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IAP GUIDEBOOK ON IMMUNIZATION

Editors

Dr. Raju C Shah

Dr. Nitin K Shah
Dr. Shyam Kukreja

IAP Committee on Immunization 2005-2006

Chairperson: Dr. Raju C. Shah

Co- Chairperson: Dr. Nitin K. Shah
Convener: Dr.Shyam Kukreja

Members: Dr. Rohit Agarwal

Dr. Indra Shekhar Rao
Dr. Shivananda
Dr. Nigam P Narain
Dr. Sangita Yadav

Ex-officio members: Dr. Deepak Ugra

Dr. Tapan Kumar Ghosh
Dr. VN Yewale
Dr. Naveen Thacker
Dr AP Dubey
Dr Surjeet Singh

Address for correspondence:

Indian Academy of Pediatrics

Kailas Darshan, Keneddy Bridge
Near Nana Chowk
Mumbai India 400 007
Tel: +91-22-3889565
E-mail: iapcoff@bom5.vsnl.net.in

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 Preface

Immunization is the single most successful child survival s t rat egy the world over. Immunization also reduces
morbidity to great extent. Due to progress in molecular biology and genetic engineering a number of new vaccines
have become available and many more are in the pipeline. Many of the developed countries have reduced their
vaccine preventable disease burden by using this tool very effectively.

As Pediatricians we must be conscious of the fact that the immunization needs of the children are quite dynamic.
A vaccine which may not be considered important today may become n ecessary in future as more informat ion
about the epidemiology of the disease becomes available. The inclusion of an y n ew v accine in the universal
immunization program of a country depends on disease epidemiology, availability of safe vaccine, economic
constraints and logistic problems. Unfortunately the limiting factor most of the times in developing countries like
India is the affordability.

There is always a need to update knowledge and co n cep t s es pecially in the field of immunization as there is
continuous flow of new knowledge. Also one must try to objectively understand a difference between a public
health measure paid for by the government and a personal safety measure instituted by the individual at one's own
cost due to certain limitations.

To get the most benefits for any vaccine (herd effect), adequate immunization coverage is required. Unfortunately,
in our country the routine immunization coverage rates have slipped down over the last few years. This is a matter
of great concern to all of us. This has been one of the major obstacles in polio eradication program. There is an
urgent need to reinforce quality immunization services and our academy has always been at the forefront of this
initiative.

We are sure this updated guidebook will continue to serve as ready reckoner on issues concerning vaccines and
immunization in our country.

Dr. Raju C Shah Dr. Nitin K. Shah Dr. Shyam Kukreja

Chairperson, IAPCOI 2005- 2006 Co-Chairperson, IAPCOI Convener, IAP COI 2005- 2006
2005-2006
President IAP 2005
President IAP 2006

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Contents

Introduction 5

Historical aspects 6

Basic immunology 8

National immunization schedule 10

Commonly used vaccines 11

Newer vaccines 24

Vaccines used in special circumstances 27

Combination vaccines 30

IAP Immunization Time-Table 34

Immunization in special circumstances 36

Adverse reactions following immunization 42

The cold chain 44

Surveillance for vaccine preventable diseases 49

Vaccination in the current millenium 50

IAP COI meeting report and policy updates 51

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 Introduction
Protect ion from preventable diseases, disabilities and
death through immunization is the birth right of every
child. Immunization is one of the most co s t-effective
health intervention s known to mankind Over the last
three decades, a lot of progress has been made globally
as far as protection against the eight important vaccine
preventable diseases is concerned - from less than 5%
children who were protected against these diseases in
the early 1970s, to as many as 75% being protected
now. Small pox has been eradicated and we are at the
threshold of eliminating polio.
An effective National Immunization strateg y can help
decrease childhood morbidity and mortality, especially
in developing countries. It must, however, be clear that
immunization strategies may vary from co u n try to
country depending on the local req u irements. This
guide book represents the collective effo rts of the
members of the Indian A cademy of Pediatrics
Co mmittee on Immunization (IAP COI). We are aware
that unanimity may not always be possible as far as the
need and timing of certain newer vaccines are
concerned, but we have made efforts t o arriv e at a
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consensus based on the current evidence from the
literature. The IAP Immunization Time Table
represents the 'best individual practices schedule' for a
given child and would necessarily be at some variance
from the National Immu n ization Schedule of the
Government of India, which is meant for the public at
large. With the availability of many newer vaccines, it
is necessary that some of these should be considered for
routine immunization and the immu nization schedule
has to be changed accordingly.
Unfortunately, there is lack of authentic data on
epidemiology of most infectious diseases in our country.
However that should not deter us from using some of
these vaccines till such data is generated. Many
decisions on incorporation of new vaccines in t he
immunization program have, therefore, to be based on
data from other parts of t h e world. This may appear
unscientific to some, but is a reality and is the only way
out at present.
 Historical Aspects
Though Dhanvantri, t h e father of Indian
Medicine, sp o ke of preventing certain infectious
diseases t h rough immunization, the first successful
vaccine in the modern era was developed b y Edward
Jenner in 1796 when he used cowpo x inoculation
(vaccination) to protect against smallpox. Louis
Pasteur developed a h ig h ly effective vaccine against
rabies, which was used for post-exposure prophylaxis.
It was first given to a child in 1885. Since then many
other vaccines have been developed in rapid succession.
Experience with smallpox eradicat io n p ro g ram
convinced the health policy makers that immunization
was the most powerful and cost-effective measure for
control of vaccine preventable diseases. At the global
level, an organized immunization program came into
exis tence in the year 1974 under the banner of the
World Health Organization (WHO). This was
christened as the 'Expanded Program on Immunization'
(EPI). The term "Exp anded" referred to the provision
of adding more antigens to vaccinatio n s chedules,
extending coverage to all corners of a country and
spreading services to reach the less privileged sections
o f the society. The EPI program focused on children
below 5 years of age and pregnant women. The
vaccines included were BCG, DTP, OPV, Measles and
TT. The primary health care concept as enunciated in
the 1978 Alma Ata Declaration in cluded immunization
as one of the strategies for reaching the goal of 'Health
for All' by the y ear 2000. The Government of India
adopted the EPI in 1978 with the t win objectives of
reducing the mortality and morbidity resulting from
vaccine preventable diseases of childhood, and to
achieve self-sufficiency in the production of vaccines.
The program started with BCG, DTP and Typhoid
vaccines - it did not include measles vaccine. OPV was
added only in 1979 and measles later on. Ty p h oid
vaccin e continued to be a part of our national
immunization schedule until 1985. Program coverage
of 85% was envisaged, but this could not be achieved
for several years and independent evaluations showed
very low coverage rates in many parts of our country.
Th erefore, a change of strategy was considered
necessary.
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In 1985, the EPI was s upplanted by the Universal
Immunizat ion Program (UIP). The main objectives of
UIP were: i) universal immunization and reduction in
mortality and morbidity due to vaccine prev entable
diseases ii) self-sufficiency in vaccine production iii)
establishment of a functional cold chain system, and iv)
the introduction of district level monitoring system. In
this program the emphasis was s hifted from the
under-five to under-one age group, thereby reducing the
number of potential beneficiaries. It considerab ly
reduced the denominator for percentage coverage. The
vaccines recommen d ed were BCG, DTP, OPV and
Measles for infant s an d TT for pregnant women. It
should be noted that UIP envisaged 100% coverage of
pregnant women with 2 doses of tetanus toxoid (or a
booster dose, as applicable) and at least 85% coverage
of infants. Under the UIP, the govern ment also aimed
to establish logistics of vaccine production and supply
as well as training of medical and p aramedical
personnel. The Government of India subsequently set
up a " Technology Mission on Vaccination and
Immunization of Vulnerable Po pulation, especially
Children" to cover all asp ect s of the immunization
activity from research and development to actual
delivery of services to the target population.
Since switching over to UIP in India there has been a
significant decline in many of the vaccine preventable
diseases, such as poliomy elitis, neonatal tetanus,
diphtheria, wh o o p ing cough and measles. The UIP
became an integral component of Child Survival and
Safe Motherhood Program (CSSM) in 1992 and then
part of Reproductive and Child Health Program (RCH)
in 1997. Supplemen t ary immunization activities
against poliomyelit is were started in 1995-96. In 2002,
Hepatitis B vaccination was initiated in selected areas
targeting the urban poor.
The WHO also endorsed global efforts at immunization
through Universal Childhood Immunization (UCI) in
1990 - the name given to a declaration sponsored by
UNICEF as part of the 40th anniversary of the United
Nations in October 1985. Efforts were undertaken to
initiate research for the development of newer vaccines,
to improve vaccine product ion technologies and to
u n d erstand the epidemiology of diseases. These
developments were highlighted in 1990 at the Summit
for Children, where it was claimed that EPI had indeed
been a global success with 80% reported coverage with
the six vaccines. In 1992, the WHO also set a target for
universal Hepatitis B immunization. It aimed to
incorporate Hepatitis B vaccine in the immunization
schedules o f all member countries by 1997. However
unfortunately less than 50% of t h e countries have
actually introduces Hepatitis B vaccine in their
National Schedule. India has recently accepted its
inclusion in National schedule and the coverage will
expand in a phased manner.
These global efforts at immunization were launched
under the banner "Children Vaccine Initiative" (CVI)
in 1991 with support from several in t ernational
agencies like the WHO, UNICEF, World Bank and the
Rockefeller Foundation. CVI aimed at development of
newer vaccines, improvement in vaccine production
technolo g ies and vaccine quality. These efforts were
further co nsolidated under the "Global Program on
Vaccines and Immunization" (GPV) in 1993 reflecting
the EPI and UCI init iative and combining these with
the CVI. The focus of GPV is on sustaining high
vaccine coverage, developing global surv eillance
network and evolving eradication strategies. The
"Global Alliance for Vaccines and Immunization"
(GAVI) was set up in 1999 as an international coalition
of multination al funding agencies (e.g. Bill and
Melinda Gates Foundation, Rockefeller Foundation),
v accin e man u fact u re r s , n o n - g o v ern men t al
organizations and the governments of 74 d ev eloping
nations. GAVI organizes its activities through a
vaccin e fund. The main objectives of GAVI are as
follows: i) impro v in g acces s t o s u s t ainable
immunization services ii) expanding use of all existing
safe and effective vaccines iii) accelerat ing the
development and introduction of new vaccines iv)
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augmenting research and d ev elopment on vaccines
against HIV, malaria and tuberculosis v) making
immunization coverage an integral part of international
development initiatives. The GAVI Ind ia Project has
been instrumental in launching free Hepatitis B
immunizatio n in some of the urban slums. It has also
endeavored to promote safe injection practices and use
of auto-disable syringes for immunization as part of a
countrywide initiative.
A surv ey conducted in 2002 under the RCH showed
that immunization coverage rates in India have been
d eclining, since 1999. The Government of India h as
recently lau n ched an Immunization Strengthening
Project with the objectives of i) strengthening routine
immunization with the aim of raising the percentage of
fully immunized children t o ab ove 80% ii) eliminating
polio and achieving polio eradication iii) reviewing and
developing a new vision of the immunization program
in the medium term keep in g in view the development
of new epidemiological patterns, availability of new
vaccines and delivery mechanisms and advances in cold
chain technologies iv) improving surveillance and
monitoring mechanisms. The National Institute of
Health and Family Welfare has been identified as the
nodal institute for coordination and implementation of
the program an d the training shall be carried out
through five regional inst it u tes. Training of mid-level
managers, including persons actively involved in
immunization program at the district and state level, is
an integral component of this project. The project was
started in 50 poorly performing districts of 8 priority
states of Uttar Pradesh, Bihar, Madhya Pradesh,
Rajasthan, Oriss a, Gujarat, Assam and West Bengal.
These newer initiatives have improved overall coverage
in these districts. Unfortunately last report of National
family and health survey released in 3rd week of Nov
'06 do not confirm this improvement.
 Basic Immunology
The Greek work "immune" means "to be protected".
Protection offered by the introduction of various
antigens or ready-made antibodies is called acquired
immunity. The process by which t h is acquired
immunity is obtained is known as 'immunization'. This
is of two types, active and passive. When specific
antigens evoke the required immune response in the
system it is called active immunization, and when
antibodies are supplied readymade in th e form of
immune g lo b u lins and sera it is known as passive
immunization.
Pathogenic infectious ag en t s induce disease and the
host immune system responds with immunity , first to
ensure recovery and then to offer protection from
disease if the same patho gen were to be encountered
again. A vaccine is composed of one or more antigens
of the pathogen, which will induce a protective immune
response without suffering from the disease.
Vaccines consist of attenuated live organisms (eg. oral
polio vaccines, oral typhoid vaccine, varicella vaccine,
measles vaccine), whole inactivated org anisms (e.g.
pertusis vaccine, whole cell typhoid vaccine, rabies
vaccine, inactivated polio vaccine), modified exotoxins
called "toxoids" (e.g. diphtheria toxoid, tetanus toxoid),
or subunits (e.g. polysaccharide antigens of Salmonella
typhi or Haemophilus influenzae type b and the surface
proteins of hepatitis B virus).
Vaccines mimic infection with the respective pathogen,
but without the asso ciated risk of developing the
disease. The consequent immune response may be
manifested through hu moral (i.e. antibody) immunity
or cell mediated immunity (CMI) or both. If the antigen
preferentially stimulates Th1 series of T helper
lymphocytes, a strong lymphocytic respons e is
obtained; if Th2 series is preferentially stimulated, the
ultimate express ion of immunity is predominantly
humoral. Carbohydrate antigens are T cell independent;
hence they stimulate B cells directly without T helper
cell modulation. This results predominan t ly in a IgM
response wit h out IgG production or induction of
immunological memory. BCG elicits CMI without an
easily demonstrable humoral component.
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BCG, oral polio v accine and Hepatitis B vaccines can
be given soon after birth as the maternally derived
immunity apparently does not interfere with the vaccine
"take" On the other hand, live measles vaccine may be
inhibited in the presence of detectable maternal
antibody in the infant's circu lation. Measles vaccine,
therefore, should only be given after at least 9 months
of age ; similarly, MMR vaccine is given only after 12
months of age.
Timing of vaccination depends upon the age at which
the disease is anticipated as well as on the feasibility of
administering the vaccine at that time. For instan ce,
neonatal tetanus can only be prev en t ed through
maternal immunization by ensuring adequate titers of
transplacent al antibodies and not by immunization of
the baby at birth.
Vaccines are selected based on three important criteria
viz. necessity, safety and efficacy. All vaccines are
subjected to the following trials before being licensed:
Phase I Trial: Human volunteers - for tolerance, safety
Ph as e II Trial: Human volunteers - for immu n e
response, safety
Phase III Trial: For field efficacy, safety
Further, before a vaccine is act u ally marketed it
undergoes sterility, purity and potency tests at the level
of the manufacturer and the Drugs Controller General
of India.
Most of the currently used childhood vaccines do not
interfere with the vaccine "take" of one another. These
can be, therefore, given simultaneously and several
antigens can be g iv en the same day, if required. In
general, the interval between two doses of the same
v accine, say for instance DTP, should be at least 4
weeks; preferably 8 weeks. An interval of 4 weeks
would obviously result in completion of the primary
schedule at an earlier age an d may perhaps make it
easier for the parents to remember their follo w-up
appointments. Th is way the drop out rates may also
decrease. BCG and OPV can be given from the day of
birth until 2 weeks of age, s o that there would be 4
weeks gap until the next contact for immunization at 6
weeks. If the opportunity to give BCG / Hepatitis B was
not available in the neonatal period, it may be given at
6 weeks, s imultaneously with DTP and OPV. Some of
the viral vaccines (e.g. measles, varicella) may be
associated with possible short lasting suppression of the
immune system and it may be advisab le to avoid
administratio n of other vaccines within 4 weeks of
these. There is, however, very little objective evidence
to show t h at this immunosuppression is clinically
significant.

Terminology

Vaccination: process of inoculating the vaccine/antigen.

Immunization: process of inducing immune response which may be humoral or cellular.

Seroconversion: change from antibody negative state to antibody positive state.

Seroprotection: a stage of protection from disease, due to the presence of detectable antibody.

Antibody titer: the reciprocal of the highest serum dilution at which antibody has been detected.

Geometric mean: the mean antibody titer in a g ro u p o f in d ividuals [usually titer from those who have
seroconverted (GMT)]

Each time a vaccine is given the doctor should explain anticipated adverse reactions and due date for the next
to the mother the nature of vaccine, t h e n umber of session of immunization.
doses needed, the disease likely to be prevented,

Types of Vaccines

Type of Antigen Examples

Live bacteria, attenuated BCG, Ty21a

Live virus, attenuated OPV, MMR, varicella
Inactivated bacteria Pertussis, whole cell killed typhoid
Inactivated virus IPV, rabies, HAV
Toxoid Tetanus, diphtheria, Td
Capsular polysaccharide Typhoid Vi, Hib, meningococcal,
pneumococcal
Viral subunit HBsAg
Bacterial subunit Acellular pertussis

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 National Immunization Schedule

Age Vaccines

Birth BGG, OPV0 for institutional deliveries

6 weeks DTP1, OPV1 (BCG if not given at birth)

10 weeks DTP2, OPV2

14 weeks DTP3, OPV3

9 months Measles

16-24 months DTP, OPV

5-6 years DT*

10 years TT**

16 years TT

For pregnant women

Early in pregnancy TT1 or booster

One month after TT TT2

*A second d o s e of DT vaccine should be given at an interval of one month if there is no clear history or
documented evidence of previous immunization with DTPw.

** A second dose of TT vaccine should b e g iv en at an interval of one month if there is no clear history or
documented evidence of previous immunization with DTPw, DT or TT vaccines

(Source: Govt. of India (1994) National Child Survival and Safe Motherhood Program, M in is t ry of Health and
Family Welfare, New Delhi)

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 Commonly Used Vaccines
A. Vaccines Against Diseases Covered Under EPI
BCG Vaccine
Bacillus Calmette Guerin vaccine is derived from the
bovine tuberculosis strain and was first developed in
1921. It was the result of painstaking efforts by t h e
French microbiologist Albert Calmette and the
veterinary surgeon Camille Guerin who performed 231
repeated subcultures over 13 years. It continues to be
the only effective vaccine against tuberculosis The two
common strains in use are Copenhagen (Danish 1331)
and Pasteur of which the former was produced in India
at the BCG Laboratories, Guindy, Tamil Nadu till
recently.
BCG induces cell-mediated immunity but t h e
protective efficacy is a matter of debate and is very
difficult to q u an t ify BCG vaccine is more effective
against t h e development of hematogenous spread of
Mycobacterium tuberculosis (which results in milliary
and meningeal forms of the disease against which it
has a protective efficacy of 50-80%), than against the
development of pulmonary tuberculosis where it has a
protective efficacy of less than 50%.
The vaccine contains 0.1-0.4 million live viable bacilli
per dose. It is supplied as a lyophilized (freeze-dried)
preparation in vacuum sealed multi-dose dark colored
ampoules. The lon g n ecked BCG ampoule should be
cut carefully by gradual filing at the junction of its neck
and body, as sudden gush of air in the vacuum sealed
ampoule may lead to spillage of th e contents. The
vaccine is light and heat sensitive and deteriorates on
exposure to ult ra violet rays. Sterile normal saline
should be used for reconstitution. As t h e vaccine
contains no preservative, bacterial contamination may
occur with repeated use. Therefore, once reconstituted,
the vaccine should be used within 4 hours with the
left-over being discarded after the session.
In lyophilized form it can be stored at 2-80 C for up to
12 months, without losing its potency. One should
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ensure maintenance of cold chain during transport and
storage. Th e recommended dose is 0.1 ml of
reconstituted vaccine irrespective of the age and weight
of the baby. Injection of BCG should be strictly
intradermal, using a Tuberculin syringe and a 26G
need le. The convex aspect of the left shoulder is
preferred for easy visualization of the BCG scar. The
selected site may be swabbed clean using sterile saline
- local antiseptics are unnecessary.
A wheal of 5 mm. at the injection site indicates
successful intradermal administrat ion of the vaccine.
Subcutaneous administration of BCG is associated with
an increased incidence of BCG aden it is . The injected
site usually shows no visible change for several days
Subsequently, a papule develops after 2-3 weeks, which
increases to a size of 4-8 mm. by the end of 5-6 weeks.
This papule often heals with ulceration and results in a
s car after 6-12 weeks. Although the preferred time o f
vaccination is soon after birth, it could be given up to
the age of 5 years. If no reaction is seen at the local site
even after 12 weeks, it is an in dication to repeat BCG
presuming that BCG has not taken up.
Adverse reactions - The ulcer at vaccination site may
persist for a few weeks before formation of the final
scar. No treatment is required for this co ndition.
Secondary infection at the vaccination site may require
an t imicro b i a l s . I p s i l a t eral axillary / cerv ical
ly mphadenopathy may develop a few weeks/months
after BCG vaccination. Antitubercular therapy is of no
benefit in such situations and should not be
administered. The nodes regress spontaneously after a
few months. It should also be noted that if fine needle
aspiration cytology of the nodes is carried out, stain for
acid-fast bacilli may b e p o sitive. These are bovine
vaccine bacilli and should not be misconstrued as being
suggestive of tuberculous disease. In some children the
nodes may even liquefy and result in an ab s cess.
Surgical removal of the nodes or repeated needle
aspiration is the treatment of choice - again,
antitubercular therapy is not recommended in this
Oral Polio Vaccine
Oral polio vaccine (OPV) remains the vaccine of choice
for polio eradication in India. It is a suspension of over
1 million particles of poliovirus types 1, 2 and 3. It is
supplied with a stabilizing agent, namely magnesium
chloride. The vaccine, therefore, is quite stable under
refrigeration.
When OPV is given by mout h , t h e vaccine viruses
reach the intestines where they must establish infection
(vaccine virus "take") before an immune response may
occur. A high level of gut immunity ensures that
vaccinated children would not participate in the chain
of transmission of wild (pathogenic) polioviruses. For
reasons that are not clearly understood, OPV "take"
rates may be somewhat variable. Seroconversion rates
after three doses of OPV average 73%, 90% and 70%
for Types I, II and III respectively. It is for this reason
that multiple doses of OPV are necessary before
90-95% of children develop immune responses to all
three poliovirus typ es . IAP recommends at least 5
routine doses of OPV, d u ring infancy and 2 more
repeat doses; at 16-18 months and 5 years. In addition
to the routine OPV doses , " Pulse OPV doses" every
year on Nat io n al Immunization Days (NIDs) and
sub-National Immunization Days (sNIDs) until the age
of 5 years are also mandatory.
Polio eradication is defined as no case of paralytic
poliomyelitis by wild polioviru s in last three calendar
years along with absence of wild poliovirus in the
community, when excellent clinical and virological
surveillance exists and the coverage of routine OPV is
more than 80%. Polio elimination is defined as no case
of paralytic poliomyelitis by the wild poliovirus in one
calendar year with other criteria being the s ame as in
eradication . A d eq u at e immu n izat io n , clinical
surveillance and appropriate virological investigations
in all children with acute flaccid paralys is (AFP) are
the cornerstones of polio eradication.
OPV should be stored at -200 C at the state and district
level and in the freezer at the clinic level. The vaccine
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s it u at ion also. Disseminated BCG infection is
extremely unusual but may occur in children with
cellular immunodeficiency.
must reach the outreach facility at 2-80 C in vaccine
carriers with ice packs. Breastfeeding and mild
d iarrh ea are n o co n t rain d icat io n t o OPV
adminis t rat ion. If a substantial amount of OPV is
vomited or regurgitated wit hin 5-10 minutes of
administration, the dose should be given again. If this
repeat dose is also not retained, neith er of the doses
s hould be counted and the vaccine shou ld b e
re-administered at a later visit.
Adverse reactions - OPV is an excellent vaccin e and
the WHO Global Polio Eradicat io n Initiative is at the
threshold of achieving its goal of eradicating wild
polioviruses. By mid-2006 polio has been elimin ated
from all countries other than India, Pakistan,
Afghanstan, Nigeria, Niger and Egypt. For developing
cou n t ries OPV is still the vaccine of choice for
eradicating wild poliovirus and would continu e t o be
used until wild poliovirus circulation ceases. However,
like any other vaccine its use is associated with certain
risks.
OPV has been associated with occurrence of Vaccine
Associat ed Paralytic Poliomyelitis (VAPP) Today, as
we move towards p o lio eradication, VAPP is more
common than paralysis due to wild polioviruses and
has, therefore, become an increasingly contentious
issue for all pediatricians . The risk of VAPP would
continue to be there as long as we are using OPV as the
preferred vaccine against poliomyelitis. It has been
estimated that the global VAPP burden is in the range
of 250-800 cases an nually. Nearly 50 cases of VAPP
are reported to occur in India annually. Approximately
half of all VAPP cases are associated with the Type 2
OPV strain.
The second major problem with u s e of OPV is the
emergence of circulating Vaccine Derived Polio
Viruses (cVDPVs), which are mutants that re-acquire
wild virus-like properties and have been associated with
outbreaks of paralytic polio. cVDPVs usually aris e in
communities with low population immunity especially
when polio vaccine coverage rates decline but OPV use
continues. The duration and extent of spread of
cVDPVs are dependent on the magnitude of the
immunity gap. As lo n g as OPV is in use it is
mandatory that very high immunization coverage is
maintained so as to decrease the risk of emergence of
cVDPV. W hereas VAPP occurs in individual cases,
cVDPV can result in large outbreaks. It has been
suggested that mass OPV campaigns should be
s ynchronized with the cessation of OPV use o n ce
eradication of wild poliovirus has been achieved, so as
t o eliminate the risk of VAPP and the emergence o f
cVDPVs. At the same time, a gradual transition to IPV
should be encouraged.

Polio Eradication

Why do we need pulse immunization against polio?
Simultaneous administration OPV to all susceptible
infants and children interferes with circulation of wild
poliovirus in the community. It is, therefore, important
to ensure complete coverage with OPV during NIDs so
that no wild poliovirus remains in circulation.
• Maintaining high routine infant
immunization coverage with OPV.
• Conducting mass campaigns (i.e. pulse
immunization against polio).
• Development of sensitive surveillance.
• Organization of mop-up campaigns.

Core strategies for eradication of polio include:

Inactivated Polio Vaccine (IPV)

IPV is formaldehyde killed poliovirus grown in monkey could be given at 4 weeks interval without any
kidney cell/human diploid cells. Old IPV contained 20, compromise in the seroconversion rates.
8 and 32 D antigen units of types 1, 2 and 3
Scientifically and immunologically schedule of giving
polioviruses respectively. All curren tly used IPV
two doses of IPV starting at 2 months of age and given
vaccines are enhanced potency IPV (elIPV) which
at 2 months interval followed by a booster at around 15
cotains 40, 8 and 32 D antigen units of type 1, 2 and 3
mo n t h s is similar to a schedule of giving 3 doses
respectively. Currently term IPV means eIPV. It is
starting from 6 weeks of age and given at 4 weeks
highly immunogenic. Seroconversion rates are 90-95%
interval followed b y a booster at 15 months (even in
after two doses given after the age of 2 months and at
developing countries). However in our country the later
2 months interval and 99% after three doses given even
schedule of 3 primary doses is better logistically as it
when it is started at 6 weeks of age and given an 4
can be given along with DTP at 6, 10 and 14 weeks
weeks interval It produces excellent humoral immunity
followed b y a booster at 15 months. In any case the
as well as local pharyngeal and, possible in testinal
b irt h d o se of OPV must be given and all the OPV
immunity. The vaccine is very safe. It is now licensed
doses on the days of NIDs / SIAs should be given to all
to be used in India by Drug controller of India.
the children.
IPV can be used in combination with DTwP and Hib
As the number of wild poliovirus cases in the country
vaccines without compromising seroconversion or
decreases, it is inevitable that one would have to shift
increasing side effects. Ideal age to give first dose of
fro m OPV to IPV in the next few years. The
IPV is 8 weeks an d the interval between two doses
government sh o uld, therefore, consider incorporating
should also be 8 weeks. However if 3 primary doses are
IPV in the national immunization schedule in a phased
given, vaccine could be started at 6 weeks of age and

13
manner. IPV can also be an additional tool to eradicate
wild polio from last few high risk difficult districts.
IPV is also the vaccine of choice in patients with
immunodeficiency and th e preferred vaccine in
children with symptomatic HIV infection.
Post-polio eradication scene and polio immunization:
IA P believes that it will be unsafe and unethical t o
continue to use OPV in post-p o lio eradication era.
Following concept s should be kept in mind while
deciding India specific guidelines for post-polio
eradication immunization.
1. It will be unethical and unsafe to continue to
use OPV after zero wild polio case and zero
transmission status is achieved due to risk of
VAPP following OPV.
2. It will be unwise to discontinue use of polio
immunization altogether after zero polio
status is achieved due to fear of cVDPV and
iVDPV. Past experience from some
countries has shown that countries which
have eradicated wild polio virus and have
slackened in their routine polio
immunization programs have experienced
cVDPV outbreaks. These outbreaks of
cVDPV were curtailed by strengthening
routine immunization and giving 2 or more
DTPw Vaccine
The combination of diphtheria t o xoid, tetanus toxoid
and whole cell killed pertussis vaccine (DTPw) is
popularly known as the "triple antigen" DTP is the core
vaccine in all childhood immunization services. It is
one of the oldest combination vaccines and has been in
continuous use for more than 55 years. Tetanus an d
diphtheria toxoids are adsorbed on insoluble aluminium
salts which act as adjuvants and enhance the antitoxin
responses to both the antigens. While the two toxoids
are highly immunogenic (95-100%), the pertussis
vaccine (even after 3 doses) has a protective efficacy of
about 70-90% only.
Adverse reactions - Local (pain and redness) and
systemic (fever) side-effects of the DTPw vaccine are
almost entirely due to the pertussis component. Whole
cell pertus s is vaccine has been incriminated in the
14
rounds of SIAs using OPV. However in
post-polio eradication era, it will be
unethical and unsafe to reintroduce OPV in
such areas. It will force us to depend on the
stocks of WHO or any such agency for OPV
vaccine should out-break of wild polio or
cVDPP occur. Hence India should preempt
the emergence of cVDPV and has to become
self sufficient in stock-piling enough polio
vaccine now to meet any such unforeseen
eventuality in future.
3. Looking at the above problems, IAP
recommends that India should switch over to
IPV, preferably as IPV-DTP, in its routine
immunization program gradually in
post-polio eradication era. India should
encourage indigenous manufacturer to
produce enough IPV so that it becomes
affordable so that is will be possible to
switch to IPV in due course, looking at the
huge requirement of the number of doses.
Adverse reactions - Th e vaccine is very safe. As IPV
contains trace amounts of streptomycin, neomycin and
polymyxin B, allerg ic reactions may be seen in
in d iv id u als wit h hypersen s it iv it y t o t h es e
antimicrobials.
induction of a neurological reaction in v ery rare
instances; however, there has been no conclusive proof
for this and the vaccine should not be denied to
children with seizure disorders or st ab le neurological
conditions (e.g. Cerebral palsy, developmental delay).
The results of the National Childhood Encephalopathy
Study (NCES) in the United Kingdom clearly show that
there is no causal relationship between administration
of DTPw vaccine and development of chronic
neurological disease in children. Convulsions following
DTPw v accine are distinctly rare, and may only
represent n o t h ing more sinister than fever triggered
seizures. Progressive/evolving n eurological illnesses,
however, are a relative contraindication to first dose of
DTPw immunization. For children who develop
persistent inconsolable cry of more t h an 3 hours
duration, hyperpyrexia - fever > 40.50 C or hypotonic
- hypo responsive episode HHE (collapse/shock like
stage) within 48 hours of DTPw admin is t ration,
seizures with or without fever within 72 h ours of
admin is tration of DTPw, the decision to administer
further doses of DTPw should be carefully evaluated
and discussed with the parents These events were
regarded as absolute contraindications in the past. They
are now considered mere precaut ions because these
events generally do not recur with the next dose and
they have not been proven to cause permanent sequelae
If a similar adverse reaction recurs with the subsequent
Acellular Pertussis Vaccine (DTPa)
DTPa vaccines are of various types depending on the
number of constituent components viz. two component
DTPa containing pertussis toxin (PT) and filamentous
haemagglutinin (FHA); three co mponent DTPa
containing pertact in in addition to PT and FHA; five
component DTPa containing agglutinogens 2 and 3 in
ad d ition to PT, FHA and pertactin. Though a five
component DTPa vaccine may be expected to elicit a
more robust immune response as compared to two and
three component DTPa vaccines, the overall efficacy of
DTPa vaccines is comparable to the DTPw vaccine.
Dose: 0.5 ml by intramuscular injection.
• If parents are not willing for DTPw
administration after the adverse reaction with
the previous dose, DTaP can be recommended
in such circumstances as this vaccine is less
reactogenic.
• If encephalopathy (major alteration of
sensorium or illness with seizures lasting > 24
hours) occurs within 7 days of DTPw
administration, further doses of DTPw and
15
dose only then pertussis vaccine is contraindicated for
future administration.
DTP and DT vaccines need to be stored at 2-80C. These
vaccin es s hould never be frozen, and if frozen
accidentally, it should be discarded. DTP must be
injected intramuscularly and the preferred site is th e
anterolateral as p ect of the thigh. The IAP COI
recommends 5 doses of DTP - three in infancy with two
boosters at 18 months and 5 years. The DTPw or DTPa
vaccines can be administered up to the age of 7 years.
After the age of 7 years, Td should be given.
DTaP are contraindicated. Pertussis vaccine
should not be given in such cases and instead
DT should be administered in the future.
• In case immediate anaphylaxis occurs after
DTwP administration, further DTwP/DTPa
should be avoided because of uncertainty about
which component of these vaccines has caused
the reaction, as is true with any vaccine.
The IAP COI unequivocally endorses the continued use
o f DTPw vaccine because of its proven efficacy an d
safety. DTPa Vaccine may u ndoubtedly have fewer
minor side-effects (like fever, local reactions at
injection site and irritability) but this minor advantage
can not justify the inord in at e costs involved in the
routine use of this vaccine. DTPa vaccines are also by
no means more effective than the whole cell pertussis
vaccine. These are, therefore, not recommended for
universal immunization in our country at present.
There is, however, no bar to offering these vaccines to
children from families who opt for the slight advantage
of fewer minor side-effects.
Tetanus Toxoid

This vaccine contains Tetanus Toxoid 5 LF. It is a
highly heat stable and effective vaccine. Bo o s t ers of
this vaccine may be given at 10 and 16 years and
thereafter every 10 years. After completing the full
course of seven doses, there is no need for additional
doses during pregnancy at least for the next 10 years.
Thereafter a single booster every 10 years wo u ld be
s u fficient to extend immunity for another 10 years -
boosters should not be given more frequently than this.
The practice of giving TT after every injury should be
discouraged.
immunized, two doses of TT at least one month apart
should b e given during pregnancy so that protective
antibodies in ad equate titers are transferred to the
newborn for prevention of neonataltetanus. The second
dose of TT should be administered at least 2 weeks
before delivery. A single dose of TT would suffice for
subsequent pregnancies that occur in the next 5 years;
thereafter, 2 doses of TT would again be necessary. For
previously unimmunized schoo l age children, primary
TT immunization consists of two doses given 4 weeks
apart.

For pregnant women who have not been previously

Tetanus Immunoglobulin (TIG)

It is a liquid preparation containing immunoglobulins, Dose: for Prophylaxis: 250-500 IU IM.

mainly IgG, obtained from the plasma of healthy
Therapeutic: tetanus neonatorum: 500-1000 IU IM or
donors.
250 IU intrathecal.
In dications: Unimmunised or inadequately immunized
In children and adults: 500-1000 IU IM and/or 250-500
individuals with burns, roadside injuries and compound
IU intrathecal.
fractures.

Adverse reactions: Local pain, fever, flush in g ,

headache and chills may occur.

Td Vaccine (Tetanus Toxoid, Reduced Dose Diphtheria)

Td contains the usual dose of tetanus toxoid and only 2 words Td should replace TT boosters at 10 and 16
units of diphtheria toxoid. It is recommended for use in years).
children above 7 years of age IAP COI recommends the
routine use of Td at the age of 10 and 16 yrs (in other

16
17
Measles Vaccine

Measles vaccine used in our country is derived from the of virus within the body. This infection mimics wild
live attenuated Edmon s t o n Zagreb strain grown in measles virus infection but is usually asymptomatic.
human dip lo id cell culture. Other strains, which have Some children may develop a short lasting fever 7-10
been used for vaccination, include Schwarz, Moraten days after vaccination often accompanied by a macular
and Edmonston B. It is supplied freeze-dried and has a rash. Paracetamol may be given to control/reduce fever.
shelf life of 1-2 years, or even longer. The vaccine may Vaccinees do not shed the virus.
be stored frozen or refrigerated. After reconstitution the
Most infants are protected fro m measles by the
vaccine is very heat-labile and should be used within 4
maternally acquired antibodies until about 6-8 months
hours, wit h the unused vaccine being discarded.
of life. If measles vaccine is given in t h e presence of
Reconstituted vaccine should not be frozen . Measles
measu rable titers of maternal antibody, the vaccine
v accine does not contain any preservative, therefore
efficacy may be reduced. In order to achieve t he best
strict asepsis should be maintained while diluting and
balance between these competing deman d s o f early
aspirating contents from the multi-dose vial. Some
protection and high seroconversion, completed 9
cases of staphylococcal sepsis/toxic shock syndrome
months of age has been recommended as the
associated with use of this vaccine have occurred from
appropriate age for measles v accination in India. In
bacterial contamination of the vaccine. The v accine
case of an outbreak, however, the vaccine can be given
should be injected subcutaneously, preferably over the
to infants as young as 6 months with a recommendation
upper arm / anterolateral thigh.
for an additional MMR/Measles at 12-15 months.
Being a live attenuated virus vaccine, it resu lt s in
sub-clinical or attenuated infection and multiplication

B. Vaccines Recommended Against Diseases Not Covered Under EPI

MMR Vaccine
Globally, most co u n t ries use MMR instead of single
antigen measles vaccine. MMR vaccine contains 1000
TCID50 of measles, 5000 TCID50 of mu mp s and 1000
TCID50 of ru b ella v iru s . It is administered
subcutaneously in the upper arm/anterolateral thigh. It
is dispensed in single as well as multi-dose
formulations; the diluent is available separately. The
vaccine is given as a 0.5 ml dose. Measles and MMR
vaccines are supplied in lyophilized formulation and
should be frozen for long-term storage. In the clinic
these vaccines can be stored between 2 to 8 0 C. Th e
vaccines should be p rotected from light. Once
reconstituted, vaccine should be used within 4 hours.
The IAP COI recommend s administration of MMR to
all children. It should als o b e given to all adolescent
g irls not previously immunized and to hospital staff
likely to come in contact with pregnant mothers. There
is no upper age limit for this vaccine. It may be noted
that the states like Delhi, Goa h ave included and few
states like Tamilnadu, Mah arashtra, etc. are likely to
include MMR in its universal immunization program.
For infants given measles vaccine at 9-12 months,
MMR vaccine may be given between 15-18 months of
age. If measles vaccine was missed altogether in
infancy, one dose of MMR can be given at or after 12
months. The vaccine can be given along with other
vaccines like DTP, OPV and Hib.

18
Mumps Vaccine
The mumps component in MMR vaccine contains live
attenuated mumps virus not less than 5000 TCID50 per
dose. Vaccines are derived from Leningrad-Zagreb,
Jerryl Lynn, RIT 4385 or Urab e A M9 strains and are
grown in chick embryo/human diploid cell cultures.
Vaccinees do not shed the virus. There is no evidence
that mumps vaccination is associated with development
of either au t is m or Crohn's Disease. There is no
difference in efficacy between various strains of mumps
vaccine.
Aseptic meningitis is known to occur following mumps
vaccine, though the incidence quoted is as rare as 1 in
10,000 to 1 in 100,000 d o ses of vaccines used. The
clinical s everity of the vaccine induced aseptic
meningitis is very mild and often may go unnoticed and
all the cases recover without any permanent sequelae.
Hence all the mumps vaccines are equally safe.
Monovalent mumps vaccine or combination with
rubella as MR vaccine is not available in our country.

Rubella Vaccine

Rubella vaccine currently available commercially is constituent of MMR) in young children through public
derived from RA 27/3 vaccine strain grown in human health measure with sub-optimal coverage of the target
diploid/chick embryo cell cultures. It is available population may be counter-productive as it may shift
either as a monovalent vaccine as a part of the epidemiology of rubella to the rig h t with more
combination vaccine - MMR. It contains live clinical cases occurring in young adu lt s leading to
attenuated virus not less than 1000 TCID50. It is a
paradoxical increase in cases of CRS. This has been
highly immunogenic vaccine with seroconversion
shown to occur using mathematical models. Direct
rates of 95% It provides long term and probably life
long protection; vaccine failures are uncommon. evidence from some Latin American countries als o
Vaccinees do not shed the virus. corroborates these concerns.
As a pediatrician one should be aware that rubella
Normally use of rubella vaccine (monovalent or as a
vaccination is mainly directed at preventing congenital
constituent of MMR) in young ch ildren through
rubella syndrome (CRS) and not at preventing rubella
individual p ract itioners alone would not lead shift of
infection per se, as the latter is usually benign an d
epidemiology in adolescents and adults as the coverage
inconsequential. By controlling the incidence of rubella
of target populat io n is miniscule by private
infections, CRS can be significantly reduced. There is
practitioners In case MMR is incorporated in universal
paucity of reliable data on occurrence of CRS in India.
program and adequate coverage is not achieved, a shift
On the basis of what ever information is available CRS
in epidemiology of rubella is quite possible. Hence
incidence is qu it e low in India. This is suggestive of
MMR though a co s t effective vaccine should not be
wide circulation of wild rubella virus in yo u n g
introduced through public health facilities in areas
children. Seroprevalence of ru bella antibodies in
wh ere co v erag e fo r routine immunization is
majority of pregnant women in few studies in India
consistently less than 80%.
support this view.

Haphazard use of rubella vaccine (monovalent or as a

19
Hepatitis B Vaccine
In India, 1-4% of individuals are found to be chronic
carriers of Hepatitis B Virus (HBV). Infection with
HBV may occur perinatally (v ertical transmission),
during early childhood (the so-called horizontal
spread ), through sexual contact or nosocomially. It
should be noted t h at in our country horizontal route
(e.g. ch ild to child) route and the vertical route (i.e.
mother to child) are the major routes of transmission of
hepatitis B.
Younger the age of acquisitio n of HBV infection,
higher the chances of becoming a chronic carrier. It is
believed that as many as 90% of those who are infected
at birth go on to become chronic carriers. In fect ion
with HBV is one of the most important causes of
chronic hepatitis, cirrhosis of liver and hep atocellular
carcinoma. 30% of the chronic carriers go on to
develop chronic liver disease. These are all preventable
by early childhood immunization. It is for this reason
that the World Health Organization has recommended
u niversal Hepatitis B vaccination. As many as 150
countries have n ow included HBV in their national
immunization sch ed u les . In Ju n e 2002, the
Government of India also initiated the incorporation of
HB vaccine as a univ ersal vaccine through a pilot
program which will be scaled up in a phased manner.
HB v accine is a highly purified recombinant DNA
vaccine produced in the yeast species Hansenula
polymorpha, Saccharomyces cerevisiae or Pichia
pastoris. It is adjuvanted with aluminiu m salts and
should be stored at 2-80 C. The vaccine should not be
frozen - if frozen accidentally, the it should be
discarded. It should be injected intramuscularly in the
anterolat eral thigh. The usual pediatric dose (< 12
years o f ag e) is 0.5 ml corresponding to 10µg of the
antigenic component. Adult dose is twice the pediatric
dose. The vaccine is hig h ly immunogenic and
seroconversion rates are greater than 95% after a three
dose schedule. Antibody titers greater than 10 mIU/ml
are considered protective. The dose may be increased
when vaccinating immunocompromized individuals
e.g. patients on chemotherapy for malignant conditions
or those with chronic ren al failure awaiting
hemodialysis.
HB vaccine may be given in any of the follo win g
20
schedules:
1. Birth, 1 and 6 months
2. Birth, 6 and 14 weeks
3. 6, 10 and 14 weeks
Immunologically 0 - 1 - 6 months schedule of hepatitis
B immunization has been most widely used and proven
to be ideal with high antibody titers at the end of the
v accination. However now that HB vaccination is
integrated into the existing immun ization program
(UIP) in India, d u e to operational issues at a national
level one has to piggy back on the available contacts for
routine immunization i.e. DTP wh ich is given at 6, 10
and 14 weeks of age. At the same time birth dose has to
be given to cover for the vertical route. Hence IAP COI
recommends 0 - 6 - 14 wks schedule for public
measure. In case birth dose has been missed, 6 - 10- 14
wks sched u le can be followed. In office practice, one
can still use 0 - 6wks - 6 months schedule. As on now,
from the d ata available, none of the above schedules
needs a booster.
Th e p urpose of Hepatitis B vaccination is to prevent
chronic in fection and development of chronic liver
disease / hepatocellular carcinoma later in life. An ideal
HB vaccine schedule should, therefore, address vertical
as well as h orizontal modes of transmission of the
virus.
Pregnant women should be counseled and encouraged
to opt for HBsAg screening. If the mother is known to
be HBsAg negative, HB vaccine can be g iv en along
with DTP at 6, 10 and 14 weeks/6 months as there is no
special requirement to start vaccinat ion at birth itself.
This 6-10-14 wks schedule may be easier to implement
in the context of the national immunization program as
higher vaccination coverage may be achieved with
earlier administration of vaccines.
If the mother's HBsAg stat u s is not known, it is
important that HB v accination should begin within a
few hours of birth so that perinatal transmission can be
prevented. Any one of the following schedules may be
used for this purpose; birth, 6 and 14 weeks or birth, 6
wks and 6 months.
If the mother is HBsAg positive (and especially HBeAg
positive), the baby should be given Hepatitis B Immune
Globulin (HBIG) within 24 hours of birth, along with
HB vaccine (at birth, 6 and 14 weeks or birth, 6 weeks
and 6months) using two separate syringes and separate
sites for injection. If HBIG is not available (o r is
unaffordable), HB vaccine may be given at 0, 1 and 2
months with an additional dose between 9-12 months.
It has been suggested by many authorities that in
infancy the third dose of HB vaccine should be given at
least 16 weeks after the firs t d ose & at least 8 weeks
after the second dose and not before 6 months of
chronological age, as it presumably gives longer lasting
immunity. However this view is being challenged as
HB vaccine is a T-cell dependent vaccine, the titers at
the end of immunization schedule may not be
important so far as it is well above the protective level.
There would occur anamnestic response with the titers
going up should there occur contact with th e v irus
again in future. As logistically, it is easier to combine
HB vaccine program with the DTP vaccine, it can be
given in 0-6-14 weeks schedule too The vaccination
schedule need not be changed for preterm and
small-for-dates babies; in the case of extremely preterm
babies, ho wev er, vaccination should commence only
Hepatitis B Immunoglobulin (HBIG)
HBIG provides immediate passive immunity and is
recommended in situations wherein there has been
acute expos u re t o HBsAg infected material e.g. by a
needle-stick injury. Clinical trials h ave demonstrated
90% reduction in risk of transmis s ion following such
exposure if HBIG is used alon g wit h Hepatitis B
vaccine. HBIG does n o t interfere with antibody
response to simultaneous HB vaccine. It is for t h is
reason that individuals who have had recent accidental
exposure to hepatitis B virus should be given combined
passive-active immunization. It is also useful in
prevention of mo t her to child transmission and
transmission following sexual exp o s u re like in rape
cases. Lastly HBIG is indicated in o ncology patients
who may not respond adequately to Hepatitis B vaccine
as they are immune compromised follo win g the
malignancy as well its therapy.
21
after initial stabilization.
For older children and adults the preferred schedule is
0, 1 and 6 months, '0' being the elected date for the first
dose.
In immunocompetent individuals HB vaccine induces
an effective immunological memory that lasts life-long
and protects against symptomatic acute illness and
development of chronic HB infection on exposure to the
virus. Boosters of HB vaccine are, therefore, not
necessary under usual circumstances.
HB vaccination is now being integrated into t he
existing immunization program in India. It was
introduced in 15 cities an d 32 districts in the initial
phase; selection of districts was based on achievement
of targets of 80% or more DTPw-3 coverage under
routine immunization based on evaluation surveys.
Under this program, the vaccine is being provided free
of cost to infants living in u rb an slums. The program
will be expanded to include additional cities and
districts within a certain timeframe. It is envisaged that
HB vaccination will be introd u ced in all districts of
India by 2007.
Adverse Reactions: Transient, mild pain at the site of
injection and itching may be seen in a small proportion
of recipients.
Special Precauti ons : HBIG should never be
administered intravenously.
Dose: Adult s : 1000-2000 IU; Children:- 32-48 IU/kg
bod y wt . This should be administered as soon as
following exposure, preferably within 48 hours though
it can be administered even if the patient reports late up
to 7 day s after exposure. Neonates: 100-200 IU. The
first dose should be administered as soon as after birth
up to within 5 days of birth. An additional d o se of
32-48 IU/kg of body weight may also be given between
2-3 months after initial dose.
Typhoid Vaccines
Enteric fever is endemic in India and is a major public
health problem. Th ree vaccines were available for
clinical use till recently. However now only Vi typhoid
The Whole Cell Inactivated Typhoid Vaccine (TA/TAB)
Heat-killed, phenol-preserved or the acetone inactivated
lyophilized whole cell Salmonella t yphi vaccines were
inexpensive products that have been in use in India for
a long time. The p rotective efficacy of acetone
inactivated preparation is more than that of the phenol
preserved vaccine but the former is more difficult to
prepare and is associated with more side-effects. Both
vaccin es contain Salmonella typhi 1000 million
organisms per ml. Protection begins 4 weeks after
vaccination. Use of these vaccines may be associated
with fever, local pain and malaise due to the endotoxins
in bacterial cell wall. A pure S. typhi vaccine is less
reactogenic than the combined TA/TAB vaccines. The
vaccin e is very safe and is reasonably effective if
revaccination can be carried out on a regular basis. The
vaccine efficacy has been estimated to be 50-70% in a
meta-analysis of the randomized co ntrolled trials
available.
The Vi-Capsular Polysaccharide Vaccine
Th e vaccine consists of purified Vi-cap s u lar
polysaccharide, which during natural infection inhibits
p hagocytosis and serum bactericidal activity an d is
responsible for virulence of the bacteria. It h as
reasonable efficacy o f 50-60% in children and low
reactogenicity. Protection begins within two weeks of
vaccination and the biological marker is anti-Vi
antibodies. It is not very effective in children below two
years of age because it is an unconjugated
Oral Live Attenuated Ty21a Vaccine:
22
vaccine is available commercially.
The vaccine appears to be protective through the
induction of antibodies against cell wall somatic (O)
and flagellar (H) antigens- these antibodies can act as
a biological marker of the vaccine. It may interfere with
the interpretation of the Widal test. It is effective even
in child ren below 2 years of age and can be given to
infants > 6 months of age Primary vaccination requires
two d o s es , 4 o r more weeks apart, given
subcutaneously. Pediatric dose of the vaccine is 0.25 ml
in children aged 6 month s -10 years and 0.5 ml in
order children. The vaccine should be stored at 2-80 C.
It should never be frozen. Revaccination is necessary
every 2-3 years to sustain an o ptimum immune
response and should be done preferably before the onset
of summer.
Unfortunately, this vaccine is not being manufactured
in India at present
polysaccharide vaccine as available in our country at
present. Cost of the vaccine though a limiting factor in
past, is now reasonably priced. The vaccine is available
as an isotonic phenolated buffer solution; the dose is
0.5 ml. containing 25µg of the polysaccharide. It can be
given intramuscularly or subcutaneously. The vaccine
s h ould be stored at 2-80 C. It should never be frozen.
Adverse effects are mild and include pain and swelling
at injection site.
Salmonella typhi Ty21a is a live attenuated strain with
a mutation in gal E gen e and lacks the enzyme
UDP-gal 4 epimerase. It is genetically stable and is not
known to revert to virulence. The efficacy has been
shown to 50-60% with the capsule form and near 90%
with th e liquid form (not available commercially). It
provides protection by inducing local gut immunity but
there is no biological marker of this vaccine. The
vaccine is supplied in an enteric coated formulation as
the bacteria are acid labile. It can be given to children
six years of age and above as the capsules have to be
swallowed intact.
The vaccine is given on an empty stomach in three
The efficacy of all typhoid vaccines at best is 50-70%
Hib Conjugate Vaccines
Haemophilus influenzae type b (Hib) is an important
invasive pathogen cau sing invasive diseases like
pneumonia, meningitis and bacteremia. Majority of
cases occur in children below 2 years of ag e. Hib
vaccination is given routinely in the d eveloped
countries for last many years. Countries with sensitive
disease surveillan ce systems have shown significant
declines in in v asive Hib disease following the
incorporation o f this vaccine in their national
immunization programs. Recently published data of the
Invasive Bacterial Infections Surveillance (IBIS) group
from six referral hospitals in India (Lancet, 2003) show
that Hib is a common cause of meningit is in our
country.
Hib capsular polysaccharide vaccine is a very effective
and safe vaccine. A number of PRP conjugate Hib
vaccines are available of which t wo are available in
India viz. HbOC (with CRM 197 mutant diph t h eria
toxin as conjugate) and PRP-T (with tetanus toxoid as
conjugate). PRP-OMP (wit h meningococcal outer
membrane protein as conjugate) is no t available in
India HbOC and PRP-T vaccines show only a marginal
increase in antibody levels aft er the first dose with a
marked increase after the secon d and even better
23
sittings, on alternate days. The capsule should never be
op en ed before ingestion. Protection begins within a
week after completion of the course and the protective
efficacy is as good as other available typhoid vaccines.
Immunization needs to be repeated every 3-5 years
The vaccine should be stored at 2-80C. Antimicrobials
active against S. Typhi should not be used 3 days before
and 7 days after oral typhoid vaccine administration as
these may interfere with the v accin e "take".
Unfortunately this vaccine is also not available now in
our country.
response after the third dose. On the other hand,
PRP-OMP shows an increase in antibody level after the
first dose itself with only marginal increases after the
second and third doses. It is for this reason that while
3 doses of HbOC and PRP-T are recommended for
primary vaccination, only 2 doses of PRP-OMP are
recommended for this purpose. In spite of these
apparent differences, these three vaccines when used in
the recommended doses have similar efficacy.
The vaccination schedule for Hib consists of three doses
when initiated below 6 months, 2 doses between 6-12
months and 1 dose between 12-15 mon t h s , with a
booster at 18 months. The interval between two doses
should b e at least 4 weeks. If vaccination is delayed
until 15 months, a single dose may suffice. It is highly
efficacious vaccine, the protective efficacy being 95%.
As Hib d isease is essentially confined to infants and
young children, the vaccine is not necessary for
children above 5 years. Hib vaccine is stored at 2-80 C.
The IAP COI reco mmen d s use of Hib vaccine for all
children . It is particularly recommended to be given
p rior to splenectomy and in patients with sickle cell
disease.
C) Vaccines That Need to Be Given After Discussion With Parents
Varicella Vaccine
Chicken pox is usually a self limiting and generally
b enign disease affecting mostly children and youn g
adults. Complications of varicella may be mo re
commonly seen in immunocompromised individuals,
adults and pregnant women. Takahashi et al developed
a live attenuated vaccine from the Oka strain in Japan
in the early seventies. The vaccine has been in clinical
use in Japan since 1989 and in the United States since
1995. The vaccine can be administered to any healthy
individual above the age of 12 months who has not had
varicella previously.
Varicella vaccines in use today are all derived from the
original Oka strain but the virus contents may vary
from one manufacturer to anoth er. The recommended
dose is 0.5 ml and the minimum infectious virus
content should be 1000 Plaque Forming Units. The
vaccine is administered subcutaneously. A single dose
is sufficient b elo w 13 years of age, after which two
doses (at 4-8 weeks interval) are required. The vaccine
is not recommended for ch ild ren below 12 months of
age. Though vaccine manufacturers recommend to use
this vaccine at 12 months, breakthrough infections can
be less if used after 15 months of age. Hence IAP COI
recommends to use this vaccine after the age o f 15
months. It is a highly effective vaccine and protective
immunity, humoral as well as cellular, develops in
95-99% individuals. The immunity appears to be long
lasting.
The IAP COI opines that varicella vaccine is not
recommended fo r universal immunization in India at
present. One has to emphasize the generally benign
nature of an d rarity of complications with varicella
infection in young children. It may be offered to
children fro m h igh socio-economic strata of society
after explaining the pros and cons to the parents on a
one-to-one "named child" basis. It may be prescribed to
adolescents who have not had varicella in past (or are
known to be varicella IgG neg ative) especially if they
24
are leaving h o me for studies in a residential
school/college. It is indicated in children with chronic
lung/heart disease, humoral immunodeficiencies, HIV
infection (but with C4 counts above 15% of the age
related norms), leukemia (but in remission and off
chemotherapy for atleast 3-6 months) and those on long
term salicylates/high dose lone t erm oral steroids.
Varicella vaccin e is also recommended in household
contacts of immunocompromised children. It may also
be considered in children attendin g crèches and day
care centers. When used for post-exposure prophylaxis
it should be administered within 72 hours of varicella
exposure - it should be noted, however, that the efficacy
of the vaccine in preventing varicella under such
circumstances is not very clear. Varicella vaccine is
also indicated in susceptible adolescents and adults if
they are inmates of or working in the ins t itutional set
up e.g. s ch o ol teachers, day care center workers,
military personnel and health care professionals.
The vaccine is stored at 2-80C and can be administered
subcutaneously or intramuscularly. It should be
protected from light and needs to be used within 30
minutes of its reconstitution.
Adverse reactions - It includes fever, vaccine
ass o ciated rash, pain redness and swelling at
vaccination site. When used in adult females,
pregnancy should be avoided for at least 4 weeks after
vaccination.
Varicella zoster immunoglobulin (VZIG) is used for
passive post-exposure prophylaxis in immunodeficient
individuals who have been exposed to varicella or
herpes zoster and are unlikely to have d et ectable
antibody levels. It should be given to the neonate if the
mother develops varicella 5 days before to 2 days after
delivery. It has to be given by intramuscular injection
and the dose is 125 units/10 kg body weight.
Hepatitis A Vaccine
Hepatitis A virus (HAV) infection is a relatively benign
infection in young ch ildren as many of them have
completely asymptomatic sub-clinical infection For
instance as many as 50% of children between 2-5 years
and 85% of those below 2 years who acquire HAV
infection, may continue t o remain anicteric and may
develop non-specific symptoms like any other viral
in fection. In adults hepatitis A is frequently
symptomatic and mortality is much higher than in
children. The disease severity increases irrespective of
age, in those with underlying chronic liver disease.
Inactivated HA vaccines d eriv ed from HM 175/GBM
strains and g ro wn on MRC5 human diploid cell lines
are now available. The virus is formalin inactivated and
adjuvanted with aluminimum hydroxide. It has been
suggested that the vaccine can be used any time after
18 months of age when the maternally derived antibody
levels have declined; It is given in a two dose schedule,
6 months apart. The adult formulation should be used
after t h e recommended cut-off age of 15 years
according to one manufacturer and 18 years according
to the other The vaccine is given intramuscularly and
the protective efficacy is 94-100% Immunity appears to
be long lasting and boosters are not recommended at
present.
The IAP COI o p ines that HA vaccine is not
Pneumococcal Vaccines
Streptococcus pneumoniae is a common cau s e of
invasive bacterial diseases responsible for a significant
proportion of potentially fatal con d it io n s like
pneumonia and meningitis in children. It also leads to
conditions like otitis media and sinusitis, which may
have morbidity but little or no mortality. In developing
countries, this organism is believ ed to be the
commonest cause of bacterial pneumonia. Peak
incidence of pneumococcal disease is between 2 to 24
months of age. Based on the capsular polysaccharide
antigen, p neumococci are classified into 85 different
serotypes. Of these, about 10 serotypes account for most
25
recommended for universal immunization in India at
present. One has to emphasize the generally benign
nature of disease and very small number of children
developing complications with Hepatitis A infection in
young children. It may be offered to children from high
s o cio-economic strata of society after explaining the
pros and cons to the parents on a one-to one "named
child" basis. It may be prescribed to adolescents who
have not had viral hepatitis in past (or are known to be
HAV-IgG negative), especially those who are leav ing
home for further studies. It is recommended in all
patients with chronic liver d isease (who are HAV
seronegative) and family contacts of patients with
chronic liver disease. It may be offered to household
contacts of patients with acute HA virus infection - in
t h e latter case the vaccine must be given within 10
days; however, it may not always be effective under
such circumstances when the contact has had the same
source of infection as the index patient. It may also be
considered in children attending crèches and day care
centers and in travelers from abroad (e.g. non-resident
Indians) visiting endemic areas.
The vaccine is stored at 2-80C.
Adverse reactions: It includes local pain and local
induration.
infections. The common pathogenic stereotypes
reported in children in Western countries are 1, 4, 5, 6,
9, 11, 14, 15, 18, 19 and 23. It appears that the
serotypes causing invasive disease in developed
countries are different from the ones which are found
in developing countries. According to results of the
Invasive Bacterial Infection Surveillance (IBIS) study,
the common serotypes responsible for invasive disease
in children below five y ears of age in India include 6,
1, 19, 14, 4, 5 and 7. Serotypes 1& 5 accounted for
29% of disease in India. Thou g h prevalence of
penicillin resistance is almost negligible at present
there is some evidence that the prevalence of resistance
to penicillin amongst the p neumococci may be
gradually increasing, thereby highlighting the need for
an effective vaccine.
Two types of pneumococcal vaccines are currently
available - the 23-valent unconjugated polysaccharide
v accine and the 7-valent conjugate polysaccaharide
vaccine. Immunity is serotype specific.
The 23-valent polysaccharide vaccine contains the
following serotypes - 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V,
10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F,
23F, 33F. It is capable of preventing almo s t 85% of
in vasive disease (pneumonia, men in g it is an d
bacteremia) caused by pneumococci. Immunization,
however, is not effective for prevention of otitis media.
Each dose is 05 ml containing 25ug polysaccharide of
each of the 23 serotypes co n tained in the vaccines.
However, as it is an unconjugated polysaccharide
vaccine it does not result in immunological memory.
This vaccine is poorly immunogenic in children below
two years of age i.e. children who are at highest risk of
invasive disease. The dose is 0.5 ml and the vaccine is
given intramuscularly or subcutaneously. This vaccine
may be us ed in h igh-risk groups above the age of 2
years. Revaccination is recommended after 5 years. It
is recommended for children with asplenia, sickle cell
d isease and nephrotic syndrome. It is als o
recommen d ed for HIV infected children. It may be
offered to those with underlying chronic illnesses like
renal diseases, cardiovascular diseases or diabetes.
The heptavalent conjugate vaccine (PCV-7) contains
the following sero t y p es -4, 6B, 9V, 14, 18C, 19F, and
23F. It is coupled with a non-toxic variant of diphtheria
toxin (CRM197) and has aluminium phosphate as the
adjuvant. Conjugation of polysaccharide with protein
CRM197 makes it immunogenic below 2 years of age.
In February 2000 this vaccine (PCV-7 Prevnar) was
licensed in US fo r ad ministration to children below 5
yrs of age. The development of this v accine was
prompted by the observation that young children below
2yrs of age are dis p ro p ortionately affected by the
serious pneumococcal infection and recognition of the
fact that available 23 valent polysaccharide vaccine was
non immunogenic in t h is age group 2 yrs. Conjugate
vaccine is used in a 3-dose schedule in infancy at 4-8
weeks interval followed by a booster at 15-18 months of
age and has protective efficacy of 95-99% ag ain st
26
invasive pneumococcal disease caused by the serotypes
covered by the vaccine. The dose is 0.5 ml. and the
vaccine is given intramu scularly. Pneumococcal
vaccines are s tored at 2- 80 C. Conjugate vaccine
should not be frozen.
Since the introdu ct io n of PCV-7 in the childhood
vaccine schedule in US, there has been a dramatic
reduction in the in cidence of invasive pneumococcal
disease not only in the children who are vaccinated but
also non-vaccinated young children in their contact and
a milder but statistically sign ificant decrease in
invasive disease in their adult contacts, suggesting
s trong herd effect. Similar herd effect was seen in the
form of overall reduction in the disease caused by drug
resistant serotypes in the community. Though there has
been replacement of t h e vaccine serotypes by
non-vaccine serotypes in the nasal carriage studies,
fortunately this has not been seen significantly in the
invasive diseases studies. However there is a need for
continuous surveillance for the serotype involved in
invasive cases from time to time.
Healthy children: Th e IAP COI does not recommend
u s e o f this vaccine for universal immunization in our
country at present. PCV - 7 covers approximately 50 to
55% percent of pneumococcal serotypes responsible for
invasive pneumococcal disease in India offering about
50 to 55% protection in infants & ch ild ren in India.
The vaccine may be offered to healthy children above
the age of 6 weeks t ill 2 years after explaining the
parents on one to one "named child" basis.
High risk group: There are certain children who are at
high risk of severe invasive pneumococcal disease with
high mortality. This includes children with Sickle cell
d is eas e, as p len ia, primary immu n o d eficien cy
s y n d ro me s , H I V, c h i l d r e n w i t h s ev ere
cardio-respiratory illness and children with chro nic
illn es ses like renal diseases, diabetes etc., nephrotic
syndrome, cerebrospinal fluid rhinorrhea etc. For such
children IAP COI recommends age appropriate doses
of 7 valent conjugated pneumococcal vaccine routinely
till 5 years of age. For children above 2 years, a dose of
23 valent unconjugated pneumococcal vaccine is also
recommended to be given after one priming dose of
conjugated vaccine.
Adverse reactions - Injection site so reness, malaise,
low grade fever.
D. Vaccines Used in Special Circumstances
Meningococcal Vaccines
Neisseria meningitides accounts for 30-40% cases of
meningitis in children up to the age 15 years. It is the
only bacterium capable of causing large scale epidemics
of meningitis. There are 12 kn o wn serogroups but
majority of the disease causing is o lat es belong to
serogroups A, B, C, Y and W135. Epidemic disease is
typically associated with type A (occasionally type C)
and usually occurs in cycles every 7-14 years, especially
in the African meningitis belt which extends acro s s
A frica from Senegal to Ethiopia. In India also almo s t
all epidemics were of type A Such group A epidemics
are usually due to a single strain of the pathogen. Some
of the recent outbreaks in Western Asia have been due
to W135. En d emic disease occurs worldwide and is
mostly caused by serogroups B, A, or C although group
Y has been increasingly incriminated in recent reports.
In India endemic cases are mainly due to type B. As a
rule, endemic disease occurs primarily in children and
adolescents, with highest attack rates in infants aged
3-12 months. Severe meningococcal disease occurs
p rimarily in children and adolescents, with highest
attack rates in infants aged 3-12 months. Severe
meningococcal disease is associated with high
case-fat ality rates (5-15%) even where adequate
medical facilities are available. Chemoprophylactic
measures are in general insufficient for t he control of
this disease because secondary cases comprise only 1-2
% of all meningococcal cases.
Immu n ity following meningococcal infection is
s erogroup specific. Unconjugated meningococcal
vaccines are based on combinations of group-specific
capsular polysaccharides - either bivalent (A and C) or
tetrav alent (A, C, Y and 135). The recommended
single dose of the reconstituted vaccine contains 50 µg
of each of the individual polysaccharides. A conjugate
group C vaccine has also been marketed in developed
countries.
Unconjugated meningococcal vaccines, like all other
polysaccharide vaccines, do not induce immunological
27
memory. The group C, Y, and W135 components,
moreover, are not very immunogenic in children below
2 years of age. Meningococcal group C conjug at e
vaccine, on the other hand, is efficacious even in the
youngest children.
Meningococcal vaccine is indicated fo r use (as an
adjunct along with chemoprophylaxis) in close contacts
of patients with t h e d isease. It may be considered in
child ren with complement deficiency, prior to
splenectomy and those asplenia and sickle cell anemia.
It is also recommended during disease outbreaks
(caused by serogroups included in the vaccine) and
prior to travel to the high endemicity meningococcal
belt in the African continent. Meningococcal vaccine is
mandatory for all Haj pilgrims and is necessary for
residential students in some of the universities abroad.
The IAP COI does not recommen d t h is vaccine for
universal immunization in our country at present. It
can be given to children ab ove 2 years of age during
disease epidemic and is administered subcutaneously or
intramuscularly. In special circumstances (e.g. during
group A epidemic to close household contacts , close
household contact) it may be offered to even younger
infants but the protective efficacy is likely to be low in
this age group. The dose is 0.5 ml. Revaccination may
be considered after 3-5 years if the individual is still at
risk. The vaccine is stored at 2-80C.
A conjugate meningococcal serogroup C vaccine has
been part of ro u t in e immunization in the United
Kingdom since Novemer 1999 as it is t h e commonest
cause of meningococcal disease in children there - three
doses are g iven at 4-8 weeks interval along with the
routine childhood immunizations. Two doses of the
vaccine suffice for children in age group 6-12 months
and one dose in older children.
Adverse reactions - Fever and pain at injection site.
Japanese Encephalitis Vaccines
Japanese encephalitis (JE) is one of the most important
causes of viral encephalitis in Asia. In India, JE is
believed to be responsible for approximately 2000-3000
clinical cases and 500-600 deaths every year. As there
is no anti-viral drug treatment, JE vaccination remains
the single most important control measure. Contrary to
popular belief JE vaccine should n ot be used as an
"outbreak response vaccine" It should rather be given
to all children 1-15 y ears of age living in highly
endemic areas (e.g. Andhra Pradesh, Ut t ar Pradesh,
Karnataka). The vaccine may also be offered to visitors
to endemic areas if the duration of stay is likely to
exceed four weeks.
Currently three types of JE vaccines are available e.g.
(a) mouse brain-derived and inactivated Nakayama
Strain vaccine (b) cell culture-derived inactivated
vaccine and (c) cell culture-derived live attenu at ed
vaccine.
Mouse Brain-Derived Inactivated JE Vaccine
This vaccine is produced in In d ia at the Central
Research Institute, Kasauli. Commercially available
vaccine is imported. It is given subcutaneously - 0.5 ml
in ch ildren 1-3 years, and 1 ml in older children.
Primary immunization consists of three doses given on
0, 7 and 30 days - 0 being the elected date. A booster
dose is recommended after 1 year and subsequently at
three year intervals.
Adverse reactions: Include fever, malaise, local
tenderness and redness in 20% of recipients. In recent
years, several cases of acute encephalitis temporally
linked to JE vaccinat ion have also been reported.
Anap h y lactic reactions are known to occur with this
vaccine. This vaccine was also produced by s o me
international vaccine manufacturers like A ventis
Pasteur (now Sanoffi Aventis), however they have
stopped manufacturing of this vaccine recently and are
trying to switch over to vero cell cultured vaccine.
Inactivated Primary Hamster Kidney Cell derived
Vaccine
This vaccine made from Primary Hamster Kidney cell
line was used in China in millions o f doses. However
with the availability of the Sa-14-14-2 live vaccine, this
28
vaccine has been given up.
Cell culture derived live SA-14-14-2 vaccine
Th is v accine is based on a stable neuro-attenuated
strain of JE virus (SA-14-14-2). It was firs licensed for
use in 1988 in People's Republic of Ch in a and over
sixty million doses per year are being used there. Now
it is also licensed for use in Nepal, S. Korea and India
This live attenuated vaccine constitutes to over 50% of
global production of all JE vaccine. Dose is 0.5ml at all
ages. It is given by subcutaneous route. Initial studies
done on this vaccine demonstrated an efficacy of about
80% with single dose and 98% with 2 doses. However,
more recent studies have shown efficacy reaching 99%
even with single dose. As per a WHO report no serious
adverse effects (other than anaphylaxis) have been
reported over 20-y ear period (1979 - 1998). This
vaccine is not available in commercial market in India,
however it has been used for public health by Govt. of
India in 2006.
Use of Sa-14-14-2 live JE vaccine in India in 2006:
Recognizing the need to control JE in high ly endemic
districts, GOI has initiated a pilot project of
immunizing children from h y perendemic districts
against JE in 2006. 7 d is t rict s in UP, 2 in Assam and
one each in West Bengal and Karnataka were targeted
this year. SA-14-14-2 live JE vaccine was used
man ufactured by Chengdu institute of Biological
Products, Chengdu, China. It was given in a campaign
mode to children aged 1-15 years. It was g iven as
single dose subcutaneously usin g A D syringe. The
whole campaign was carried out from 15th May to 15th
July 2006. 11 million children were target ed as
b eneficiaries and 9 million children actually received
the vaccine i.e. nearly 86% of the target was achieved.
UP recorded 96% coverag e ag ainst all expectations.
There were 504 adverse effects following the campaign
of which 482 were minor adverse effects. 22 deaths
were reported but none were causally related to the
vaccine as cleared by an expert committee set up to
monitor the adverse effects. Based on the success and
safety of this year, similar campaign is planned for
ot h er areas in coming years. From next year this
vaccine will be included in the routine immunization
schedule for the new birth cohorts in these areas.
Influenza Vaccine
Influenza virus is an ortho my xovirus. There are three
antigenic types (A, B and C) with several subtypes of
each based on two surface an t ig ens - hemagglutinin
and neuraminidase Influenza virus, especially type A,
is characterized by frequent mutations - antigenic drifts
and antig en ic shifts. It is of the utmost importance,
therefore, that the vaccine should incorporate t h e
current strain p revalent during that time. Current
inactivated influenza vaccines are produced from virus
grown in emb ryonated hen's eggs, and are of three
types : wh o le v iru s , s p lit -p ro d u ct , s u b unit
surface-antigen formulations. Whole-virus vaccines are
associated with increased adverse reactions, especially
in children, and are currently not used. Most influenza
vaccines are split-product vaccines, p roduced from
detergent treat ed , highly purified influenza virus, or
s u rface-an t ig en v accin es containing purified
hemagglutinin and neuraminidase.
Vaccines are usually trivalent, containing 15 µg each of
two influen za A subtypes (H1N1 and H3N2) and one
influenza B strain. The present vaccine contains 15 µg
of hemagglutinin o f each of the three WHO
reco mmended strains (Northern Hemisphere) for the
season 2004-2005.
1) A/New Caledonia/20/99 (H1N1) like strain [variant
A/New Caledonia/20/99 (IVR - 116)];
2) A/Fujian/411/2002 (H3N2) - like strain [varian t
A/Wyoming/3/2003 (X-147)];
3) B/ Sh anghai/361/2002 - like strain [variant
B/Jingsu/10/2003].
29
Vaccines elicit a relatively strain-specific humoral
response, have reduced efficacy against antigenically
drifted viruses and are ineffective against unrelated
strains. The influenza vaccine is therefore unique as the
precise composition has to be changed periodically in
anticipation of the prevalent influenza strain expected
to circulate in a given year. The vaccine is effective for
only a short period, usually 6 month s to 1 year and a
new vaccine is brought every year. The WHO reviews
vaccine composition biannually and updates antigenic
content depen d ing on prevalent circulating subtypes
based on the data obtained from its chain of reference
laboratories from world over to provide antigenically
well-matched vaccines.
Influenza vaccine is highly immu n ogenic and is
associated with minimal side effects. When used for the
first time the vaccine is given in 2 doses in children 6
months to 8 years of age; only one dose is sufficient
above 8 years. Revaccination is d o ne with a single
annual dose, which is given before the peak influenza
season. The vaccine is administered intramuscularly,
the dose being 0.25 ml. in ch ildren below three years
and 0.5 ml thereafter. This vaccine is cu rrently
recommended for u s e only in high-risk children and
adolescents e.g . individuals with chronic pulmonary
an d card iac d is eas e, s ickle cell d is eas e,
immunodeficiency, HIV infection, s y s temic lupus
erythematosus, diabetes mellitus and t h o se on long
term aspirin therapy. Influenza vaccine is also
recommended to be giv en for severe cases of asthma
who need oral corticosteroids frequently.
Combination Vaccines

A combination vaccine consists of two or more separate

immunogens that have been physically combined in a
single preparation. These immunogens may pertain to
Current status of new combination vaccines
the many antigens/ serotypes of the given pat h o g en
(e.g. poliovirus vaccines) or of multiple pathogens (e.g.
DTP v accine). This concept differs from that of Already developed
simultaneous vaccines, which, although ad ministered
concurrently, are physically separate. The combining of DTPw + Hib
multiple related o r unrelated antigens into a single DTPw + Hepatits B
vaccine is not a new concept. The first combination
vaccine was trivalent influenza vaccine, which was DTPw + IPV
developed as far back as 1945. This was followed by
DTPw + IPV + Hib
hexavalent pneumococcal vaccine in 1947 and DTP
vaccine in 1948. Combination vaccines in common use DTPw + Hib + Hepatits B
include diphtheria and tetanus toxoid, available alone
(DT, dT) or with pertussis vaccine (DTP); inactivated DTPw + Hib + IPV
(IPV) or live oral (OPV) trivalent polio vaccine and DTPw + IPV
MMR vaccine.
DTPa + IPV
The number of vaccines in the immunization schedule
is increasing every year with the result that these DTPa + Hib
schedules are getting increasingly more complex. Many
DTPa + Hib + Hepatits B + IPV
parents opt for one single injection of combination
vaccines at a given visit, rather than g etting a large Hepatitis A + Hepatitis B
number of simultaneous injections. Use of combination
vaccines is also likely to result in logistic advantages - MMR + Varicella
reduced burden on the cold chain and reduced storage
requirements and syringes/needles apart from easier
record keeping. A number of combination vaccines are Under development
now available in the Indian market. The IA P COI
DTPa + Hib + IPV + Hepatitis B + Hepatitis A
endorses the use of combination vaccines, but with the
following cautionary statements:

• The manufacturer's recommendations should Available for use in India

be adhered to strictly
• “Mixing" of vaccines in the same syringe (prior DTPw + Hib
to injection) should not be done as far as
DTPw + HB
possible, unless specifically recommended by
the manufacturer; in the latter case the DTPw + Hib + HB
manufacturer's instructions should be followed
strictly. DTPa + Hib
• Combination vaccines should not be viewed as
being more effective than vaccines given HA + HB
separately.

30
Rabies Vaccines
The disease is caused by a single stranded RNA virus
belonging to the family Rhabdoviridae. It is almost
always fat al. Rab ies is caused by the bite of a rabid
animal, which is usually a dog in our country.
Scratches or licks on mucous membranes by affected
animals have also been kn o wn to transmit the virus.
The incubation period averages 4-6 weeks but can be
very variable and may range from five days to more
than one year. Rabies is endemic in our country - India
accounts for almost 50% of mortality in the world
There are two types of vaccines available in India
Modern tissue culture vaccines (MTCV)
• Purified Chick Embryo Cell (PCEC) vaccine -
1 ml per dose.
• Human Diploid Cell Vaccine (HDCV) - 1 ml
per dose.
• Purified Vero Cell Vaccine (PVRV) - 0.5 ml
per dose.
• Purified Duck Embryo Vaccine (PDEV) - 1 ml
per dose.
All tissue culture vaccines have almost equal efficacy
and any one of these can be used.
Nerve tissue vaccine
This is no longer recommended because of its poor
efficacy and life threatening adverse effects in the form
of neuroparalytic reactions.
Post exposure prophylaxis
In order to remove as much of the rabies virus as
possible, immediately cleanse the wound with soap and
flush thoroughly under running water for 10 minutes .
Then treat with 70% alcohol or tincture iodine or
povidone iodine. Rabies immunoglobulin (RIG) should
be infiltrated in and around the wo u n d in case of all
Day of Vaccination D0 D3
Thai Red Cross Regime 2 2
Updated TRC Regime 2 2
31
severe b it es or bites in the upper extremities, trunk,
head and face (wound category 3). Intramuscular
injection of RIG is not recommended. The dose of
human rabies immunoglobulin (HRIG) is 20 U/kg
while that of equine rabies immunoglobulin (ERIG) is
40 U/kg. Skin testing is recommended before using
ERIG but is not n ecessary when using HRIG. Any
suturing of wound should be avoided. When suturing is
unavoid ab le for purpose of hemostasis, it must be
insured that RIG has been infiltrated in the wound prior
to suturing.
Rabies vaccine is administered intramuscularly in
anterolateral thigh on days 0, 3, 7, 14 and 30 as per the
Essen protocol, with day '0' being the day of
commencement of vaccination. A sixth dose on day 90
is optional and may be offered to patients with severe
debility or those who are immunosuppressed. Children
are given the same dose as ad ults. Rabies vaccine
should never be injected in the gluteal region.
Several other schedules of rabies vaccination have been
proposed. These include the 2-1-1 intramuscular
schedule (Zagreb schedule) - two IM doses on day 1,
one IM dose on day 7 and one IM dose on day 21; the
2-2-2-1-1 intrad ermal schedule (Thai Red Cross
TRC-ID schedule) in which two ID doses are given on
days 1, 3 and 7, followed by one ID dose o n days 30
and 90 - ID dose is 1/5th the IM d o s e; the 8-4-1-1
intradermal schedule (Oxford schedule) - 0.1 ml of
PCEC vaccine is given ID at eight sites on day 0, at
four sites on day 7 and at one site only on days 30 and
90. The intradermal schedules have the obviou s
advantage of being inexpensive and have b een used
successfully in Thailand, Philippines and Sri Lanka.
Based on the recommendations of the expert group as
well as WHO, the Drug Controller General of India
(DCGI) has recently decided to allow ID route
administration o f tissue culture based anti rabies
vaccine fo r post exposure prophylaxis in a phased
manner. The following schedules as recommended by
D7 D14 D28 D90
2 0 1 1
2 0 2 0
ICMR are permitted in the 1st phase (Table below)
Vaccines reco mmended in the first phase of ID route
administration are purified verocell rabies vaccine
(Senofi Pasteur) and purified chick embryo cell vaccine
(Chiron Behring). The unit dose of 0.1ml for ID should
have at leas t 0.25 units. The criteria for selection of
Antirabies centre for ID use are
• Attendance of minimum 50 patient per day for
post exposure prophylaxis
• Have adequately trained staff to give ID
inoculation
• Can maintain cold chain and ensure adequate
supply of disposable syringes and needles.
This ID administration is not recommended in
individu al practice. Also it does not make economic
sense to practice it for individual cases.
Pre-exposure prophylaxis
Pre-exposure prophylaxis became a reality only after
the availability of MTCVs. This should be offered to
in d iv iduals in high risk occupations (e.g. veterinary
surgeons, wildlife workers, dog breeders, postmen).
Any of the tissue culture vaccines can be given for this
purpose - three doses are given intramuscularly on days
0, 7 and 28. A booster is given one year after primary
immunization and every five years thereafter.
The vaccine is stored at 2-80C. Side-effects include
local pain and induration.
For Re-Exposure after completed (and documented) pre
or post exposure prophylaxis two doses are given o n
days 0 and 3. Antirabies antibody titers > 0.5 IU/ml are
considered protective.
32
Rabies Immunoglobulin (RIG)
There are 2 types of RIG:
(1) Human rabies immunoglobulin (HRIG - do s e is 20
U/kg body weight)
(2) Equine rab ies immunoglobulin (ERIG - dose is 40
U/kg body weight).
RIG is indicated in all cases of category three wounds
where it should be infiltrated thoroughly into and
around the wound. The remaining part if an y is to be
injected IM into the deltoid region or anterolateral
aspect of thigh away from the sit e o f vaccine
administration to avoid vaccine neutralization. It
contains specific an t irabies antibodies that neutralize
the rabies virus and provide passive protection. In case
RIG dos e (q uantity) is insufficient for adequate
infiltration of extensive or multiple wound, it may be
diluted with equal volume of normal saline so th at all
the wounds can be thoroughly infiltrated.
If RIG could not be given when antirabies vaccination
was began , it should be administered as early as
possible but no later than the seventh day after the first
dose of vaccine was given. From the eight day onwards,
RIG is not indicated since an antibody response to the
vaccine is presumed to have occurred.
HRIG is a liquid or freeze-dried preparation containing
immunoglobulins (mainly IgG) and is obtained from
the p las ma of donors immunized against. In case of
ERIG, skin testing is recommended prior to use.
Adverse reactions: Tenderness/stiffness at t h e
injection site, low grade fever; sensitization may occur
after repeated injections.
 WHO Recommendations for Management of Animal Bites
Type of contact with suspected
Category or confirmed domestic or wild
animals* or animal
unavailable for observation
I Touching or feeding of animals,
licks on intact skin
II Nibbling of uncovered skin,
minor scratches or abrasions
without bleeding, licks on
broken skin
III Single or multiple transdermal
bites or scratches, contamination
of mucous membrane with saliva
(i.e., licks)
33
Recommended treatment
None if reliable case history is
available
Administer vaccine immediately
Stop treatment if animal
remains healthy throughout an
observation period of 10 days, or,
if the animal is euthanised and
found to be negative for rabies by
appropriate laboratory technique
Administer rabies
immunoglobulins and vaccine
immediately Stop treatment if
animal remains healthy
throughout an observation period
of 10 days, or, if the animal is
euthanised and found to be
negative for rabies by
appropriate laboratory technique
IAP Immunization Time Table

Age Vaccine

Birth BCG, OPV0 , Hepatitis B1

6 weeks DTPw1 / DTPa1 , OPV1, Hepatitis B2, Hib1
10 weeks DTPw2 / DTPa2 , OPV2, Hib2
14 weeks DTPw3 / DTPa3 , OPV3, Hepatitis B3 *, Hib3
9 months Measles
15- 18 months DTPw B1 / DTPa B1, OPV B1 , Hib B1 , MMR
2 years Typhoid+
5 years DTPw B2 / DTPa B2, OPV B2
10 years Td# / TT
16 years Td# / TT
Pregnant women: 2 doses of Td # / TT

* Third dose of Hepatitis B can be given at 6 months age

+Revaccination every 3-4 years
# Td preferred over TT

Vaccines that can be given after discussion with parents

Age Vaccine

More than 15 months Varicella vaccine#

More than 18 months
More than 6 weeks
Hepatitis A vaccine+
Pneumococcal conjugate vaccine*
#
Below 13 years of age one dose, over 13 years of age 2 doses at 4-8 weeks
interval
+
2 doses at 6- 12 months interval
* 3 primary doses at 6, 10, and 14 weeks, followed by a booster dose at 15
months

34
It should be noted that the IAP Immunization
Time-Table is, in effect, the 'Best Individual
Practices' schedule for a given child and may be
somewhat different from the National Immunization
Schedule. This is because of the fact that the former
is meant to be used for an individual, rather than for
the pediatric community as public health measure at
large The two schedules are, however, not in conflict
with each other. Also, as pediatricians we must be
conscious of the fact that the immunization needs of
children in a country are quite dynamic - a vaccine
which may not be considered important today may
become necessary in future as more information
about the epidemiology of the disease becomes
available. Further, in developing countries
affordability of the vaccines is a critical issue and any
decision on incorporation of a new vaccine in the
immunization schedule has to take this fact into
consideration. The IAP COI has based its
recommendations based on the best available
evidence at present. It is heartening to note that some
of the recommendations of the IAP COI in the past
have been instrumental in changing governmental
policies and also the immunization schedules being
followed by some states.
Notes on the Time Table
1. The IAP endorses the continued use of whole
cell pertussis vaccine because of its proven
efficacy and safety. Acellular pertussis vaccines
may undoubtedly have fewer side-effects (like
fever, local reactions at injection site and
irritability), but this minor advantage does not
justify the inordinate cost involved in the
routine use of this vaccine.
2. If the mother is known to be HBsAg negative,
35
HB vaccine can be given along with DTP at 6,
10, 14 weeks/ 6 months. If the mother's HBsAg
status is not known, it is advisable to start
vaccination soon after birth to prevent perinatal
transmission of the disease. If the mother is
HBsAg positive (and especially HBeAg
positive), the baby should be given Hepatitis B
Immune Globulin (HBIG) within 24 hours of
birth, along with HB vaccine.
3. For Non EPI and Newer Vaccines, Varicella,
Hepatitis A and Congujate Pneumococcal
vaccines should be offered only after one to one
discussion with parents. Also refer to the
individual vaccines notes for recommendations.
4. Combination vaccines can be used to decrease
the number of pricks being given to the baby
and to decrease the number of clinic visits. The
manufacture's instructions should be followed
strictly whenever "mixing" vaccines in the
same syringe prior to injection.
5. At present, the only typhoid vaccine available
in our country is the Vi Polysaccharide vaccine.
Revaccination may be carried out every 3-4
years.
6. Under special circumstances (e.g. epidemics),
measles vaccine may be given earlier than 9
months followed by MMR at 12-15 months.
7. During pregnancy, the interval between the two
doses of TT should be at least one month.
8. Continue using OPV till we eradicate polio in
our country. IPV can be used additionally for
individual protection.
9. OPV must be given to children < 5 years of age
at the time of each supplementary
immunization activity.
 Immunization in Special Circumstances
Immunization in preterm infants
In general, all vaccines may be administered as per
schedule according to the choronological age
irrespective of birth weight or period of gestation.
Children receiving corticosteroids
Children receiving oral corticosteroids in high doses
(e.g. Prednisolone 1-2 mg/kg/day) for more than 14
days should not receive live virus vaccines until the
steroid has been discontinued for at least one month.
Children awaiting splenectomy
Children with loss of splenic function are at high risk
of serious infections with encapsulated organisms. If
surgical splenectomy is being planned, immunization
Vaccination in children in children with HIV infection
Children infected by HIV are particularly vulnerable
to severe, recurrent, or unusual infections by vaccine
preventable pathogens. It must be emphasized that
routine immunizations seem to be generally safe in
such children, but the immune response following
vaccination would depend upon the degree of
immunodeficiency at that point of time. Immune
36
Very low birth weight / preterm babies can be given
immunizations after initial stabilization.
Killed vaccines are safe but may be incompletely
effective in such situations. Patients on topical or
inhaled steroid therapy should not be denied their age
appropriate vaccines.
with pnueumococcal, Hib and meninggococcal
vaccines should be initiated a few weeks prior to
splenectomy.
attrition associated with viral replication may
particularly interfere with memory responses.
Consideration should be given to readministering
childhood immunizations to such children when their
immune status has improved following anti-retroviral
therapy.
IAP Recommendations for Immunization of HIV Infected Children

Vaccine Asymptomatic HIV Infection Symptomatic HIV Infection

BCG Yes (at birth) No

DTPw / DTPa Yes (at 6, 10, 14 weeks) Yes
OPV Yes (at 6, 10, 14 weeks) Yes / IPV
Measles Yes (at 6 and 9 weeks) Yes
MMR Yes Yes (CD4% >15%)
Hepatitis B Yes (as for uninfected Yes (double each dose)
children)
Hib Yes Yes
Typhoid Vi Yes Yes
Pneumococcal Yes Yes
Influenza Yes ( > 6 months of age) Yes
Varicella Yes (2 doses at 6-8 weeks Yes (2 doses at 6-8 weeks
interval) interval, CD4% > 15%)
Hepatitis A Yes Yes

Vaccination schedule for children not immunized in time

It may be noted that vaccination catch-up regimens table depicts the suggested schedule which may be
may be difficult to construct for older children and followed in cases of children who have not been
must necessarily de individualized. The following offered any immunization.

37
Vaccination Schedule for an Unimmunized Child

Age Less than 7 years More than 7 years

First visiit BCG*, OPV* , DTPw / DTPa, Td, HB

HB

Second visit (one month later) OPV*, DTPw / DTPa, HB Td, HB

Third visit (one month later) Measles / MMR, Typhoid MMR, Typhoid

Fourth visit (6 months after first DTPw / DTPa, HB HB

visit)

Every 3 years Typhoid Typhoid

* OPV and BCG recommended up to 5 years of age.

** Varicella vaccine one dose up to 13 years and hepatitis A vaccine two doses 0 and 6 months to be offered only
after discussing with parents on a one to one basis

It may be noted that Measles/MMR vaccines may as well be given at the first visit itself (along with t he other
vaccines) if compliance is likely to be a problem. However it is preferable to give it at a later visit if pat ient
compliance is not a problem.

Lapsed immunization

There is no need to restart a vaccine series regardless scheduled should be completed at the next available
of the time that has elapsed between individual doses. opportunity. In case of unknown or uncertain
Immunizations should be given at the next visit as if immunization status, however, it is appropriate to
the usual interval had elapsed and the immunization start the schedule as for an unimmunized child.

Missed opportunity for immunization

This is defined as a situation when a child visits a contradictions to immunization. Any dose not given
health care facility and is not immunized. Minor at the recommended age should be given at any
illness (e.g. fever, diarrhea, respiratory infections) subsequent visit when indicated and feasible.
and malnutrition should not be construed as

38
Simultaneous administration of multiple vaccines

Both killed and live vaccine can be administered individual vaccines. However, prudence demands
simultaneously without decreasing the efficacy of the that the vaccines be administered at different sites.

Immunization of adolescents

Adolescents should be considered an appropriate age for "top-up" immunization as well as for adminis tration
of certain vaccines which may not have been indicated earlier. However, this should always be done after
careful counseling.

Vaccination Schedule in Adolescents

Vaccine Age

Td Booster at 10 and 16 years

MMR vaccine One dose if not given earlier

Hepatitis B 3 doses (20 mcg) 0, 1, and 6 months, if not given earlier

Typhoid vaccine Vi Polysaccharide vaccine every 3 years

Varicella vaccine* One dose up to 13 years and 2 doses (at 4 to 8 weeks interval) after 13
years of age if not given

earlier.

Hepatitis A vaccine* Two doses 0 and 6 months if not given earlier

* Only after discussing with parents on a one to one basis

Immunization for travelers

The risk of travelers contracting infectious d is ease
depends on the region/country to be visited, duration of
trip and nature and conditions of t rav el. Uniform
recommendation s are not possible because the
epidemiolog y o f d is eas es d iffers in various
geographical areas. The physician should try and
update routine immunizat ion and also provide
destination specific immunizations. For instance,
vaccines commonly recommended for Indian travelers
include yellow fever vaccine for those intending to go
to destinations in South America an d Subsaharan
Africa (except in infants les s t han 9 months and
pregnant ladies) and meningococcal vaccine for those
intending to go on a Haj pilgrimage. Similarly, visitors
comin g to India from Western Europe/North America
are usually advised vaccination against typhoid and
Hepatitis A, especially if the stay is likely to be
prolonged.

39
Vaccination of children with bleeding disorders or those receiving anticoagulants

Needles less than 23G should be used for injection and pressure, without rubbing, for at least 5 minutes.
the parents should be asked to apply firm and sustained

Beast-feeding and Vaccination

Breastfeeding does not adversely affect immunization
and is, therefore, not a con t raindication for any
vaccine. Neither inactivated n or live vaccines
administered to a lactating woman affects the safety of
breas t -feeding for infants. There is no risk of
transmissio n of Hepatitis B virus from an HBsAg
carrier mother to her baby through breast milk if HB
vaccination is started at birth.

40
 Injection Safety Issues
Injectio n s afety is an important issue for any
immunization program Wash or disinfect hands prio r
to preparing injection material. Avoid giving injections
if skin is infected or compromised by a local infection
(such as a skin lesion or weeping dermatitis ). Ev en
small cuts should b e co vered. Always use a sterile
syringe and needle for each injection and to reconstitute
each unit of medication. If single use syring es an d
needles are not available, use equipment designed for
steam st erilization. Document the quality of the
s t erilizat ion process using time, St eam an d
Temperature (TST) spot indicators.
Prepare each injection in a clean designated area where
blood or body fluid contamination is unlikely. Clean
skin prior to injection with a disinfectant and wait for
it t o dry. Do not use cotton balls stored wet in a
multi-use container. If multi-dose vials are used, always
pierce the septum with a sterile needle but do not leave
the needle in place in the stopper of the vial. If using an
ampoule that requires a metal file to open, protect
fingers with a small gauze pad when opening the
ampoule. Anticipate and take measures to prevent
sudden patient movement during and after injection.
All in t ramuscular injections in children should be
given only on th e anterolateral aspect of thigh at the
junction o f t h e middle and lower third - the gluteal
41
region must be avoided as sciatic nerve injury is a real
risk especially in neonates, malnourished and
struggling children. It is not often appreciated that the
nerv e is within the reach of the standard needle even
when the injection is given in the upper outer quadrant
of the buttock. It is also know that the immune
response of some of the vaccines (especially rabies)
administered in the gluteal region is not optimum.
It is important for health personnel to understand that
'sharps' must be immediately co n t ained in a 'sharps'
box. The needle must not be recapped or manually
mutilated after use. To prevent reuse, the syringe may
be cut and the needle defanged using a syringe/needle
destroyer. Syringes and needles should be disposed of
carefully in leak-proof and puncture proof contain ers
an d n eedles and waste management should be given
due attention.
Auto-disable (AD) syringes are single-use, self-locking
syringes designed in such a way that these are rendered
unusable after single use. These are made from
clean-burning plastics and emit very low levels of toxic
fumes. These are now being promoted for rou tine
immunization and may well become the norm in years
to come. The Government of India has decided to use
AD syringes in Immunization program.
 Adverse Reactions Following Immunization
A d v erse reactions following immunization can be
broadly classified as local and systemic. Although such
occurrences are uncommon, every physician who is
dealing with immunization should anticipate and be
prepared to manage these events whenever they occur
It is mandatory for every immunization clinic t o h ave
an emergency kit for resuscitation.
Local reactions are especially common aft er the
adsorbed vaccines (e.g. DTPw/DT) - no treatment other
than symptomatic management is necessary. Whole cell
killed typhoid vaccines are also ass ociated with
particularly significant local reactions. Ulcer formation
after BCG vaccination is normal and no intervention is
usually required - the ulcers may sometimes take many
weeks to heal.
Anaphylactic reactions are distinctly unusual but have
been reported following Measles, MMR, Hib and
Hepatitis vaccines. Such reactions may be secondary to
42
allergy to egg (e.g . Measles, MMR, yellow fever,
influenza vaccines), gelatin (e.g. MMR, Varicella,
Yellow fever vaccines), certain antimicrobials (e.g .
Neomycin in MMR, Varicella and Inactivated Polio
vaccines) or thiomerosal (e.g. DTP, TT vaccines).
It should be noted that it might often be difficult to
prove a definite cause-effect relationship between a
vaccine an d a given complication. It may be prudent
not to ascribe all adverse reactions to a vaccine, which
has been given in the recent past before ascertaining all
facts about the case. Many adverse effects may result
from inappropriate vaccination technique or storage of
the product.
Each member of the Academy is requested to report
any case of suspected adverse reaction follo wing
immunization to IAP committee on immunization
through IAP office.
 Adverse Reactions Following Immunization

Adverse Vaccine Symptoms Management

Reaction

Anaphylaxis Any vaccine Within minutes • Adrenaline

• Cardiopulmonary
• Acute decompensation of circulatory resuscitation
shock • IV volume expanders
• Hypovolemic shock • Hysrocortisone
• Laryngospasm /edema • Dopamine/
• Acute respiratory distress Dobutamine

H y p o t en s i v e DTP • Acute pallor • IV fluids

hyporesponsive • Transient decreased level or loss of • Oxygen
episode consciousness
• Decrease or loss of muscle tone

Incessant crying DTP • Within 48-72 hours of immunization • Sedation with

• Excessive, inconsolable crying Triclofos 50 mg/ Kg
• Paracetamol 10-15
mg/ Kg per dose
• Feeding advice

T o xic Sh o ck Measles vaccine • Within 30 minutes to few hours • IV fluids

Syndrome contamination • Mounting fever • Antimicrobials
• Vomiting cloxacillin 50-100
• Diarrhoea mg? Kg per day
• Septic Shock • Steroids
• Supportive therapy

Lymphadenitis BCG • Within 2 to 6 months • If firm, no treatment

• Firm to soft axillary lymphadenitis • If soft or fluctuant,
1.5- 3 cms size aspiration/ surgical
excision
• ATT not indicated

Ba c t e ria l Any vaccine After days to weeks • Antibiotics

abscess • Antipyretics
fluctuant to firm • Drainage

M o d era t e t o Any vaccine No n fluctuant swelling / redness 3-10 Paracetamol

s ev ere l o c al cms in size at the injection site
reaction

Seizures wit h DTP Always generalised • Anticonvulsants

fever (rare) • IV fluids (if need be)
Measles

43
 The Cold Chain

A vaccine has two characteristics - safety and potency.

The potency of a vaccine is maintained by 'cold chain' Order of sensitivity of vaccines to heat
This term refers to the system of transporting, storing Most sensitive
and distributing vaccines in a potent state at the
recommen d ed t emp erat ure from the point of BCG (after reconstitution)
manufacture to the point of use. In es s en ce, it is OPV
considered to play a crucial role in the success of any
immunization program However potent a vaccine may Measles (both before and after reconstitution)
be, if the cold chain is not maintained from the source
Hepatitis B
of vaccine manufacture to the place of vaccination, the
vaccine efficacy will suffer. Vaccine potency once lost DTP
cannot be restored. The essential components of a cold
chain include: DT

1. Personnel responsible for vaccine distribution BCG (before reconstitution)

2. Appropriate equipment to store and transport Tetanus toxoid
Least sensitive
vaccines
3. Appropriate transport facilities
4. Maintenance of equipment
5. Monitoring

Sensitivity of vaccines to freezing

Vaccines damaged by freezing Vaccines that can be frozen without harm

DTP OPV

DT Measles/ MMR

TT BCG (before reconstitution)

Hepatitis B

Hib

Td

Typhoid (whole cell killed vaccine)

Hepatitis A

44
The cold chain involves two complementary aspects:
a) the set chain represented by the walk-in cold
rooms, deep freezers and refrigerators and
b) the mobile chain represented by isothermic boxes
and vaccine carriers.
Equipment
a) Walk- in freezers (WIF): are established in all
the states ; are u sed for bulk storage of OPV and
measles vaccines and for preparing frozen ice packs at
state s t ores; maintain a temperature of -200C and are
available in 2 sizes - 16.5 & 32 CU Mt; freezers are
provided with two identical cooling units and standby
generator sets.
b) Walk in cold rooms (WIC): are used fo r bulk
storage of vaccines at the man ufacturer, state and
regional levels which store vaccines for abou t 4-5
districts; maintain a temperature recorders and alarm
systems.
c) Deep freezers: are used for storage of OPV/
Measles//MMR vaccines and preparation of ice-packs;
DTP/DT/TT/Hepatitis B vaccines should not be stored
in deep freezers; have a top opening lid and are
availab le in 2 models -140 & 300 liters; cabinet
temperature is maintained between -18 to -200C; in
case of power failure these freezers can maintain
cabinet temperature for 18 - 26 hours, if n o t o p ened.
All districts have been provided 2-5 large freezers
whereas most of the PHCs have one small deep freezer.
A b o u t 25-30 ice packs (8-10 kg ice) and 35-40 ice
packs (12-14 kg ice) can be frozen in one day in 140L
and 300L deep freezers respectively.
d) Ice lined refrigerators (ILR): may have either
ice tubes or ice packs filled wit h water upto 90% of
their volumes; o n freezing there is formation of an
inner lining of ice; this enables the temperature to stay
within a safe range even when there is electricity
supply for only 8-12 hours in a day; are available in 2
sizes (140 & 300 liters) - the former is supplied to
district headquart ers while the latter is supplied to
PHCs; in top opening ILRs the temperatures is least at
the bottoms - t h is should be used for storing
OPV/Measles/MMR; DTP / DT/ TT/ Hepatitis B
vaccines should be kept near the top in a s ep arate
container to avoid accidental freezing. The Electrolux
type of ILR (Model TCW 1151) can also be used as a
freezer by a changeover switch inside the compressor
45
chamber in situations where OPV is to be stored for
long duration (at -200C) or there is increased demand
of ice-packs.
e) Domestic refrigerators: meant for vaccine
storage should not be used for any ot h er p urpose;
should be kept away from heat and direct su n lig ht;
should have ice-packs fo r freezer compartment and
water bottles in the shelves; these help in maintaining
low temperatures in case of power failure; no vaccine
should be stored in the baffle tray or the door shelves;
periodic defrosting is necessary; this is generally done
whenever the layer of ice exceeds 5-6 mms. The usual
temperature within the main compartment of a
domestic refrigerator is between 4-100C while t h at of
the freezer compartment is between 0 to -40C.
The vaccines can be placed as follows:
• Freezer compartment: OPV / Measles /
MMR
• Top shelf: BCG / Measles / MMR
• Middle shelf: DTP / DT / TT/ Typhoid/
Hepatitis A / Hib
• Lower shelf: Hepatitis B / Varicella
• Crispator: Diluents
• Baffle tray: should be kept empty
f) Cold boxes or isothermic boxes: are well
insulated, solid and thermetically (air tight) sealed
boxes packed with frozen ice packs at the bottom, sides
and at the top; available in 2 sizes - 5 & 20L; these are
supplied to all peripheral centers and are used for
transportation of large amounts of vaccines to outreach
facilities - 1500 vaccine doses can be carried in a 5L
box and 6000 doses in a 20L box; vaccines should be
placed in cartons or polythene bags and then placed in
direct contact with fro zen ice packs; in emergency
situations, can also be used to store vaccines and frozen
ice packs for up to 5 days; the hold over time is more
than 90 hours for a 5L, and 6 days for a 20L, cold box
at 430C ambient temperature, if the cold box is not
opened at all. In general a cold box of 5L can
acco mmo date one month's supply of a PHC (30,000
population), while a cold box of 20L capacity can
accommodate one month's supply for a CHC (100,000
population).
Cold boxes can also be used in h ealth centers for
storage of vaccines and ice packs in case of electricity
failure or breakdown of other cold chain equipment. Ice
packs should be made from tap water - water should be
filled in the icepack up to the level marked.
g) Vaccine carriers: are s maller versions of cold
boxes and are used to carry small quantities of vaccines
(e.g. 16-20 vials) for distribution to outreach facilities;
these contain 4 fully frozen ice packs (0.36 liters each)
and an inner plastic lining; can maintain temperatures
for 2 days if the packs are frozen and lid is kept tightly
clo sed. DTP/DT/TT/Hepatitis B vials should be
wrapped in plastic to avoid direct contact with ice.
h) Day carriers: are smaller versions of vaccine
carriers and are used to carry still small quantities of
vaccines (e.g. 6-8 vials) of vaccine; have provision for
only 2 frozen ice-packs; can be used to store vaccines
for 6-8 hours; vaccines in day carrier should be issued
on the day of immunization only; presently, the use of
day carriers is not encouraged.
i) Ice packs: are made of polyethylene and weigh
approximately 80 gm; t h e dimensions are 163 x 90 x
33 mms; co ntain 0.36L of water; never add salt to the
water. Ice packs are used to line the sides of cold boxes,
vaccine carriers and day carriers.
Storage of vaccines
All vaccines are safe at temperatures between 2-80C for
at least 6 months. If a freezer is available, it should be
used for storage of OPV and Measles/MMR vaccines.
The latter vaccines should be kept frozen at -200C
when stored fo r t h e long term - at this temperature
these vaccines have a shelf life of 2 years. Even these
v accines, however, can be kept at 2-80C for short er
periods e.g. 6- 12 months for OPV and 18-24 months
for measles.
DTP / DT / TT / Typhoid (T-series vaccines), HB and
Hep A vaccines should never be frozen. The freezing
point for adsorbed DTP vaccine is between -5 to 10oC.
Freezing time depends on the number of doses in the
vial and the temperature. It takes about 110 to 130
minutes at -10oC. The "Shake Test" can be used to
determine if these vaccine has been frozen at any time:
shake the vial so t h at the sediments, if any, are
completely mixed ; wait for 15 minutes; if the vaccine
is not uniformly mixed or the sediments/ flocculations
are still found settled at the bottom, the vaccine is likely
to have been frozen at some time. Such vials should be
discarded.
At a temperature of 2-8oC, DTP/ DT/TT/ Hepatitis
B/Hepatitis A/Varicella and Hib vaccines have a shelf
46
life of 24 months. Diluents should be stored at 2-8oC -
these should not be us ed b ey ond 4 hours. Vaccines
should be transported o n ly in cold boxes or vaccine
carriers - vacuum flasks should never be used for this
purpose.
It is recommended that vaccines should not be stored
for more than 3 months at the district lev el and for
more than 1 month at the level of primary health
center. No vaccines sh o uld ever be stored at the
sub-centers. Expiry dates of vials shou ld b e checked
once a week. While storing vaccines fo llo w the
"First-In-First-Out (FIFO)" and "First to Expire
First-Out (FEFO)" rules.
During shipment and transportat ion, temperature and
time sensitive monitor marks are used to check the cold
chain. Dial t h ermometers are used to monitor the
temperature in refrigerators/ice-lined refrigerators
(ILRs) and are kept in every unit. Alcohol stem
t h ermometers are much more sensitive and accurat e
t h an dial thermometers and can record temperatures
fro m - 50oC to +50oC. These can be used for deep
freezers and ILRs . Temperature monitoring should be
done twice a day in the case of ILRs and deep freezer
and once a day in the case of walk-in coolers, where
vaccines are stored in bulk for longer periods. A break
in the cold chain is indicated if temperature rises above
+8oC or falls below +2oC in the case of ILR and other
refrigerators and above -180C in the case of deep
freezers.
The Vaccine Vial Monitor
(VVM) is a time an d temperature sensitive colored
label that provides an indication of the cumulative heat
to wh ich the vial has been exposed. VVMs were first
introduced on OPV vials supplied to UNICEF and
WHO in 1996. The VVM warn s t h e end user when
exposure to heat is likely to have degraded the vaccine
beyond an acceptable level. It is used especially for
temperatures monitoring of OPV, which is the most
thermo lab ile of all vaccines. If the VVM indicates
proper storage of OPV in a given center, it can be
presumed that oth er vaccines would also be potent.
VVMs increas e the flexibility in handling of vaccines
in the field.
Interpretation of the colour change of VVM is as
follows:
1. Inner square is lighter than outer circle: If the
expiry date has not passed, vaccine can be used.
2. Inner square matches colour of outer circle or is
darker than outer circle: vaccine should be discarded.
The VVM provides in formation about the heat
exposure of the vial over a period of time - the change
in colour is gradual but irreversible. However there may
be other factors which can also affect the potency of
vaccine (e.g. storage beyond the expiry date) and these
may not be reflected in the VVM . Loss of potency
depends upon the degree of temperature elevation as
well as duration of exposure. Tetanus toxoid is the least
heat sensitive vaccine.
The manufacturer's instructions regarding shelf life of
a given vaccine must be rigorously followed. Measles
vaccine loses viability quickly if kept at temperatures
above 400C. Reconstituted measles vaccine should be
kept protected from heat and light during an
immunization session and the left-over discarded after
the session. OPV would lose viability if kept at 22-25oC
for more than a d ay . Opened vials of OPV, however,
may be used in subsequent sessions at a given health
facility if it has b een p reserved at 2-8oC. OPV vials
u sed in the field setting or an outreach facilit y o r
during a pulse immunization session must be discarded
at the end of the day. Vaccine vials (single/multi-dose)
should be gently shaken before use to ensure that the
co n t en ts are clear and not granular or flaky. Vaccine
vials should not be taken out to the field more than 3
times - after that these are best discarded irrespective of
whether these have been opened or not.
When using multidose vials it may be ad v isable to
schedule all immunizations to a fixed day every week.
This reduces wastage o f v accine and minimizes the
risks of contamination/loss of potency. One can send
OPV vials for viab ilit y test with the help of the local
health authorities. OPV has been taken as an indicator
of quality of cold chain as t h is v accine is more heat
labile than other vaccines and is easier to test. The test
t akes only 7 days. Open vials can also be sen t an d ,
id eally, the vials should be lifted from all levels - i.e.
from the periphery after the immunization sess ion,
PHC, CHC, district and reg ional stores. Testing
facilities are available at the Central Research Institute
47
(Kasauli), National Institute of Communicable Disease
(Delhi), Enterovirus Research Centre (Mumbai),
School of Tro p ical Medicine (Kolkata) and other
centers. Samples from different immunization sites
should be collected in vaccine/day carriers with fully
frozen ice packs and transported to the headquarters by
o b s erv ing "reverse cold chain" If delays in
transportation are anticipated, th e samples should be
kept in a deep freezer/ILR before these are sent to the
testing lab o ratory. The WHO recommends that in
countries where VVM is being used for monitoring
cold chain, OPV sample testing is not required.
Recen tly Government of India is following this
recommendation.
The Future
Advances in sugar-glass drying technology now allow
manufacturing of vaccines which can be stored and
tran s p orted at tropical room temperatures. Trehalose,
a disaccharide, has long term stabilizing ability and can
be effectively used for this purpose. Dried measles
vaccine stabilized with trehalose has been found viable
after 2 months at room temperature while DTPa can
withstand a temperature of 600C for 12 weeks . Oral
polio vaccine, however, has failed to 'dry' successfully.
If all vaccines can be successfully 'dried', there will no
longer be a need for maintenance of co ld chain - this
will also result in substantial cost savings.
Supply of vaccines
A ll UIP vaccines are available free of cost to all
practitioner from lo cal health authorities. One is
allowed to collect profes s ional fees for the services
rendered. However, the utilizatio n report should be
submitted periodically.
When buying from market individual practitioners
should ensure that vaccines are procured directly from
a stockist with appropriate cold chain facilities, rather
than off the shelf from a nearby retailer. Vaccum flasks
should never be used for an outreach activity.
 Stability of Vaccines at Different Temperatures

Vaccine Temperature in oC

2- 8 22- 25 35- 37 > 37

D T / TT (a s 3-7 years Many months At least 6 weeks 2 weeks at 45OC

mo n o v a le n t
v accines or as
co mp o n en ts of
combined vaccine)

Pertussis vaccine 18- 24 mo n t h s , Variable, but does Variable 10% lo s s o f

but there is a n o t e xceed 2 potency per day
steady decrease in weeks
potency

Freeze dried BCG 1 year 20- 30% of Variable Unstable

vaccine viability after 3
months
Re c o n s t it u te d Should be used within 4 hours. This recommendation is based on the fact that:
BCG vaccine
1. There is a risk of contamination as BCG vaccine contains no bacteriostatic agent.

2. Concern over loss of viability.

F r e e ze d r i e d 2 years 1 month 1 week 50% lo s s o f

measles vaccine viab ilit y in 2-3
days at 41OC

R ec o n s t i t u t e d Should be u sed
measles vaccine within 4 hours

OPV 6- 12 months 50% lo ss o f Very u n s t ab le. Very u n s t ab le.

viability after 3 Significant loss of Significant loss of
weeks viability within 1- viability within 1
3 days day at 41OC

Inactivated Polio 1- 4 years De c lin e o f Variable Pre c i s e data

Vaccine (IPV) D-antigen content lacking
for Type I after 20
days

Hepatitis B 2- 4 years Many months Many weeks St a b le fo r man y

days at 45OC

Rabies HDCV 3- 5 years 3 months 4 weeks No data

available

48
 Surveillance for Vaccine Preventable Disease (VPDS)
Surveillance is a French word, which means "watching
with attentio n, suspicion and authority" Disease
surveillan ce under the Universal Immunization
Program refers t o the collection, analysis and use of
data on VPD to improve action to p rev ent these
diseases As higher levels of vaccination coverage are
achieved, the role of disease surveillance becomes
increas ingly important to document the impact of a
giv en immunization program. A sensitive surveillance
system is required to direct program resources to areas
of greatest need and to ident ify areas for special or
more intensive interventions. A g o o d surveillance
system can det ect program failures and impending
outbreaks and can also be used to assess vaccine
efficacy.
Any sat isfactory national immunization program
should result in gradual decline of the VPDs. All cases
of VPDs should be reported to the local health authority
within 48-72 hours for taking prompt action at the field
level.
The WHO had declared 3 district objectives for the year
2000 A.D.
1) Polio eradication
2) Neonatal tetanus elimination
3) Measles reduction
49
It is a pity that none of these targets have been met so
far. The revised target for certification of polio
eradication and neonatal tetanus elimination is the year
2007. The nomenclat u re used for control of the three
diseases is rather specific because while it is possible to
eradicate polio v irus from the planet, it may not be
feasible to eradicat e the tetanus bacilli, which are
u biquitous. However, by immunizing all mothers wit h
tetanus toxoid it is possible to at least eliminate
neonatal tetanus. Similarly while it may be possible to
eradicate measles in the future, at the present time one
can only hope to preven t measles mortality by
preventing measles in the vast majority of immunized
children.
Acute Flaccid Paralysis (AFP) surveillance is an
essential component of polio eradication. A min imum
AFP rate of 1/100,000 children below 15 years o f ag e
is required to ensure that adequate surveillance exists
at the ground level. At present most of the parts of the
coun try have excellent and adequate surveillance.
Every case of AFP should be reported to local health
authority.
 Vaccination in Current Millenium

The future holds lot of promise as far as prevention of

disease through vaccination is concerned. We are likely Viral Vaccines
to witness more refined vaccination techniques, Rotaviurs vaccine
improved antigens and safe vaccines.We are likely to
g et many new combo vaccines also. "Naked" DNA Respiratory Syncitial Virus vaccine
vaccines and administration of antigens through viral Dengue fever vaccines
vectors/edible plants may completely revolutionize
childhood vaccination programs. Some vaccines which HIV vaccine
may soon become available for clin ical use are as
Hepatitis C vaccine
follows:

Protozoal vaccines
Bacterial vaccines
Malaria vaccine
Enterotoxicogenic E. coli vaccine

Shigella vaccine Websites for additional information

Cholera vaccine The following websites may provide useful information

-
Streptococcal vaccine for rheumatic fever
www.who.int/vaccines; www.immunizationinfo.org;
Helicobacter pylori vaccine
www.v accin es .o rg ; www.in ejc t io n s afet y .o rg ;
www.vaccinealliance.org;

www.aap .o rg ; www.cd c.g ov/nip; www.path.org;

www.childrensvaccine.org

www.unicef.org

50
 Update of IAP Immunization Policies, Guidelines And Recommendations
[Report of IAP COI Meetings ( July 16th & 17 2005, New Delhi; Oct. 1 2005 New Delhi; April 2, 2006
Mumbai; and July 28, 2006 New Delhi)]

The Indian A cademy of Pediatrics Committee on
Immunization (IAP COI) conducted its deliberations
and reviewed its stand on various policies, guidelines
an d reco mmendations pertaining to childhood
immu n ization. As has been enunciated earlier,
"policies" are the decisions taken by the Academy in
relation to the scientific principles and practice of
immunization. "Policies" are expected to be pract iced
by all members of Academy. 'Guidelines" relate to
those items wh ich are outside the purview of policy,
and for which guidance is necessary. Guidelines usually
pertain to newer vaccines or issue related to them.
"Recommendations" are, in general, what the academy
in its role of advocacy on behalf of children, requests
other agencies, the Go v ernment of India or other
professional bodies.

IAP Policies on Immunization, 2006

a few districts, no new vaccine has been introduced in

On NTAGI
The IAP welcomes the establis h ment of the National
Technical Advisory Group o n Immunization (NTAGI)
by the Government o f India. This followed a formal
recommendation from the IAP, given a couple of years
ago. The Secretary, Department of Family Welfare is
t he Chairperson of the committee while the Assistant
Commissioner, Immunization Program is its Member
Secretary. The IAP COI ap p reciates that the IAP is
represented on this important committee by its
incu mb ent President and recommends that the
Chairperson/Convener of the IAP COI .should also be
invited as a member of this committee.
On Universal Immunization Program (UIP)
The IAP continues to endorse and reiterate its support
to th e n at io n al immunization schedule while
recognizing the fact that much more needs to be done
for meeting the current immunization requiremen t s of
the children of our country. It is a fact that except for
the recent phased introduction in Hepatitis B vaccine in
the national program in the last 25 years. All vaccines
under UIP sh o u ld continue to be available free of
charge to all eligible children.
On Polio Eradication Goals and SIAs
The Academy fully supports the Government of India
in the use o f oral polio vaccine (OPV) for the pulse
immunization program against polio. It is our
considered opinion that, in sp it e of some operational
hiccups, we must continue with this program and bring
it to its logical conclusion, i.e. till wild polio virus is
eradicated from our country. IAP advocates that some
st ep s are required to be taken to overcome the last
hurdles in achieving the goals of polio eradication as
fast as possible. These include operationalizatio n of
birth dose of OPV all over the country, at least in areas
with wild polio virus transmission continuing;
strengthening of routine immunization; better quality
of SIAs and role of IPV in difficult areas where wild
polio virus circulation is still continuing.

51

Inactivted Polio Vaccine (IPV)
(Role of IPV vis a vis OPV)
OPV is cheaper & being given orally and so mo re
acceptable. However it is less efficacious in tropical
country like India due to in terference with other
enteroviruses and other unknown factors It also needs
strict co ld chain maintenance. Where as IPV is more
efficacious, less thermolab ile and has no chance of
inducing vaccine induced paralysis. Of late IPV h as
been shown to induce local g u t immunity as well as
herd effect. Coverage of children less than 2 years in
high risk areas with 2-3 doses of IPV can b e an
additional tool to eradicate polio from our country. The
cost and availability of vaccine can be a problem.
Post-polio eradication scene and polio immunization:
IAP believes that it will be unsafe and u n et hical to
continue to use OPV in post-po lio eradication era.
Following concepts should be kept in mind while
deciding India specific guidelines for post-polio
eradication immunization..
• It will be unethical and unsafe to continue to
use OPV after zero wild polio case and zero
transmission status is achieved due to risk of
VAPP and cVDPV following OPV.
• It will be unwise to discontinue use of polio
immunization altogether after zero polio status
is achieved due to fear of cVDPV, iVDPV. Past
experience from some countries has shown that
countries which have eradicated wild polio
virus and have slackened in their routine polio
immunization programs have experienced
cVDPV outbreaks. These outbreaks of cVDPV
were curtailed by strengthening routine
immunization and giving 2 or more rounds of
SIAs using OPV. However in post-polio
eradication era, it will be unethical and unsafe
to reintroduce OPV in such areas. It will force
us to depend on the stocks of WHO or any such
agency for OPV vaccine, should out-break of
wild polio or cVDPP occur. Hence India should
52
preempt the emergence of cVDPV and has to
become self sufficient in stock-piling enough
polio vaccine now to meet any such unforeseen
eventuality in future.
• Looking at the above problems, IAP
recommends that India should switch over to
IPV, preferably as IPV-DTP, in its routine
immunization program in post-polio
eradication era. India should encourage
indigenous manufacturer to produce enough
IPV so that it becomes affordable so that it will
be possible to switch to IPV in due course,
looking at the huge requirement of the number
of doses.
Practitioner keen to use this vaccine may use the
vaccine as 3 primary doses followed b y o ne booster
dose with DTwP / DTaP. OPV must be given to these
children as birth dose and on the NIDs and SIAs.
On number of routine DTP/OPV doses
The IAP COI endorses the use of five d o s es of
DTP/OPV at 6, 10 and 14 weeks and thereafter at
15-18 months and 5 years respectively. An additional
dose of OPV is to be given at birth to all where possible
and one more additional dose along with measles
vaccine. It should be noted that we continue to endorse
the use of DTP (rather than DT as in t h e national
program) and OPV at 5 years.
On Vaccines not covered in EPI
The IAP COI suggests that the UIP s h o uld be
supplemen ted by the following vaccines: Hepatitis B
(HB), HIB, MMR and typhoid. Td should replace TT at
10 and 16 years. Parents, however, should b e made
aware of the availabilit y an d need of these vaccines.
Varicella an d Hepatitis A vaccines are still not
recommended for routine use. Pn eu mococcal PCV-7,
liv e attenuated SA-14-14-2 Japanese Encephalitis
Vaccines are the new vaccines which have become
available in India. Tdap and Rota virus are the vaccines
which are likely to be available in near future.
IAP COI stand on RECOMMENDED vaccines not covered under EPI
Hepatitis B vaccine
HB vaccine may be given in any of t h e following
schedules:
(i) Birth, 1 and 6 months
(ii) Birth, 6 and 14 weeks/6 months
(iii) 6, 10 and 14weeks/6 months
Immunologically 0 - 1 - 6 months schedule of hepatitis
B immunization has been most widely used and proven
to be ideal. HB vaccination is now been integrated into
the existing immunization program (UIP) in India. Due
to operational issues at a national level one has to piggy
back on the av ailable contacts for routine
immunization, hen ce 0 - 6 - 14 wks schedule is
recommended. In case birth dose has been missed, 6 -
10- 14 wks schedule can be followed. In office practice,
one can still use 0 - 6wks - 6 months schedule.
The purpose of Hepatitis B vaccination is to prevent
chronic infection and development o f chronic liver
disease / hepatocellular carcin o ma later in life. An
ideal HB vaccine schedule should, therefore, address
vertical as well as horizontal modes of transmission of
the virus.
If the mother is HBsAg positive (and especially HBeAg
positive), the baby should be given Hepatitis B Immune
Globulin (HBIG) as soon as possible after birth,
preferably within 24 Hours of birth, along with HB
vaccine. The injections should be given at two separate
sites. If HBIG is not available (or is unaffordable), HB
vaccine may be given at 0, 1 and 2 month s with an
additional optional dose between 9-12 months.
Boosters of HB vaccine are n o t n ecessary in
immun o co mpentent individuals. The vaccination
schedule need not be changed for preterm babies, in the
case of extremely preterm babies, however, vaccination
should commence only after initial stabilization.
The IAP COI recommends universal immunization
53
against Hepatitis B.
MMR Vaccine
MMR should be promo t ed as a universal vaccine. It
should be given at around 15-18 months of age and at
least 3 months after the measles vaccine. It should also
be given to all adolescent girls and young women not
previously immunized, as also to hospital staff likely to
come in co n tact with pregnant mothers. There is no
upper age limit for this vaccine.
Typhoid Vaccine
The IAP COI strongly recommends the use of typhoid
vaccine for all children. Of the 3 types of vaccines (viz.
Vi-polys ach aride, whole cell inactivated and oral
Ty-21a), only the Vi-polysacharide vaccine is freely
available in our country at present. It is recommended
to be given after the age of 2 years followed by
revaccination every 3-5 years. The government should
explore the possibility of manufacturing this vaccine in
the public sector on large scale so that t h e costs are
brought down.
Hib Vaccine
Hib vaccine should be offered to all children and may
be given at 6, 10 an d 14 weeks along with DTP. A
booster is given at 15-18 months. If vaccination is
s t arted after 6 months of age, only two doses (at 4-8
weeks interval) need be given as primary schedule with
a booster at 15-18 months. If vaccination is started
between 12-15 months of age, only one dose need be
given, with a booster at around 18 months. After 15
months of age only one dose of the vaccine needs to be
given- no boosters are required u n d er such
circumstan ces. The vaccine need not be given after 5
years of age. Hib vaccine is also recommended for all
high risk children, irrespect ive of age, prior to
splenectomy and also in patients with sickle cell
disease. IAP COI strongly recommends GOI to include
this vaccine in UIP.
IAP COI stand on vaccines that are given after discussion with parents:
Hepatitis A Vaccine
Hepatitis A (HA) vaccine is not recommen d ed for
universal immunization in India at present. One has to
emphasize the generally benign nature of and rarity of
complications with Hepatitis A infection in young
children. It may be offered to children from high
socio-economic strata of society after explaining the
pros and cons to the parents on a one-to one "named
child" basis. It may be prescribed to adolescents who
have not had viral hepatitis in past (or are known to be
HAV-IgG negative) especially if they are leaving home
for studies in a residential school/college.
HA vaccine is indicated fo r all patients with chronic
liver disease as well as household contacts of patients
with chronic liver disease as well as household contacts
of patients with HA virus infection - in the latter case
the vaccine must be given within 10 days; it may,
however, be not always effective under such
circumstances if the contact has the same source of
infection as the index patient. It may also be considered
in children attending crèches and day care centers and
in travelers from abroad (e.g. non-resident Indians)
visiting endemic areas.
It is given in a 2-dose schedule, 6 months apart after
the age of 18 months The adult formulation should be
used after the recommended cut-off age: 15 years
according to one manufacturer and 18 years according
to the other. The vaccine is given intramuscularly and
the protectiv e efficacy is 94-100%. Boosters are not
recommended at present.
Live attenuated Hepatitis A Vaccine
The live attenuated Hepatitis A Vaccine has been
licensed for use in China since 1992. The manufacturer
claims 92 to 100 percent seroconversion with single
54
dose administered by subcutaneous route. This vaccine
has recently been licensed for use in India. There is
only one Indian study con d u ct ed at Pune on this
vaccine showing 95% seroconversion. The vaccine has
not been studied extensively outside China. This
vaccine should be subject ed to post marketing
surveillance for efficacy and adverse reactions in India.
However, for 100% seroconversion second dose after 6
months n eed s to be considered as recommended in
China.
Varicella Vaccine
The IAP COI opines that varicella vaccine is not
recommended for universal immunization in India at
present. One has to emphasize the gen erally benign
natu re of and rarity of complications with, varicella
in fection in young children. It may be offered t o
children after ag e of 15 months from high
socio-economic strata of society after explaining the
pros and cons to the parents on a one-to-one "named
child" basis. It may be prescribed to adolescents who
have not had varicella in past (o r are known to be
varicella IgG negative) especially if ther are leaving
home for studies in a residential school/college.
It is indicated in children with ch ro nic lung/heart
disease, humoral immunodeficiency, HIV infection (but
with CD 4 counts above 15% of the age related norms),
leukemia (but in remission and off chemotherapy for at
leas t 6-12 weeks) and those on long term
s alicy lat es/steroids. Varicella vaccin e is als o
reco mmen d ed in hous e h o ld c o n t act s of
immu n ocompromised children. It may also be
considered in children attending crèches and day care
centers.
Varicella vaccine is also indicated in susceptible
adolescents and adults if they inmates of or working in
the institutional set up e.g. school teachers, day care
center wo rkers, military personnel and health care
professionals.
A single dose suffices between the ages of 1-13 years,
after which a 2-dose schedule (4-8 weeks apart) is
recommended.
reactions to a previous dose of whole cell pertussis
vaccine. These include:
1. Convulsions with/without fever occurring within 3
days
2. Persistent inconsolable crying for 3 or more hours
within 48 hours

Acellular Pertussis Vaccine 3. Collapse or shock-like state within 48 hours

The IAP COI endorses the continued use of whole cell 4. Temperature > 40.50C within 48 hours
p ertussis vaccine (as DTPw) because of its pro v en
efficacy and safety. Acellular pertussis vaccines may Conjugate Pneumococcal Vaccines (PCV-7)
undoubtedly have fewer minor side-effects (like fever,
The IAP COI does not recommend use of this vaccine
local reactions at injection site and irritability), but this
for universal immu n ization for healthy children in our
small advantage dose not justify the inordinate costs
country at present. PCV - 7 co v ers only 50 to 55
involved in the routine u s e of this vaccine. It is ,
percent of pneumococcal seroty p es responsible for
t h erefo re, not reco mmen d ed for un iv ers al
serious invasive pneumococcal diseas e in infants &
immunization in our country at present. There is ,
children in India. The v accine may be offered after
however, no bar to offering these vaccines to children
explaining the parents on o ne to one "named child"
from families who opt for the vaccine for the slight
b asis. However it is recommended routinely in h ig h
advantage of fewer minor side-effects.
risk group children up to the age of 5 years.
Use of acellular pertussis vaccine should, however, be
considered in children who have had s ig n ificant

IAP Stand on vaccines for special circumstances

efficacy reaching 99% even with single dose. As per a

Live Japanese Encephalitis (JE) Vaccine
W HO report no serious adverse effects (other than
(SA-14-14-2) anaphylaxis) have been rep o rt ed over 20 year period
(1979 - 1998). This vaccin e is not available
This vaccine is bas ed on a stable neuro-attenuated
commercially in India; it has been used this y ear in
strain of JE virus (SA-14-14-2). It was firs licensed for
seven endemic districts after importing it from
use in 1988 in People's Republic of China and over
Chengd u Institute of Biologicals, China. From the
sixty million doses per year are being used there. Now
av ailable safety data, the vaccine was found to be
it is also licensed for use in Nepal, S. Korea and India
extremely safe.
This live attenuated vaccine constitutes to over 50% of
global production of all JE vaccine. Dose is 0.5ml at all
Meningococcal Vaccines
ages. It is given by subcutaneous route.
Meningococcal vaccine (bivalent A, C or tetravalent A,
Init ial studies done on this vaccine demonstrated an
C, Y, W135) is indicated for use (as an adjunct along
efficacy of about 80% with single dose and 98% with 2
with chemoprophylaxis) in clos e co ntacts of patients
doses. However, more recent studies have shown

55
with the disease. It is also indicated in high risk
in d iv id u als (e .g . t h o se with
hyposplenia/asplenia,complement deficien cy ) and
IAP COI stand on future vaccines:
Tdap
In the western world it is being felt that there is a need
to vaccinate adolescents and adult s with pertussis
vaccine. There the epidemiology has undergone a
marked shift since the introduction of mass childhood
vaccination programs, the proportion of pertussis cases
in older children, adolescents and adults though n o t
great in numbers have relatively increas ed, making
them the source of transmission to very young infants
who are unimmunized or partially immunized and this
age group is more vulnerable to dis eas e related
complications and mortality.
The Tdap vaccin e h as been incorporated as booster
dose during adolescence in the immunization schedule
of few developed countries. This provides booster to
waning immunity in adolescents thus leading to
individual protection and prevention of transmission of
disease to susceptible infants and children.
In India the epidemiology of pertuss is is not well
known and there is lack of information reg arding
epidemiological shift. So the Tdap vaccine is n ot
recommended for universal use at present. This vaccine
may be of particular use for children who have missed
their 2nd booster of the DPT and are more than 7 years
of age.
Rota Virus Vaccine
Rotavirus is common cause of d iarrhea all over the
world. Almost all children get infected by the age of 5
yrs. In India, of the children hospitalized for rotavirus
diarrhea, 50% were < 6 months, 75% < 9 months and
nearly 100% < 2 y rs. It is estimated that risk of death
follo wing rotavirus diarrhea is 1 in 290 cases in
56
during epidemics It is recommended for those who are
going for Haj pilgrimage.
developing countries 53% of rotavirus deaths occur in
Africa & 42% in Asia. It is estimated that 100,000
children d ie each year in India due to rotavirus
diarrhea.
As rotavirus d iarrhea occurs in spite of highest
standards of hygiene it cannot be prevented by public
health measures like s afe water supply and good
sanitations. For prevention universal immu n ization
appears to be the only answer.
The first vaccine against rotavirus was tetravalent
rhesus-human rotavirus vaccine (RRV-TV vaccine,
Ro t ashield: Wyeth Lederle). This vaccine licensed in
USA in 1998 and recommend ed for universal use had
to be withdrawn when an increased rate of
intussusceptions was shown to occur after vaccine
administration.
Recently a new Pentavalent bovine-human reassortant
vaccine from Merck (Rotateq) has been licensed in
USA. Another Rotavirus vaccine - a live at t enuated
human (G1P8) monovalent vaccine from GSK (RIX
4414 Rotarix) has recently been licensed in Latin
American countries and some A s ian Countries. Both
these vaccines have been found to be safe and highly
efficacious.
Trials of these vaccines have not been initiated in India
so far. There is a great diversity of Ro t avirus strains
prevalent in India. There is need to know the efficacy
of these vaccines in India before any recommendations
can be mad e on the use of existing vaccines. Other
Rotavirus vaccine being developed are LLR vaccine in
China which is in phase II / III trials and the newborn
strain vaccine in India.

Combination Vaccines
The number of vaccines in the immunization schedule
is increasing every year and this tren d is likely to
continue for the next few years. Many parents opt for
one single injection of combination vaccines at a given
visit, rather than come repeatedly for the various
individual vaccines or take multiple pricks on a single
day for vaccines that are now in cluded in the
immunization time- table. A number of combination
vaccines are now available in the Indian market. The
IAP COI endorses the use of combination vaccines, but
with the following cautionary statements:
1. The manufacture's recommendations should be
On Adolescent Vaccination
The Academy endorses the continued use of Td/tetanus
toxoid at 10 and 16 years and thereafter every 10 years.
HB vaccine may be offered in th e 0, 1 and 6 months
sched u le as mentioned earlier under individual
vaccines, if the child has not received it earlier. MMR
vaccine should be offered to all children who have not
received it earlier - there is no upper age limit for this
vaccine. The Academy encourages the use of typhoid
vaccin e for all adolescents. Hepatitis A and varicella
vaccines should be used in selected cases as mentioned
above.
On Immunization Records
Every vaccine given to a child must be documented on
a card/ booklet. We recommended the IAP Health and
57
adhered to strictly
2. Extemporaneous " mixing" of vaccines in the same
syringe (prior to injection) should not be done as far as
possible, unless specifically recommended b y the
manufacturer; in the latter case the manufacture's
instructions should be followed strictly
3. The advantage of a combination vaccin e is the
convenience of fewer clinic visits for the parents and
fewer pricks for the child
4. Combination vaccines should not be viewed as being
more effective than vaccines given separately
Immunization card to be used for this purpose. Parents
must be instructed to keep the document safely and
present it to their doctor whenever required.
On Advertisements in the Lay Media
Some of the multinational companies have been using
the lay media (television, electronic media and
news p apers/magazines) for placing advertisements
pertaining to optional/combination vaccines. We opine
that this is uneth ical. The IAP placed a formal
complaint before th e Drug Controller General of India
and the Union Health Ministry. This led to the issuance
o f a letter by the Drug Controller to the concern ed
companies requesting them for the withdrawal of these
advertisements. We are hopeful the companies would
see reason and refrain from lay advertising.
IAP 2006 Recommendations for other agencies including Ministry of Health and Family
Welfare, Govt of India
The IAP COI has formulated several specific
recommendations to other agencies pertaining to
immunization.
• The IAP recommends that the Academy should be
represented on NTAGI by incumbent President and
the Chairperson/Convener of IAP COI
• At 5 years of age booster immunization should be
done with DTP rather than DT.
• The Academy recommends that inactivated polio
vaccine should be introduced in the routine
immunization in a phased manner, now that it is
licensed in the country.
• The Academy strongly recommends that Hepatitis B,
HIB and M M R Vaccines should be included in the
national immunization schedule with immediate
effect.
• The Government should actively consider inclusion
of typhoid vaccine in the national immunization
schedule. The Academy suggests use of
58
Vi-polysaccharide vaccine for this purpose.
• The Academy supports the decision of the
Government to discontinue production of animal
brain rabies vaccine. However we need to ensure
adequate supplies of indigenously produced chick
embryo/tissue culture vaccines at affordable costs.
Intradermal route of cell cultured vaccine as per the
recent approval and the guidelines of the Drug
Controller General of India should be encouraged
and the minimum number of vaccinees stipulated in
the guidelines should be brought down to 10 (the
number of doses obtained from one vial of vaccine).
• The Academy again reiterates its previous
recommendation to the Federation of Obstetric and
Gynecologic Societies of India to adopt a policy of
routine testing of all pregnant women for HBV
infection. If the mother is HBsAg positive, the baby
should be given HBIG plus HB vaccine soon after
birth.
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