per cup to be brewed. Pour boiling water
over the leaves and allow to steep for 3-5
minutes, depending on the type of tea.
Finally remove the leaves or teabags from
the vessel and pour the tea, adding sugar (or
an artificial sweetener), milk, lemon, as
desired.
Tea & health
In modern times, tea is one of the
world’s least expensive beverages, and after
water is the most commonly used beverage.
Because it is made with boiled - & therefore
sterile water - tea is safe to consume in areas
where water quality may be less than satisfactory.
Over the millennia tea has maintained a
reputation for contributing to good health.
Buddhist monks in China & Japan who were
physicians used tea to help people through
illnesses. Even today tea is employed in ancillary
therapy for individuals who suffer from various
infections, colds or chronic diseases. Tea is a
diuyretic and produces both warmth (if it is
served hot) and coolness (because it promotes
evaporation of water from the skin) in the body.
Moreover, steam of hot tea moisturizes the nose,
mouth and throat. The caffeine in tea is also a
‘pick-me-up’.
Caffeine for soft drinks & medicine
is produced from the processed tea ‘fluff’ &
waste. Caffeine in tea was once called
‘theine’, but since it is chemically identical to
caffeine in coffee, the separate term has been
abandoned. Depending on the type of tea, a
150 ml cup may contain 30-50 mg of caffeine,
only 1/3rd of that found in a cup of coffee.
Because of its origin in the East,
maximum research on health benefits of tea has
been conducted in the Eastern region. However,
since 1980s, laboratories in the USA & Canada
(and a few in Europe) have started showing
interest in research on relation between tea and
preventive or promotive health. Their findings
were summarized at the First International
Conference on Tea & Health, held in New York
in 1991. The research suggested that people who
drink tea regularly have a lessened risk of
coronary heart disease. This was also highlighted
that tea has a beneficial effect in warding off
cancers of the stomach, esophagus, and lung.
New research suggests that the caffeine in tea
may play a role in such cancer prevention. Black
tea & green tea had very similar (if not identical)
preventive effects, and a few findings showed
delayed growth and even regression of cancers in
laboratory animals.
Encouraged by the research findings, the
role of tea in prevention of others diseases and
disorders is being probed all over the world.
There are suggestions that the lower risk of lung
cancer in Japanese men, who smoke many more
cigarettes on per capita basis than their American
counterparts, may be attributable to their tea
drinking habit.
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The preventive effect of green & black tea is
attributable to the presence of specific
polyphenols that can act as powerful
antioxidants. Research has shown that the
risk of heart disease and many types of
cancer is lowered by the raised antioxidant
level in the bodies of those who drink tea
and , conversely, the conditions promoting
these diseases involve abnormally low levels
of oxidation.
Tea polyphenols also modify
intestinal bacterial flora, leading to a
decrease in the levels of undesirable bacteria
and contributing to the maintenance and
increase of desirable bacteria. Tea is, in fact,
is the culture medium for kombucha (the tea-
fungus), which is a symbiotic bacterial
culture used in alternative medicine. Tea can
have a specific anti-bacterial action and a
limited effect against specific viruses.
Recent results suggest that
Alzheimer’s disease may occur less
frequently in aging people who are regular
tea drinkers.
Ceffeine in tea is sufficient to
account for its pleasant, slightly stimulating
effect on mental function, and is the reason
for tea’s popularity as a morning beverage.
At the same time the amount is low enough
to preclude any overdosage.
Decaffeinated tea, prepared by solid
CO2 extraction, contains polyphenols but no
caffeine. It retains the taste of tea and is
beneficial to those who can’t take caffeine or
for the ones who want an evening cup
without the attendant risk of insomnia.
Decaffeination can be done at home: Brew a
first infusion, discard it, & brew a second
from the same tea. Caffeine is extracted from
tea in 1-2 minutes, and so a second infusion
will have a weaker taste & no caffeine.

Antioxidants prevent cellular damage caused by reactive oxygen species.

Flavonoids – a group of phenolic compounds – are known antioxidants. Approximately
30% of the tea solids in a typical infusion is composed of flavonoids, whereas about 5%
of the water soluble solid extract of tea is formed by flavonols like quercetin,
kaempferol, myricetin, and their glycosides. Catechins are highly potent flavonoids
present in tea and serve as the best dietary source of natural antioxidants. Of these
catechins, epigallocatechin gallate is present maximally in green tea – forms 10% of dry
weight. Methylxanthines, mainly in the form of caffeine, are present in a proportion of
1/3rd of its content. In addition tea contains theanine, an important aminoacid.
Interflavonoid linkages resulting in formation of proanthocyanidines are being studied
at present.
Antioxidants protect the body against the damaging effects of free radicals
generated in the body durng conversion of glucose and fat to energy, exercise, and by
the action of sunlight on skin. Oxidative stress induced by overproduction of reactive
oxygen species disrupts cellular function. They can interact to form reactive molecules.
These reactive molecules can be counteracted by antioxidants like vitamin C, tocopherol,
carotenoids and flavonoids.
Flavonoids found in tea are 20 times more powerful as antioxidants as vitamin C.
Polyphenols have been proven to inihibit lipid hydroperoxide formation. Their
scavenging properties have been demonstrated against many offensive oxidants
including superperoxide radicals, free radicals, and peroxinitrite. They are known
chemopreventors for protection, romotion and progression of various forms of tumour.
In this regard, epigallocatechin gallate with 5 polyphenol moieties is considered the
most potent tea antioxidant.

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 Indian J for Practising Doctor; Vol I; No. 4
Patient Education
Asthma
Asthma is a chronic airway
disease that involves episodic attacks of
breathing difficulty, wheezing,
coughing, or tightness in the chest. Just
what triggers these attacks varies from
one person to another, but allergies
probably account for the majority of
symptoms in people with susceptible
airways. Other influences can include
cold air, respiratory infections (including
colds), smoke and environmental
pollutants, sudden changes in
temperature or humidity, and strenuous
exercise. Only rarely is asthma attributed
to emotional or psychological distress,
although for many years this was
considered one of the prime triggers.
During an asthma attack the
muscles tighten around the tubes inside
and leading to the lungs (the bronchi),
and the lining of the tubes becomes
swollen and inflamed. Often thick mucus
accumulates in the airways as well. In all
cases airflow is restricted, and emptying
the lungs of air becomes particularly
difficult. These attacks can last
anywhere from several minutes to
several days. Although severely
restricted airflow can be life-threatening,
in most cases the attacks are mild or
moderate. In fact, by avoiding triggers
and using appropriate medications, most
people with asthma can lead active,
healthy lives.
Asthma has become increasingly
common in early childhood, affecting as
many as 10 percent of all children,
probably because of a rise in both
outdoor and indoor pollution. Up to the
age of 10, boys are twice as likely as
girls to have asthma, but by the preteen
years the numbers even out. By age 20,
as well as throughout the remainder of
life, women are about 3 times more
likely than men to be diagnosed with
asthma. They are also more likely to be
hospitalized for asthma and to die of an
attack.
Some of the differences in
diagnoses are undoubtedly attributable to
the greater propensity of women to seek
medical attention for any condition. The
differences may also be related to the
fact that asthma in men is often
misdiagnosed as some other respiratory
condition, such as chronic obstructive
lung disease or emphysema. Even so,
there is now some intriguing evidence
that at least some of the explanation for
women’s susceptibility lies in hormonal
differences. Also, women frequently
have conditions (such as arthritis,
menstrual cramps, and headaches) that
lead them to use aspirin and other anti-
inflammatory drugs which, in rare cases,
may trigger asthma attacks. In addition,
women may be exposed more frequently
than men to certain inhaled allergens,
such as the mites that grow in house dust
and other indoor pollutants. Despite the
many strides made in sharing household
duties, a woman allergic to dust mites
still is much more likely to be the one
who does the vacuuming than a man
with similar susceptibilities.
There is no evidence that asthma
attacks become more severe or more
frequent during pregnancy, but asthma
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can pose particular problems for a
woman expecting a baby. This is
because restricted airflow to the mother
can potentially deprive the fetus of
oxygen. During pregnancy many women
who do not have asthma notice changes
in breathing patterns or difficulty
breathing because the growing uterus
changes the shape of the chest cavity. In
pregnant women with asthma, these
body changes can make asthma attacks
more difficult to control than normal.
Still, most women with asthma can
expect to stay healthy and have healthy
babies if they continue to take their
medications under the supervision of a
clinician who is aware of their
pregnancy.
Who is likely to develop asthma?
The susceptibility to asthma
appears to be inherited, and people with
allergies are particularly likely to
develop it at some point. Among the
allergens that trigger attacks in people
with susceptible airways are dust mites,
molds, pollens, animal dander, and
certain foods. As much as 8 percent of
the population is also allergic to food
additives called sulfites (whitening
agents), and they may experience an
almost immediate asthma attack after
eating foods containing these chemicals.
Sulfites are often found in dried fruits
and vegetables, wine, beer, potatoes,
dehydrated seafood soups, baking mixes,
fruit drinks, and certain soft drinks.
Susceptible people exposed to
large amounts of smoke (whether from
cigarettes or wood-burning stoves),
gasoline fumes, fresh paint, and other
environmental pollutants may have
frequent attacks of asthma.
What are the symptoms?
The classic symptoms of an
asthma attack are wheezing (noisy
breathing), coughing (especially at
night), tightness in the chest, shortness
of breath, and labored breathing.
Symptoms may begin upon exposure to
the offending trigger or may develop
slowly over many hours. Often attacks
develop in the middle of the night.
In a severe attack breathing
becomes rapid and shallow, heartbeat
quickens, and the skin pales or takes on
a bluish cast. It may be necessary to use
accessory neck and abdominal muscles
in order to support breathing. Sometimes
a person with longstanding asthma
becomes barrel-chested as the chest
expands to accommodate enlarged lungs
-the body’s way of compensating for
constricted airways.
How is the condition evaluated?
Usually asthma is diagnosed by a
clinician only after several attacks have
occurred. Various tests including
pulmonary function tests can help
differentiate asthma from other
respiratory diseases. Once asthma has
been diagnosed, the clinician may
suggest seeing an allergist, who can do
skin tests to see if there are any
identifiable allergens underlying the
attacks. The clinician may also suggest
keeping a diary to help determine if the
attacks can be linked to any particular
substances or situations.
How is asthma treated?
Active asthma attacks are usually
treated with a short-acting
bronchodilator, such as albuterol, which
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opens the airways by relaxing smooth
muscle. Corticosteroid medication in an
inhaler or in oral form, such as
prednisolone or prednisone, reduces
inflammation, which is a key mechanism
of asthma attacks. Because it takes at
least 6 hours for corticosteroids to take
effect even if inhaled, bronchodilators
are used to provide immediate relief of
symptoms.
Once the attack is under control,
the physician may prescribe maintenance
medications, such as cromolyn, which
reduce the chances that the airways will
become inflamed. Corticosteroids are
usually continued on a maintenance
basis, in the inhalable form; long-term
treatment with oral preparations is
avoided if possible because they are
associated with adverse side effects.
Many asthma medications are
available in aerosol form and can be
inhaled into the lungs in specific
amounts through a device called a
metered-dose inhaler. The medications
are also available as tablets and syrups.
The aerosol inhalers fit inside a purse
and should be carried at all times to
stave off emergency attacks.
Bronchodilators are also available in a
solution for use in an electric nebulizer,
which produces a mist that the patient
breathes through a hand-held inhaler
attached by tubing to the machine. The
mist may provide added relief at home
during prolonged attacks.
Bronchodilators can also be taken
systemically if necessary. Nose sprays
can help dry up the stuffy or runny nose
which often accompanies allergic
asthma.
Although some asthma
medications are available over the
counter, the condition should be
evaluated by a clinician before these are
tried.
Most asthma drugs are
considered safe for use during
pregnancy. If antibiotics are prescribed
to treat the upper respiratory infections
that can trigger asthma, tetracycline or
sulfa drugs should be avoided because of
adverse effects on the fetus.
Corticosteroids used in inhaled form are
preferred over oral forms during
pregnancy, since relatively little drug
can reach the fetus through this route.
But because severe asthma attacks can
be life-threatening to the pregnant
woman and so potentially damaging to
the fetus, systemic steroids are
considered an appropriate tradeoff for
pregnant women with severe asthma,
even though their safety for the fetus has
not yet been proved or disproved.
In the past, people with known
allergies received desensitization shots
to reduce susceptibility to allergens.
Today, however, allergists often
advocate eliminating or reducing
exposure to the allergen as a first course
of action, partly because desensitization
shots must be taken quite frequently, are
not always effective, and are
uncomfortable and expensive.
Anyone with asthma needs to be
under the regular care of a clinician. This
is because it often takes a good deal of
trial and error before the right
combination of medications and
preventive steps can be determined.
How can asthma be prevented?
Although the underlying physical
cause of asthma cannot be prevented,
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minimizing the frequency of asthma
attacks boils down to eliminating or
reducing exposure to anything known to
trigger them. This is not always easy and
is sometimes impossible, in which case
the only recourse is heavy reliance on
medications. The many asthma attacks
that develop for no apparent reason
obviously cannot be prevented either.
Anyone who suspects certain allergens
or environmental sources can try one or
more of the following tactics.
Minimize dust and other household
allergens
Ordinary household dust consists
of a number of different materials that
trigger asthma attacks, including the
feces of dust mites and cockroaches, pet
dander, and microscopic fabric fibers.
Frequent dusting and vacuuming can
minimize dust exposure over the long
run, but often these well-intentioned
efforts only stir some of the lighter-
weight particles into the air, where they
are readily inhaled. For this reason,
someone other than the allergic person
should be assigned these dust-busting
tasks and the allergic person should stay
out of the room for at least half an hour
after cleaning.
An alternative is to invest in a
double-filtered vacuum cleaner or, better
yet, a so-called high-efficiency
particulate arresting (HEPA) vacuum
cleaner. HEPA air cleaners are a good
investment for the bedroom, if not the
whole house, because so much time is
spent in that room during sleep. Many
allergists also recommend more extreme
measures such as ripping out carpeting,
eliminating all stuffed and upholstered
furniture, and removing books and dust-
catching knickknacks, but not all people
are willing or able to take these steps
(nor do they necessarily help). Perhaps a
more practical alternative is to cover the
affected person’s mattress and
pillowcase with airtight rubber covers,
wipe these down with water on a weekly
basis, wash bedding frequently in very
hot water, and keep the bedroom in
particular as dust-free as possible. If
there is a forced-air heating system in
the home (which disperses dust even
more than other heating systems), it
should be equipped with an effective air
filter to trap offending particles.
Various steps can be taken
against specific allergens found in dust.
If dust mites are the problem, for
example, agents lethal to the mites,
called acaricides, can be applied to
carpeting although these are probably
not safe for use in the home of a
pregnant woman. A cockroach problem
may be reduced by having the house or
apartment fumigated regularly by an
exterminator. As for animal dander, the
best solution is clearly to avoid owning a
dog, cat, or other furry pet and to avoid
long stays at homes inhabited by these
animals. If this is impossible, having
someone who is not allergic wash the pet
on a weekly basis can be a significant
help.
Avoid molds and pollens
Because many of these
substances are prevalent only during
certain seasons, the best tactic for those
unable to exile themselves temporarily
to another climate may be to stay
indoors as much as possible, preferably
in a home, car, or office with air-
conditioned or filtered air. At all times of
the year, shampoos and skin creams
should be checked to make sure they do
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not contain extracts of cottonseed,
flaxseed, or other natural substances that
are sometimes allergenic. Those allergic
to mold and dust mites in particular may
want to invest in a dehumidifier, since
humidity above 20 percent encourages
the growth of these organisms. Adding a
few drops of chlorine bleach to cut
flower arrangements and changing the
water daily can also help prevent mold.
Also, because soil and water can foster
the growth of molds, it is a good idea to
keep indoor plants to a minimum. If
there is a humidifier in the home, it
needs to be cleaned regularly to prevent
the growth of molds and other allergens.
Exercise with care
Even though exercise often
triggers asthma attacks, there is no
reason people with asthma should have
to forgo an activity so important to
health and well-being. In fact, regular
exercise that develops lung capacity is
generally recommended. Just what steps
need to be taken to keep exercise safe,
however, will vary with the individual.
If exercise itself triggers attacks,
it is often sufficient to inhale a
bronchodilator before beginning the
exercise. If cold or rapid temperature
changes trigger attacks, it is best to
restrict exercise to places with warm,
humidified air (such as swimming pools
or gymnasiums). If it is necessary to
walk in the cold air, problems can be
reduced by wearing a warm scarf or
mask around the mouth and nose and
breathing through the nose in order to
warm, filter, and humidify the air before
it reaches the lungs. If pollen plays a role
as well as exercise, it makes sense to
exercise indoors during allergy season.
Be wary of aspirin and other anti-
inflammatory drugs
Because many drugs used to
reduce pain seem to promote asthma
attacks, anyone with asthma should use
these drugs with caution until she is
certain they do not pose a problem for
her. Aspirin (acetylsalicylic acid), which
is sold under a variety of brand names, is
a common culprit. Other analgesics that
often cause problems are ibuprofen and
other non-steroidal anti-inflammatory
drugs (NSAIDs).
Avoid smoke and other pollutants
Anyone with asthma should cut
out cigarettes and steer clear of other
people’s smoke whether it is secondhand
smoke from a cigarette or smoke from a
woodstove, burning leaves, or an
industrial chimney. It is also advisable to
stay inside during pollution or ozone
alerts in urban areas and to avoid
breathing fumes from fresh paint,
turpentine, insecticides, deodorants,
chlorine, cleaning fluid, and other
irritants.
Eliminate foods that cause problems
If the problem is a solitary food
such as peanuts, this is relatively easy to
avoid. It can be quite an ordeal,
however, when the allergy is to eggs,
milk, or flour ingredients that are often
hidden in processed foods or foods
prepared in restaurants. Anyone who
reacts to sulfites needs to be particularly
careful in restaurants and should
routinely check all labels on packaged
foods eaten at home. The Food and Drug
Administration (FDA) recently banned
the use of these agents on fresh fruits
and vegetables and made it mandatory
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for manufacturers to include a notice on
labels if detectable amounts of sulfites
are present in a food.
Consider getting a flu shot
If asthma is triggered by
respiratory infections, it is a good idea to
have a flu vaccination every year. Other
household members might also consider
getting shots, to minimize the chances
that they will bring an infection home.
Also, if at all possible, contact with
people who have viral infections
(including colds) should be avoided.
68
Viral Hepatitis: Recent
Progress
Rohini Bhan & Arvind Bhan
Viral hepatitis is still one of the most
common causes of acute and chronic liver
disease worldwide. Viral hepatitis is a
subject of profound concern and results in
about 10,000 new papers each year, from
molecular structure to newest treatments.
Major new advances have been made in our
knowledge of these diseases, many during
the past two years.
Five hepatotropic viruses A to E are
now recognised and all are important public
health issues, although more so in some
countries than others. Three additional
viruses, Hepatitis G, TT virus, and SEN-V
have been discovered recently, but have to
be proved to be hepatotropic and pathogenic
to liver.
It is evident that these viruses,
although similar in some respects, have a
number of intriguing differences. Most are
RNA viruses but Hepatitis B and TT virus
are DNA viruses. Each belongs to a different
virus family and, with the exception of
Hepatitis D virus, has unique features that
have resulted in being classified in a new
genus within family. Two viruses (Hepatitis
B and C) are enveloped and two (Hepatitis
A and E) are not, whereas the Hepatitis D
virus requires an envelope provided by the
surface-coat material of Hepatitis B virus
for it to propagate. Only Hepatitis B virus
integrates into the host DNA. Two viruses
(Hepatitis A and E) are spread enterically
and cause acute illness, whereas three
(Hepatitis B, C, D, G, TTV and SEN-V) are
spread parenterally and Hepatitis B, C and
D cause chronic disease. Hepatitis G, TTV
and SEN-V are also thought to cause mild
acute and chronic disease. Although viral
factor may contribute to the nature of the
disease they cause, the host's immunologic
reaction to the presence of virus in
hepatocytes emerges as the dominant
mechanism of liver-cell damage and
inflammation1. Newer medications in the
form of interferon-α and nucleoside
analogues have been added to the
armamentarium of chronic viral hepatitis.
Liver transplantation has been established
as an effective therapy for patients with end-
stage liver disease2 (Bzowej NH 1999). This
review discusses the recent advances in our
knowledge of viral hepatitis A to E and viral
hepatitis Non-A-to Non-E, focussing on the
literature of the past few years.
A. New Agents of Viral Hepatitis
Non-A -To-Non-E Viral Hepatitis
The list of potential hepatotropic
viruses continues to grow, with the
recent discovery of the GB virus-C, the
TT virus, and the SEN virus. Prevalence
rates of the GB virus-C have ranged
from 1.2% to 13% among healthy blood
donors from all over the world. Higher
prevalence rates have been reported
among intravenous drug users. Similarly,
the TT virus has a global distribution.
However, in spite of numerous reports of
the presence of both of these viruses in
various kinds of liver diseases, definite
evidence linking them to a specific
disease, or illness is lacking. The SEN
virus is thought to be a novel viral agent
that may be linked to cryptogenic
chronic hepatitis, but data are awaited.
Hepatitis G
The Hepatitis G virus (HGV) is a
single-stranded DNA virus that is
included in the Flaviviridae family and
shares a 27% homology with HCV. The
name HGV actually denotes 2
independent viruses, HGV and GBV-C.
The HGV has not yet been isolated.
 Indian J for Practising Doctor; Vol I; No. 4
Hepatitis G virus, was first isolated in 1995.
Two lines of investigations led to its
discovery: 1) an agent termed GBV-C was
recovered from a human following the
identification of similar viral isolate, GBV-A
and GBV-B, isolated from tamarinds
infected with serum from a surgeon (G.B.)
with hepatitis, and 2) a blood-borne virus
was isolated from plasma from a patient
with chronic hepatitis and designated
Hepatitis G virus (HGV). These two human
isolates (GBV-C and HGV) are now
considered strains of the same virus and
have amino acid sequence homology of 95%.
Although Hepatitis G virus (HGV)
can cause chronic infection and
viraemia, it is a rare cause of hepatic
inflammation and most infected persons
are asymptomatic. Histologic evidence
of HGV infection is rare, and serum
aminotransferase concentrations usually
are normal 3. Currently no conclusive
evidence indicates that HGV causes
fulminant - or chronic disease and co-
infection does not seem to worsen the
course of infection with Hepatitis B
virus (HBV) or Hepatitis C virus (HCV).
The HGV has been reported in
adults and children throughout the
world. Infection has been reported in
10% to 20% of adults with chronic HBV
or HCV infection, indicating that co-
infection is a common occurrence. The
primary route of spread is through blood
transfusions, but HGV also can be
transmitted by organ transplantation.
Other important risk factors include
injection drug use, haemodialysis, and
homosexual and bisexual relationships,
indicating that sexual transmission may
occur. Transplantation transmission
seems to be rare and has been associated
with high-titre maternal viraemia; when
it occurs, infection usually becomes
persistent in infants.
The incubation period is not yet
known. Currently, HGV infection can be
diagnosed only by identifying viral
genomes by using polymerase chain
reaction (PCR) assay. No serologic test
is available. In United States 1% to 2 %
blood donors are viraemic as defined by
the presence of viral nucleic acid in their
blood.
TT Virus (TTV)
A group in Japan, in December
1997, reported yet another transfusion-
transmissible virus discovered via the
use of cloning and DNA sequence
analysis. This novel, single-stranded
linear DNA virus has been designated
TT-virus or TTV after the initials of the
first patient (TT) from whom the virus
was isolated. The virus is un-enveloped
and has been associated with biopsy-
proven, post-transfusion hepatitis of
unknown aetiology. TTV has a
significant prevalence in the United
States, United Kingdom, Japan, Thailand
and Germany.
Transaminase activity or liver
histological score is not significantly
increased among TTV positive patients4 .
The Hepatitis B infection (HBV) and
Mediterranean origin are the risk factors
associated with TTV infection. TTV is a
widely spread infectious agent with a
weak pathogenesity. TTV infection does
not impact on liver damage with HCV
infection. TTV infection also does not
affect the development and progression
of hepatocellular carcinoma.
Cryptogenic cirrhosis (one in which the
cause of cirrhosis is not evident)
accounts for 5% to 15% patients with
chronic liver diseases in the United
States, supporting that unidentified viral
agents are associated with liver disease5 .
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TTV DNA is detected by PCR and
by phylogenetic analysis. (Phylogenesis
is the evolutionary development of a
species, as distinguished from ontogeny,
development of the individual.) TTV
strains can be divided into 6 genotypes
using phylogenetc analysis. The majority
of TTV-DNA sequences are related to
genotypes 1 and 2 as described in
Europe.
Hepatitis SEN-V
In July 1999, the Diasorin
Research Centre in Bresica, Italy, found
that a novel virus, provisionally named
SEN-V, caused acute and chronic
hepatitis, probably accounting for many
cases of Non A-to-G hepatitis. This virus
is parenterally transmitted, and therefore,
appropriate screening of blood and blood
products could control its spread. In
addition, this virus appears capable of
co-infecting patients who have other
types of viral disease raising the
possibility that it may aggravate their
clinical course and/or their response to
treatment6.
Hepatitis F
In 1994, French researchers
reported the isolation of an enteric agent
responsible for sporadic cases of Non-A-
E hepatitis and named the virus Hepatitis
F (HFV), for hepatitis French virus.
However, their findings have not been
confirmed by others and the term HFV is
currently unclaimed.
B. Hepatitis-A-To-E
Hepatitis A
Hepatitis A virus (HAV) is an
enterovirus in the family of
Picornaviridae. It has only one serotype.
The genome is a single strand of
positive-sense RNA. Hepatitis A is the
most frequently reported vaccine
preventable disease in the developed
world. The risk of Hepatitis A in patients
with chronic liver disease has been
confirmed and the efficacy of Hepatitis
A vaccine in these patients has been
proved7. The reduction in the incidence
of Hepatitis A in developed countries
will only be achieved by routine
childhood vaccination rather than by
targeted vaccination of high-risk group.
Unlike Hepatitis B virus (HBV)
transmission by blood via parental routes
can occur but is unusual in Hepatitis A
infection.
Hepatitis B
The advances in molecular
biology techniques in the past decade
have led to the clarification of Hepatitis
B viral DNA sequences. However, much
remains to be established regarding the
emerging Hepatitis B mutants. Several
putative forms of Hepatitis B virus have
been isolated, but their epidemiology,
natural course of infection and clinical
significance remain sketchy.
Compounding these problems are factors
created by human interventions, such as
HBsAg mass immunization,
chemotherapy of chronic HBV patients
and HBIg prophylaxis of orthoptic liver
transplant (OLT) patients, which tend to
encourage new mutants to emerge.
Hepatitis B virus: A complex structure
Hepatitis B (HBV) is a
Hepadnavirus. It is a small enveloped
DNA virus containing 3.2 kb. The
Hepatitis B virion consists of a surface
and a core. The core contains a DNA
polymerase and the e-antigen. The DNA
structure is double-stranded and circular.
There are four major polypeptide
reading frames (genes): the S (surface),
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the C (core), the P (polymerase) and the
X (transcriptional, transactivating). The
S gene consists of two regions, the pre-
S1, pre-S2 and encodes the surface
proteins (HBsAg). Very rarely a
mutation may occur in the S gene and
may abort the HBsAg with the result that
a person may be HbsAg negative but
still have virus present as determined by
HBV DNA. The C gene is divided into
two regions, the pre-core and the core,
and codes two different proteins, the
Core antigen (HBcAg) and the E antigen
(HBeAg)
HBV Mutants
Because HBV uses a reverse
transcription mechanism, mutations are
fairly common. It is now known that
HBV mutates far more frequently than
the usual DNA virus but less than
rotaviruses. During the last 7 years a
series of HBV mutants have been
recognized. The most important of these
is the so-called pre-core mutation, in
which there is a defect in the pre-core
region of HBV DNA. This mutation
results in the failure to express HBeAg.
The pro-core may stop production of
HBeAg and these persons will be
HBsAg positive, HBV DNA positive,
but HBeAg negative. The pre-core
mutation has been implicated in the
pathogenesis of fulminant hepatitis and
may be responsible for severe
exacerbations of chronic hepatitis
associated with HBV infection. In
general, patients with this mutant are
more likely to progress to cirrhosis and
hepatic insufficiency, compared to
infection with wild strains.
A wide geographical variation
seems to emerge from pre-core mutants.
As high as 25% of chronic HBV
infections in patients in Delhi were
found to be caused by pre-core and
surface mutants. If pre-core mutants
become a clinically important problem,
it will be important to incorporate them
into the next generation of Hepatitis B
vaccine8 . Although the efficacy of HBV
immunization is well proven, cases of
vaccine failure leading to chronicity,
acute self-limited symptomatic hepatitis
and in some cases, fulminant hepatitis
has been reported. In some of these
cases, anti-HBsAg neutralization-
resistant mutants or/naturally occurring
escape mutants have been identified.
Vaccine escape mutants have also been
identified in newborns from infected
mothers who had been vaccinated at
birth. Clearance of HBV infection results
from complex immune mechanisms
including TH1 cytokines significantly
associated with HLA class II alleles.
Escape HBV mutants, especially pre-
core mutants influence the outcome.
To make it even more complex,
the HBsAg particles are antigenically
complex and these antigenic
determinants have been identified. There
is a single common determinant
designated a, and four sub-determinants
designated d, y, w, and r. Thus, the four
major determinants are: adr, ayw and
ayr.
Extra-hepatic Associations Although
uncommon, a number of conditions
associated with Hepatitis B antigen-
antibody complexes have been
recognised. These include: polyarteritis,
glomerulonephritis, polymyalgia
rheumatica, Guillian-Barre syndrome,
myocarditis and essential mixed
cryoglobulinaemia - sometimes only a
test tube finding9
Clinical Course Hepatitis B is
transmited by parenteral, congenital and
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sexual routes. Fulminant disease carries
a 1.2% mortality. Up to 10% of patients
develop a chronic hepatitis complicated
by cirrhosis or hepatocellular carcinoma.
Congenital infection brings a high risk of
hepatocellular carcinoma.
Treatment Lamivudine is a major
advance in the therapy of chronic
Hepatitis B. Although drug resistant
mutants may be selected during therapy,
additional nucleoside analogues
including adefovir are promising.
Aggressive combination therapy has
emerged as a promising strategy from
chronic Hepatitis B and C. Liver
transplantation has become routine for
end stage Hepatitis B virus liver
disease10. The spontaneous risk for viral
recurrence after transplantation is high,
but has been decreased effectively in
Hepatitis B-positive recipients with the
use of HBIG and lamivudine11.
Hepatitis B vaccine: Safety and efficacy
Concerns have been raised by
reports of multiple sclerosis (MS) or
other demyelinating diseases occurring
in adults who had recently received
Hepatitis B vaccine. There are three
hypotheses that could explain the
observed cases of demyelinating
diseases following HB vaccine: (1)
coincidence, because of the large
number of HB vaccine doses
administered in the developed world,
many of them in age groups where
symptoms of MS first occur.
(2)"triggering": an increased risk of
symptomatic demyelination following
HB vaccine, which would act as
"trigger" in individuals predisposed to
develop MS or CNS demyelinating
diseases - these individuals would have
developed demyelination with or without
an altered natural history after some
immunologic or other precipitating
factor and (3) a true causal relationship
between HB vaccination and MS or
other CNS demyelinating disease.
Evidence to support the first
hypothesis includes the fact that no
statistically significant association was
found between Hepatitis B vaccine and
MS in the limited studies conducted to
date. Further the age and sex
distributions of MS cases reported
through spontaneous reporting of MS
reporting systems match the recognised
age and sex distribution of MS cases that
preceded the use of the vaccine and are
not correlated with vaccine
administration.
In support of hypothesis of an
increased risk of MS after HB
vaccination seen as a precipitating factor
is that some studies have shown slightly
elevated odds ratios, although these were
not statistically significant. Evidence
inconsistent with this hypothesis is the
observation that no increased risk was
found in another study.
The data available to date, although
limited, do not demonstrate a causal
association between HB vaccination and
CNS demyelinating diseases, including
MS12.
The present studies support the
WHO recommendations that all
countries should have universal infant
and/or adolescent immunization
programmes and continue to immunize
adults at increased risk of HB infection
as appropriate.
Studies have shown that the
vaccine is 95% effective in preventing
children and adults from developing
chronic infection if they have not yet
been infected. In many countries where
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8% to 15% of children used to become
chronically infected with HBV, the rate
of chronic infection has been reduced to
less than 1% in immunized group of
children.
Hepatitis C
Ten years have elapsed since
identification of Hepatitis C virus
[HCV]) was first reported. This
remarkable achievement occurred after
more than 20 years of intense efforts by
investigators worldwide following
observation that at least one additional
viral agent, other than Hepatitis A and
Hepatitis B, was the major cause of post-
transfusion hepatitis13.
The viral agent HCV is an enveloped,
positive-stranded RNA virus with a
genome that consists of 10,000
nucleotides. The virus is a member of
flavivirus family, which also includes
other parenterally spread viruses such as
yellow fever and dengue. At least 6
genotypes as well as a number of
subtypes have been identified. A
correlation seems to exist between the
genotype and clinical course of infection
and its treatment. For example,
genotype1, which is common in the
United States, seems to be most virulent
of the genotypes and more resistant to
treatment. Unfortunately HCV is a very
mutagenic virus, a characteristic that
enables it to survive the immune defence
mechanisms of the host. As a result more
than 75% of the adults acquiring acute
infection go on to develop chronic
Hepatitis C with continuing HCV
infection14.
Epidemiology Three per cent of the
world population has been infected with
Hepatitis C virus (HCV). Epidemiology
has shifted from transfusion to non-
transfusion settings. Intravenous drug
abuse is currently the main risk but
nosocomial (hospital) infection is also a
concern.
Nosocomial spread is potentially
important and in some instances
preventable. It has been shown, for
example, that in many chronic
haemodialysis patients, there is 20% to
30% prevalence of ant-HCV positivity in
the absence of any clear parenteral risk
factors.
A recent Australian report has
raised the possibility of HCV
transmission through contaminated
anaesthetic equipment intra-operatively.
This is the first case report of patient-to-
patient transmission of HCV.
Transmission of HCV by endoscopy is
also possible, as suggested by a French
report that highlights the importance of
meticulous cleaning of endoscopic
instruments, including biopsy channel.
Injection-Associated Hepatitis C In Egypt
An increasing body of evidence suggest that
a large proportion of hepatitis infections in
Egypt were caused by unsafe injection
practices during the last decades. In
particular, improperly sterilized needles
appear to have been used to treat
schistosomiasis. Approximately 13% of the
Egyptian population is infected with
Hepatitis C virus leading to a high burden
of chronic liver disease, cirrhosis, and liver
cancer as well as mortality resulting from
these diseases. The tartaric emetic
intravenous injections were given twice a
week for 7 weeks to treat schistosomiasis.
The tartaric emetic is an antimonial
compound. The use of injections to treat
schistosomiasis stopped about 15 years ago;
the current treatment for schistosomiasis is
oral administration of praziquintel.
Evidently, this practice has resulted in a
large reservoir of the virus that has
contributed to the spread of infection in the
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country. This is one of the historic events in
which the introduction of a new modality or
a new technique was considered initially of
major credit to the patient but later,
unfortunately, turned out to be a virtual
catastrophe. Such events are not rare in the
history of medicine.
The UK researchers have found
that delivering at-risk babies by
caesarean section may protect the infants
from the Hepatitis C virus.
Pathology There is correlation
between hepatitis quasi species and the
progression of liver disease. The quasi
species hypothesis suggests that viruses,
particularly RNA viruses, circulate as
mixed populations of closely related
variants. Changing population dynamics
may lead to alterations in the relative
dominance of one or more variants, and
new variants emerge. Quasi species may
have relevance for the capacity of a virus
to evade immune control. They have
been documented in Hepatitis C virus
infection, typically a chronic infection
with a varying clinical impact amongst
patients.
Three independent factors seem
associated with fibrosis progression in
HCV: age, daily alcohol consumption of
50g or more and male gender. Median
duration of progression to cirrhosis is
about 30 years. At the cirrhotic stage,
about 3-5% of patients per year develop
hepatocellular carcinoma. There is little
evidence that direct cyto-pathogenecity
plays a significant role in the liver cell
injury. The spontaneous Hepatitis C
virus clearance is determined by class II
antigens (mainly DQB10301) and
female sex, while viral genotype plays
no role15. HCV also infects extrahepatic
cells which seem critical in the
pathogenesis of any extrahepatic
manifestations9. The recent identification
of CD81 protein as one the HCV
receptor candidates may help to
understand how chronic HCV infection
may trigger a wide spectrum of clinical
manifestations, autoimmune or even
lymphoproliferative, through potent
continuous B cell activation in the
context of various host and/or
environmental cofactors. Hepatitis C
virus infection occurs with increased
frequency in patients with non-
Hodgkins's lymphoma. Evidence of prior
infection with HCV is common in
patients with non-Hodgkin's
16
lymphoma .
Clinical course and treatment
Infection may cause a mild acute
hepatitis but many cases are
asymptomatic: fulminant hepatitis is
rare. HCV infection persists up to 80%
of patients; up to 35% of these develop
cirrhosis, liver failure and hepatocellular
carcinoma between 10 and 30 years
later. This occurs because frequent virus
mutation results in immunologically
distinct quasi-species, allowing the
organism to escape immunological
control.
Among patients with chronic
Hepatitis C, 48 weeks of treatment with
interferon/ ribavirin therapy produced a
response rate of 28% among those with
genotype 1 and 66% with other
genotypes. Similar differences were
found in combination therapy among
patients who had relapsed following
previous interferon (IFN) therapy. Viral
load prior to treatment has been clearly
shown to be predictive of response to
interferon treatment, with increased viral
load associated with decreased rate of
response. In patients non-responsive to
interferon, a second course of interferon
alone has non-beneficial effect whereas
combination therapy may induce
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response in 25% of patients. The
combination therapy is recommended in
all situations. Viral eradication should
not be the only objective of the treatment
since histological improvement may be
obtained despite persisting viral
replication with prolonged maintenance
of antiviral therapy17.
Hepatitis D
The Hepatitis D virus (also called
delta virus) is a small circular RNA
virus. The Hepatitis D virus is
replication defective and therefore
cannot propagate in the absence of
another virus. In humans, Hepatitis D
virus infection only occurs in the
presence of Hepatitis B infection.
A patient can acquire Hepatitis D
virus infection at the same time as s/he is
infected with the Hepatitis B virus. This
is called co-infection. A patient with
Hepatitis B can be infected with
Hepatitis D virus at any time after acute
Hepatitis B virus infection. This is called
super-infection18.
Hepatitis virus super-infection
should be suspected in a patient with
chronic Hepatitis B whose condition
suddenly worsens. There is usually an
obvious history of continued exposure to
blood or blood products (e.g. an active
intravenous drug user). A particularly
aggressive acute Hepatitis B infection
could suggest Hepatitis D co-infection.
Co-infection or super infection with
Hepatitis D virus in a patient with
Hepatitis B is diagnosed by the presence
of antibodies against the Hepatitis D
virus. IgM antibodies indicate acute
infection.
Interferon-α is used to treat
patients with chronic Hepatitis B and
Hepatitis D infection. Some studies have
suggested that a dose higher than that
usually used for Hepatitis B infection
may beneficial.
Hepatitis E
Hepatitis E virus consists of small,
32 to 34 nm diameter, icosahedral, non-
enveloped particles with a single-
stranded, positive-sense, 7.5-kb RNA.
The virus has two main geographically
distinct strains, Asian and Mexican;
recently, novel isolates from non-
endemic areas and a genetically related
swine HEV have been described. HEV is
responsible for large epidemics of acute
hepatitis and a proportion of sporadic
hepatitis cases in the Indian
subcontinent, Southeast and central Asia,
the Middle East, parts of Africa, and
Mexico19. Clinical illness is similar to
other forms of acute viral hepatitis
except for pregnant women, in whom
illness is particularly severe with a high
mortality rate. Sub-clinical and
unapparent infection may occur,
however, chronic infection is unknown.
No specific treatment is available. Use
of clean water and proper sanitation is
currently the most effective method of
prevention. Passive immunization has
not been proved to be effective, and
recombinant vaccines for travellers to
disease-endemic areas and for pregnant
women currently are being developed20.
Hepatitis E virus (HEV) is an
important cause of enterically-
transmitted acute viral hepatitis in
several less-developed countries and is
transmitted by faecal-oral route. Data on
duration of viral excretion and viraemia
during HEV infection are limited.
Investigation of an outbreak of Hepatitis
E in Lucknow suggested that extended
viral excretion and viraemia, particularly
those extending beyond the duration of
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biochemical hepatitis, are distinctly
rare21. Thus, in disease-endemic areas,
individuals who have recovered from
acute Hepatitis E are unlikely to serve as
a reservoir of HEV infection.
C. Viral Hepatitis: Pathology And
Pathogenesis
The histological features of viral
hepatitis have not changed and light
microscopic examination remains
essential for making diagnosis and
classification of chronic hepatitis and the
provision of objective parameters on
grading and staging22. However, new
understanding and knowledge of viral
pathogenesis, host immune responses,
the biological behaviour of the causative
viral agents and, in particular, viral
interference in multiple hepatotropic
viral infections must be taken into
consideration in the interpretation of
histopathological and
immunopathological findings of liver
tissues. The study by Huang et al
(1997)23 presents some histopathological
analyses on multiple hepatotropic viral
infections. The diagnostic histological
criteria for acute hepatitis remain
applicable in such settings. However, the
cause of acute flare up in chronic
hepatitis could not be determined
without clinical, virological and
serological information. Routine
histopathology cannot distinguish a new
infection from an acute exacerbation due
to high level of viral replication or
mutant virus. A battery of immuno-
cytochemical stains for viral antigens is
helpful, but caution must be exercised in
suggesting a specific viral aetiology due
the fact that suppression of pre-existing
viral antigens can be pronounced when
the new or concurrent infection is
Hepatitis C virus related. Furthermore,
even in the presence of normal
aminotranserase concentrations,
considerable liver pathology can be
found in 10% to 20% of HBsAg and anti
HBVe positive individuals. Such
pathology is not associated with the
occurrence of pre-core stop codon
mutations24.
It is especially noteworthy to note
the little-appreciated fact that half the
patients with hepatocellular carcinoma
who test negative for HBsAg have HBV
DNA sequences in their tumours.
Cytokines play an important role
in the defence against viral infections,
both indirectly, through determination of
the predominant pattern of host response
and directly, through inhibition of viral
replication. However, in the context of
an inflammatory response against a
virus, cytokines may also lead to liver
damage. The importance of this is best
illustrated in viral Hepatitis B (HBV). In
acute HBV infection, a vigorous
polyclonal cellular immune response is
critical; thus type 1 cytokine release is
essential to initiate an effective immune
response. The cytokines released by
CD4+ and CD8+ cells also play an
important role in down regulation of
HBV replication, demonstrating that it is
possible to control a viral infection
without the death of infected cells.
However, if there is a defect in the acute
response, HBV becomes chronic; in that
case, the presence of an ongoing sub-
optimal inflammatory reaction can
activate the process of hepatic fibrosis.
In Hepatitis C infection, the role of
cellular immune responses and cytokines
is less clear. Hepatitis C may be resistant
to inhibition by cytokines, so cytokines
may have a more prominent role in liver
damage than controlling viral
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replication. Both Hepatitis B and C may
have specific mechanisms to inhibit
cytokine production, highlighting the
critical role these molecules in recovery
from infection25.
D. Laboratory Evaluation Of
Viral Hepatitis
Although they are referred to as
"liver function tests," elevation of serum
AST, ALT and GGT actually are
indicative of hepatocellular damage.
Slight elevations of AST and ALT do
not always predict mild disease, and
both can fall with end-stage liver failure.
The most useful indicator of hepatic
synthetic function is the prothrombin
time (PT)26. In some cases of Hepatitis
A, a falling aminotransferase level may
predict a poor outcome if the decline
occurs in conjunction with rising
bilirubin level and prolonged PT. This
combination of findings indicates that
massive hepatic injury has occurred,
resulting in few functioning hepatocytes.
Acute Hepatitis A is diagnosed by a
positive IgM anti-HAV. The additional
findings of IgG anti-HAV, in the
absence of IgM, indicates a resolved
Hepatitis A infection with lasting
immunity. Patients who have been
immunized against Hepatitis A may
have undetectable antibody titers by
standard commercially available
laboratory assays. Diagnostic antibodies,
anti-HAV IgM appear before jaundice
develops and persists for three months.
Both acute and chronic hepatitis B
infections are diagnosed by the presence
of HBsAg. HBsAg positivity warrants
investigation of Hepatitis D co-infection
or super infection, as defined by the
presence of IgM anti-HDV. Hepatitis D
can occur only in the presence of HBsAg
positivity. Acute Hepatitis B infection
always is associated with the presence of
IgM anti-HBc. IgG anti-HBc positivity
indicates a resolving infection or chronic
Hepatitis B. The presence of HBeAg
indicates active viral replication and
high infectivity. Anti-HBe appears when
viral replication ceases. Resolved
hepatitis B and lasting immunity either
from infection or immunization are
associated with the presence of anti-
HBs.
Hepatitis C virus cannot be
cultured. Hepatitis C is associated with
the detection of anti-HCV by enzyme-
linked immunosorbent assay, but this
test must be followed by supplemental
specificity tests to substantiate the
diagnosis, including recombinant
immunoblot assay (RIBA) or
measurement of HCV RNA by
polymerase chain reaction (PCR).
PCR assays for HCV infection are
used commonly in clinical practice in the
early diagnosis of infection, for
identifying infection early in life e.g.
perinatal transmission when maternal
serum antibody interferes with the
ability to detect antibody produced by
the infant, and for monitoring patients
receiving antiviral therapy. A patient
with positive PCR result for Hepatitis C
is infected with Hepatitis C virus even if
serologic markers for Hepatitis C are
negative. A negative PCR result for
Hepatitis C with positive result for
serological markers 1) indicates past
Hepatitis C infection, 2) indicates acute
HCV infection with transitory negative
PCR phases, 3) may indicate a patient
who has passively received anti-HCV
immunoglobulins during a blood
transfusion.
Radioimmuno assay and enzyme
immuno-assay for anti-HDV (Hepatitis
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D virus) are available commercially, at
referral laboratories. Tests for IgM-
specific ant-HDV antibody and HDAg
are research procedures at present. If
markers for HDV infection exist, co-
infection with HBV usually can be
differentiated from super-infection of an
established HBsAg carrier by testing for
IgM Hepatitis B core (HBcIgM)
antibody; absence of this core antibody
suggests that the person is an HBsAg
carrier. Methods for detection of HDV
RNA are available.
Recombinant DNA technology
has resulted in development of
antibodies to Hepatitis E virus (HEV)
particles, and IgM and IgG assays are
available to distinguish between acute
and resolved infections. IgM antibody to
viral antigen becomes positive after
about one week of illness. Viral RNA
can be detected in stool and serum by
PCR. Diagnosis of Hepatitis E is usually
made by detection of specific IgM
antibody, which disappears rapidly over
a few months; IgG ant-HEV persists for
at least a few years.
The only diagnostic tests for Hepatitis G
virus infection are PCR assays. They are
used to detect HGV RNA
E. Viral Hepatitis: Indian Scenario
Acute hepatic failure (AHF) in India
almost always presents with
encephalopathy within four weeks of the
onset of acute hepatitis. Viral hepatitis is
the cause in approximately 95-100% of
patients, who therefore constitute a more
homogeneous population than AHF
patients in the West. In India, Hepatitis
E (HEV) and Hepatitis B (HBV) viruses
are the most important causes of AHF;
these two viruses cause approximately
60% of cases. Hepatitis B virus core
mutants are very important agents in
cases of where Hepatitis B results AHF
in this country. Half of the patients with
AHF are female, one quarter of whom
are pregnant. Therefore, pregnant
females who contract viral hepatitis
constitute a high-risk group for
development of AHF. However, the
outcome of AHF in this group is similar
to that in non-pregnant women and men.
In AIIMS, Delhi, approximately one-
third of AHF patients survive with
aggressive conservative therapy,
whereas, two-thirds of deaths occur
within 72 hours of hospitalisation
(Acharya SK et al 2000).
Hepatitis D is not uncommon in India. In
a study reported from Bombay (Banker
1992), out of 331 cases of Hepatitis B,
148 patients had an evidence of Hepatitis
D as well. Fulminant hepatitis developed
in 39 patients, 32 of whom had Hepatitis
B and 20 of these (63%) also had
Hepatitis D. These findings indicate the
extent of association of Hepatitis D with
Hepatitis B and the high-risk of fatal
fulminant hepatitis in these patients.
*********************************
79
 distinct H and L chains. The pairing of H
Immunology Update and L chains in a quasi-random manner
further expands the number of distinct
B-Lymphocyte Ig molecules that can be formed.
Development The H-chain variable region
is initially expressed in association with
Gazala Shakoor
the product of the m-constant (C)-region
_______________________________
gene. Together these elements encode
the m IgH chain, which is used in
B-lymphocytes are derived
immunoglobulins of the IgM class. The
from haematopoietic stem cells by a
successful completion of the process of
complex set of differentiation events.
Ig gene rearrangement and the
Various molecular mechanisms which
expression of the resultant IgM on the
lead to maturation of the early B lineage
cell surface marks the transition between
cells into mature B-lymphocytes occur
the pre-B and B-cell states. The newly
in the foetal liver and, in adult life,
differentiated B cell initially expresses
principally in the bone marrow.
surface immunoglobulin solely of the
Interaction with specialized stromal cells
IgM class.
and their products, including cytokines
such as interleukin-7 (IL-7), are critical
The cell completes its
to the normal regulation of this process.
maturation process by expressing on its
surface a second class of
The key events in B-cell
immunoglobulins composed of the same
development occur in cells designated
L chain and the same H
pro-B cells and pre-B cells. They centre
chain variable region but of a different
about the assembly of the genetic
H-chain C region; this second Ig H chain
elements encoding the antigen-specific
is designated d, and the immunoglobulin
receptors of B cells, which are
to which it contributes is designated IgD.
immunoglobulin (Ig) molecules
specialized for expression on the cell
The differentiation process is
surface. Immunoglobulins are
controlled at several steps by a system of
heterodimeric molecules consisting of
checks that determines whether prior
heavy (H) and light (L) chains, both of
steps have been successfully completed.
which have variable (V) regions that
These checks depend on the expression
contribute to the binding of antigen and
on the surface of the cell of
that differ in sequence from one Ig
appropriately constructed Ig or Ig-like
molecule to another. In addition, the
molecules. Pre-B cells that fail to
heavy and light chains contain regions
express the preliminary complex do not
that are not variable but constant (C
move forward to future differentiation
regions).
states. That eliminates inefficient cells
from maturation process.
In pro-B and pre-B cells,
genetic elements encoding variable B-Lymphocyte Activation
portions of heavy & light chains are such A mature B cell can be
which add diversity so to result in the activated by an encounter with an
generation of a very large number of antigen expressing epitopes that are
 Indian J for Practising Doctor; Vol I; No. 4
recognized by its cell-surface
Immunoglobulin. The activation process
may be a direct one, dependent on cross-
linkage of membrane Ig molecules by
the antigen (cross-linkage-dependent B-
cell activation), or an indirect one,
occurring most efficiently in the context
of an intimate interaction with a helper T
cell, in a process
often referred to as cognate help.
Cross-lineage-dependent B-cell
activation: When B cells encounter antigens
that bear multiple copies of an epitope that
can bind to their surface Ig, the resultant
cross-linkage stimulates biochemical signals
within the cell leading to B-cell activation,
growth, and differentiation.
Resting B cells can bind antigens
that bear epitopes complementary to their
cell-surface immunoglobulin (Ig). Even if
the antigen cannot cross-link the receptor, it
will be endocytosed and enter late
endosomes and lysosomes where it will be
degraded to peptides. Some of these
peptides will be loaded into class II MHC
molecules and brought to the cell surface,
where they can be recognized by CD4+ T
cells that bear receptors specific for that
peptide/class II complex. This interaction
allows an activation ligand on the T cells
(CD40 ligand) to bind to its receptor on B
cells (CD40) and to signal B-cell activation.
In addition, the T cells secrete several
cytokines that regulate the growth and
differentiation of the stimulated B cell.
In many instances, B-cell activation
events may result from both pathways of
stimulation.
Because each B cell bears
membrane Ig molecules with identical
variable regions, cross-linkage of the
cell-surface receptors requires that the
antigen express more than one copy of
an epitope complementary to the binding
site of the receptor. This requirement is
fulfilled by antigens with repetitive
(multiple) epitopes. Among these
antigens are the capsular polysaccharides
of many medically important
microorganisms such as pneumococci,
streptococci, and meningococci. Similar
expression of multiple identical epitopes
on a single immunogenic particle is a
property of many viruses because they
express multiple copies of envelope
proteins on their surface. Cross-linkage-
dependent B-cell activation is a major
protective immune response mounted
against these microbes. The binding of
complement components to antigen or
antigen-antibody complexes can increase
the magnitude of the cross-linkage-
dependent B-cell activation due to the
action of a receptor for complement,
which, together with other molecules,
increases the magnitude of a B-cell
response to limiting amounts of antigen.
Cognate help allows B cells
to mount responses against antigens that
cannot cross-link receptors and, at the
same time, provides co-stimulatory
signals that rescue B cells from
inactivation when they are stimulated by
weak cross-linkage events. Cognate help
is dependent on the binding of antigen
by the B cell’s membrane Ig, the
endocytosis of the antigen, and its
fragmentation into peptides within the
endosomal / lysosomal compartment of
the cell. Some of the resultant peptides
are loaded into a groove in a specialized
set of cell-surface proteins, the class II
major histocompatibility complex
(MHC) molecules. The resultant class II
/peptide complexes are expressed on the
cell surface; these complexes are the
ligands for the antigen-specific receptors
of a set of T cells designated CD4+ T
cells. CD4+ T cells that have receptors
specific for the class II/peptide complex
expressed on the B-cell surface
recognize and interact with that B cell.
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 Indian J for Practising Doctor; Vol I; No. 4
That interaction results in the activation
of the B cell through the agency of cell-
surface molecules expressed by the T
cells (e.g., the CD40 ligand [CD154])
and cytokines produced by the T cell.
The role of the B-cell receptor for
antigen is to create
the T-cell ligand on the surface of
antigen-specific B cells; activation of the
B cell derives largely from the action of
the T cell. However, in many
physiologic situations, receptor cross-
linkage stimuli and cognate help
synergize to yield more vigorous B-cell
responses.
B-Lymphocyte Differentiation
Activation of B cells
prepares them to divide and to
differentiate either into antibody-
secreting cells or into memory cells, so
that there are more cells specific for the
antigen used for immunization and these
cells have new properties. Those cells
that differentiate into antibody secreting
cells account for primary antibody
responses. Some of these antibody
secreting cells migrate to the bone
marrow where they may continue to
produce antibody for an extended period
of time and may have lifetimes in excess
of 1 year.
Memory B cells give rise to
antibody-secreting cells upon re-
challenge of the individual. The
hallmark of the antibody response to re-
challenge (a secondary response) is that
it is of greater magnitude, occurs more
promptly, is composed of antibodies
with higher affinity for the antigen, and
is dominated by immunoglobulins
expressing g, a, or e C regions (IgG,
IgA, or IgE) rather than by IgM, which
is the dominant Ig of the primary
response.
Division and differentiation
of cells into antibody-secreting cells is
largely controlled by the interaction of
the activated B cells with T cells
expressing CD154 and by their
stimulation by T-cell-derived cytokines.
The differentiation of
activated B cells into memory cells
occurs in a specialized micro-
environmental structure in the spleen
and lymph nodes, the germinal centre.
The process through which increase in
antibody affinity occurs also takes place
within the germinal centre. The latter
process, designated affinity maturation,
is dependent on somatic hypermutation.
The survival of cells within the germinal
centre depends on the capacity to bind
antigen so that as antigen availability
diminishes, cells that have higher
affinity receptors, either naturally or as a
result of the hypermutation process,
have a selective survival and growth
advantage. Thus, such cells come to
dominate the population.
The process through which
a single H-chain V region can become
expressed with genes encoding C
regions other than m and d is referred to
as Ig class switching. It is dependent on
a gene translocation event through which
the C-region genes between the genetic
elements encoding the V region and the
newly expressed C gene are excised,
resulting in the switched C gene being
located in the position that the Cm gene
formerly occupied (Fig. 3). This process
also occurs in germinal centres.
B1 or CD5+ B-Lymphocytes
A second population of B
cells (B1 cells) has been described that
differs from the dominant B-cell
population (sometimes designated B2
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 Indian J for Practising Doctor; Vol I; No. 4
cells or conventional B cells) in several
important respects. These cells were
initially recognized because some
express a cell-surface protein, CD5, not
generally found on other B cells. B1 B
cells are quite numerous in foetal and
perinatal life, but scant and restricted in
adult life. Whether B1 B cells derive
from a separate set of stem cells found in
the foetal liver but absent from (or
present only at low frequency in) the
adult bone marrow is still a matter of
controversy. The alternative view is that
B1 B cells are derived from conventional
B cells as a result of cross-linkage-
dependent B-cell activation. B1 B cells
appear to be self-renewing, in contrast to
conventional B cells, in which division
and memory are antigen driven.
B1 B cells appear to be
responsible for the secretion of the
serum IgM that exists in non-immunized
animals, often referred to as natural IgM.
Among the antibodies found in such
"natural" IgM are molecules that can
combine with phosphatidyl choline (a
component of pneumococcal cell walls)
and for lipopolysaccharide and influenza
virus. B1 B cells also produce
autoantibodies, although they are
generally of low affinity and in most
cases not pathogenic. It is believed that
B1 B cells are important in resistance to
several pathogens and may have a
significant role in mucosal immunity.
B-Lymphocyte Tolerance
One of the central problems
facing the immune system is that of
being able to mount highly effective
immune responses to the antigens of
foreign, potentially pathogenic, agents
while ignoring antigens associated with
the host’s own tissues. The mechanisms
ensuring this failure to respond to self-
antigens are complex and involve a
series of strategies. Chief among them is
elimination of cells capable of self-
reactivity or the inactivation of such
cells. The encounter of immature, naive
B cells with antigens with repetitive
epitopes capable of cross-linking
membrane Ig can lead to elimination of
the B cells, particularly if no T-cell help
is provided at the time of the encounter.
This elimination of potentially self-
reactive cells is often referred to as
clonal elimination. Some self-reactive
cells, rather than dying upon encounter
with self-antigens, may re-express the
proteins needed for immunoglobulin
gene rearrangement and undergo a
further round of such rearrangement.
This process, referred to as receptor
editing, allows a self-reactive cell to
substitute a new receptor and therefore
to avoid elimination.
There are many self-antigens that
are not encountered by the developing
B-cell population or that do not have the
capacity to cross-link B-cell receptors to
a sufficient degree to elicit the clonal
elimination/receptor editing process.
Such cells, even when mature, may
nonetheless be inactivated through a
process that involves cross-linkage of
receptors without the receipt of critical
co-stimulatory signals. These
inactivated cells may be retained in the
body but are unresponsive to antigen and
are referred to as anergic. When
removed from the presence of the
anergy-inducing stimulus, such cells
may regain responsiveness.
********************************
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 Indian J for Practising Doctor; Vol I; No. 4
Screening
Cervical Cancer
Manzoor Kadri
____________________________
The cervix is the lower part of
the uterus that opens into the vagina.
Cervical cancer, accounting for 40% of
all cancer mortality, is the second most
common cause of cancer death for
women worldwide - surpassed only by
breast cancer. At the same time it is a
disease that is almost 100 percent
curable with accurate screening and
early detection. In India, it is the greatest
killer in women of the menopausal age.
Early marriages, poor sexual hygiene
and growing extra-marital and pre-
marital contacts make the occurrence of
this cancer increasingly common.
Human papilloma virus (HPV) has been
implicated as the agent causing this
cancer.
Traditional cervical screening
tests for the cancer include the Pap
smear and the pelvic exam. During a
pelvic exam, the physician will check for
abnormalities in the size or shape of the
patient’s uterus, vagina, ovaries,
fallopian tubes, bladder and rectum.
Using a speculum, the upper portion of
the vagina and cervix will also be
examined. During a Pap smear, the
physician collects cells sitting at the
surface of the cervix using a small
wooden spatula or a brush. These cells
are smeared on a slide and sent to the
laboratory for analysis under a
microscope. The procedure is painless.
The guidelines of The American
College of Obstetricians and
Gynecologists (similar to the American
Cancer Society guidelines) advise that
"All women who are or who
have been sexually active or who have
reached age 18 should undergo an
annual Pap test and pelvic examination.
After a woman has had three or more
consecutive, satisfactory annual
examinations with normal findings, the
Pap test may be performed less
frequently at the discretion of her
physician."
Cervical cancer does not develop
immediately from normal cervix cells.
The cervix goes through a "pre-
cancerous" phase where the cells grow
closer together first. This pre-cancerous
stage is called "dysplasia". The
cancerous and pre-cancerous cell
changes in the cervix can be detected by
pap smear. It is also used to diagnose
viral infections of the urogenital system
like genital warts and herpes, and
sexually transmitted diseases.
If the cells look normal, no
treatment is necessary. The Pap test may
show that the patient has an infection.
The doctor may treat her for the
infection and suggest that she has
another Pap test in several months. If the
cells look abnormal, more tests like
colposcopy and cervical conization may
be necessary. The doctor will discuss the
test results and advice for follow-up
exam. A Pap test is not 100% accurate, it
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 Indian J for Practising Doctor; Vol I; No. 4
is a screening test. Nevertheless, it is a
simple, effective and low-cost
technology for detecting cervical cancer
in its early stages, when it is treatable,
and has been available for over 30 years.
The incidence of cancer and
deaths from cervical cancer has
significantly declined over the years
Risks factors for cancer of the cervix
1. Multiple sexual partners (or
sexual partners who have had
multiple partners)
2. Starting sexual intercourse at
an early age
3. Viral infection, such as HPV,
human immunodeficiency
virus (HIV), or herpes
simplex virus (HSV)
4. Weakened immune system
5. Previous cancer of the lower
genital tract
6. Smoking
Screening for cervical cancer
1 Cervical cancer screening is
recommended yearly
starting when women
are aged 18 years or they
become sexually active, if
younger than 18 years.
2 Less frequent screening is
done if the patient has a
negative Pap smear result 3
years in a row or if she is
not sexually active.
3 No upper age limit for
screening exists because the
because of prevention, screening, and
early detection by the Pap smear. In the
United States, about 2-3 million
abnormal Pap smear results are found
each year. Most of them indicate the
early stages of disease and need
reasonable observation by doctor.
incidence of cancer of the
cervix increases with age at
a time when women may be
less likely to get a Pap
smear. Most of these
cancers are diagnosed in
women older than 50 years.
Even after menopause,
women should continue to
have regular Pap smears.
4 The National Cancer
Institute encourages women
aged 65 years and older to
get Pap smear at least every
2 years and every year if at
higher risk and advised by
their doctor. Many older
women believe they no
longer need Pap smears
(and think they are not at
risk for cervical cancer)
because of their age, or
because they may not be
sexually active, or because
they have had a
hysterectomy. That is not
correct. These women need
Pap smears because their
risk is higher.
5 If you have had your uterus
removed, yearly screening
should be performed if there
is a history of abnormal Pap
smear results or other lower
genital tract cancer.
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 Indian J for Practising Doctor; Vol I; No. 4
Patient Education
Osteoarthritis
(Rohini Bhan)
____________________________
Sometimes called degenerative
joint disease, osteoarthritis results when
the cushioning cartilage in the joints
breaks down, causing pain and stiffness.
It is the most common form of arthritis.
It is perhaps the most common and
oldest disease affecting humans. With
the improvement in life expectancy from
55 yrs to 70 yrs on an average, most
persons past the age of 60 have
osteoarthritis to a certain degree.
Osteoarthritis is termed
primary osteoarthritis when it occurs in
the absence of a particular cause.
Secondary osteoarthritis can be
attributed to an obvious underlying
factor such as injury (previous fractures),
infections, hormonal disorders, or as a
consequence of another type of arthritis
such as rheumatoid arthritis. Obesity
(overweight) may also lead to secondary
osteoarthritis in the weight bearing
joints.
Joint pain is the usual
symptom. Initially the pain comes on
after overwork and is relieved by rest.
Later, as the disease progresses, pain
occurs even while resting. Rarely is the
pain felt far from the affected joint. This
is known as referred pain in medical
parlance. Some people with
osteoarthritis in their hips feel referred
pain in their knees.
Treatment for osteoarthritis
Osteoarthiritis can’t be cured
and, so far, doctors can’t reverse joint
degeneration. But many medications can
treat the pain, and some new therapies
show promise of slowing or stopping
cartilage destruction.
Treatment focuses on relieving
pain, preventing the joints from further
damage, and helping you stay active.
Working with health professionals, the
patient can learn to avoid stressing his
joints, compensate for any loss of
flexibility or mobility, and strengthen
muscles to better support already
weakened joints.
In cases of severe cartilage
loss, surgery can help. Total joint
replacement is now commonplace,
relieving pain and restoring mobility to
many people who would be unable to
function otherwise. A note about
medications: Many of the prescription
drugs prescribed for osteoarthritis have
side effects. Be sure to discuss treatment
benefits and risks with your doctor.
Weight Loss
Extra stress on your joints wears
out your cartilage faster. If you are
overweight, your doctor will urge you to
trim down to a weight appropriate for
your age and height. However, avoid
crash diets though. A combination of
exercise and diet works best.
Painkillers
Creams, gels and lotions
containing various kinds of painkillers
are popular over – the – counter
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 Indian J for Practising Doctor; Vol I; No. 4
treatments. Rubbed onto the painful
joint, they work either by stimulating
sensations that distract the pain or by
blocking pain nerves.
Counter irritants distract
the sensation of pain. Some contain
salicylates, which are aspirin and work
as local pain relievers.
A cream or gel that
contains capsaicin, which is found in
cayenne pepper, interrupts substance P, a
neuro - transmitter believed to carry pain
message to the brain.
Glucocorticoid injections
Injection directly into or
around the joint are sometimes given to
relieve pain and swelling. People have
different reactions. For some, it gives
immediate relief that can last for a long
time. Others don’t respond at all.
Doctors don’t like to give these
injections more than four times a year
because of the risk of cartilage damage
Assistive devices
Canes, splints, braces, and other
assistive devices that help support the
joints or relieve stress and pain can help
the patient get around better and reduce
his risk of falling. If the patient has
osteoarthritis in his hands or wrists,
specially designed kitchen tools,
doorknobs, and other gadgets can ease
the strain of day to day tasks.
Warm- water exercise
Swimming and doing other aerobic
water exercises in a heated pool can help
you exercise without putting pressure on
your joints.
Surgery
The patient might benefit from
surgery if his osteoarthritis progresses to
the point where it seriously interferes
with his ability to move easily, causes
severe pain or deforms hisr joints.
More common types of surgery for
osteoarthritis include
Debridement The surgeon smoothes
out irregular joint surfaces, and removes
loose bits of bone or cartilage that could
be contributing to inflammation.
Osteotomy Doctors cut and re- set
bones to realign the joint. This procedure
is most often performed on the knee
joint.
Arthrodesis
Also called “ joint fusion”, the doctor
may suggest this surgery when joints are
seriously damaged. It is usually done on
sections of the spine but may involve
ankles and other joints.
Arthroplasty
This is another term for total
joint replacement; the damaged joint is
removed and replaced with a plastic or
metal joint. Most often done on knee and
hip joints, arthroplasty can be done on
any joint except those of the spine.
However, artificial joints usually have to
be replaced after 10 to 20 years, which
means they are a last choice for a young
person who would require several
replacements over time.
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 Indian J for Practising Doctor; Vol I; No. 4
Role of Cefexime in
Paediatric UTI
Srividya Rao
________________________________
Urinary tract infection (UTI) is
quite common and, among the
ambulatory patients, is exceeded in
frequency only by respiratory and gastro-
intestinal infections. Bacterial infections
of the urinary tract are the commonest
cause of both community acquired and
nosocomial infections in patients
admitted to American hospitals1. UTI
accounts for about 6% of new
consultations in general practice in
Europe and Scandinavia2. Women are
especially prone; about 5-6% of all
sexually active women have bacteriuria3,
which in them is associated with
increased mortality.4. The cumulative
prevalence of asymptomatic bacteriuria
in female increases about 1% per decade
throughout life5, why more women
acquire bacteriuria with increasing age is
not known. In addition to causing
considerable discomfort and ill health
UTI, overt as asymptomatic, can lead to
complications within and outside the
urinary tract. In the developing countries,
particularly in rural areass, the problem
is compounded by the fact that patients
are late to seek treatment. At the same
time, because of lack of facilities, vast
majority of urinary infections are treated
empirically and only a small minority
can get pre-therapy testing.
The incidence of urinary tract
infection varies with age and sex. In the
first year of life, the male:female ratio is
at least 3:1. After the first year, however,
there is a female preponderance.
Bacteriologically, urinary tract infection is
detected by growth of a significant number
of organisms (>105/ml) of a single species of
bacteria in urine.
Clinical features
It must be remembered that UTI
is one of the most common bacterial
infection in infants and children. Rapid
evaluation and prompt appropriate
evaluation is needed to prevent renal
parenchymal damage which may lead to
hypertension and chronic renal failure.
Unlike adults, symptoms are
generally non-specific in the paedriatic
age group. Infants and younger children
may present with irritability, fever, poor
feeding, vomiting or diarrhoea. The
typical symptoms (dysuria, frequency of
urination, and flank pain) become
common with increasing age.
Every child with a suspicion of
UTI requires evaluation for presence of
complications and the risk of
recurrences. History should include
voiding habits. This should include
general physical examination, blood
pressure, abdominal examination,
genitalia, perineal sensation and deep
tendon reflexes.
Urine analysis (for microscopic
examination) can be used to start
treatment, but UTI can be confirmed
only by urine culture. Dipsticks tests (for
leucocyte esterase and nitrite tests) are
not available in India.
Diagnosis depends on
Careful history
Urine analysis
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 Indian J for Practising Doctor; Vol I; No. 4

Urine culture

For culture a clean catch midstream sample is collected directly into a sterile container,
after cleaning urethral orifice with soap and water. If urethral sample is not possible, a
sample is collected by suprapubic aspiration or urethral catheterization.
.

Definitions in Urinary Tract Infection

Bacteriuria Presence of bacteria in the urine. Asymptomatic bacteriuria has at least 105
colony forming units (CFU)/ml – termed significant bacteriuria – on 2
successive cultures with or without pyuria in a patient without symptoms.

Cystitis Inflammation of bladder. Definition of acute cystitis includes dysuria, urgency

and/or frequency with only 102 CFU/ml in mid-stream specimen.
Acute Acute bacterial infection of kidney, characterized by chills and often high
pyelonephritis fever, flank pain as well as tenderness.
Re-infection An infection with a different strain or serological type after eradication of
previous infection
Relapse Consecutive urinary infection caused by the same strain or serotype of bacteria.
Persistence Continued presence of the micro-organisms isolsated at the beginning of the
treatment.
Recurrent UTI Patients with at least 2 infections within 6 months or more than 3 during a
single year in which initial episode is resolved and is followed by another
infection
Complicated The patient has conditions that predispose or promote the development or
Infection persistence of infection.

Treatment gentamicin combination or 3rd generation

cephalosporins as cefotaxime or
Children who are too toxic and ceftriaxone).
infants <3 months should be given Children older than 3 month, who are not
parenteral antibiotics (Ampicillin & toxic, may be given oral antibiotics.
hospitalization, and prevents nosocomial
infection.

Role of cefixime

Conventionally, a young, febrile Cefixime is a 3rd-generation oral

child with UTI would be hospitalized for
intravenous antibiotics. However, with
the availability of potent oral agents, the
consensus is shifting towards ambulatory
management. This decreases the cost of
treatment, avoids inconvenience of
cephalosporin that is highly active
against a broad range of gram negative
and some gram positive aerobic bacteria.
It achieves a bactericidal concentration in
urine of children.

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 Indian J for Practising Doctor; Vol I; No. 4

Studies conducted to compare It is concluded that for

oral and combined oral and intravenous
therapy in young children (1 month to 2
year of age) showed promising results
for former route of administration. Short-
term clinical outcome (sterilization of the
urine and defervescence) and long-term
morbidity (incidence of re-infection, and
incidence & extent of renal scarring at 6
months) were comparable. In addition to
convenience of administration, the cost
of therapy was reduced by half.
Cefixime was found to be the only oral
antibiotic which could be used alone for
serious forms of UTI like acute
pyelonephritis.
The drug is as a monotherapy, 8 mg/kg in
single dose ot two divided 12-hourly doses
for 14 days; double dose on the first day.
Alternatively, an IV antibiotic may be used
for first 3 days followed by oral cefixime for
the remaining 11 days (switch-therapy).
Plasma & urine concentrations of
the drug are well above the reported
minimal & urinary concentrations for
most common urinary tract pathogens for
up to 12 and 24 hours after
administration respectively.
uncomplicated UTI, cefixime is equal to
or more effective than other usual
treatments, and has a low rate of side
effects.
Cefixime is a 3rd-generation oral
cephalosporin that is highly effective against
a broad-range of gram –ve and some gram
+ve bacteria. In uncomplicated UTIs, it is
equal to or more effective than other usual
treatments, and has a low rate of side-effects.
Results of various studies performed across
the world have indicated that cefoxime can
be used as monotherapy or switch-therapy
in uncomplicated UTI in children.
Role in prophylaxis: As UTIs occur
frequently and recurrently in children,
prompt therapy is required to avoid renal
damage. Prophylaxis of re-infection is
equally important. Cefixime has been
shown to be very effective in longterm
prophylaxis of urinary infections
associated with urinary anomalies. Low-
dose cefixime prophylaxis (2mg/kg
bodyweight) was found to be as effective
as other urinary prophylactics like
nitrofurantoin.********

β-lactam antibiotics inhibit peptidoglycan synthesis. Thus, like penicillin, cephalosporins

act by inhibiting cell wall synthesis. Their targets are biosynthetic enzymes,
transpeptidases, carboxypeptidases, and endopeptidases. Penicillin-binding proteins,
PBPs (pencillin-sensitive enzymes) are found in different organisms sensitive to
cephalosporins, and each bacterial species possesses a characteristic set of PBPs, with
different affinity to β-lactams. The differences of activity between oral cephaloporins are
related to their affinity for PBPs. Moraxella catarrhalis has 9 PBPs. E. coli posseses 8
different PBPs; the major target for oral cephalosporins is PBP3. 3rd generation
cephalosporins show good affinity for PBP2,4 & 5 of H. influenzae. Anti-staphylococcal
activity requires inhibition of PBP 2 & 3. The lack of activity of cefixime against S. aureus
and coagulase-negative staphylococci is due to poor binding tp PBP2. (Ed)

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Further reading

• Bloomsfield P, Hodson EM, Craig JC. Antibiotics for acute pyelonephritis in Children.
Cochrane Database Syst Rev 2003; 3: CD003772.
• Bryskier, AJ & Belfiglio SR. Cephalosporins: Oral. In: Antimicrobial Therapy &
Vaccines, LuVL, Merington TC (ed), 1999, Williams & Wilkins, USA; pg 710
• Fanos V, Cataldi L. Cefixime in urinary tract infections with special reference to
pediatrics. Overview. J Chemothe 2001; 13: 112-27
• Hamilton-Miller J. Cefixime for switch therapy. Chemother 1998; 44: 24-7
• Hoberman A, Wald ER, Hickey RW. Oral versus initial intravenous therapy for UTI in
young, febrile children. Pediatrics 1999; 104: 79-86
• Mamzoridi K, Kasterridou N, Peonides A. Pharmakokinetics of cefixime in children with
UTI after a single dose oral dose. Pharmacol Toxicol 1996; 78: 417-20
• Shetty, GS. UTI management in children: Advantage cefixime. Antimicrobial Update.
2003; 8-10
• Shigi Y, Matsumoto Y, Kaizo M. Mechanism of action of the new orally active
cephalosporins. Jpn J Antibiot 1984; 37: 790-96

More than 100 brand preparations of cefixime trihydrate are available in the Indian market.
The formulation is available as 200 & 100 mg tablets, 50 mg dispersible tablets (DT), and 30-ml
dry syrup [50 mg/tsf].

________________________________________________________________________

Joseph Lister (1827-1912), was a

British surgeon, whose discovery of
antiseptics in 1865 greatly reduced the
number of deaths due to operating-room
infections. Born in Upton, Essex, and
educated at the Universities of London
and Edinburgh, Lister began to study the
coagulation of blood and the
inflammation that followed injuries and
surgical wounds. In 1861 he was
appointed surgeon of the Glasgow Royal
Infirmary in a new surgery unit designed
to reduce gangrene and other infections,
then thought to be caused by bad air.
Despite his efforts to keep surgical
instruments and rooms clean, the
mortality rate remained close to 50 per Joseph Lister

cent.

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About half of all patients recovering from surgery
died of infections before British surgeon Joseph
Lister’s discovery of antiseptics in 1865. Lister
found that mortality rates dropped to 15 percent
when he used carbolic acid in the operating
environment and on patients’ wounds.
Believing infection to be caused
by airborne dust particles, Lister sprayed
the air with carbolic acid (now called
phenol), a chemical that was then being
used to treat foul-smelling sewers. In
1865 he came upon the germ theory of
the French bacteriologist Louis Pasteur,
whose experiments revealed that
fermentation and putrefaction were
caused by micro-organisms brought in
contact with organic material. By
applying carbolic acid to instruments and
directly to wounds and dressings, Lister
reduced surgical mortality to 15 per cent
by 1869.
Lister's discoveries in antisepsis
met initial resistance, but by the 1880s
they had become widely accepted. In
1897 he was made a baron by Queen
Victoria, who had been his patient.

Phenol, formerly called carbolic acid, is an aromatic organic compound, C6H5OH. It is

weakly acidic and resembles the alcohols in structure. The colourless, needlelike crystals
of purified phenol melt at 43° C (109° F) and boil at 182° C (360° F). During storage the
crystals become pink and finally reddish brown. Phenol is soluble in organic solvents
and slightly soluble in water at room temperature, but infinitely soluble above 66° C
(150.8° F). It is a constituent of coal tar.

Phenol was first used as a disinfectant in 1867 by the British surgeon Joseph Lister
for sterilizing wounds, surgical dressings, and instruments. Dilute solutions are useful
antiseptics, but strong solutions are caustic and scarring to tissue. Less irritating and
more efficient germicides have replaced phenol, but it is widely used in the manufacture
of resins, plastics, insecticides, explosives, dyes, and detergents, and as raw material for
the production of medicinal drugs such as aspirin.

A phenol derivative, phenolphthalein (C20H 14O4), is a chemical compound

prepared by a reaction between phenol and phthalic anhydride in the presence of
sulphuric acid; it is used as an indicator for acidity or alkalinity.

The term phenol is also used for any of a group of related acidic compounds that
are hydroxyl derivatives of aromatic hydrocarbons, such as methylphenols (cresols) and
resorcinol.

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 Indian J for Practising Doctor; Vol I; No. 4
Wastes from Healthcare Activities
A Consideration.
_________________Muzaffar Ahmad_________________
Health-care activities - for instance,
immunizations, diagnostic tests, medical
treatments, and laboratory examinations -
protect and restore health and save lives.
But what about the wastes and by-
products they generate?
From the total of wastes
generated by health-care activities,
almost 80% are general waste
comparable to domestic waste. The
remaining approximate 20% of wastes
are considered hazardous materials that
may be infectious, toxic or radioactive.
The wastes and by-products cover a
diverse range of materials, as the
following list illustrates:
Infectious wastes - cultures and
stocks of infectious agents, wastes from
infected patients, wastes contaminated
with blood and its derivatives, discarded
diagnostic samples, infected animals
from laboratories, and contaminated
materials (swabs, bandages) and
equipment (disposable medical devices
etc.); and
Anatomic - recognizable body parts
and animal carcasses. Infectious and
anatomic wastes together represent the
majority of the hazardous waste, up to
15% of the total waste from health-care
activities.
Sharps - syringes, disposable scalpels
and blades etc. Sharps represent about
1% of the total waste from health-care
activities.
Chemicals - for example solvents and
disinfectants; and
Pharmaceuticals - expired, unused,
and contaminated; whether the drugs
themselves (sometimes toxic and
powerful chemicals) or their metabolites,
vaccines and sera. Chemicals and
pharmaceuticals amount to about 3% of
waste from health-care activities.
Genotoxic waste - highly hazardous,
mutagenic, teratogenic1 or carcinogenic,
such as cytotoxic drugs used in cancer
treatment and their metabolites; and
Radioactive matter, such as glassware
contaminated with radioactive
diagnostic material or radiotherapeutic
materials;
Wastes with high heavy metal
content, such as broken mercury
thermometers. Genotoxic waste,
radioactive matter and heavy metal
content represent about 1% of the total
waste from health-care activities.
The major sources of health-care
waste are hospitals and other health-care
establishments, laboratories and research
centres, mortuary and autopsy centres,
animal research and testing laboratories,
blood banks and collection services, and
nursing homes for the elderly.
High-income countries can
generate up to 6 kg of hazardous waste
per person per year. In the majority of
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low-income countries, health-care waste
is usually not separated into hazardous or
non-hazardous waste. In these countries,
the total health-care waste per person per
year is anywhere from 0.5 to 3 kg.
HEALTH IMPACTS
Health-care waste is a reservoir
of potentially harmful micro-organisms
which can infect hospital patients,
health-care workers and the general
public. Other potential infectious risks
include the spread of, sometimes
resistant, micro-organisms from health-
care establishments into the environment.
These risks have so far been only poorly
investigated. Wastes and by-products can
also cause injuries, for example radiation
burns or sharps-inflicted injuries;
poisoning and pollution, whether through
the release of pharmaceutical products,
in particular, antibiotics and cytotoxic
drugs, through the waste water or by
toxic elements or compounds such as
mercury or dioxins.
Sharps
Throughout the world every year
an estimated 2 000 million injections are
administered. And not all needles and
syringes are properly disposed of,
generating a considerable risk for injury
and infection and opportunities for re-
use.
Worldwide, 8-16 million hepatitis B,
2.3 to 4.7 million hepatitis C and 80
000 to 160 000 HIV infections are
estimated to occur yearly from re-use of
syringe needles without sterilization.
Many of these infections could be
avoided if syringes were disposed of
safely. The re-use of disposable syringes
and needles for injections is particularly
common in certain African, Asian and
Central and Eastern European countries.
Regarding injection practices, public
health authorities in West Bengal, have
recommended a shift to re-usable glass
syringes, as the disposal requirements for
disposable syringes could not be
enforced.
In developing countries, additional
hazards occur from scavenging on waste
disposal sites and manual sorting of the
waste recuperated at the back doors of
health-care establishments. These
practices are common in many regions of
the world. The waste handlers are at
immediate risk of needle-stick injuries
and other exposures to toxic or infectious
materials.
Vaccine waste
In June 2000, six children were
diagnosed with a mild form of smallpox
(vaccinia virus) after having played with
glass ampoules containing expired
smallpox vaccine at a garbage dump in
Vladivostok (Russia). Although the
infections were not life-threatening, the
vaccine ampoules should have been
treated before being discarded.
Radioactive wastes
The use of radiation sources in
medical and other applications is
widespread throughout the world.
Occasionally, the public is exposed to
radioactive waste, usually originating
from radiotherapy treatments, that has
not been properly disposed of. Serious
accidents have been documented in
Goiânia, Brazil in 1988 in which four
people died from acute radiation
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 Indian J for Practising Doctor; Vol I; No. 4
syndrome and 28 suffered serious
radiation burns. Similar accidents
happened in Mexico City in 1962,
Algeria in 1978, Morocco in 1983 and
Ciudad Juárez in Mexico in 1983.
Risks associated with other
fractions of health-care wastes, in
particular blood waste and chemicals,
have been relatively poorly assessed, and
need to be strengthened. In the
meantime, precautionary measures need
to be taken.
RISKS ASSOCIATED WITH WASTE
DISPOSAL
Although treatment and disposal
of health-care wastes aim at reducing
risks, indirect health risks may occur
through the release of toxic pollutants
into the environment through treatment
or disposal.
Landfilling can potentially result in
contamination of drinking water.
Occupational risks may be associated
with the operation of certain disposal
facilities. Inadequate incineration, or
incineration of materials unsuitable for
incineration can result in the release of
pollutants into the air. The incineration
of materials containing chlorine can
generate dioxins and furans, which are
classified as possible human carcinogens
and have been associated with a range of
adverse effects. Incineration of heavy
metals or materials with high metal
contents (in particular lead, mercury and
cadmium) can lead to the spread of
heavy metals in the environment.
Dioxins, furans and metals are persistent
and accumulate in the environment.
Materials containing chlorine or metal
should therefore not be incinerated.
Only modern incinerators are able to
work at 800-1000°C, with special
emission-cleaning equipment, can ensure
that no dioxins and furans (or only
insignificant amounts) are produced.
Smaller devices built with local materials
and capable of operating at these high
temperatures are currently being field-
tested and implemented in a number of
countries.
At present, there are practically no
environmentally-friendly, low-cost
options for safe disposal of infectious
wastes. Incineration of wastes has been
widely practised, but alternatives are
becoming available, such as autoclaving,
chemical treatment and microwaving,
and may be preferable under certain
circumstances. Landfilling may also be a
viable solution for parts of the waste
stream if practised safely. However,
action is necessary to prevent the
important disease burden currently
created by these wastes.
In addition, perceived risks
related to health-care waste management
may be significant. In most cultures,
disposal of health-care wastes is a
sensitive issue and also has ethical
dimensions.
WASTE MANAGEMENT - REASONS FOR
FAILURE
The absence of waste
management, lack of awareness about
the health hazards, insufficient financial
and human resources and poor control of
waste disposal are the most common
problems connected with health-care
wastes. Many countries do not have
appropriate regulations, or do not enforce
them. An essential issue is the clear
attribution of responsibility of
appropriate handling and disposal of
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waste. According to the ‘polluter pays’
principle, this responsibility lies with the
waste producer, usually being the health-
care provider, or the establishment
involved in related activities.
STEPS TOWARDS IMPROVEMENT
Improvements in health-care waste
management rely on the following key
elements:
The build-up of a comprehensive
system, addressing responsibilities,
resource allocation, handling and
disposal. This is a long-term process,
sustained by gradual improvements;
Awareness raising and training
about risks related to health-care
waste, and safe and sound practices;
________________________________________________________________________
Reduction of rectal
prolapse
Shabnam Bashir
______________________________
Rectal prolapse is a rare condition
characterized by an abnormal protrusion of
the rectum through anus. Partial prolapse
involves the mucosa and submucosa and is
most common in children who are less than 3
years of age. Peak incidence occurs in the 1
to 2 year age group and may be a result of
recently acquired erect posture and voluntary
control over defecation. Prolapse of entire
rectal wall is termed procidentia and occurs
more often both in older children with
underlying disease and in debilitated elderly
adults.
In most cases of childhood rectal
prolapse, the cause is unknown. Diarrhoea or
straining with bowl movement is a common
Selection of safe and
environmental-friendly management
options, to protect people from
hazards when collecting, handling,
storing, transporting, treating or
disposing of waste.
Government commitment and
support is needed to reach an overall and
long-term improvement of the situation,
although immediate action can be taken
locally.
Health-care waste management is
an integral part of health-care, and
creating harm through inadequate waste
management reduces the overall benefits
of health-care.
provoking factor. Children with weak rectal
musculature such as those with
meningomyelocele, prune belly syndrome,
and extrophy of the bladder are predisposed
to rectal prolapse. Procidentia in an older
child warrants an investigation for disease
associated with this condition such as cystic
fibrosis, rectal polyps or illnesses associated
with ascites or a sustained cough.
Patients with rectal prolapse present
with a painless protrusion from the rectum
that often resolves spontaneously, folds of
mucosa protruding through the anus. Full
thickness rectal prolapse must be
differentiated from hemorrhoids, a prolapsed
rectal polyp, or an intussussception extruded
via the anus.
Indications of reduction
Manual reduction of a rectal
prolapse that has not reduced spontaneously
is always indicated. Reduction is also
necessary if the prolapse is prolonged or if
passive congestion or bleeding has occurred.
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Unlike with adults, simple mucocal prolapse
in the pediatric population does not require
surgical evaluation unless it is recurrent or
recalcitrant to routine management. Prolapse
as a complication of anorectal surgery
requires specialized surgical procedures for
its correction.
Contraindications to reduction
There are no absolute
contraindications for the reduction of a rectal
prolapse. If vascular compromise of the
prolapsed segment is evident, perform
reduction immediately. Admit these patients
to the hospital because they are at risk for
bowel perforation.
Complications
The rectal prolapse itself may be
complicated by bleeding or ulceration.
Rarely, the prolapsed bowl can become
gangrenous if the prolapse is prolonged.
Rupture of a vascularly compromised
segment could occur during manual
reduction but has not been reported in the
pediatric literature.
Equipment
The only equipment required for reducing a
rectal prolapse are gloves, a lubricant and some
gauze pads. A sedative, that is appropriate for the
age of the patient and the level of anxiety, may be
necessary
Techniques
Place the adequately sedated patient
in a prose position over the parent’s lap or in
the knee chest position on the examination
table. Use lubricated gloves to place 4x4
gauze pads at the 3 and 9 o’ clock position of
the prolapse. Gauze improves grip on the
mucosa. Apply firm, gentle pressure to
reduce the direction of the prolapse. Such
pressure can be achieved by pressing on the
prolapse with both thumbs while stabilizing
the hands on the buttocks (fig 1); alternately,
the index and middle fingers may be used to
compress the prolapse while an assistant
holds the patient As such as 15 minutes of
pressure is often required to complete the
reduction. Perform a digital rectal
examination to ensure that the reduction is
complete. Instruct the patient to lie on his or
her side after the procedure. If the prolapse
recurs immediately, tape the buttocks
temporarily.
Surgery may be warranted if there is
no response to conservative management..
Surgery includes peri-rectal injection of
sclerosing agents with which many authors
report an excellent success rate. Major
surgical procedures as performed on adults
are rarely necessary in children.
Remarks
In the case of acute rectal prolapse in
children, it is first necessary to ascertain the
diagnosis by distinguishing it from
hemorrhoids, a prolapsed polyp, or extruded
intussusception. Hemorrhoids occur
primarily in adolescents, are purple in color,
and are contiguous with one wall of the anal
mucosa so that a palpating finger cannot
endfile?? the entire hemorrhoid. Prolapsed
polyps often are palpable within the rectum
as a small growth on stalk. Again they are
from a single wall of the rectum and not
from the entire circumference.
Intussusception is a diagnosis suspected on
clinical grounds in a lethargic child who is
vomiting. On physical examination, the
circular folds of the mucosa of the
intussusception may appear as a full
thickness rectal prolapse. The extent of the
prolapse and the clinical history and
examination lead to the diagnosis of
intussusception. After manual reduction, it
is of utmost importance to address the
primary problem. Because straining with
stools is the most common inciting event for
rectal prolapse, prescribe stool softeners and
lubricants such as mineral oil. In addition,
recommend a child toilet seat for toilet-
trained children to reduce the spreading of
the gluteal folds during defecation. Patients
with recurrent prolapse require a workup for
cystic fibrosis and a barium enema to rule
out rectal polyps or other lesions that may
act as a lead point for the prolapse.
*************************************
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Special Supplement

Drug Use
in Hepatic Impairment*

*(based on WHO
Recommendations)

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 Indian J for Practising Doctor; Vol I; No. 4

Drug use in Hepatic Impairment

Liver disease may alter the response to drugs. However, the hepatic reserve
appears to be large and liver disease has to be severe before important changes in drug
metabolism take place. The ability to eliminate a specific drug may or may not correlate
with liver' s synthetic capacity for substances such as albumin or clotting factors, which
tends to decrease as hepatic function declines. Unlike renal disease, where estimates of
renal function based on creatinine clearance correlate with parameters of drug elimination
such as clearance and half-life, routine liver function tests do not reflect actual liver
function but are rather markers of liver cellular damage.

The altered response to drugs in liver disease can include all or some of the following
changes:

• Impaired intrinsic hepatic eliminating (metabolizing) capacity due

to lack of or impaired function of hepatocytes.

• Impaired biliary elimination due to biliary obstruction or transport

abnormalities (for example, rifampicin is excreted in the bile
unchanged and may accumulate in patients with intrahepatic or
extrahepatic obstructive jaundice).

• Impaired hepatic blood flow due to surgical shunting, collateral

circulation or poor perfusion with cirrhosis and portal
hypertension.

• Altered volume of distribution of drugs due to increased

extracellular fluid (ascites, oedema) and decreased muscle mass.

• Decreased protein binding and increased toxicity of drugs highly

bound to proteins (for example phenytoin) due to impaired
albumin production.

• Increased bioavailability through decreased first-pass metabolism.

• Decreased bioavailability due to malabsorption of fats in

cholestatic liver disease.

In severe liver disease, increased sensitivity to the effects of some drugs can
further impair cerebral function and may precipitate hepatic encephalopathy (for example
morphine, pethidine). Oedema and ascites in chronic liver disease may be exacerbated by

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drugs that cause fluid retention (for example acetylsalicylic acid, ibuprofen, prednisolone,
dexamethasone).

Usually drugs are metabolized without injury to the liver. A few drugs cause dose-
related hepatotoxicity. However, most hepatotoxic reactions to drugs occur only in rare
persons and are unpredictable. In patients with impaired liver function the dose-related
hepatotoxic reaction may occur at lower doses whereas unpredictable reactions seem to
occur more frequently. Both should be avoided.

Information to help prescribing in hepatic impairment is included in the following

table. The table contains only those drugs that need dose adjustment. However, absence
from the table does not automatically imply safety as for many drugs data about safety are
absent; it is therefore important to also to refer to the individual drug entries.

Table of drugs to be avoided or used with caution in liver disease

Drug Comment

Abacavir No dosage adjustment required in mild hepatic impairment;

avoid in moderate or severe hepatic impairment

Acetylsalicylic acid Avoid-increased risk of gastrointestinal bleeding

Alcuronium Possibly slower onset, higher dose requirement and

prolonged recovery time

Allopurinol Reduce dose

Aluminium hydroxide In patients with fluid retention, avoid antacids containing

large amounts of sodium; also avoid those causing
constipation (can precipitate coma)

Aminophylline Reduce dose

Amitriptyline Sedative effects increased (avoid in severe liver disease)

Amoxicillin + Clavulanic acid

Monitor liver function in liver disease. Cholestatic jaundice
reported either during or shortly after treatment; more
common in patients over the age of 65 years and in males;
duration of treatment should not usually exceed 14 days

Azathioprine May need dose reduction

Bupivacaine Avoid (or reduce dose) in severe liver disease

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Carbamazepine Metabolism impaired in advanced liver disease

Ceftriaxone Reduce dose and monitor plasma concentration if both

hepatic and severe renal impairment

Chloral hydrate Can precipitate coma (avoid in severe impairment)

Chloramphenicol Avoid if possible-increased risk of bone-marrow depression;

reduce dose and monitor plasma-chloramphenicol
concentration

Chlorphenamine Sedation inappropriate in severe liver disease-avoid

Chlorpromazine Can precipitate coma; hepatotoxic

Ciclosporin May need dose adjustment

Cimetidine Increased risk of confusion; reduce dose

Ciprofloxacin Hepatitis with necrosis reported

Clindamycin Reduce dose

Clomifene Avoid in severe liver disease

Clomipramine Sedative effects increased (avoid in severe liver disease)

Clonazepam Can precipitate coma

Cloxacillin Cholestatic jaundice may occur up to several weeks after

treatment has been stopped; administration for more than 2
weeks and increasing age are risk factors
Codeine Avoid or reduce dose-may precipitate coma

Contraceptives, oral Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Cyclophosphamide Reduce dose

Cytarabine Reduce dose

Dacarbazine Dose reduction may be required in mild to moderate liver

disease; avoid if severe

Daunorubicin Reduce dose

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Dextromethorphan Avoid or reduce dose-may precipitate coma

Diazepam Can precipitate coma

Didanosine Insufficient information but consider dose reduction

Doxorubicin Reduce dose according to bilirubin concentration

Doxycycline Avoid (or use with caution)

Efavirenz In mild to moderate liver disease, monitor liver function;

avoid in severe hepatic impairment

Ergometrine Avoid in severe liver disease

Ergotamine Avoid in severe liver disease-risk of toxicity increased

Erythromycin May cause idiosyncratic hepatotoxicity

Ether, anaesthetic Avoid

Etoposide Avoid in severe hepatic impairment

Fluconazole Toxicity with related drugs

Fluphenazine Can precipitate coma; hepatotoxic

Furosemide Hypokalaemia may precipitate coma (use potassium-sparing

diuretic to prevent this); increased risk of hypomagnesaemia
in alcoholic cirrhosis

Glibenclamide Increased risk of hypoglycaemia in severe liver disease;

avoid or use small dose; can produce jaundice

Griseofulvin Avoid in severe liver disease

Haloperidol Can precipitate coma

Halothane Avoid if history of unexplained pyrexia or jaundice

following previous exposure to halothane

Heparin Reduce dose in severe liver disease

Hydralazine Reduce dose

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Hydrochlorothiazide Avoid in severe liver disease; hypokalaemia may

precipitate coma (potassium-sparing diuretic can prevent
this); increased risk of hypomagnesaemia in alcoholic
cirrhosis

Ibuprofen Increased risk of gastrointestinal bleeding and can cause

fluid retention; avoid in severe liver disease

Indinavir Reduce dose to 600 mg every 8 hours in mild to moderate

hepatic impairment; not studied in severe impairment

Iopanoic acid Avoid in severe hepatic disease

Isoniazid Avoid if possible-idiosyncratic hepatotoxicity more

common

Levonorgestrel Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Lidocaine Avoid (or reduce dose) in severe liver disease

Lopinavir with Ritonavir Avoid oral solution because of propylene glycol content; use
capsules with caution in mild to moderate hepatic
impairment and avoid in severe impairment

Magnesium hydroxide Avoid in hepatic coma if risk of renal failure

Magnesium sulfate Avoid in hepatic coma if risk of renal failure

Medroxyprogesterone Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Mefloquine Avoid for prophylaxis in severe liver disease

Metformin Avoid-increased risk of lactic acidosis

Methotrexate Dose-related toxicity-avoid in non-malignant conditions (for

example, rheumatic disorders)

Methyldopa Manufacturer advises caution in history of liver disease;

avoid in active liver disease

Metoclopramide Reduce dose

Metronidazole In severe liver disease, reduce total daily dose to one-third

and give once daily

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Minocycline Avoid (or use with caution)

Morphine Avoid or reduce dose-may precipitate coma

Nalidixic acid Partially conjugated in liver

Nelfinavir No information available-manufacturer advises caution

Nevirapine No information available-manufacturer advises avoid

Nifedipine Reduce dose

Nitrofurantoin Cholestatic jaundice and chronic active hepatitis reported

Norethisterone Avoid in active liver disease and if history of pruritus or

cholestasis during pregnancy

Ofloxacin Reduce dose in severe liver disease

Paracetamol Dose-related toxicity-avoid large doses

Pentavalent antimony compounds

Increased risk of liver damage and hepatic failure in pre-
existing liver disease

Pethidine Avoid or reduce dose-may precipitate coma

Phenobarbital May precipitate coma

Phenytoin Reduce dose to avoid toxicity

Prazosin Initially 500 micrograms daily; increased with caution

Prednisolone Adverse effects more common

Procainamide Avoid or reduce dose

Procarbazine Avoid in severe hepatic impairment

Promethazine Avoid-may precipitate coma in severe liver disease;

hepatotoxic

Propranolol Reduce oral dose

Propylthiouracil Reduce dose;

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Pyrazinamide Avoid-idiosyncratic hepatotoxicity more common

Rifampicin Impaired elimination; may be increased risk of

hepatotoxicity; avoid or do not exceed 8 mg/kg daily

Saquinavir Plasma concentration possibly increased; manufacturer of

gel-filled capsules advises caution in moderate hepatic
impairment and avoid in severe impairment; manufacturer
of capsules containing saquinavir mesilate advises caution
in severe impairment

Sodium nitroprusside Avoid in severe liver disease

Sulfamethoxazole + Trimethoprim
Manufacturer advises avoid in severe liver disease

Suxamethonium Prolonged apnoea may occur in severe liver disease due to

reduced hepatic synthesis of pseudocholinesterase

Testosterone Preferably avoid-possibility of dose-related toxicity and fluid

retention

Theophylline Reduce dose

Thiopental Reduce dose for induction in severe liver disease

Valproic acid Avoid if possible-hepatotoxicity and hepatic failure may

occasionally occur (usually in first 6 months)

Verapamil Reduce oral dose

Vinblastine Dose reduction may be necessary

Vincristine Dose reduction may be necessary

Warfarin Avoid in severe liver disease, especially if prothrombin time

already prolonged

Zidovudine Accumulation may occur

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