You are on page 1of 20

C.

Immunization and Vaccine Preventable Diseases

UNICEF/Pirazzi

1
THE PROBLEM: The Need for Immunization only 42% of children 12-23 months
had received all six of their primary
A SIGNIFICANT Of global deaths among children, less vaccines, with a wide variation
PROPORTIONS than five years of age, a significant among states. States with poorer

OF DEATHS AMONG proportions die of vaccine preventable immunization rates generally have
diseases. These include 770,000 deaths higher child mortality rates (Figure 1).
CHILDREN, LESS due to measles and 200,000 deaths due
THAN FIVE YEARS to neonatal tetanus. Many of these A successful immunization program is an

OF AGE, ARE FROM children are already otherwise indication of a strong and functioning
compromised by malnutrition or other public health system. The low
VACCINE infectious diseases. immunization rates in India are a cause
PREVENTABLE of great concern.

DISEASES In a country like India, by vaccinating


1000 infants we can prevent about 30 Why are we not achieving
deaths from measles, 10 deaths from higher immunization coverage
whooping cough, and five cases of rates?
lifelong disability from polio.
Vaccinating 1000 women with tetanus There are several reasons that have
toxoid (TT) prevents five deaths from been put forward for poor immunization
neonatal tetanus. rates, both globally and in the Indian
context. According to
Immunization is one of the most cost- the Ministry of Health and Family
effective public health interventions Welfare, Government of India,
available. Yet, a large proportion of the main reasons for the low
vulnerable infants and children in immunization rates and poor vaccine
India are not receiving this simple effectiveness as identified by the
intervention. Across India in 1998-99, National Family Health Survey 1998-99

FIGURE 1
Childhood Mortality and Immunization in Selected States

160
Under 5 Mortality Rate/1000 Births

140

120
Vaccine Coverage %

100
Madhya Pradesh
Uttar Pradesh

80
Rajasthan

Andhra Pradesh

60
Orissa
Bihar

West Bengal
India

40

20

0
Vaccine coverage % U5MR

Source: National Family Health Survey 1998-99

2
(NFHS-II) and the qualitative surveys • Parental non-acceptance of A. The Immunological basis of
are the following:* immunization due to various Immunization
• Inadequate delivery of health reasons:
services (supply shortages, vacant o Lack of information/ Basis of Immunization
staff positions, lack of training) awareness of day/time/place Immunization is based on the principle
• Poor maintenance of the cold of immunization sessions that if the body is exposed in a
chain o Lack of awareness of the controlled manner to infective agents,
• Inadequate supervision and importance of/need for it develops the capacity to fight
monitoring of the program immunization infections in future. This ability is the
• Weak surveillance for all vaccine- o No one available to take a immunity status of the body against
preventable diseases except polio child to the sessions specific infection, and functions on the
• Injection safety not assured o Lack of faith in immunization inherent ability of the body to
• No provision made for medical o Doctors advising against recognise, fight and memorise its
waste disposal immunization in some cases actions against an infective agent.
• General lack of inter-sectoral
coordination, resulting in missing It is clear from the above list that the How does a vaccine protect an
opportunities to improve problem lies at various levels in the individual child?
immunization coverage and quality system, including planning, training, A vaccine contains an antigen, such as
• Date, place, and time of implementation and monitoring of the a bacteria or virus or part of the
immunization sessions varied, program. Some of these relate to organism that is capable of provoking
making it difficult for parents to inadequate resources; some to an immune response in the body. Upon
access services inadequate use of available resources; administering the vaccine, there is an
• Inadequate technical capacities either due to poor knowledge and immune response in the body similar
among service providers, such as a training or due to inadequate to that of the original microbe. The
lack of clarity on proper methods management systems. This section will vaccine however, does not cause the
of reconstitution of vaccines, and attempt to fill the information gaps disease, and the immune response to
the administration of intradermal and to provide a rational basis for the antigen protects the body from any
injections strengthening the operational aspects invasion by such a microbe in the
• Complacency, for several reasons of the program. future.
such as the belief that since some
disease are not common they are
not important, or a mistaken
belief that measles is common and
therefore not a dangerous disease
• Lack of support for ANMs from
other staff at the health centers.
• Lack of updated information,
education and communication(IEC)
materials.

* Introduction of Hepatitis B Vaccine in the Source:


Universal Immunization Programme: Immunization
A Handbook for Programme Managers and in Practice.
WHO/EPI/
Medical Officers. Child Health Division,
TRAM/98.12
Department of Family Welfare, Ministry of
Health and Family Welfare, Government of
India; July 2002. A child being given an intramascular injection.

3
Infection: What is it?
We live in an environment full of millions of kinds of microorganisms — germs that are too small to see with the naked eye.
These microorganisms are of different types — viruses, bacteria, fungi, single-celled parasites and a few others. Some of them
live on and in us, coexisting happily on our skin, and in our mouths, noses, intestines and other surfaces. Most of them do not
harm us in the normal course of life. Sometimes, however, we become unwell because one or another microorganism, capable
of causing harm gets into the body. We say that the person has been infected by the microorganism. The manifestations of the
infection, such as fever or pain or swelling are symptoms that tell us that the person has a disease. Some examples of common
infections are:

• Caused by viruses, such as common cold, measles, hepatitis, rabies, AIDS


• Caused by bacteria, such as abscess, cholera, typhoid, tuberculosis, whooping cough
• Caused by fungi, such as candidiasis (or thrush), ringworm
• Caused by single-celled parasites, such as malaria, amebiasis

Immunity: Our defence against infections


Every animal, including human beings, have a natural defence against infections, without which survival would be impossible.
This natural defence comes from a system in the bodies of animals called the immune system. “Immunity” is the protection
that the immune system provides us.

The immune system: The immune system consists of various kinds of cells, including mostly white blood cells. The basis for
immunity is the ability of some of the cells of the immune system to recognize any other cells or parts of cells that they come
in contact with as “self” or “not-self” — as “part of my own body” or “something foreign”, and the ability of the immune
system to capture and destroy what is foreign, while leaving alone what belongs to the body.

The Antigen: Identification markers that enable immune cells to say whether a substance is its own or foreign, are molecules,
usually made of protein, that are present on the surface of (or sometimes inside) every cell. The shapes of these molecules are
unique for every organism, and the immune cells can recognize shapes that are different from those of similar molecules on
the body’s own cells. Molecules that are recognized by the immune system as foreign are called “antigens”.

Antibodies: Once an antigen is recognized as foreign, the immune system begins a process of capturing, isolating and
destroying the foreign material. For doing this, it may use other molecules that combine with the antigen and make it easy to
destroy. These molecules produced by the immune system (to match in shape with part of the foreign molecule, much like a
key fitting into a lock) are called “antibodies”. At the same time, the immune system may also produce special cells capable of
capturing and destroying that particular antigen. For some infections, the antibodies produced are the main defence (such as
against measles), and in the case of other infections, the special cells are the main defence (such as against tuberculosis).

Immunity is specific: Since antigenic molecules are usually unique to a particular organism, the antibodies and cells that the
immune system produces are helpful against only that organism. Usually, the immune system is able to memorize the
characteristics of the antigen, and respond very rapidly when the same antigen enters the body at a later date. This is why we
generally do not get second attacks of some of the infectious diseases, such as measles or tuberculosis. In some cases, the body
produces large amounts of antibodies that last a long time, and in other cases, just remembers the antigen and produces cells
or antibodies only when the antigen enters the body again.

As a child gets older, she gets exposed to more and more organisms in the environment, and her immune system learns to
recognize and destroy each of them. This is why children suffer so many common infections when young, but later become
immune to the same infections. We use this ability of the immune system to recognize and destroy an antigen to protect
ourselves against certain infections with the use of vaccines. A vaccine contains antigens of a particular organism and provokes
the immune system to recognize, remember and produce antibodies and cells that can destroy that antigen, if and when the
organism enters the body at a later date.

Types of immune response: When the immune system learns to recognize and respond to an antigen, we call it active
immunity; when readymade antibodies are injected from outside, such as for the treatment of diphtheria or tetanus, we call it
passive immunity. Another example is the way a newborn baby is born with a number of different kinds of antibodies acquired
from the mother from across the placenta, or the way it later gets antibodies from the breast milk of the mother. While active
immunity is the ability to remember an antigen for a long time, passive administered antibodies have a short life span of a few
weeks or months, since they themselves are destroyed over a period of time.

Abberations of the immune sytem: The immune system is not perfect, however, and immunity acquired may be partial (such
as against malaria). In some cases, the immune system may itself be the target of the infection, such as in the case of the
Human Immunodeficiency Virus (HIV) that causes AIDS. Here, the body’s ability to fight other infections becomes badly
affected, and the person gets infected by organisms that normally would not be able to cause disease.

4
Types of Vaccines

• Live attenuated vaccines are derived from disease-causing viruses or bacteria that have been weakened under laboratory
conditions. They will grow in vaccinated individuals, but because they are weak, they will cause either no disease or only a
mild form. Examples: BCG, OPV, Measles vaccines.

• Inactivated vaccines are produced by growing virus or bacteria and then inactivating them with heat or chemicals.
Because they are not alive, they cannot grow in a vaccinated individual. Inactivated vaccines may be whole-cell or part of
a cell, or they can be an inactivated toxin (toxoid). Examples: Inactivated Polio vaccine (IPV), DPT vaccine.

Both types of vaccines are difficult to “purify” completely, that is, to ensure that they contain only those antigens that are
completely safe and effective. Vaccines that are not pure tend to produce more undesirable effects, which are difficult to
predict. In order to make vaccines safer, it is desirable to include only that antigen which is needed. This can be achieved using
recombinant DNA technology, where DNA molecules from unrelated cells are used to produce the specific antigenic protein.
Such vaccines are called recombinant vaccines. Hepatitis B vaccine is an example of a recombinant vaccine. It is possible that
in the future, most vaccines will be recombinant vaccines, and the existing live and inactivated vaccines will be phased out.

How does an immunization rare to see epidemics in communities It also does not work where the
program protect a whole where a large proportion of individuals transmission of infection does not
community? are immunized. This phenomenon is involve another case, such as tetanus.
Many infections pass from person to called herd immunity, just as a herd of
person, either by direct contact or animals provides protection to weak Variance of the Schedule
through breathing in organisms individuals within. Women who have received three doses
breathed or coughed out by an of DPT during childhood or additional
infected individual. This chain of Herd immunity works best where close doses of tetanus toxoid-containing
infection can continue as long as there contact is necessary for transmission of vaccine during their school years do not
are non-immune, vulnerable the infection, such as in measles. need all five doses of tetanus toxoid
individuals in the community to catch It does not work where all individuals (TT) in adulthood for protection. They
and pass on the infection. are equally exposed to a common must retain their vaccination cards for
source of infection, such as an health workers to determine the
When a few individuals are vaccinated, epidemic of typhoid or hepatitis from a number of additional doses they need.
they are protected from the infection, contaminated drinking water source. Continued on page 9...
while the non-immune individuals
continue to catch and pass on the
TABLE 1
infection among themselves. As more Vaccines Used in Immunization Programs in Developing Countries
and more individuals are vaccinated,
Vaccine Type Supplied As
it is possible to reach a stage where
BCG Live attenuated A dry powder in a glass vial, reconstituted in
the remaining non-immune individuals bacteria normal saline (the supplied diluent) before use*
are also protected, as long as there are OPV Live attenuated A liquid form in a plastic dropper bottle
enough immune individuals in the viruses

chain of infection between the person Diphtheria Toxoid DPT/DT, a liquid in an injection vial

who brings in the disease into the Pertussis Killed bacteria DPT, a liquid in an injection vial
Tetanus Toxoid DPT/DT/TT, a liquid in an injection vial
community and the non-immune
Measles Live attenuated Dry powder in a glass vial, reconstituted in double
individuals in the community. viruses distilled water (the supplied diluent) before use*

DPT: A mix of toxoid of Diphtheria, Pertussis bacteria and toxoid of Tetanus


While this does not provide perfect DT: Diphtheria and Tetanus toxoids
individual protection (since the non- TT: Tetanus toxoid
OPV: Oral Polio Virus
immune may at times chance to come *The diluents for BCG and measles are not interchangeable
in contact with a diseased person), it is

5
The Vaccine Preventable Diseases

Vaccines are available against a number of diseases, but as per the national immunization schedule, six diseases have been
identified as the ones which are vaccine preventable and as the ones which contribute significantly to infant mortality and
morbidity. The diseases are tuberculosis, diphtheria, pertussis (whopping cough), tetanus, poliomyelitis (polio) and measles.
Features of Vaccine Preventable Diseases

Tuberculosis (TB) disease and gives them some Prevention: The most effective way
protection against recurrence at a is through immunization of children
later age. BCG does not prevent TB in their first year of life with three
itself and provides little protection doses of diphtheria toxoid (available
against the pulmonary forms. It is in the form DPT), which provides
not recommended for adults. over 95% protection against
diphtheria for at least 10 years.
Diphtheria
Pertussis (Whooping Cough)

A bacterial illness causing chronic


disease that affects people of all
ages, it is one of the most important
public health problems worldwide.

TB usually attacks the lungs, but


almost every organ of the body can
be affected, including the bones, A bacterial infection, mainly of the
joints, and brain. upper respiratory tract, where the A bacterial infection of the lower
major symptoms are produced by a respiratory tract.
Case Definition*: A patient in whom toxin released by the organism.
TB has been bacteriologically Case Definition*: A person with
confirmed, or has been diagnosed by Case definition*: An illness cough lasting at least two weeks
a clinician. characterized by laryngitis or with at least one of the following:
pharyngitis or tonsillitis and the • Fits of coughing
Transmission: Spread through the presence of adherent membrane of • Intake of breath accompanied
air when an infected person coughs, the tonsils, pharynx and/or nose. by a whooping sound
spits, or sneezes. Spreads rapidly • Vomiting immediately after
where people live in crowded Transmission: Spreads easily through coughing and without any other
situations, are poorly nourished, and the air by droplets (from sneezing apparent cause.
cannot obtain treatment. and coughing) and secretions from
the nose, throat, and eyes of an Transmission: Spread by droplets
Morbidity and Mortality: Nearly two infected individual. from the nose and throat of an
million people die from TB each infected person; spreads easily
year. Nearly 1% of the world’s Morbidity and Mortality: In 1999, among susceptible people who live
population is newly infected with TB according to the World Health in crowded conditions.
each year. Organization (WHO), approximately
5,000 cases of diphtheria were Morbidity and Mortality: Eight
Prevention: BCG vaccine protects reported worldwide. Between 5% percent or more of unprotected
infants with TB from progressing to and 10% of patients die, even with children get pertussis, and 1%
a more dangerous form of the treatment. percent of those who get the disease

6
die. It causes an estimated 300,000 stiff or has spasms (i.e. jerking of Case Definition*: Any child under
deaths per year. Newborns get very the muscles), or both. fifteen years of age with acute
little protective antibodies from the flaccid paralysis (AFP) or any person
mother, and even very young infants Transmission: Organism enters the with paralytic illness at any age
can get infected. A third of all cases body of a newborn by the traditional when polio is suspected.
are less than 6 months old, and half practice of applying dung, mud,
of all deaths from pertussis are dirt, plant powders or ash on the Transmission: Highly communicable,
infant deaths. umbilical cord stump or when transmitted through person to person
unclean instruments are used for contact with infected feces or
Prevention: The most effective way cutting the umbilical cord. It is not secretions from nose and mouth.
is to immunize children with three spread from person to person.
doses of DPT within the first year of Morbidity and Mortality: All non-
life. Immunization against pertussis Morbidity and Mortality: Every year, vaccinated individuals will acquire
is not fully protective in all children, 200,000 infants die from tetanus in the infection if the virus is in the
but helps reduce severity of the their first month of life. The case environment.
disease, and thus to prevent fatality is approximately 80%. Only • 95% infections are silent (show
malnutrition. It also helps prevent 5% of cases are reported. no effect), 4% have mild flu-like
epidemics by inducing herd illness.
immunity. Antibiotics may be given Prevention: Elimination of neonatal • 1% become paralyzed or lame,
to shorten the period of tetanus (reducing incidence to less 0.5% will be lame for life.
communicability. than 1 case per 1000 live births). • 0.1% will die during the acute
• Giving 3 doses of tetanus toxoid phase.
Tetanus (TT) to at least 80% of all women
of childbearing age at the There has been a 99% decrease in
highest risk, preferably to all the number of confirmed polio cases
women. due to the worldwide Polio
• Health education and promotion Eradication Initiative (PEI). Wild
of clean delivery practices poliovirus is only present in 7
focusing on the “five cleans”: countries, of which three nations
clean hands, clean delivery (India, Nigeria and Pakistan) account
surface, clean thread and clean for 99% of cases.
blade to tie and cut the umbilical
cord, and a clean cord, to which Prevention: Polio Eradication
nothing is applied. Strategies
A bacterial illness usually following • Routine immunization — all
contamination of wounds by soil or Poliomyelitis (Polio) countries should immunize at
feces, where the damage is done by least 90% of infants in the first
a toxin released by the organism. year of life with four doses of
While any unimmunized child can be Oral Polio Vaccine (OPV). This
infected, the commonest incidence should continue regardless of
in developing countries is in the other immunization drives.
neonatal period following unsafe • Supplementary immunization —
childbirth. through national immunization
days (NIDs) all children less than
Case Definition of neonatal five years of age should receive
tetanus*: Any neonate with a normal OPV, regardless of their previous
ability to suck and cry during the immunization status.
first two days of life, and who, A viral illness, introduced through • Acute flaccid paralysis
between three and 28 days of age, the gastrointestinal tract, affecting surveillance and laboratory
cannot suck normally and becomes mainly the central nervous system. investigation — to ensure that

7
all cases are detected and to Rapidly transmitted in large Transmission: Child-to-child
investigate stool samples for families, crowded homes, urban transmission through open wounds or
identification of wild poliovirus. areas and schools. shared implements that contain
• Campaign approach — to blood or body fluids, accounts for the
eradicate polio the system of Morbidity and Mortality: Kills an majority of infections world wide.
all or non is followed. It is estimated 770,000 children each Exposure of babies to maternal blood
based on the fact that if all year. The high risk of death is or other fluids during delivery if she
children are immunized related to young age, crowding, is a carrier, use of contaminated
together at the same point the malnutrition, pneumonia, acute and needles and syringes for injections
replacement of the wild virus chronic diarrhea, dysentery, and transfusions and transmission
by vaccine virus will take place blindness due to concurrent vitamin through sexual activity are other
simultaneously leaving no point A deficiency, and lowered resistance methods.
source of remaining wild virus. to other infections, including TB.
The risk of death is very high in large Prevention: Hepatitis B vaccine is
The campaign approach is epidemics, and these are common due to be phased in under the GAVI
done through: where immunization coverage is low. initiative. WHO recommends that
o National immunization days Infection with measles depresses the hepatitis B vaccine be offered to all
o Mop-up campaign. Mop up immune system, depletes the body’s children under one year of age in all
rounds in areas that have store of vitamin A, and leaves countries. Hepatitis B vaccine is
reported polio cases or for children susceptible to diseases like usually given as a 3-dose series, with
difficult to reach children pneumonia and diarrhea. Prolonged each dose at least 4 weeks apart.
in areas where wild polio and severe illness can lead to severe
virus transmission is malnutrition.
occurring. Hepatitis B is currently not on the
Prevention: Measles vaccination is primary immunization schedule in
Measles one of the most effective preventive India, but is being introduced in a
measures available. All children phased manner.
should be immunized with a dose of
measles vaccine within first year of
life. Maternal anti-measles
antibodies, passed while in the
womb, provide immunity to infants
against measles infection until they
are at least 6 months of age. With
the mother’s antibody still present,
the vaccine virus may be unable to
multiply to produce enough
A viral illness, mainly of the antibodies in the system, leaving the * Case definitions given here are the
respiratory tract. child still susceptible. The WHO clinical case definitions used by
recommended age for measles public health systems to monitor the
Case Definition*: Any person in vaccination in developing countries occurrence of these diseases. The
whom a clinician suspects measles is therefore nine months. definitions are broad, allowing all
infection, or any person with fever likely cases to be accounted for or
and maculopapular rash and cough, Hepatitis B suspected. Many cases suspected on
runny nose or conjunctivitis (i.e. red Hepatitis B is a viral infection of the the basis of these definitions will turn
eyes). liver. If not fatal, acute infection out to be some other disease when
either resolves or progresses to examined and tested individually.
Transmission: Extremely infectious, chronic infection, which may lead to These are not necessarily criteria used
transmitted by respiratory droplets cirrhosis or liver cancer several by doctors to definitively diagnose and
expelled by infected individuals. decades later. treat individual patients.

8
TABLE 2: Immunization Schedule for Children Followed in India

Age Vaccine Dose Route Site

Birth BCG 0.05 ml Intra-dermal (within skin) Left upper arm

OPV0 2 drops Oral Mouth

6 weeks DPT1 0.5 ml Intra-muscular (in the muscle) Outer part of mid-thigh

OPV1 2 drops Oral Mouth

10 weeks DPT2* 0.5 ml Intra-muscular (in the muscle) Outer part of mid-thigh

OPV2* 2 drops Oral Mouth

14 weeks DPT3* 0.5 ml Intra-muscular (in the muscle) Outer part of mid-thigh

OPV3* 2 drops Oral Mouth

9 months Measles 0.5 ml Sub-cutaneous (under the skin) Outer part of mid-thigh

Vit A 100000 IU Oral Mouth

18-24 months DPT 0.5 ml Intra-muscular (in the muscle) Outer part of mid-thigh

OPV 2 drops Oral Mouth

5 years DT 0.5 ml Intra-muscular (in the muscle) Outer part of mid-thigh

Source: Adapted from Handbook for Vaccine Administrators, Child Health Division, MoHFW, GOI
* The minimal interval between doses should be 28 days (4 weeks).

Are vaccines safe? Does


TABLE 3 immunization produce any adverse
Tetanus Toxoid Immunization Schedule (Women of Child Bearing Age) effects?
Dose When to give Expected Duration of Vaccines for childhood diseases are very
Protection safe — serious adverse effects are
TT1 As early as possible in pregnancy, or at first extremely rare.
contact when a girl reaches childbearing age None

TT2 At least 4 weeks after TT1 One to three years However, adverse events following
immunization can occur even in the
TT3 At least six months after TT2 or in next pregnancy Five years
safest of programs. There is an active
TT4 At least one year after TT3 or in next pregnancy 10 years
surveillance program monitoring
TT5 At least one year after TT4 or in next pregnancy All child bearing years
adverse effects of vaccines.
Source: WHO
Childhood infectious diseases are a far
Continued from page 5... vaccine on the same visit. Similarly, it is greater health risk to children than
It is safe and effective to administer important that pregnant women be adverse effects of vaccines.
all EPI vaccines on the same day at given TT immunization whenever they
different sites of the body. It is also a present for a health visit, regardless of Causes of adverse events are classified
health priority for the individual child trimester. under the following categories:
and the community, for health services 1. Program error: An error in vaccine
to maximize opportunistic The vaccination schedule should preparation, handling or
immunization. A previously un- not be restarted from the beginning administration such as injecting in
immunized child presenting at 9 even if the interval between doses has the wrong place, using unsterile
months of age, would therefore exceeded the recommended interval by equipment or giving the wrong
receive BCG, DPT, OPV and measles months or years. vaccine.

9
2. Vaccine reaction: The reaction of TABLE 4: Vaccines and their Adverse Effects
a particular individual to the Vaccine Normal reaction Adverse effects1
properties of the vaccine. These
BCG After injection a small raised Swelling of the glands in the armpit or
can be: lump appears which disappears near the neck, or a sterile abscess2
a) Local reactions such as pain, in 30 minutes. It is followed by
a small red sore in 2 weeks,
swelling at the site of the
which heals in the next few
injection; weeks leaving a small scar
b) Systemic or generalized OPV None No common side effect.
reactions such as fever, Vaccine associated paralysis occurs very
rarely — in approximately 1 in 2400000
headache, loss of appetite; or
doses administered
c) Allergic reactions which are
DPT — Mild fever3 Local swelling and pain4
the most serious and most — Soreness Rarely, high fever and prolonged crying.
rare reactions. Very rarely neurological complications,
3. Coincidental: The adverse event including convulsions 5

occurs after immunization has Measles None Mild fever and rash lasting for 2-3 days
appear a week after immunization in
been given but is not caused by
10-15% of vaccinated children
the vaccine or its administration.
1
In addition to the mentioned adverse effects, any injection given with an unsterile syringe or
4. Unknown: The adverse event
needle can cause a local infection, including an abscess. Similarly, any vaccine (just as any medicine
cannot be directly related to the or even food item) can in rare cases cause severe allergic reactions.
2
This is either due to an excess dose or because it is injected subcutaneously and not intra-dermally
vaccine, its administration, or 3
Fever beginning after 24 hours is unlikely to be due to vaccination
any identifiable cause. 4
This may be because the vaccine was not injected into the muscle, or due to the use of frozen
vaccine.
5
This is due to the whole-cell pertussis component in the currently used vaccine. Acellular vaccine
Table 4 alongside lists the adverse has far milder side effects, but the vaccine is expensive.
effects of vaccines.

TABLE 5: Common Mistakes in the Immunization Program

Health Worker Practice Possible improvements


Screening: Lack of proper screening of children and women for Improve screening. Check children’s and woman’s immunization
immunization status status every time a client visits a health facility or outreach site,
regardless of the reason for the visit. Encourage mothers to bring
immunization cards every time they visit a health facility. This
will help determine eligibility for immunization and avoid missed
opportunities.

False beliefs: Sometimes, there is a belief on the part of health Train vaccinators to give all vaccines due at the time of client’s
workers or parents that giving too many vaccines at once will visit. For example, a nine-month old child may be given DPT and
harm a child. Some health workers mistakenly delay the measles OPV and measles vaccine. Vaccines are as safe and effective in
immunization because they believe that it must be the last combination as they are individually
immunization given to the child

False contraindication: Both health workers and parents may Eliminate false contraindication. Children with low-grade fever,
hesitate to immunize a sick child, though there are few true a cold, diarrhea, vomiting, or other mild illness can safely be
contraindications to immunization. vaccinated. Prematurity, LBW, and breast-feeding are not reasons
to withhold immunization. Malnourished children must be
immunized because they are much more likely to die from a
vaccine preventable disease.*
Multi-dose vials: Health workers often hesitate before opening Clarify policy on multi-dose vials. Governments (central or
vaccine for one or a few clients for fear of running out of state) need to set out policies on when to open multi-dose vials
vaccines before the next delivery. and when to continue using them on following days.

* It is only ethical that severely malnourished or sick children contacted during an immunization session be referred and/or treated appropriately.

10
Immunization in the Presence of HIV

Children with HIV infection have compromised or weakened immune systems. Live attenuated vaccines are a risk because
the vaccines can cause a form of the disease. Children with weakened immune systems may not be able to fight off even a
mild infection. The disease that the vaccine is intended to prevent may be very severe in HIV-infected children. The risk of
the disease must be balanced against the risk of the effects of the vaccine. In addition, most infants and children with HIV
do not show symptoms, so it is difficult to know if they should be excluded from a particular vaccine injection.

Taking these factors into account, the WHO recommends the following with respect to the vaccines that present the
greatest threat to HIV-infected children:

BCG: Should be given to all infants, even if their mothers have HIV, unless the infant shows HIV/AIDS symptoms, which is
highly unlikely. This practice will protect HIV-positive and negative children who are at high risk of exposure to tuberculosis
because their mothers are HIV-infected, and so are likely to have tuberculosis as well.

OPV: Children without HIV/AIDS symptoms should be immunized with OPV according to standard schedules.

Measles: As measles infection can be very severe in HIV-infected children, an early dose at six months is recommended,
followed by the scheduled dose at nine months for those who are known to be infected with HIV. The overall risk of adverse
events from the vaccine is relatively low compared with the risk of measles infection in HIV-infected children. Children
should not be screened for HIV antibody status before receiving measles vaccine.

Note: These are current recommendations at the time of preparing this guide and may be subject to change.

Reconstitution of vaccine
Injection Sites for immunizations
Use a sterile syringe and needle to
remove diluent from its ampoule to Intramucular
reconstitute freeze-dried vaccine. Subcutaneous
Intradermal

Always use the diluent provided by the


manufacturer for that same vaccine
Dermis (skin)
for reconstitution, and maintain at a
Subcutaneous
temperature of +20 to +80 C. layer

Take the whole amount of diluent for Muscle


reconstitution.

Once reconstituted, wrap the vaccine


vial in the foam pad from a vaccine
carrier, in paper, or in foil to protect it
Delivery of vaccines
from direct sunlight. All vaccines, except polio (OPV) which is delivered orally, are delivered by
injection. For the delivery of the vaccine the site of the injection varies.
Keep the wrapped vials on ice. • BCG vaccine for TB is given intradermally i.e. within the skin.
• DPT is given intramascularly i.e. within the muscle.
Appropriately dispose reconstituted • Measles is given subcutaneously.
vaccines (i.e. vaccines should not be A combination of vaccines can be given together but only the site of the
preserved for re-use, 6 hours after vaccine and the needle and the syringe used should be different.
reconstitution).

11
B. Operational Guidelines and use individual volunteers (e.g. Change 2. Reducing Drop-Outs
their Basis: Improving Agents) and community-based groups If a child does not receive all the doses
Immunization Coverage and (e.g. Self Help Groups) to assist in this required for full protection, the
Quality effort. resources that have been used to
partially vaccinate that child are
I Improving Immunization Improving and expanding outreach: mostly wasted.
Coverage Outreach must be well planned,
organized and supported. Vaccines, Program Mangers should regularly
What approaches improve the use sterile syringes and needles, vaccine monitor the dropout rate of their area,
of immunization services? carriers, ice packs, and other supplies find out causes and take measures to
1. Reaching the unreached by: must be available in the right amount, solve the problem. The causes may be
Ensuring no one is left out: It should in the right place, and at the right related to vaccine and other essential
be possible to account for every family time. To maximize utilization of limited supplies (e.g. vaccine stocks), or to
and child in the catchment area of a resources and to assure continuity of communication and community
program, especially where preventive outreach services strategies must merge awareness (e.g. unaware of the need
health services are universally available other services with immunization on a to return), or some other obstacles
without a fee. This has been achieved single fixed day at a fixed site known to (e.g. timing of the session).
in programs through meticulous periodic the community in advance (e.g. Vitamin
surveys and the use of area maps A supplementation, antenatal care and 3. Improving a community’s
owned by communities (social maps). other health services). participation to receive primary
immunization services
Improved scheduling: Immunization Targeting services to meet urban People usually use immunization
sessions should be scheduled to be needs: Vaccination coverage is usually services if they know what services are
convenient for parents. Session lower in high-risk urban areas. Reaching offered and where and when they are
schedules for any facility should be the unreached urban slum population is available.
reviewed at least once in a year and very important because:
changed (if necessary) to reflect the a. Population density increases the Discuss immunization services with
current needs of the community. intensity of disease transmission communities in each service delivery
b. Measles and pertussis often begin area. If people are not coming to
Raising awareness: Families need to in cities and towns and then spread sessions, or if too many people are
know about the immunization services to rural areas attending, the days or times of the
before they can use them. Local health c. The poor sanitation and poor immunization sessions may need to
workers play an important role in nutrition found in densely change. Immunization sessions can be
increasing community awareness and populated slums increases their risk held conjointly with other health
creating demand for services. They can of severe illness. events such as fixed-service days to
improve access. Families will return to
receive immunization if they know
For outreach, when there is a shortage of staff, scheduling visits to when to come back, have been treated
individual villages every two months instead of every month permits respectfully, and have confidence that
health workers to reach twice as many villages, provided high they will receive the immunizations
coverage is achieved at each visit. The prolongation of the interval that they come for.
between two doses of DPT/OPV vaccines or delay in measles vaccine
by a month in all villages under such circumstances is far less harmful Table 6, page 13 lists obstacles to
than reaching only some of the villages regularly and the rest not at routine immunization and potential
all or very infrequently. solutions.

12
TABLE 6: Obstacles to Routine Immunization and Potential Solutions

Obstacles to Immunization Potential Solutions


Lack of information • Health education sessions
• Home visits by health workers
• Regularly updates and reconciliation of records/registers used by health workers
• Use of community volunteers
• Use of community based organizations
Poor services • Better planning of sessions
• Training of vaccinators
• Accurate ordering of vaccine and improvements in logistics
Time constraints • Health education for parents
• Better session scheduling
Social, cultural or political barriers • Better planning
• Health education
• Use of Community Based Organizations/ NGOs
• Use of Change Agents
Misinformation • Health education
• Use of Community Based Organizations/ NGOs
• Use of Change Agents
Distance • Planning immunization services to cover all families in the catchment area
• Better scheduling of sessions

II Improving the quality of


immunization services

Cold Chain, Vaccine Storage and


Supply
What is a Cold Chain?
The equipment, people and procedures
that keep the vaccines cold enough to
remain viable during their journey
from the site of manufacturing to the
TABLE 7: Vaccine Vulnerability
point of use is called a “cold chain”.
Some vaccines are more sensitive to Vaccine Exposure to heat/light Exposure to cold Temperature
heat and light and some are more
BCG Relatively heat stable but Okay to freeze +2°C to +8°C
sensitive to cold. If a vaccine is sensitive to light
exposed to too much heat, light, or
OPV Sensitive to heat and light Okay to freeze +2°C to +8°C
cold, it can be damaged and lose its
Measles Sensitive to heat and light Okay to freeze +2°C to +8°C
potency or effectiveness. See Tables 7
and 8 for details. DPT Relatively heat stable Freezes at -3°C
Should not be frozen +2°C to +8°C

Hepatitis Relatively heat stable Freezes at - 0.5°C


What is Injection Safety?
B Should not be frozen +2°C to +8°C
A safe injection is defined by the WHO
TT Relatively heat stable Freezes at - 3°C
as one that:
Should not be frozen +2°C to +8°C
• Does not harm the recipient
• Does not expose the health care Source: Handbook for Vaccine Administrators, Child Health Division, MoHFW, GOI
worker to any avoidable risk
If DPT, TT, DT and Hepatitis B vaccines are frozen they lose their potency and, therefore,
• Does not result in waste that is should be discarded. The “Shake Test” can determine whether DPT, DT, TT or Hepatitis B
dangerous to the community. vials have been frozen.
Continued on page 15...

13
Shake Test Shake vials vigorously for 10 seconds and place them on
Take a vaccine vial of the same type, manufacturer and batch a flat surface. Continuously observe their rate of
number as the vaccine vial you want to test. Freeze the vial for sedimentation for 20 minutes.
at least 10 hours at –10°C until the contents are solid, and then
Compare the deliberately frozen vial next to the suspect vial
let it melt. This is the “control” sample and should be labeled
as “frozen” to avoid its use for vaccination.
Deliberately Frozen Suspect
Then take a vaccine vial from the batch that you suspect has been Control Vial Test Vials
frozen. This is the “test” sample. Vigorously shake the control and
test samples for 10 seconds, place both vials on a flat surface to USE THIS VACCINE
If the sendiments in
rest, and continuously observe them over the following 30 minutes. the suspect vial
settles more slowly,
View both vials against the light to compare the rate of the suspect vaccine
sedimentation. If the test sample shows a much slower may be used
Almost
sedimentation rate than the control sample, the test sample has Clear
DO NOT USE THIS
probably not frozen and may be used. VACCINE
Thick
If the sendiments in
However, if the sedimentation rate is higher and the test sample Sediment
the suspect vial settles
contains flakes, the test sample has probably been damaged by at the same rate and
freezing and should be withdrawn from use. The health worker contain flakes, the
suspect vaccine may
must notify the supervisor immediately to ensure that any other NOT be used
damaged vials are also identified and withdrawn from use.

TABLE 8: Basic Features of Cold Chain Equipment

Equipment Place Temperature Utilization Holdover time* Storage capacity

Ice Lined Regional Store +2°C to +8°C BCG, DPT, TT, Hep-B At 43°C 62 hrs after 60,000 doses (mixed
Refrigerator & District H.Q. vaccine 8 hrs continuous antigen) & 20,000
(ILR) 300 Liters power supply doses of OPV

ILR 140 Liters PHC +2°C to +8°C BCG, DPT, TT, Hep-B At 43°C 62 hrs after 25,000 doses (mixed
vaccine 8 hrs continuous antigen) & 18,000
power supply doses of OPV

Deep Freezer Regional Store -20°C Preparation of ice packs, 4 hours 150,000-200,000
300 Liters & District H.Q. OPV & Measles vaccine doses

Deep Freezer PHC -20°C Preparation of ice packs At 43°C 62 hrs after Approximately
140 Liters 8 hrs continuous 20 Ice Packs
power supply

Cold Box State, +2°C to +8°C All vaccines can be stored 5 days 52 Ice Packs & 6000
20 Liters Regional and for transportation or in doses of mixed
District H.Q. case of power failure antigens

Cold Box District H.Q.& +2°C to +8°C All vaccines can be stored 3 days 20 Ice Packs & 1500
5 Liters PHC for transportation or in doses of mixed
case of power failure antigens

Vaccine Carrier Sub-center +2°C to +8°C All vaccines can be carried 24-36 hours 4 Ice Packs &15-20
(1.7 Liters) in small quantity for vials of mixed
vaccination sessions antigens

Day carrier Sub-center +2°C to +8°C All vaccines can be carried 6-8 hours 2 Ice Packs & 6-8
(0.85 Liter) in small quantity for vials of mixed
vaccination sessions antigens

* Holdover time in case of power failure


Source: Operations Guide for Program Managers, Child Health Division, MoHFW, GOI

14
BCG, OPV and Measles vaccines will lose their potency when exposed to too much heat or light. The damage of heat
and light is cumulative and cannot be reversed by re-freezing the vaccine. It is important therefore to maintain the
proper temperature for all vaccines when carrying them from the PHC to the immunization site.

What is a Vaccine Vial Monitor (VVM)? How to pack vaccines in the Vaccine Carrier

A VVM is a small colored disk printed on a vial label or for freeze-dried vaccine • Remove ice packs from the freezer and keep
placed on the vial cap. A square inside the disk darkens irreversibly when them outside for 15 minutes until they begin to
exposed to heat over time. By comparing the color of the inner square to that “sweat”. This prevents accidental freezing of
of the outer ring, users can determine the extent to which the vaccine inside vaccines that may come in contact with the
has been exposed to heat. VVMs have been available on all vials of OPV. ice packs.
• Place ice packs into the vaccine carrier along
When health workers use VVMs correctly, they can: the sides
• Identify heat-damaged vaccine and discard it • Place OPV and BCG vaccine inside the vaccine
• Avoid unnecessarily discarding vaccine because of suspected heat exposure carrier near the ice packs along the walls
• Extend accessibility to vaccinations in remote areas beyond the reach of • Wrap DPT, DT, TT and Hepatitis B in thick paper
the cold chain and then place them in the vaccine carrier,
• Monitor the amount of vaccine discarded due to excessive heat exposure away from the ice packs
• Identify cold chain problems • Close lid securely

Dos and Don’ts to maintain proper temperature of vaccine in the field

Dos Don’ts

• Keep the Vaccine Carrier in the shade • Don’t leave the Vaccine Carrier in sunlight
• Keep opened vials of Measles, OPV, and BCG on an ice • Don’t leave the lid open
pack • Don’t drop or sit on the Vaccine Carrier
• Keep the lid of the Vaccine Carrier always closed during • Don’t carry vaccine in handbags
the session • Don’t keep DPT, DT, TT, and Hepatitis B vaccines on the ice
• Keep the lid of the Vaccine Carrier on in transit pack during the session

Continued from page 13... Types of syringes and needles used reuse them without adequate
In developing countries, 16 billion for immunization sterilization. Since they cannot be
injections are given annually; of which Sterilizable (reusable) syringes and properly sterilized, they are a
50% are unsafe causing dangerous needles: These syringes are usually potential public health hazard, and
health risks to recipients, health made of glass (or plastic) and the WHO recommends that they not be
workers and the public. needles all-steel. After use, they used by public health programs for
should be immersed in an antiseptic immunization.
Why is injection safety important? solution, before being thoroughly Auto-disable (A-D) syringes: A pre-
The first rule of health care is “First do rinsed and cleaned in water and sterilized and pre-packed syringe with
not harm”* . Unsafe injection practices sterilized in a steam sterilizer. After a fixed needle and plastic cap,
can cause transmission of serious many rounds of use, reusable syringes designed to get locked after a single
infections like HIV, hepatitis B and C. and needles are also disposed off in use. These cannot be reused, and so
the same manner as single-use ones. are safer, but more expensive.
How can safe injection be ensured? Pre-filled, single dose, non-reusable
There are different methods of Single use syringes and needles: devices: Similar to the A-D, but pre-
ensuring safe injection practices, the Standard disposables: Plastic syringes filled with vaccine, maintained in a
most important of them are by with steel needles (often with plastic cold chain, ready for use. The most
changing the practices of health care hubs) that are pre-sterilized and expensive, and least appropriate for
providers. See Table 9 on page 16. packed in a sealed package. These large immunization programs.
syringes have a potential for abuse,
* A part of the Hippocratic oath that doctors
are expected to take on graduation since unscrupulous practitioners may See Table 10 on page 16.

15
TABLE 9: How Safe Injection Practices Can be Ensured

Methods Safe Practices

Keep hands clean and the • Wash hands before preparing injection materials
injection site clean • Wash injection site with clean swabs and clean water

Use sterile injection equipment • Always use a sterile syringe and needle for each injection and during reconstitution
every time • If auto-disabled syringes are not available, sterilize equipment using steam sterilizer
• Document the quality of the sterilization process using time, steam, and temperature (TST)
spot indicators

Prevent contamination of vaccine • Designate a clean area for preparation of injection


and injection equipment • Always prick the cap of the vial with a sterile needle and syringe
• Do not leave the needle in the cap of the vial
• Discard any needle that has touched any non-sterile surface
• Do not touch the needle while pushing it into the injection site

Sterilise equipment before re-use • Assume that all used equipment is contaminated with body fluid of any form
• Re-sterilize equipment before re-use

Safe disposal of all sharps • Deposit used sharps (e.g. needles) in a safety box or a hard-board box or other puncture
proof and leak proof containers
• Dispose safely/handle the box/container containing used sharps carefully

Prevent needle stick injuries • Never re-cap a used syringe to avoid accidental needle-stick injury
• Place in a puncture and leak proof sharp container within reach of the vaccine administrator
• Put used syringes and needles in the sharp container immediately after giving an injection
• Seal the container when it is three-quarter full

Prevent public access to • Seal the sharp container before carrying to the designated area for disposal
used needles • Dispose off syringes and sharp waste, under close supervision of managers, in an efficient,
safe, and environmentally friendly way to protect the community from intentional and
accidental exposure to used injection equipment

Single-use syringes and needles


generate a large volume of potentially TABLE 10: When to use these syringes?
dangerous waste, which is difficult to
Single use syringes Reusable syringes
dispose of, particularly in developing
country settings. Appropriate for all immunization sessions Used for routine immunization.
but most useful during campaigns
to avoid repeated sterilization of syringes Appropriate for fixed site immunization,
and needles but not for campaigns

Safe for recipient of the vaccine Safe when proper cleaning and sterilization
can be ensured

If not properly disposed can pose high risk If not properly cleaned and sterilized can
to the population as they may be reused pose serious risk to the vaccine recipient

Use disposable syringes only where they Need replenishment only after certain
can be safely disposed after use period of time (may be used for an average
of 50 sterilizations)
Auto-disposable (A-D) syringe

16
How are used syringes and
Safe Handling and Disposal of Sharps needles disposed off?

To prevent needlesticks during transport or storage, sharps disposal


containers should be:
• Puncture proof and leak proof,
• Labeled with a warning that can be understood by local people, and
• Sealed so they remain closed when stacked

Do not fill sharps disposal containers completely full


When only three-quarters full, sharps disposal containers should be sealed
and discarded to prevent needlesticks that occur when the lid is pushed
down against an overly-full box, or when people must put their hands too
close to the points of contaminated needles. Sharps disposal containers
should be filled only once and discarded immediately to minimize risk of
needlesticks by workers who empty them.

Syringe safety box.

Safety Boxes: A safety box is a


puncture proof sharp container where
used syringes and needles are placed
immediately after injection. If a safety
Too Full 3/4 Full box is not available, health workers
Unsafe Safe
may use an alternative puncture proof
Needle Needle container, such as a pitcher or jug
Disposal Disposal
made of mud (burned) or plastic,
which should not be re-used. After a
session, the entire box can be
Filling sharps disposal containers more than three-quarters full may cause needlesticks. incinerated, or disinfected by burning
and buried.
Transporting contaminated waste
Transporting contaminated waste can expose others to disease and injury. Disposal Methods for syringes and
Consider the following points when transporting waste: needles

• Delays in the disposal of contaminated needles may increase the Incineration: Burning by heating to
occurrence of accidents. Containers should be collected for very high temperatures, this is
incineration or other forms of destruction (burn and bury) as soon as considered the best method that
possible at the end of the immunization session. reduces everything to ash. However,
incinerators are expensive to establish
• Contaminated needles should not be transferred from container to and maintain, and are not generally
container. available to public health programs in
developing countries.

17
Incineration can completely destroy
needles and syringes by burning at How to Build an Infectious Waste Burial Pit
temperatures above 800 C. The high
0

temperatures kill microorganisms and An infectious waste burial pit is


reduce the volume of waste to a easy to use and maintain, but
minimum. Properly functioning there are some disadvantages.
incinerators ensure the most A pit of this size can be difficult
complete destruction of syringes and to dig if the ground is hard, and
needles, and produce less air waste pits are not appropriate
pollution than burning at lower where heavy rains or floods are
temperatures. Some hospitals have common or where the water table

5m
on-site incineration, while others use is near the surface. And unlike
incinerators at other facilities, such as incineration or burning, burying
cement factories. safety boxes in a pit does not
reduce the volume of waste.
However, if a burial pit is the best
solution for your situation, this is
2m
the best way to construct the pit:

Materials needed for construction


• Tools (shovels, pickaxe)
• Concrete or corrugated on rings.
• Cement or nuts and bolts.

Building the pit (this pit has a capacity of 20 m3)


• Select a proper site for the pit
— Do not dig the pit close to water sources such as wells or spring
Source: MOH, Cambodia

water.
— The ground should be of low permeability.
• Dig a hole approximately 2 m x 2 m x 5 m
— Insert rings if necessary to reinforce the hole.
— A fence should be put round the burial pit to avoid accidents and
unauthorized access by humans or scavengers.
• The walls should have a negative slope (narrow at the top, wider at the
Incinerator — different incinerators work in
different ways.
bottom).
• Line the bottom of the pit with a material of low permeability, such as

Burying after disinfection: Less clay.

desirable, but more practical, the used


Using the pit
instruments are first disinfected by
• Dump only non-anatomical waste in the pit.
burning, and then buried in a deep pit.
• Seal the pit with soil and concrete before it is full of waste. Leave
This method can usually be used by
approximately 50 cm to properly seal off the pit.
immunization service providers in the
• The abandoned pit must be marked with a warning so that it is not used
field, with some training and support.
in the future.

See adjoining Box for details on how to Source: World Health Organization, www.healthcarewaste.org
build an infectious waste burial pit.

18
A summary of lessons from the global experience in immunization programs
• In immunization, past accomplishment is no guarantee of future performance:
Annual investment and sustained commitment are required to protect each cohort of children, in each year, in
each district. A strong primary (or “routine”) immunization program is recognized as a prerequisite to achieving
equitable and timely protection, to achieve disease reduction and elimination goals, and to prepare the ground
for the introduction of new vaccines. Immunization needs to be viewed as an essential component of primary
health care, maternal and child health, infectious disease control, emergency humanitarian assistance, social
transition and health reform.

• Immunization program caught in a ‘Development Dilemma’:


Under-funded, bottom-up, long-term strategies in delivering the Expanded Program of Immunization (EPI) have
had to compete with well-funded, top-down, disease-specific initiatives.

• False perceptions that the job of immunizing the population has been completed and that diseases have been
controlled:
Reports from several countries have noted health-worker and government complacency regarding routine
immunization.

• A primary immunization program requires a systems approach:


That is staff training, development of supply chains, systems of management and monitoring, communications and
behavior change, engagement of communities and adequate finances. Solving just one aspect of the program,
e.g. vaccine supply, is insufficient. Several developing countries have attempted to get 100% of vaccine supplies,
at the expense of paying or training staff to deliver the program.

• Coordination is critical:
No one partner can single-handedly deliver the immunization program. Successful immunization programs have
largely been where adequate public health resources and political commitment have gone hand in hand.

Further Reading

1. Black RE, Morris SS, Bryce J; Where and why are 10 million children dying each year? Lancet 2003; 361: 2226-2234.

2. Expanded Programme On Immunization; Module 1–8, WHO, Geneva; 1998.

3. GAVI Progress Report; The Global Alliance for Vaccines and Immunization; November 2002.

4. Immunization Essentials: A Practical Field Guide. BASICS II; October 2003.

5. Increasing Immunization Coverage at the Health Facility Level; UNICEF.

6. Keeping global immunization a critical priority, Just the Basics; BASICS II.

7. Introduction of Hepatitis B Vaccine in the Universal Immunization Programme: A Handbook for Programme Managers & Medical Officers,
Child Health Division, Department of Family Welfare, Ministry of Health and Family Welfare, Government of India; July 2002.

8. National Family Health Survey (NFHS-2), 1998-99, International Institute of Population Sciences. Measure DHS, ORC Macro, pp 202-229.

9. National Health Programs of India, National Policies and Legislation Related to Health, J Kishore, 3rd Edition.

10. Steinglass Fields R, BASICS II, Immunization: Challenges and Opportunities, Global Healthlink 2000; 103: pp 15 and 22.

19
20

You might also like