IAP Guidebook on immunization

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2. 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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3. 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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4. 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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5. Introduction
Protect ion from preventable diseases, disabilities and consensus based on the current evidence from the
death through immunization is the birth right of every literature. The IAP Immunization Time Table
child. Immunization is one of the most co s t-effective represents the 'best individual practices schedule' for a
health intervention s known to mankind Over the last given child and would necessarily be at some variance
three decades, a lot of progress has been made globally from the National Immu n ization Schedule of the
as far as protection against the eight important vaccine Government of India, which is meant for the public at
preventable diseases is concerned - from less than 5% large. With the availability of many newer vaccines, it
children who were protected against these diseases in is necessary that some of these should be considered for
the early 1970s, to as many as 75% being protected routine immunization and the immu nization schedule
now. Small pox has been eradicated and we are at the has to be changed accordingly.
threshold of eliminating polio.
Unfortunately, there is lack of authentic data on
An effective National Immunization strateg y can help epidemiology of most infectious diseases in our country.
decrease childhood morbidity and mortality, especially However that should not deter us from using some of
in developing countries. It must, however, be clear that these vaccines till such data is generated. Many
immunization strategies may vary from co u n try to decisions on incorporation of new vaccines in t he
country depending on the local req u irements. This immunization program have, therefore, to be based on
guide book represents the collective effo rts of the data from other parts of t h e world. This may appear
members of the Indian A cademy of Pediatrics unscientific to some, but is a reality and is the only way
Co mmittee on Immunization (IAP COI). We are aware out at present.
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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6. Historical Aspects
Though Dhanvantri, t h e father of Indian In 1985, the EPI was s upplanted by the Universal
Medicine, sp o ke of preventing certain infectious Immunizat ion Program (UIP). The main objectives of
diseases t h rough immunization, the first successful UIP were: i) universal immunization and reduction in
vaccine in the modern era was developed b y Edward mortality and morbidity due to vaccine prev entable
Jenner in 1796 when he used cowpo x inoculation diseases ii) self-sufficiency in vaccine production iii)
(vaccination) to protect against smallpox. Louis establishment of a functional cold chain system, and iv)
Pasteur developed a h ig h ly effective vaccine against the introduction of district level monitoring system. In
rabies, which was used for post-exposure prophylaxis. this program the emphasis was s hifted from the
It was first given to a child in 1885. Since then many under-five to under-one age group, thereby reducing the
other vaccines have been developed in rapid succession. number of potential beneficiaries. It considerab ly
reduced the denominator for percentage coverage. The
Experience with smallpox eradicat io n p ro g ram
vaccines recommen d ed were BCG, DTP, OPV and
convinced the health policy makers that immunization
Measles for infant s an d TT for pregnant women. It
was the most powerful and cost-effective measure for
should be noted that UIP envisaged 100% coverage of
control of vaccine preventable diseases. At the global
pregnant women with 2 doses of tetanus toxoid (or a
level, an organized immunization program came into
booster dose, as applicable) and at least 85% coverage
exis tence in the year 1974 under the banner of the
of infants. Under the UIP, the govern ment also aimed
World Health Organization (WHO). This was
to establish logistics of vaccine production and supply
christened as the 'Expanded Program on Immunization'
as well as training of medical and p aramedical
(EPI). The term "Exp anded" referred to the provision
personnel. The Government of India subsequently set
of adding more antigens to vaccinatio n s chedules,
up a " Technology Mission on Vaccination and
extending coverage to all corners of a country and
Immunization of Vulnerable Po pulation, especially
spreading services to reach the less privileged sections
Children" to cover all asp ect s of the immunization
o f the society. The EPI program focused on children activity from research and development to actual
below 5 years of age and pregnant women. The
delivery of services to the target population.
vaccines included were BCG, DTP, OPV, Measles and
TT. The primary health care concept as enunciated in Since switching over to UIP in India there has been a
the 1978 Alma Ata Declaration in cluded immunization significant decline in many of the vaccine preventable
as one of the strategies for reaching the goal of 'Health diseases, such as poliomy elitis, neonatal tetanus,
for All' by the y ear 2000. The Government of India diphtheria, wh o o p ing cough and measles. The UIP
adopted the EPI in 1978 with the t win objectives of became an integral component of Child Survival and
reducing the mortality and morbidity resulting from Safe Motherhood Program (CSSM) in 1992 and then
vaccine preventable diseases of childhood, and to part of Reproductive and Child Health Program (RCH)
achieve self-sufficiency in the production of vaccines. in 1997. Supplemen t ary immunization activities
The program started with BCG, DTP and Typhoid against poliomyelit is were started in 1995-96. In 2002,
vaccines - it did not include measles vaccine. OPV was Hepatitis B vaccination was initiated in selected areas
added only in 1979 and measles later on. Ty p h oid targeting the urban poor.
vaccin e continued to be a part of our national
The WHO also endorsed global efforts at immunization
immunization schedule until 1985. Program coverage
through Universal Childhood Immunization (UCI) in
of 85% was envisaged, but this could not be achieved
1990 - the name given to a declaration sponsored by
for several years and independent evaluations showed
UNICEF as part of the 40th anniversary of the United
very low coverage rates in many parts of our country.
Th erefore, a change of strategy was considered Nations in October 1985. Efforts were undertaken to
initiate research for the development of newer vaccines,
necessary.
to improve vaccine product ion technologies and to
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7. u n d erstand the epidemiology of diseases. These augmenting research and d ev elopment on vaccines
developments were highlighted in 1990 at the Summit against HIV, malaria and tuberculosis v) making
for Children, where it was claimed that EPI had indeed immunization coverage an integral part of international
been a global success with 80% reported coverage with development initiatives. The GAVI Ind ia Project has
the six vaccines. In 1992, the WHO also set a target for been instrumental in launching free Hepatitis B
universal Hepatitis B immunization. It aimed to immunizatio n in some of the urban slums. It has also
incorporate Hepatitis B vaccine in the immunization endeavored to promote safe injection practices and use
schedules o f all member countries by 1997. However of auto-disable syringes for immunization as part of a
unfortunately less than 50% of t h e countries have countrywide initiative.
actually introduces Hepatitis B vaccine in their
A surv ey conducted in 2002 under the RCH showed
National Schedule. India has recently accepted its
that immunization coverage rates in India have been
inclusion in National schedule and the coverage will
d eclining, since 1999. The Government of India h as
expand in a phased manner.
recently lau n ched an Immunization Strengthening
These global efforts at immunization were launched Project with the objectives of i) strengthening routine
under the banner "Children Vaccine Initiative" (CVI) immunization with the aim of raising the percentage of
in 1991 with support from several in t ernational fully immunized children t o ab ove 80% ii) eliminating
agencies like the WHO, UNICEF, World Bank and the polio and achieving polio eradication iii) reviewing and
Rockefeller Foundation. CVI aimed at development of developing a new vision of the immunization program
newer vaccines, improvement in vaccine production in the medium term keep in g in view the development
technolo g ies and vaccine quality. These efforts were of new epidemiological patterns, availability of new
further co nsolidated under the "Global Program on vaccines and delivery mechanisms and advances in cold
Vaccines and Immunization" (GPV) in 1993 reflecting chain technologies iv) improving surveillance and
the EPI and UCI init iative and combining these with monitoring mechanisms. The National Institute of
the CVI. The focus of GPV is on sustaining high Health and Family Welfare has been identified as the
vaccine coverage, developing global surv eillance nodal institute for coordination and implementation of
network and evolving eradication strategies. The the program an d the training shall be carried out
"Global Alliance for Vaccines and Immunization" through five regional inst it u tes. Training of mid-level
(GAVI) was set up in 1999 as an international coalition managers, including persons actively involved in
of multination al funding agencies (e.g. Bill and immunization program at the district and state level, is
Melinda Gates Foundation, Rockefeller Foundation), an integral component of this project. The project was
v accin e man u fact u re r s , n o n - g o v ern men t al started in 50 poorly performing districts of 8 priority
organizations and the governments of 74 d ev eloping states of Uttar Pradesh, Bihar, Madhya Pradesh,
nations. GAVI organizes its activities through a Rajasthan, Oriss a, Gujarat, Assam and West Bengal.
vaccin e fund. The main objectives of GAVI are as These newer initiatives have improved overall coverage
follows: i) impro v in g acces s t o s u s t ainable in these districts. Unfortunately last report of National
immunization services ii) expanding use of all existing family and health survey released in 3rd week of Nov
safe and effective vaccines iii) accelerat ing the '06 do not confirm this improvement.
development and introduction of new vaccines iv)
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8. Basic Immunology
The Greek work "immune" means "to be protected". BCG, oral polio v accine and Hepatitis B vaccines can
Protection offered by the introduction of various be given soon after birth as the maternally derived
antigens or ready-made antibodies is called acquired immunity apparently does not interfere with the vaccine
immunity. The process by which t h is acquired "take" On the other hand, live measles vaccine may be
immunity is obtained is known as 'immunization'. This inhibited in the presence of detectable maternal
is of two types, active and passive. When specific antibody in the infant's circu lation. Measles vaccine,
antigens evoke the required immune response in the therefore, should only be given after at least 9 months
system it is called active immunization, and when of age ; similarly, MMR vaccine is given only after 12
antibodies are supplied readymade in th e form of months of age.
immune g lo b u lins and sera it is known as passive
Timing of vaccination depends upon the age at which
immunization.
the disease is anticipated as well as on the feasibility of
Pathogenic infectious ag en t s induce disease and the administering the vaccine at that time. For instan ce,
host immune system responds with immunity , first to neonatal tetanus can only be prev en t ed through
ensure recovery and then to offer protection from maternal immunization by ensuring adequate titers of
disease if the same patho gen were to be encountered transplacent al antibodies and not by immunization of
again. A vaccine is composed of one or more antigens the baby at birth.
of the pathogen, which will induce a protective immune
Vaccines are selected based on three important criteria
response without suffering from the disease.
viz. necessity, safety and efficacy. All vaccines are
Vaccines consist of attenuated live organisms (eg. oral subjected to the following trials before being licensed:
polio vaccines, oral typhoid vaccine, varicella vaccine,
Phase I Trial: Human volunteers - for tolerance, safety
measles vaccine), whole inactivated org anisms (e.g.
pertusis vaccine, whole cell typhoid vaccine, rabies Ph as e II Trial: Human volunteers - for immu n e
vaccine, inactivated polio vaccine), modified exotoxins response, safety
called "toxoids" (e.g. diphtheria toxoid, tetanus toxoid),
or subunits (e.g. polysaccharide antigens of Salmonella Phase III Trial: For field efficacy, safety
typhi or Haemophilus influenzae type b and the surface
Further, before a vaccine is act u ally marketed it
proteins of hepatitis B virus).
undergoes sterility, purity and potency tests at the level
Vaccines mimic infection with the respective pathogen, of the manufacturer and the Drugs Controller General
but without the asso ciated risk of developing the of India.
disease. The consequent immune response may be
Most of the currently used childhood vaccines do not
manifested through hu moral (i.e. antibody) immunity
interfere with the vaccine "take" of one another. These
or cell mediated immunity (CMI) or both. If the antigen
can be, therefore, given simultaneously and several
preferentially stimulates Th1 series of T helper
antigens can be g iv en the same day, if required. In
lymphocytes, a strong lymphocytic respons e is
general, the interval between two doses of the same
obtained; if Th2 series is preferentially stimulated, the
v accine, say for instance DTP, should be at least 4
ultimate express ion of immunity is predominantly
weeks; preferably 8 weeks. An interval of 4 weeks
humoral. Carbohydrate antigens are T cell independent;
would obviously result in completion of the primary
hence they stimulate B cells directly without T helper
schedule at an earlier age an d may perhaps make it
cell modulation. This results predominan t ly in a IgM
easier for the parents to remember their follo w-up
response wit h out IgG production or induction of
appointments. Th is way the drop out rates may also
immunological memory. BCG elicits CMI without an
decrease. BCG and OPV can be given from the day of
easily demonstrable humoral component.
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9. birth until 2 weeks of age, s o that there would be 4 immune system and it may be advisab le to avoid
weeks gap until the next contact for immunization at 6 administratio n of other vaccines within 4 weeks of
weeks. If the opportunity to give BCG / Hepatitis B was these. There is, however, very little objective evidence
not available in the neonatal period, it may be given at to show t h at this immunosuppression is clinically
6 weeks, s imultaneously with DTP and OPV. Some of significant.
the viral vaccines (e.g. measles, varicella) may be
associated with possible short lasting suppression of the
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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10. 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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11. Commonly Used Vaccines
A. Vaccines Against Diseases Covered Under EPI
BCG Vaccine
Bacillus Calmette Guerin vaccine is derived from the ensure maintenance of cold chain during transport and
bovine tuberculosis strain and was first developed in storage. Th e recommended dose is 0.1 ml of
1921. It was the result of painstaking efforts by t h e reconstituted vaccine irrespective of the age and weight
French microbiologist Albert Calmette and the of the baby. Injection of BCG should be strictly
veterinary surgeon Camille Guerin who performed 231 intradermal, using a Tuberculin syringe and a 26G
repeated subcultures over 13 years. It continues to be need le. The convex aspect of the left shoulder is
the only effective vaccine against tuberculosis The two preferred for easy visualization of the BCG scar. The
common strains in use are Copenhagen (Danish 1331) selected site may be swabbed clean using sterile saline
and Pasteur of which the former was produced in India - local antiseptics are unnecessary.
at the BCG Laboratories, Guindy, Tamil Nadu till
A wheal of 5 mm. at the injection site indicates
recently.
successful intradermal administrat ion of the vaccine.
BCG induces cell-mediated immunity but t h e Subcutaneous administration of BCG is associated with
protective efficacy is a matter of debate and is very an increased incidence of BCG aden it is . The injected
difficult to q u an t ify BCG vaccine is more effective site usually shows no visible change for several days
against t h e development of hematogenous spread of Subsequently, a papule develops after 2-3 weeks, which
Mycobacterium tuberculosis (which results in milliary increases to a size of 4-8 mm. by the end of 5-6 weeks.
and meningeal forms of the disease against which it This papule often heals with ulceration and results in a
has a protective efficacy of 50-80%), than against the s car after 6-12 weeks. Although the preferred time o f
development of pulmonary tuberculosis where it has a vaccination is soon after birth, it could be given up to
protective efficacy of less than 50%. 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
The vaccine contains 0.1-0.4 million live viable bacilli
presuming that BCG has not taken up.
per dose. It is supplied as a lyophilized (freeze-dried)
preparation in vacuum sealed multi-dose dark colored Adverse reactions - The ulcer at vaccination site may
ampoules. The lon g n ecked BCG ampoule should be persist for a few weeks before formation of the final
cut carefully by gradual filing at the junction of its neck scar. No treatment is required for this co ndition.
and body, as sudden gush of air in the vacuum sealed Secondary infection at the vaccination site may require
ampoule may lead to spillage of th e contents. The an t imicro b i a l s . I p s i l a t eral axillary / cerv ical
vaccine is light and heat sensitive and deteriorates on ly mphadenopathy may develop a few weeks/months
exposure to ult ra violet rays. Sterile normal saline after BCG vaccination. Antitubercular therapy is of no
should be used for reconstitution. As t h e vaccine benefit in such situations and should not be
contains no preservative, bacterial contamination may administered. The nodes regress spontaneously after a
occur with repeated use. Therefore, once reconstituted, few months. It should also be noted that if fine needle
the vaccine should be used within 4 hours with the aspiration cytology of the nodes is carried out, stain for
left-over being discarded after the session. acid-fast bacilli may b e p o sitive. These are bovine
vaccine bacilli and should not be misconstrued as being
In lyophilized form it can be stored at 2-80 C for up to
suggestive of tuberculous disease. In some children the
12 months, without losing its potency. One should
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12. nodes may even liquefy and result in an ab s cess. s it u at ion also. Disseminated BCG infection is
Surgical removal of the nodes or repeated needle extremely unusual but may occur in children with
aspiration is the treatment of choice - again, cellular immunodeficiency.
antitubercular therapy is not recommended in this
Oral Polio Vaccine
Oral polio vaccine (OPV) remains the vaccine of choice must reach the outreach facility at 2-80 C in vaccine
for polio eradication in India. It is a suspension of over carriers with ice packs. Breastfeeding and mild
1 million particles of poliovirus types 1, 2 and 3. It is d iarrh ea are n o co n t rain d icat io n t o OPV
supplied with a stabilizing agent, namely magnesium adminis t rat ion. If a substantial amount of OPV is
chloride. The vaccine, therefore, is quite stable under vomited or regurgitated wit hin 5-10 minutes of
refrigeration. administration, the dose should be given again. If this
repeat dose is also not retained, neith er of the doses
When OPV is given by mout h , t h e vaccine viruses
s hould be counted and the vaccine shou ld b e
reach the intestines where they must establish infection
re-administered at a later visit.
(vaccine virus "take") before an immune response may
occur. A high level of gut immunity ensures that Adverse reactions - OPV is an excellent vaccin e and
vaccinated children would not participate in the chain the WHO Global Polio Eradicat io n Initiative is at the
of transmission of wild (pathogenic) polioviruses. For threshold of achieving its goal of eradicating wild
reasons that are not clearly understood, OPV "take" polioviruses. By mid-2006 polio has been elimin ated
rates may be somewhat variable. Seroconversion rates from all countries other than India, Pakistan,
after three doses of OPV average 73%, 90% and 70% Afghanstan, Nigeria, Niger and Egypt. For developing
for Types I, II and III respectively. It is for this reason cou n t ries OPV is still the vaccine of choice for
that multiple doses of OPV are necessary before eradicating wild poliovirus and would continu e t o be
90-95% of children develop immune responses to all used until wild poliovirus circulation ceases. However,
three poliovirus typ es . IAP recommends at least 5 like any other vaccine its use is associated with certain
routine doses of OPV, d u ring infancy and 2 more risks.
repeat doses; at 16-18 months and 5 years. In addition
to the routine OPV doses , " Pulse OPV doses" every OPV has been associated with occurrence of Vaccine
Associat ed Paralytic Poliomyelitis (VAPP) Today, as
year on Nat io n al Immunization Days (NIDs) and
sub-National Immunization Days (sNIDs) until the age we move towards p o lio eradication, VAPP is more
common than paralysis due to wild polioviruses and
of 5 years are also mandatory.
has, therefore, become an increasingly contentious
Polio eradication is defined as no case of paralytic issue for all pediatricians . The risk of VAPP would
poliomyelitis by wild polioviru s in last three calendar continue to be there as long as we are using OPV as the
years along with absence of wild poliovirus in the preferred vaccine against poliomyelitis. It has been
community, when excellent clinical and virological estimated that the global VAPP burden is in the range
surveillance exists and the coverage of routine OPV is of 250-800 cases an nually. Nearly 50 cases of VAPP
more than 80%. Polio elimination is defined as no case are reported to occur in India annually. Approximately
of paralytic poliomyelitis by the wild poliovirus in one half of all VAPP cases are associated with the Type 2
calendar year with other criteria being the s ame as in OPV strain.
eradication . A d eq u at e immu n izat io n , clinical
The second major problem with u s e of OPV is the
surveillance and appropriate virological investigations
in all children with acute flaccid paralys is (AFP) are emergence of circulating Vaccine Derived Polio
Viruses (cVDPVs), which are mutants that re-acquire
the cornerstones of polio eradication.
wild virus-like properties and have been associated with
OPV should be stored at -200 C at the state and district outbreaks of paralytic polio. cVDPVs usually aris e in
level and in the freezer at the clinic level. The vaccine communities with low population immunity especially
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13. when polio vaccine coverage rates decline but OPV use suggested that mass OPV campaigns should be
continues. The duration and extent of spread of s ynchronized with the cessation of OPV use o n ce
cVDPVs are dependent on the magnitude of the eradication of wild poliovirus has been achieved, so as
immunity gap. As lo n g as OPV is in use it is t o eliminate the risk of VAPP and the emergence o f
mandatory that very high immunization coverage is cVDPVs. At the same time, a gradual transition to IPV
maintained so as to decrease the risk of emergence of should be encouraged.
cVDPV. W hereas VAPP occurs in individual cases,
cVDPV can result in large outbreaks. It has been
Polio Eradication
Why do we need pulse immunization against polio? • Maintaining high routine infant
immunization coverage with OPV.
Simultaneous administration OPV to all susceptible
• Conducting mass campaigns (i.e. pulse
infants and children interferes with circulation of wild
immunization against polio).
poliovirus in the community. It is, therefore, important • Development of sensitive surveillance.
to ensure complete coverage with OPV during NIDs so • Organization of mop-up campaigns.
that no wild poliovirus remains in circulation.
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
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14. manner. IPV can also be an additional tool to eradicate rounds of SIAs using OPV. However in
wild polio from last few high risk difficult districts. post-polio eradication era, it will be
unethical and unsafe to reintroduce OPV in
IPV is also the vaccine of choice in patients with such areas. It will force us to depend on the
immunodeficiency and th e preferred vaccine in stocks of WHO or any such agency for OPV
children with symptomatic HIV infection. vaccine should out-break of wild polio or
cVDPP occur. Hence India should preempt
Post-polio eradication scene and polio immunization: the emergence of cVDPV and has to become
IA P believes that it will be unsafe and unethical t o self sufficient in stock-piling enough polio
continue to use OPV in post-p o lio eradication era. vaccine now to meet any such unforeseen
Following concept s should be kept in mind while eventuality in future.
deciding India specific guidelines for post-polio 3. Looking at the above problems, IAP
eradication immunization. recommends that India should switch over to
IPV, preferably as IPV-DTP, in its routine
1. It will be unethical and unsafe to continue to immunization program gradually in
use OPV after zero wild polio case and zero post-polio eradication era. India should
transmission status is achieved due to risk of encourage indigenous manufacturer to
VAPP following OPV. produce enough IPV so that it becomes
2. It will be unwise to discontinue use of polio affordable so that is will be possible to
immunization altogether after zero polio switch to IPV in due course, looking at the
status is achieved due to fear of cVDPV and huge requirement of the number of doses.
iVDPV. Past experience from some
countries has shown that countries which Adverse reactions - Th e vaccine is very safe. As IPV
have eradicated wild polio virus and have contains trace amounts of streptomycin, neomycin and
slackened in their routine polio polymyxin B, allerg ic reactions may be seen in
immunization programs have experienced
in d iv id u als wit h hypersen s it iv it y t o t h es e
cVDPV outbreaks. These outbreaks of
antimicrobials.
cVDPV were curtailed by strengthening
routine immunization and giving 2 or more
DTPw Vaccine
The combination of diphtheria t o xoid, tetanus toxoid induction of a neurological reaction in v ery rare
and whole cell killed pertussis vaccine (DTPw) is instances; however, there has been no conclusive proof
popularly known as the "triple antigen" DTP is the core for this and the vaccine should not be denied to
vaccine in all childhood immunization services. It is children with seizure disorders or st ab le neurological
one of the oldest combination vaccines and has been in conditions (e.g. Cerebral palsy, developmental delay).
continuous use for more than 55 years. Tetanus an d The results of the National Childhood Encephalopathy
diphtheria toxoids are adsorbed on insoluble aluminium Study (NCES) in the United Kingdom clearly show that
salts which act as adjuvants and enhance the antitoxin there is no causal relationship between administration
responses to both the antigens. While the two toxoids of DTPw vaccine and development of chronic
are highly immunogenic (95-100%), the pertussis neurological disease in children. Convulsions following
vaccine (even after 3 doses) has a protective efficacy of DTPw v accine are distinctly rare, and may only
about 70-90% only. represent n o t h ing more sinister than fever triggered
seizures. Progressive/evolving n eurological illnesses,
Adverse reactions - Local (pain and redness) and
however, are a relative contraindication to first dose of
systemic (fever) side-effects of the DTPw vaccine are DTPw immunization. For children who develop
almost entirely due to the pertussis component. Whole
persistent inconsolable cry of more t h an 3 hours
cell pertus s is vaccine has been incriminated in the
14

15. duration, hyperpyrexia - fever > 40.50 C or hypotonic dose only then pertussis vaccine is contraindicated for
- hypo responsive episode HHE (collapse/shock like future administration.
stage) within 48 hours of DTPw admin is t ration,
seizures with or without fever within 72 h ours of DTP and DT vaccines need to be stored at 2-80C. These
vaccin es s hould never be frozen, and if frozen
admin is tration of DTPw, the decision to administer
further doses of DTPw should be carefully evaluated accidentally, it should be discarded. DTP must be
injected intramuscularly and the preferred site is th e
and discussed with the parents These events were
regarded as absolute contraindications in the past. They anterolateral as p ect of the thigh. The IAP COI
recommends 5 doses of DTP - three in infancy with two
are now considered mere precaut ions because these
boosters at 18 months and 5 years. The DTPw or DTPa
events generally do not recur with the next dose and
vaccines can be administered up to the age of 7 years.
they have not been proven to cause permanent sequelae
After the age of 7 years, Td should be given.
If a similar adverse reaction recurs with the subsequent
Acellular Pertussis Vaccine (DTPa)
DTPa vaccines are of various types depending on the DTaP are contraindicated. Pertussis vaccine
number of constituent components viz. two component should not be given in such cases and instead
DTPa containing pertussis toxin (PT) and filamentous DT should be administered in the future.
haemagglutinin (FHA); three co mponent DTPa • In case immediate anaphylaxis occurs after
containing pertact in in addition to PT and FHA; five DTwP administration, further DTwP/DTPa
component DTPa containing agglutinogens 2 and 3 in should be avoided because of uncertainty about
which component of these vaccines has caused
ad d ition to PT, FHA and pertactin. Though a five
the reaction, as is true with any vaccine.
component DTPa vaccine may be expected to elicit a
more robust immune response as compared to two and
The IAP COI unequivocally endorses the continued use
three component DTPa vaccines, the overall efficacy of
o f DTPw vaccine because of its proven efficacy an d
DTPa vaccines is comparable to the DTPw vaccine.
safety. DTPa Vaccine may u ndoubtedly have fewer
Dose: 0.5 ml by intramuscular injection. minor side-effects (like fever, local reactions at
injection site and irritability) but this minor advantage
• If parents are not willing for DTPw can not justify the inord in at e costs involved in the
administration after the adverse reaction with routine use of this vaccine. DTPa vaccines are also by
the previous dose, DTaP can be recommended
no means more effective than the whole cell pertussis
in such circumstances as this vaccine is less
vaccine. These are, therefore, not recommended for
reactogenic.
universal immunization in our country at present.
• If encephalopathy (major alteration of
sensorium or illness with seizures lasting > 24 There is, however, no bar to offering these vaccines to
hours) occurs within 7 days of DTPw children from families who opt for the slight advantage
administration, further doses of DTPw and of fewer minor side-effects.
15

16. Tetanus Toxoid
This vaccine contains Tetanus Toxoid 5 LF. It is a immunized, two doses of TT at least one month apart
highly heat stable and effective vaccine. Bo o s t ers of should b e given during pregnancy so that protective
this vaccine may be given at 10 and 16 years and antibodies in ad equate titers are transferred to the
thereafter every 10 years. After completing the full newborn for prevention of neonataltetanus. The second
course of seven doses, there is no need for additional dose of TT should be administered at least 2 weeks
doses during pregnancy at least for the next 10 years. before delivery. A single dose of TT would suffice for
Thereafter a single booster every 10 years wo u ld be subsequent pregnancies that occur in the next 5 years;
s u fficient to extend immunity for another 10 years - thereafter, 2 doses of TT would again be necessary. For
boosters should not be given more frequently than this. previously unimmunized schoo l age children, primary
The practice of giving TT after every injury should be TT immunization consists of two doses given 4 weeks
discouraged. 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. 17

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

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

20. Hepatitis B Vaccine
In India, 1-4% of individuals are found to be chronic schedules:
carriers of Hepatitis B Virus (HBV). Infection with
1. Birth, 1 and 6 months
HBV may occur perinatally (v ertical transmission),
2. Birth, 6 and 14 weeks
during early childhood (the so-called horizontal
3. 6, 10 and 14 weeks
spread ), through sexual contact or nosocomially. It
should be noted t h at in our country horizontal route
Immunologically 0 - 1 - 6 months schedule of hepatitis
(e.g. ch ild to child) route and the vertical route (i.e.
B immunization has been most widely used and proven
mother to child) are the major routes of transmission of
to be ideal with high antibody titers at the end of the
hepatitis B.
v accination. However now that HB vaccination is
Younger the age of acquisitio n of HBV infection, integrated into the existing immun ization program
higher the chances of becoming a chronic carrier. It is (UIP) in India, d u e to operational issues at a national
believed that as many as 90% of those who are infected level one has to piggy back on the available contacts for
at birth go on to become chronic carriers. In fect ion routine immunization i.e. DTP wh ich is given at 6, 10
with HBV is one of the most important causes of and 14 weeks of age. At the same time birth dose has to
chronic hepatitis, cirrhosis of liver and hep atocellular be given to cover for the vertical route. Hence IAP COI
carcinoma. 30% of the chronic carriers go on to recommends 0 - 6 - 14 wks schedule for public
develop chronic liver disease. These are all preventable measure. In case birth dose has been missed, 6 - 10- 14
by early childhood immunization. It is for this reason wks sched u le can be followed. In office practice, one
that the World Health Organization has recommended can still use 0 - 6wks - 6 months schedule. As on now,
u niversal Hepatitis B vaccination. As many as 150 from the d ata available, none of the above schedules
countries have n ow included HBV in their national needs a booster.
immunization sch ed u les . In Ju n e 2002, the
Th e p urpose of Hepatitis B vaccination is to prevent
Government of India also initiated the incorporation of
chronic in fection and development of chronic liver
HB vaccine as a univ ersal vaccine through a pilot
disease / hepatocellular carcinoma later in life. An ideal
program which will be scaled up in a phased manner.
HB vaccine schedule should, therefore, address vertical
HB v accine is a highly purified recombinant DNA as well as h orizontal modes of transmission of the
vaccine produced in the yeast species Hansenula virus.
polymorpha, Saccharomyces cerevisiae or Pichia
Pregnant women should be counseled and encouraged
pastoris. It is adjuvanted with aluminiu m salts and
to opt for HBsAg screening. If the mother is known to
should be stored at 2-80 C. The vaccine should not be
be HBsAg negative, HB vaccine can be g iv en along
frozen - if frozen accidentally, the it should be
with DTP at 6, 10 and 14 weeks/6 months as there is no
discarded. It should be injected intramuscularly in the
special requirement to start vaccinat ion at birth itself.
anterolat eral thigh. The usual pediatric dose (< 12
This 6-10-14 wks schedule may be easier to implement
years o f ag e) is 0.5 ml corresponding to 10µg of the
in the context of the national immunization program as
antigenic component. Adult dose is twice the pediatric
higher vaccination coverage may be achieved with
dose. The vaccine is hig h ly immunogenic and
earlier administration of vaccines.
seroconversion rates are greater than 95% after a three
dose schedule. Antibody titers greater than 10 mIU/ml If the mother's HBsAg stat u s is not known, it is
are considered protective. The dose may be increased important that HB v accination should begin within a
when vaccinating immunocompromized individuals few hours of birth so that perinatal transmission can be
e.g. patients on chemotherapy for malignant conditions prevented. Any one of the following schedules may be
or those with chronic ren al failure awaiting used for this purpose; birth, 6 and 14 weeks or birth, 6
hemodialysis. wks and 6 months.
HB vaccine may be given in any of the follo win g If the mother is HBsAg positive (and especially HBeAg
20

21. positive), the baby should be given Hepatitis B Immune after initial stabilization.
Globulin (HBIG) within 24 hours of birth, along with
For older children and adults the preferred schedule is
HB vaccine (at birth, 6 and 14 weeks or birth, 6 weeks
and 6months) using two separate syringes and separate 0, 1 and 6 months, '0' being the elected date for the first
dose.
sites for injection. If HBIG is not available (o r is
unaffordable), HB vaccine may be given at 0, 1 and 2 In immunocompetent individuals HB vaccine induces
months with an additional dose between 9-12 months. an effective immunological memory that lasts life-long
and protects against symptomatic acute illness and
It has been suggested by many authorities that in
development of chronic HB infection on exposure to the
infancy the third dose of HB vaccine should be given at
virus. Boosters of HB vaccine are, therefore, not
least 16 weeks after the firs t d ose & at least 8 weeks
necessary under usual circumstances.
after the second dose and not before 6 months of
chronological age, as it presumably gives longer lasting HB vaccination is now being integrated into t he
immunity. However this view is being challenged as existing immunization program in India. It was
HB vaccine is a T-cell dependent vaccine, the titers at introduced in 15 cities an d 32 districts in the initial
the end of immunization schedule may not be phase; selection of districts was based on achievement
important so far as it is well above the protective level. of targets of 80% or more DTPw-3 coverage under
There would occur anamnestic response with the titers routine immunization based on evaluation surveys.
going up should there occur contact with th e v irus Under this program, the vaccine is being provided free
again in future. As logistically, it is easier to combine of cost to infants living in u rb an slums. The program
HB vaccine program with the DTP vaccine, it can be will be expanded to include additional cities and
given in 0-6-14 weeks schedule too The vaccination districts within a certain timeframe. It is envisaged that
schedule need not be changed for preterm and HB vaccination will be introd u ced in all districts of
small-for-dates babies; in the case of extremely preterm India by 2007.
babies, ho wev er, vaccination should commence only
Hepatitis B Immunoglobulin (HBIG)
HBIG provides immediate passive immunity and is Adverse Reactions: Transient, mild pain at the site of
recommended in situations wherein there has been injection and itching may be seen in a small proportion
acute expos u re t o HBsAg infected material e.g. by a of recipients.
needle-stick injury. Clinical trials h ave demonstrated
90% reduction in risk of transmis s ion following such Special Precauti ons : HBIG should never be
exposure if HBIG is used alon g wit h Hepatitis B administered intravenously.
vaccine. HBIG does n o t interfere with antibody Dose: Adult s : 1000-2000 IU; Children:- 32-48 IU/kg
response to simultaneous HB vaccine. It is for t h is bod y wt . This should be administered as soon as
reason that individuals who have had recent accidental following exposure, preferably within 48 hours though
exposure to hepatitis B virus should be given combined it can be administered even if the patient reports late up
passive-active immunization. It is also useful in to 7 day s after exposure. Neonates: 100-200 IU. The
prevention of mo t her to child transmission and first dose should be administered as soon as after birth
transmission following sexual exp o s u re like in rape up to within 5 days of birth. An additional d o se of
cases. Lastly HBIG is indicated in o ncology patients 32-48 IU/kg of body weight may also be given between
who may not respond adequately to Hepatitis B vaccine 2-3 months after initial dose.
as they are immune compromised follo win g the
malignancy as well its therapy.
21

22. Typhoid Vaccines
Enteric fever is endemic in India and is a major public vaccine is available commercially.
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 The vaccine appears to be protective through the
lyophilized whole cell Salmonella t yphi vaccines were induction of antibodies against cell wall somatic (O)
inexpensive products that have been in use in India for and flagellar (H) antigens- these antibodies can act as
a long time. The p rotective efficacy of acetone a biological marker of the vaccine. It may interfere with
inactivated preparation is more than that of the phenol the interpretation of the Widal test. It is effective even
preserved vaccine but the former is more difficult to in child ren below 2 years of age and can be given to
prepare and is associated with more side-effects. Both infants > 6 months of age Primary vaccination requires
vaccin es contain Salmonella typhi 1000 million two d o s es , 4 o r more weeks apart, given
organisms per ml. Protection begins 4 weeks after subcutaneously. Pediatric dose of the vaccine is 0.25 ml
vaccination. Use of these vaccines may be associated in children aged 6 month s -10 years and 0.5 ml in
with fever, local pain and malaise due to the endotoxins order children. The vaccine should be stored at 2-80 C.
in bacterial cell wall. A pure S. typhi vaccine is less It should never be frozen. Revaccination is necessary
reactogenic than the combined TA/TAB vaccines. The every 2-3 years to sustain an o ptimum immune
vaccin e is very safe and is reasonably effective if response and should be done preferably before the onset
revaccination can be carried out on a regular basis. The of summer.
vaccine efficacy has been estimated to be 50-70% in a
Unfortunately, this vaccine is not being manufactured
meta-analysis of the randomized co ntrolled trials
in India at present
available.
The Vi-Capsular Polysaccharide Vaccine
Th e vaccine consists of purified Vi-cap s u lar polysaccharide vaccine as available in our country at
polysaccharide, which during natural infection inhibits present. Cost of the vaccine though a limiting factor in
p hagocytosis and serum bactericidal activity an d is past, is now reasonably priced. The vaccine is available
responsible for virulence of the bacteria. It h as as an isotonic phenolated buffer solution; the dose is
reasonable efficacy o f 50-60% in children and low 0.5 ml. containing 25µg of the polysaccharide. It can be
reactogenicity. Protection begins within two weeks of given intramuscularly or subcutaneously. The vaccine
vaccination and the biological marker is anti-Vi s h ould be stored at 2-80 C. It should never be frozen.
antibodies. It is not very effective in children below two Adverse effects are mild and include pain and swelling
years of age because it is an unconjugated at injection site.
Oral Live Attenuated Ty21a Vaccine:
22

23. Salmonella typhi Ty21a is a live attenuated strain with sittings, on alternate days. The capsule should never be
a mutation in gal E gen e and lacks the enzyme op en ed before ingestion. Protection begins within a
UDP-gal 4 epimerase. It is genetically stable and is not week after completion of the course and the protective
known to revert to virulence. The efficacy has been efficacy is as good as other available typhoid vaccines.
shown to 50-60% with the capsule form and near 90% Immunization needs to be repeated every 3-5 years
with th e liquid form (not available commercially). It
The vaccine should be stored at 2-80C. Antimicrobials
provides protection by inducing local gut immunity but
there is no biological marker of this vaccine. The active against S. Typhi should not be used 3 days before
and 7 days after oral typhoid vaccine administration as
vaccine is supplied in an enteric coated formulation as
these may interfere with the v accin e "take".
the bacteria are acid labile. It can be given to children
Unfortunately this vaccine is also not available now in
six years of age and above as the capsules have to be
our country.
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 response after the third dose. On the other hand,
invasive pathogen cau sing invasive diseases like PRP-OMP shows an increase in antibody level after the
pneumonia, meningitis and bacteremia. Majority of first dose itself with only marginal increases after the
cases occur in children below 2 years of ag e. Hib second and third doses. It is for this reason that while
vaccination is given routinely in the d eveloped 3 doses of HbOC and PRP-T are recommended for
countries for last many years. Countries with sensitive primary vaccination, only 2 doses of PRP-OMP are
disease surveillan ce systems have shown significant recommended for this purpose. In spite of these
declines in in v asive Hib disease following the apparent differences, these three vaccines when used in
incorporation o f this vaccine in their national the recommended doses have similar efficacy.
immunization programs. Recently published data of the
The vaccination schedule for Hib consists of three doses
Invasive Bacterial Infections Surveillance (IBIS) group
when initiated below 6 months, 2 doses between 6-12
from six referral hospitals in India (Lancet, 2003) show
months and 1 dose between 12-15 mon t h s , with a
that Hib is a common cause of meningit is in our
booster at 18 months. The interval between two doses
country.
should b e at least 4 weeks. If vaccination is delayed
Hib capsular polysaccharide vaccine is a very effective until 15 months, a single dose may suffice. It is highly
and safe vaccine. A number of PRP conjugate Hib efficacious vaccine, the protective efficacy being 95%.
vaccines are available of which t wo are available in As Hib d isease is essentially confined to infants and
India viz. HbOC (with CRM 197 mutant diph t h eria young children, the vaccine is not necessary for
toxin as conjugate) and PRP-T (with tetanus toxoid as children above 5 years. Hib vaccine is stored at 2-80 C.
conjugate). PRP-OMP (wit h meningococcal outer
The IAP COI reco mmen d s use of Hib vaccine for all
membrane protein as conjugate) is no t available in
children . It is particularly recommended to be given
India HbOC and PRP-T vaccines show only a marginal
increase in antibody levels aft er the first dose with a p rior to splenectomy and in patients with sickle cell
disease.
marked increase after the secon d and even better
23

24. C) Vaccines That Need to Be Given After Discussion With Parents
Varicella Vaccine
Chicken pox is usually a self limiting and generally are leaving h o me for studies in a residential
b enign disease affecting mostly children and youn g school/college. It is indicated in children with chronic
adults. Complications of varicella may be mo re lung/heart disease, humoral immunodeficiencies, HIV
commonly seen in immunocompromised individuals, infection (but with C4 counts above 15% of the age
adults and pregnant women. Takahashi et al developed related norms), leukemia (but in remission and off
a live attenuated vaccine from the Oka strain in Japan chemotherapy for atleast 3-6 months) and those on long
in the early seventies. The vaccine has been in clinical term salicylates/high dose lone t erm oral steroids.
use in Japan since 1989 and in the United States since Varicella vaccin e is also recommended in household
1995. The vaccine can be administered to any healthy contacts of immunocompromised children. It may also
individual above the age of 12 months who has not had be considered in children attendin g crèches and day
varicella previously. care centers. When used for post-exposure prophylaxis
it should be administered within 72 hours of varicella
Varicella vaccines in use today are all derived from the
exposure - it should be noted, however, that the efficacy
original Oka strain but the virus contents may vary
of the vaccine in preventing varicella under such
from one manufacturer to anoth er. The recommended
circumstances is not very clear. Varicella vaccine is
dose is 0.5 ml and the minimum infectious virus
also indicated in susceptible adolescents and adults if
content should be 1000 Plaque Forming Units. The
they are inmates of or working in the ins t itutional set
vaccine is administered subcutaneously. A single dose
up e.g. s ch o ol teachers, day care center workers,
is sufficient b elo w 13 years of age, after which two
military personnel and health care professionals.
doses (at 4-8 weeks interval) are required. The vaccine
is not recommended for ch ild ren below 12 months of The vaccine is stored at 2-80C and can be administered
age. Though vaccine manufacturers recommend to use subcutaneously or intramuscularly. It should be
this vaccine at 12 months, breakthrough infections can protected from light and needs to be used within 30
be less if used after 15 months of age. Hence IAP COI minutes of its reconstitution.
recommends to use this vaccine after the age o f 15
months. It is a highly effective vaccine and protective Adverse reactions - It includes fever, vaccine
ass o ciated rash, pain redness and swelling at
immunity, humoral as well as cellular, develops in
95-99% individuals. The immunity appears to be long vaccination site. When used in adult females,
pregnancy should be avoided for at least 4 weeks after
lasting.
vaccination.
The IAP COI opines that varicella vaccine is not
recommended fo r universal immunization in India at Varicella zoster immunoglobulin (VZIG) is used for
passive post-exposure prophylaxis in immunodeficient
present. One has to emphasize the generally benign
nature of an d rarity of complications with varicella individuals who have been exposed to varicella or
herpes zoster and are unlikely to have d et ectable
infection in young children. It may be offered to
children fro m h igh socio-economic strata of society antibody levels. It should be given to the neonate if the
mother develops varicella 5 days before to 2 days after
after explaining the pros and cons to the parents on a
one-to-one "named child" basis. It may be prescribed to delivery. It has to be given by intramuscular injection
adolescents who have not had varicella in past (or are and the dose is 125 units/10 kg body weight.
known to be varicella IgG neg ative) especially if they
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25. Hepatitis A Vaccine
Hepatitis A virus (HAV) infection is a relatively benign recommended for universal immunization in India at
infection in young ch ildren as many of them have present. One has to emphasize the generally benign
completely asymptomatic sub-clinical infection For nature of disease and very small number of children
instance as many as 50% of children between 2-5 years developing complications with Hepatitis A infection in
and 85% of those below 2 years who acquire HAV young children. It may be offered to children from high
infection, may continue t o remain anicteric and may s o cio-economic strata of society after explaining the
develop non-specific symptoms like any other viral pros and cons to the parents on a one-to one "named
in fection. In adults hepatitis A is frequently child" basis. It may be prescribed to adolescents who
symptomatic and mortality is much higher than in have not had viral hepatitis in past (or are known to be
children. The disease severity increases irrespective of HAV-IgG negative), especially those who are leav ing
age, in those with underlying chronic liver disease. home for further studies. It is recommended in all
patients with chronic liver d isease (who are HAV
Inactivated HA vaccines d eriv ed from HM 175/GBM
seronegative) and family contacts of patients with
strains and g ro wn on MRC5 human diploid cell lines
chronic liver disease. It may be offered to household
are now available. The virus is formalin inactivated and
contacts of patients with acute HA virus infection - in
adjuvanted with aluminimum hydroxide. It has been
t h e latter case the vaccine must be given within 10
suggested that the vaccine can be used any time after
days; however, it may not always be effective under
18 months of age when the maternally derived antibody
such circumstances when the contact has had the same
levels have declined; It is given in a two dose schedule,
source of infection as the index patient. It may also be
6 months apart. The adult formulation should be used
considered in children attending crèches and day care
after t h e recommended cut-off age of 15 years
centers and in travelers from abroad (e.g. non-resident
according to one manufacturer and 18 years according
Indians) visiting endemic areas.
to the other The vaccine is given intramuscularly and
the protective efficacy is 94-100% Immunity appears to The vaccine is stored at 2-80C.
be long lasting and boosters are not recommended at
present. Adverse reactions: It includes local pain and local
induration.
The IAP COI o p ines that HA vaccine is not
Pneumococcal Vaccines
Streptococcus pneumoniae is a common cau s e of infections. The common pathogenic stereotypes
invasive bacterial diseases responsible for a significant reported in children in Western countries are 1, 4, 5, 6,
proportion of potentially fatal con d it io n s like 9, 11, 14, 15, 18, 19 and 23. It appears that the
pneumonia and meningitis in children. It also leads to serotypes causing invasive disease in developed
conditions like otitis media and sinusitis, which may countries are different from the ones which are found
have morbidity but little or no mortality. In developing in developing countries. According to results of the
countries, this organism is believ ed to be the Invasive Bacterial Infection Surveillance (IBIS) study,
commonest cause of bacterial pneumonia. Peak the common serotypes responsible for invasive disease
incidence of pneumococcal disease is between 2 to 24 in children below five y ears of age in India include 6,
months of age. Based on the capsular polysaccharide 1, 19, 14, 4, 5 and 7. Serotypes 1& 5 accounted for
antigen, p neumococci are classified into 85 different 29% of disease in India. Thou g h prevalence of
serotypes. Of these, about 10 serotypes account for most penicillin resistance is almost negligible at present
25

26. there is some evidence that the prevalence of resistance invasive pneumococcal disease caused by the serotypes
to penicillin amongst the p neumococci may be covered by the vaccine. The dose is 0.5 ml. and the
gradually increasing, thereby highlighting the need for vaccine is given intramu scularly. Pneumococcal
an effective vaccine. vaccines are s tored at 2- 80 C. Conjugate vaccine
should not be frozen.
Two types of pneumococcal vaccines are currently
available - the 23-valent unconjugated polysaccharide Since the introdu ct io n of PCV-7 in the childhood
v accine and the 7-valent conjugate polysaccaharide vaccine schedule in US, there has been a dramatic
vaccine. Immunity is serotype specific. reduction in the in cidence of invasive pneumococcal
disease not only in the children who are vaccinated but
The 23-valent polysaccharide vaccine contains the
also non-vaccinated young children in their contact and
following serotypes - 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V,
a milder but statistically sign ificant decrease in
10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F,
invasive disease in their adult contacts, suggesting
23F, 33F. It is capable of preventing almo s t 85% of
s trong herd effect. Similar herd effect was seen in the
in vasive disease (pneumonia, men in g it is an d
form of overall reduction in the disease caused by drug
bacteremia) caused by pneumococci. Immunization,
resistant serotypes in the community. Though there has
however, is not effective for prevention of otitis media.
been replacement of t h e vaccine serotypes by
Each dose is 05 ml containing 25ug polysaccharide of
non-vaccine serotypes in the nasal carriage studies,
each of the 23 serotypes co n tained in the vaccines.
fortunately this has not been seen significantly in the
However, as it is an unconjugated polysaccharide
invasive diseases studies. However there is a need for
vaccine it does not result in immunological memory.
continuous surveillance for the serotype involved in
This vaccine is poorly immunogenic in children below
invasive cases from time to time.
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 Healthy children: Th e IAP COI does not recommend
given intramuscularly or subcutaneously. This vaccine u s e o f this vaccine for universal immunization in our
may be us ed in h igh-risk groups above the age of 2 country at present. PCV - 7 covers approximately 50 to
years. Revaccination is recommended after 5 years. It 55% percent of pneumococcal serotypes responsible for
is recommended for children with asplenia, sickle cell invasive pneumococcal disease in India offering about
d isease and nephrotic syndrome. It is als o 50 to 55% protection in infants & ch ild ren in India.
recommen d ed for HIV infected children. It may be The vaccine may be offered to healthy children above
offered to those with underlying chronic illnesses like the age of 6 weeks t ill 2 years after explaining the
renal diseases, cardiovascular diseases or diabetes. parents on one to one "named child" basis.
The heptavalent conjugate vaccine (PCV-7) contains High risk group: There are certain children who are at
the following sero t y p es -4, 6B, 9V, 14, 18C, 19F, and high risk of severe invasive pneumococcal disease with
23F. It is coupled with a non-toxic variant of diphtheria high mortality. This includes children with Sickle cell
toxin (CRM197) and has aluminium phosphate as the d is eas e, as p len ia, primary immu n o d eficien cy
adjuvant. Conjugation of polysaccharide with protein 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
CRM197 makes it immunogenic below 2 years of age. cardio-respiratory illness and children with chro nic
In February 2000 this vaccine (PCV-7 Prevnar) was illn es ses like renal diseases, diabetes etc., nephrotic
licensed in US fo r ad ministration to children below 5 syndrome, cerebrospinal fluid rhinorrhea etc. For such
yrs of age. The development of this v accine was children IAP COI recommends age appropriate doses
prompted by the observation that young children below of 7 valent conjugated pneumococcal vaccine routinely
2yrs of age are dis p ro p ortionately affected by the till 5 years of age. For children above 2 years, a dose of
serious pneumococcal infection and recognition of the 23 valent unconjugated pneumococcal vaccine is also
fact that available 23 valent polysaccharide vaccine was recommended to be given after one priming dose of
non immunogenic in t h is age group 2 yrs. Conjugate conjugated vaccine.
vaccine is used in a 3-dose schedule in infancy at 4-8
weeks interval followed by a booster at 15-18 months of Adverse reactions - Injection site so reness, malaise,
age and has protective efficacy of 95-99% ag ain st low grade fever.
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