Immunization Among Infants in an Urban Slum (Part-1)

INTRODUCTION

Millions of children are vaccinated every year, protecting them from avoidable diseases and tragic death. Every year Ministry of Health & Family Welfare undertakes to vaccinate all children of under one year age who are eligible for receiving series of vaccine. It is a real challenge to reach eligible population to achieve 100% coverage throughout the country.

 Immunization describes the whole process of delivery of a vaccine and the immunity it generates in an individual and population. Immunization is the process of inducing immunity artificially by administering antigenic substance such as an immune-biological agent or the administration of any vaccine or toxoid.  A vaccine is a special form of a disease-causing agent (e.g., virus or bacteria) that has been developed to protect against that disease. The vaccines work by building up the child’s defense against diseases². Immunization is necessary for two reasons: to protect the individual and to protect communities. Vaccines protect an entire population by preventing the spread of disease from one individual to another: the more people immunized the less chance for disease to circulate.

Medical and drug information is constantly evolving because of ongoing research and clinical experience that are often subject to interpretation.  Because of the dynamic nature of medical and drug information, decisions regarding drug or any other therapy must be based on the independent judgment of the clinician, information about a drug, and changing medical practices. Normally vaccine manufacturers produce vaccine strictly following safety norms and ensure effectiveness with current technology available. Vaccines used in the national immunization programs are extremely safe and effective. But no vaccine is perfectly safe and adverse events can occur following immunization. In addition to the vaccines themselves, the process of immunization is a potential source of adverse events. An adverse event following immunization (AEFI) is any adverse event that is believed to be caused by the immunization. Immunizations are one of the major public health success stories of the past century. Universal immunizations have led to dramatic decreases in the incidence of smallpox, paralytic polio, tetanus, diphtheria, measles, mumps, rubella, congenital rubella, and Haemophilus influenzae type b infections; incidences of all have decreased by 97%–100%¹². In addition, components, of some vaccines such as aluminium adjuvant and preservative, can lead to local or systematic irritation. As the use of vaccine increases (e.g. measles and neonatal tetanus campaigns), more vaccine reactions as well as more usage coincidental events will occur.

 An AEFI is any event or reaction that occurs after receiving a vaccine and which does not necessarily have a causal relationship with the administration of the vaccine. The most common AEFI in developing countries are programmatic error which will occur as a result of inappropriate storage, handling, preparation and administration of vaccines. Most symptoms are mild such as local injection site reactions of erythema, swelling, pruritus or pain, a fever, drowsiness or nausea. Life-threatening or severe reactions are rare occurring in 1 in 10,000 to 1 million doses administered⁵. Most reactions occur within minutes to a few days of vaccination. Live vaccines, such as MMR and chickenpox may have reactions 1-4 weeks following immunization. Immune-mediated events may occur up to 8 weeks following vaccination⁵.

 Technological advances and continuously increased knowledge about vaccines have led to investigations focused on the safety of existing vaccines which have sometimes created a climate of concern. Delivery of vaccines is a long process from distribution to health facilities to health workers to clients that involves a supply system and careful quality control to ensure that only vaccines of demonstrated quality, safety and efficacy are used. Storage of vaccines and training of health care workers are important aspects of safe delivery. Strengthening the case management of AEFI in national immunization programs is essential to ensure good practices in the administration of life-saving vaccines and to better assess epidemiological data in the population.

As vaccine-preventable infectious diseases continue to decline, people have become increasingly concerned about the risks associated with vaccines. Furthermore adverse events are taken very seriously by the countries, manufacturers and WHO. Each adverse event is investigated and causality determined, where possible. AEFI monitoring and training are essential components in immunization systems. It is important to keep adverse events in perspective. Reported adverse events can either be true adverse events, i.e. really a result of the vaccine or the immunization process, or coincidental events that are not due to the vaccine or immunization process but are temporally, associated with immunization. It is important that serious adverse events be reported immediately. It is extremely important these AEFIs are reported and investigated as they require quick response and corrective measures to prevent additional cases. This will boost public confidence in the program and also will help to improve the quality of program in long run. Incorrect information in media coverage on vaccine safety issues can further propagate and sensationalize misinformation. As a result, rumors about vaccines may spread, possibly leading to reduced immunization coverage. Therefore, children are become seriously ill, may be disabled and also increase unnecessary deaths which have very negative impact on the immunization program.  In each of the United Nations’ member states, the individual national governments create and implement their own policies for vaccination programs following the guidelines set by the EPI. Setting up an immunization program is multifaceted and contains many complex components including a reliable cold chain system, transport for the delivery of the vaccines, maintenance of vaccine stocks, training and monitoring of health workers and a means of documenting and recording which child receives which vaccines. Because vaccines are administrated to large numbers of healthy people as a preventive measure, the surveillance system for vaccine adverse events needs a more sensitive approach than for drugs.

This paper will mainly focus on the AEFI situation of infants in a selected urban slum settings, then evaluate the factor associated with it along with to classify AEFI in relation to type & dose of vaccine received and finally put forward some light to overcome those by suggesting some recommendations.

History of Immunization

 In 1798, Edward Jenner demonstrated the value of immunization against smallpox⁹.  In 1977, nearly 200 years later, smallpox was eradicated from the world through the widespread and targeted use of the vaccine. Based on the emerging success of smallpox, the World Health Organization (WHO) established the Expanded Program on Immunization (EPI) in 1974¹⁴.  Through the 1980s, UNICEF worked with WHO to achieve Universal Childhood Immunization of the six EPI vaccines (BCG, OPV, diphtheria, tetanus, pertussis, and measles).   As a result a record 106 million children were vaccinated in 2008 and global immunization rates are at their highest level ever (82% in 2008)⁴². In 1999, the Global Alliance for Vaccines and Immunization (GAVI) was created with the sole purpose of improving child health in the poorest countries by extending the reach of the EPI. The GAVI brought together a grand coalition, including the UN agencies and institutions (WHO, UNICEF, the World Bank), public health institutes, donor and implementing countries, the Bill and Melinda Gates Foundation and The Rockefeller Foundation, the vaccine industry, non-governmental organizations (NGOs) and many more. The creation of the GAVI has helped to renew interest and maintain the importance of immunizations in battling the world’s large burden of infectious diseases

The last 20 years have seen an explosion in the number of new vaccines. New vaccines against the leading causes of child deaths – pneumonia and diarrhea – offer new hope. The pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RV) protect against the leading causes of pneumonia and diarrhea, respectively. By themselves, these vaccines could save about 1 million children’s lives every year, sharply increasing the 2.5 million under-five deaths currently prevented through immunization annually. UNICEF is also working with partners so that the new vaccine momentum can enhance other interventions that help prevent deaths from these two diseases, so that the impact can be greater. The hepatitis vaccine (HepB) and Haemophilus influenzae type b (Hib) vaccines have gained increased adoption by national immunization programs over the last few years. By the end of 2009, 177 of WHO’s 193 Member States⁶⁰ were using HepB, and 157 countries Hib vaccine, in their routine immunization schedule for infants. However, chronology of history of immunization is highlighted in Annexure C.

UNICEF uses the opportunity of immunization to deliver other life-saving services, too. This includes providing regular vitamin A supplements, insecticide-treated mosquito nets to help protect families from malaria, and other locally appropriate interventions. UNICEF is a global leader in vaccine supply, reaching 40 per cent of the world’s children. Immunization is a central part of commitment to protecting the world’s most vulnerable children.  The Bangladesh EPI began in 1979 as a means of reducing vaccine preventable morbidity and mortality. In early 80s, the EPI started experimentally and gradually it was spreaded to whole of the country and programme achieved great success in the world⁵⁵.

Impact of AEFI on Immunization Programmes

Health influences the living standards of both households and countries. Beyond the direct impact of ill health on households’ living standards through out-of-pocket expenditures, it indirectly affects labor income through productivity and the number of hours that people can work. The effects of illness on income, which may take time to appear, are often long lasting. Malnourished children are less likely to attend school and less likely to learn when they do attend, reducing their productivity in later life. The devastating economic consequences of illness and death are evident at the macroeconomic level as well. The AIDS epidemic alone has been estimated to reduce rates of economic growth by 0.3 to 1.5 percentage points annually⁵⁸.

 In the 1990s, the international community recognized the importance of health in development. In a period when overall official development assistance declined, development assistance to health rose in real terms. World Bank lending for health increased, with a doubling of the share of International Development Association disbursements going to health. The 1990s saw an increased global concern over the debt in the developing world, fueled in part by a perception that interest payments were constraining government health expenditures in developing countries. The enhanced Highly Indebted Poor Country Initiative, spearheaded by the International Monetary Fund and World Bank in response to the unsustainable debt burden of the poorest countries, was explicitly geared to channel freed resources into the health and other social sectors. The Poverty Reduction Strategy Papers submitted by governments of developing countries seek debt relief or concessional (low-interest) International Development Association loans to set out their plans for fighting poverty on all fronts, including health.

As the 1990s closed, the international community decided that even more needed to be done. At the United Nations Millennium Summit in September 2001, heads of 147 states endorsed the Millennium Development Goals (MDG), nearly half of which concern different aspects of health, directly or indirectly. Several other goals are indirectly related to health—for example, the goals on education and gender. Gender equality is considered important to promoting good health among children. Other health outcomes than those included in the MDGs measure progress on health, for example, targets related to noncommunicable diseases.  Of the MDGs for which trend data are available or estimated, the fastest progress has been on malnutrition, whereas overall progress on under-five mortality and maternal mortality has been slower.

 Millennium Development Goals (MDGs) .

Adopted by world leaders in year 2000 and set to be achieved by 2015, MDGs provide concrete, numerical benchmarks for tackling the extreme poverty in its many dimensions.

The eight MDGs break down into 21 quantifiable targets that are measured by 60 indicators³⁷. Detail goals, targets and indicators of MDGs are discussed in Annexure D.  However, the goals are stated below:
Goals and Target of MGDs⁶²

Between 2006 and 2015, working on immunization and related product development should strive to prevent mobility and mortality by achieving the following goals and targets:

By 2010 or earlier

Increase coverage. Countries will reach at least 90% national vaccination coverage and at least 80% vaccination coverage in every district or equivalent administrative unit.

Reduce measles mortality. Globally, mortality due to measles will have been reduced by 90% compared to the 2000 level.

By 2015 or earlier (as the case may be)

• Sustain coverage
• Reduce morbidity and mortality
• Ensure access to vaccines of assured quality
• Introduce new vaccines
• Ensure capacity for surveillance and monitoring
• Strengthen systems

Health-related Millennium Development Goals . The health related MDGs are appended as below:

Goal 1—eradicating extreme poverty and hunger. This goal includes as a target the halving between 1990 and 2015 of the proportion of people who suffer from hunger, with progress to be measured in terms of the prevalence of underweight children under five years of age. The target implies an average annual rate of reduction of 2.7 percent.

Goal 4—reducing child mortality. The target is to reduce by two-thirds between 1990 and 2015 the under-five mortality rate, equivalent to an annual rate of reduction of 4.3 percent.

Goal 5—improving maternal health. The target is to reduce by three-quarters between 1990 and 2015 the maternal mortality ratio, equivalent to an annual rate of reduction of 5.4 percent.

Goal 6—combating HIV/AIDS, malaria, and other diseases. The target is to halt and begin to reverse the spread of these diseases by 2015.

Goal 7—ensuring environmental sustainability. This goal includes as a target the halving by 2015 of the proportion of people without sustainable access to safe drinking water.

Goal 8—developing a global partnership for development. This goal includes as a target the provision of access to affordable essential drugs in developing countries.

Source: United Nations Millennium Declaration, the United Nations Millennium Summit 2000

Four Strategic Areas for MDG⁶²: Following are the four strategic areas for MDG:

1. Protecting more people in a changing world
2. Introducing new vaccines and technologies
3. Integrating immunization, other health interventions and surveillance in the health systems context
4. Immunizing in the context of global inter-dependence.

Justification of the Study:

Immunization is essential to save children’s lives. Immunization has achieved real success in the past 20 years. It is also an affordable means of protecting whole communities and it reduces poverty. Smallpox was eradicated in 1977, a massive human Endeavour, and today polio is set to become another scourge of the past. Every year over 150 million children under the age of five are vaccinated in South Asia. Today vaccines protect nearly three-quarters of the world’s children against major childhood illnesses. UNICEF and WHO have been instrumental in assuring increased access of developing countries to high quality affordable vaccines. All EPI vaccines supplied by UNICEF are from WHO recommended sources.

As no vaccines, including all medicines are perfect, so we should be very much careful about storage, handling as well as preparation of vaccines. Vaccines are administrated to large numbers of people as a preventive measure, the surveillance system for vaccine adverse events needs a more sensitive approach than for drugs.  Coincidental AEFIs are predictable and can be estimated knowing the incidence of disease or death and the size of the target population. Programmatic errors result from mistakes in handling (storage or preparation of the vaccine) and administering the vaccine (immunization site, improper use of unsterile injection devices). It is the responsibility of the EPI program managers to monitor AEFI rates, to identify true and false AEFI and establish a system to promptly detect and address AEFI due to program errors. Failure to comply with strict procedures to assure sterility of injections may lead to cross-infections such as hepatitis B and C and HIV. To detect and address program errors, WHO strongly recommends that Member Countries develop and implement a surveillance system to monitor the safety of vaccines and immunization activities.

The study on this subject is an important not only to get an idea regarding the severity of the problem, but also act as a ready reckoner when AEFI poses serious threat to public health.

Vasantek area near Dhaka cantonment was chosen for research purpose to take data.  Mostly people lived in slums, they were low income generated people and also they had limited hygienic knowledge on their personal lives. Most of the people were daily labours, garments labours, rickshaw pullers, etc. So they were not much aware about different health issues. This study would not serve the purpose of research but also it would help them to aware more health aspects of their lives. It was convenient for researcher to take more data by visiting several occasions. Thereby, it really helped to portray the actual picture about AEFI.

The data collected for the purpose of this research will help in future for further study, weaknesses of the program will be focused highlighting the grey areas and suggestions may help the concerned authority to take appropriate necessary steps for improving the EPI activities. It will further enhance the rapid evaluation of the risk to public safety when vaccine related adverse events occur as well as appropriate and timely action to minimize risks. This is particularly important when government takes program for mass immunization campaigns.

It is required to mention that people do not have only confidence, but also there exits a fear of adverse reactions of vaccine which seriously reduce the coverage of the immunization program. The occasional severe adverse event or cluster of adverse events associated with the use of vaccines in National Immunization Programme (NIP) may rapidly become a serious threat to public health. This includes rapid evaluation of the risk to public when vaccine related adverse events occur as well as appropriate and timely action to minimize such risks. This is particularly important during mass immunization campaigns. For gaining public confidence and to make the program a successful one, there should an effective surveillance and proper case management team to take care after AEFI.  This will not only increase the immunization acceptance but also increase coverage due to improve quality of services by reducing the risks. Further, there is inadequate monitoring of immunization programs particularly in urban slums. In this regard, it needs to add that there is increasing number of new vaccines which is sometimes, less sensitize on immunization.

Conceptual Framework

Figure : Conceptual Framework

Research Question:

1. What is the proportion of Adverse Events Following Immunization due to pentavalent  (DPT,HBV and Hib) vaccine, BCG and OPV vaccine among infants in an urban slum?
2. What are the factors associated with Adverse Events Following Immunization among them?

General Objective:

To find out the Adverse Events Following Immunization situation among infants in an urban slum and the factors associated with it.

Specific Objectives:

1. To determine the proportion of Adverse Events Following Immunization among infants in an urban slum.
2. To classify Adverse Events Following  Immunization among infants in relation to type and dose of vaccine received.
3. To identify the programmatic error related to vaccination.
4. To find out the other factors associated with Adverse Events Following Immunization.

Variables:

1. Socioeconomic and demographic characteristics, e.g, age and sex of the infant, parent’s education and occupation, monthly income, family size etc.
2. Data on immunization and outcome, like types of vaccine received, no of dose received, site of injection, place of vaccination, route of injection, sources of information etc.
3. History of infant’s illness, e.g, type of symptoms, duration of illness, drug allergy, pre-existing disease, outcome of treatment, etc.

Methodology:

Study Design: This study was conducted as a cross sectional study in an urban slum.

Study Period: The study was conducted with effect from first week of January to last week of June 2011.

Study Place:               The study was conducted in an urban slum  namely Vasantek, near Dhaka Cantonment, Dhaka. The study place was selected purposively.

Study Population:      Infant under 1 year of age who had received at least one dose of vaccination. Here, parents, mainly mothers are the respondents of the study.

Selection Criteria:      Infants under 1 year of age who had received at least one dose of vaccine.

Sampling Technique:   Purposive sampling technique will be followed due to time constrain.

Sample Size:  The sample size is determined by using the following formula:

n=z²pq/d²

Where, n= the desire sample size

z= the standard normal deviation usually set at 1.96 which corresponds to the 95% confidence label.

d= the acceptable standard error as per 95%, confidence label would be 0.05

p= the prevalence rate or adverse event following immunizations of the population have

q= (1-p) or proportion of estimated person not suffering from adverse even following immunization

Here the values of above parameters are as follows:

z= 1.96

d=0.05

p=15.6%=0.16

q=84.4%=0.84

So the required sample size will be,

n=(1.96)² *0.16*0.84/(0.05)²= 206

Data Collection Technique:

• By face to face interviewing of the parents by using a semi- structured questionnaire.
• Observation.

Data Collection Instruments:

• A semi-structured questionnaire in Bangla.
• Record review in the vaccination centre.
• Check-list.

Plan for Data Processing:

a. Sorting of data.

b. Performing quality control check.

c. Data processing and analysis will be done by using SPSS window.

GLOSSARY OF TERMS

Adverse Event Following Immunization (AEFI):  A medical incident that takes place after an immunization, causes concern and is believed to be caused by the immunization.

Adverse Reaction: An undesirable outcome caused by a vaccine (or drug) where there is evidence suggesting a causal relationship. The difference between adverse events and adverse reactions is that adverse events may coincide with (i.e. occur at the same time), but not necessarily caused by, vaccine administration.

Anaphylaxis:  Severe immediate (occurring within 1 hour after immunization) allergic reaction leading to circulatory failure with or without bronchospasm and or laryngospasm/laryngeal oedema.

Arthralgia:     Joint pain usually including the small peripheral joints.

Persistent if lasting longer than 10 days,

transient: if lasting up to 10 days.

Abscess: Occurrence of a fluctuant or draining fluid-filled lesion at the site of injection with or without fever as reported by the parents.

Coincidental Adverse Events:A medical event that would have occurred whether or not the individual had received an immunization prior to the event.

Encephalopathy:       Acute onset of major illness characterized by any two of the following three conditions:

• Seizures
• Severe alteration in level of consciousness lasting for one day or more
• Distinct change in behaviour lasting one day or more.

Needs to occur within 48 hours of DTP vaccine or from 7 to 12 days after measles or MMR vaccine, to be related to immunization

Fever: The fever can be classified (based on rectal temperature) as

• Mild (38 to 38.9^oC),
• High (39 to 40.4^oC) and
• Extreme (40.5^oC or higher).

Fever on its own does not need to be reported.

Irritability:     According to the statement of parents, it is a condition occurs after vaccination in which a child responds excessively to a stimulus, e.g., quick response to annoyance, impatience.

Local Reaction:          It is defined as a kind of common or minor vaccine reaction, occurs at the site of vaccination. It consists of one or more of the following:

•   Pain
•   Swelling
•   Redness

Here, in this study local reaction were taken into account as responded by the parents mainly mother.

Pentavalent:   Pentavalent is a newly introduced vaccine comprised of DPT (Diphtheria Pertussis Tetanus), HepB and Hib. It is popularly known as “Five-in-one”.

Persistent Crying/Screaming:Inconsolable continuous crying lasting 3 hours or longer accompanied by high pitched screaming, written in the literature and followed by the researcher based on the mother’s statement.

Programme Error: A medical incident that was caused by some errors in the transportation, storage, handling or administration of vaccine.

Severe local reaction:Redness and/or swelling centered at the site of injection and one or more of the following:

•   Swelling beyond the nearest joint
•   Pain, redness, and swelling of more than 3 days duration
•   Requires hospitalization local reactions of lesser intensity occur commonly.

Seizures: Occurrence of generalized convulsions that are not accompanied by focal neurological signs or symptoms.

Febrile seizures: if temperature elevated >38^oC (rectal).

Afebrile seizures: if temperature normal

Sepsis: Acute onset of severe generalized illness due to bacterial infection and confirmed (if possible) by positive blood culture. Needs to be reported as possible indicator of programme error.

Vaccine: Biological substance that is administered to individuals to elicit immunity (protection) against a specific disease. Combination vaccines (e.g DTP) protect against more than one disease

Immunity’ is a term that originally implied exemption from military service or taxes. It was introduced into medicine to refer to those people who did not get further attacks of smallpox or plague once they had had the disease. In a wide sense the term refers to the resistance of a host organism to invasive pathogens or their toxic products. It is divided into following two main types:

Non-specific Immunity (sometimes called ‘Innate Immunity’): It includes the general protective reaction of the organism against invasion.

Specific Immunity: This is a specific reaction of the body against “non-self” foreign agents, in which its immune products react specifically with the stimulating agent. It is conventionally divided into passive and active immunity, both of which may be either natural or artificial.

Passive Immunity.     Passive immunity involves either the transfer of antibodies or in some diseases, of sensitized white blood cells, from an immune to a non-immune person. Natural passive immunity is transferred from mother to child across the placenta (and in the colostrum in subhuman primate species). Artificial transfer is the therapeutic use of various antitoxines or gammaglobulins, as in the treatment of tetanus, diphtheria, gas gangrene, snake bite, and immuno-deficiency states. The passive immunity is short-lived, depending on the life-span of the antibody or the transferred cells in the recipient. Once they disappear, the host is again susceptible to the disease. Temporary passive immunization can be produced by administration of an antibody in the form of immunoglobulin in some conditions

Active Immunity.       When a foreign substance is encountered, one of two responses is observed. Most commonly, there is an active immune response with production of specific antibodies and sensitized cells. Less frequently, an antigen-specific non response referred to as a state of immunologic tolerance may result. An active immune response can follow natural clinical or sub-clinical infection or be induced artificially, by vaccination. There are three essential characteristics of active immunity:

a. Recognition

b. Specificity

c. Memory

Definitions of AEFI. An adverse event following immunization (AEFI) is an unwanted or unexpected event occurring after the administration of vaccine(s). Such an event may be caused by the vaccine(s) or may occur by chance after vaccination (ie. it would have occurred regardless of vaccination). Most vaccines cause minor adverse events such as low-grade fever, pain or redness at the injection site. The frequency of adverse events can be classified as follows: very common (>10%), common (1–10%), uncommon (0.1–1%), rare (0.01–0.1%) and very rare (<0.01%)⁴. WHO defines an adverse event following immunization as: “a medical incident that takes place after immunization causes concern and is believed to be caused by the immunization.”¹⁰

There are three key aspects to this definition⁵¹.

1. Firstly, it is deliberately loose to encourage reporting of events. This is because it does not restrict the type of event (other than being a health consequence) nor limit the time window after immunization, nor attempt to determine whether the immunization may have been responsible, i.e. it is events, not reactions, that are reported.
2. Secondly, it describes a belief about causality that requires investigation.  The belief that immunization was responsible may turn out to be correct, incorrect, or impossible to assess.
3. Thirdly, describing an event as an AEFI does not and must not imply causality. (There is only a belief of causality). Only after investigation, it may be possible to assign causality.

Within this framework an AEFI can be either:

1. Caused by the vaccine or immunization process (causally associated) or
2. A coincidental event that, by chance, happened after immunization (temporally associated).

In other words, an AEFI is any untoward medical occurrence in a vaccine that follows immunization and that does not necessarily have a causal relationship with the administration of the vaccine. The adverse event may be any unfavorable and/or unintended sign, abnormal laboratory finding, symptom or disease⁷. Again an AEFI or vaccine associated adverse event (VAE) is defined as an untoward, temporally associated event following immunization that might or might not be caused by the vaccine or the immunization process.

 Serious AEFI.            Serious AEFI is an AEFI that:

(1)        Results in death;

(2)        Is life threatening?

(3)        Requires in-patient hospitalization or prolongation of an existing hospitalization;

(4)        Results in persistent or significant disability/incapacity;

(5)        Causes a congenital anomaly/birth defect;

(6)        Is medically important.

Life-Threatening Event:       Life threatening event is an event/a reaction in which the client was at risk of death at the time of the event/reaction; it does not refer to an event/a reaction that hypothetically might have caused death if it were more severe. Example: anaphylaxis

Medically Important Events: Medical and scientific judgment should be exercised in deciding whether other situations should be considered as serious such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the client or may require intervention to prevent one of the other outcomes listed in the definition above. These should also be considered serious. Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm or convulsions that do not result in hospitalization.

Unusual or Unexpected AEFI:        An event that is not identified in nature, severity, or frequency among the currently known adverse effects associated with the administration of the product. For example, first reports of intussusceptions following rotavirus immunization. Please refer to the current product information or labeling.

Serious AEFI versus Severe:            The term “severe” is not synonymous with serious, and it is used to describe the intensity (severity) of a specific event (as in mild, moderate or severe). The event itself, however, may be of relatively minor medical significance (such as severe headache). Seriousness (not severity), which is based on client/event outcome or action criteria, serves as guide for defining regulatory reporting obligations.

Adverse Event versus Adverse Reaction: An Adverse Event is a noxious and unintended response to a vaccine that occurs at doses normally used or tested for the diagnosis, treatment or prevention of a disease.

An Adverse Reaction, in contrast to an Adverse Event, is characterized by the fact that a causal relationship between the drug and the occurrence is suspected.

Classification:  An AEFI can be classified as:

In other way, it can be classified into following headings:

a. Vaccine-Induced Event.

(1)        Non-specific inflammatory responses (injection site reaction, fever)

(2)        Immune-mediated response (anaphylaxis)

(3)        Consequence of replication of microbial agents in vaccine (febrile rash)

(4)        Direct toxic effect of vaccine component or contaminant

b.Vaccine Potentiated Event.

(1)        Vasovagal response (syncope)

(2)        Hyperventilation

(3)        Stress-related

c. Immunization Error.

(1)        Inappropriate transportation or storage

(2)        Failure to adhere to recommended schedule

(3)        Use of expired product or wrong diluents

(4)        Incorrect: dosage, injecting equipment, sterile technique, route or site of injection

d.Other Event.

(1)        Infection

(2)        Reaction to concomitant medication

(3)        Response to environmental allergen or toxin

(4)        Manifestation of complication of birth injury or inherited condition

(5)        Trauma

(6)        Psychogenic illness

e.Unknown.      Cause of the event cannot be determined.

Based on casual association, AEFI may also be classified as (i) definitely (ii) Probably (iii) Possibility (iv) unlikely to be related to the vaccine. Again it can be also classified as serious or non serious.

Causes of AEFI.     There are four possible causes of an AEFI:

a.   Vaccine Reaction: An event caused by some component of the vaccine – the active component of the vaccine itself, the preservative, the stabilizer or other. The majority of vaccine reactions is “common” and expected, mild, settle without treatment and have no long-term consequences. More serious reactions are very rare and are usually of a fairly predictable (albeit extremely low) frequency.

b. Program Error: An event caused by an error in vaccine preparation, handling or administration.

c. Coincidence: An event where something happens after the immunization but is not caused by the vaccine or the program.

d. Injection Reaction:      An event arising from anxiety about the injection. This reaction is unrelated to the content of the vaccine.

 Vaccine Reactions.               

These reactions are caused by a constituent of the vaccine. In some cases this will be the vaccine antigen (the substance that generates immunity), and is thus a side effect of the immunological process of generating immunity. In other cases it will be caused by other vaccine constituents (e.g. preservatives, stabilizers, antibiotics, or residual substance from the manufacturing process) or the adjuvant that is added to boost the vaccine’s immunogenicity.

 Category of Vaccine Reactions.      

It is of two types:

a.  Common, usually minor and self-limiting

b.   Rare and more serious

The reason that there are only these two types of vaccine reaction is that any vaccine that caused a serious reaction that was even relatively common would either not be licensed for use or withdrawn when the frequency of the serious adverse event is identified. An example of this was the withdrawal of the first rotavirus vaccine because it was found to cause intussusception in about 1 in 10,000 vaccinees. Similarly, oral polio vaccine (OPV) is no longer used in most industrialized countries because it carries a risk of about 1 in 2 – 3 million of causing polio. However, the current use of OPV in developing countries and its previous use in other countries, reflects the fact that the vaccine risks need to be balanced against the risk of the disease and the cost of the alternative (inactivated vaccine in the case of OPV).

Common Vaccine Reactions. 

The common reactions are caused by the body’s response to the vaccine antigen(s) and the other vaccine constituents. In general they occur within 24-48 hours of vaccination and are self-limiting. However reactions following live vaccines (e.g. MMR) may be delayed and resemble a mild version of the disease.

¹   Between MMR group and placebo group

²    More in placebo injected children

Common reactions are usually a local reaction at the site of injection and/or systemic symptoms. For the local reaction there is pain, swelling and/or redness at the injection site, which can vary in severity and last for up to for a few days. The systemic symptoms can include fever and a range of non-specific symptoms (e.g. irritability, malaise, ‘off-colour’, loss of appetite). For live virus vaccines, the systemic symptoms can be a mild form of the disease (e.g. fever, rash for measles vaccine). The common reactions usually take place within a day or so of immunization – except for live attenuated vaccines such as measles/MMR, where reactions occur  6 to 12 days after immunization (the time taken for the vaccine virus to replicate). Common reactions are usually only last a few hours to a few days. The frequency and severity of these common reactions vary by vaccine and by person.

Children up to 50%1-6%RareMeasles¹Upto 10%Up to 5%Up to 5%OPVNoneLass than 1%Lass than 1%⁴DPT²Up to 50%Up to 50%Up to 60%Treatmentü  Cold cloth at injection Site

ü  Paracetamol³

• Give extra fluid
• Wear cool clothing
• Tepid sponge or bath
• Paracetamol³

ü  Give extra fluid

ü  Paracetamol³

¹              Local reactogenicity varies from one vaccine product to another, depending on the strain and number of viable bacilli

²              With whole cell pertussis vaccine. A cellular pertussis vaccines rate lower.

³              Paracetamol Dose: up to 15mg/kg every 4 hours, maximum of 4 doses in 24 hours.

⁴              Diarroea, Headache and/ or muscle pain.

Reference: Epidemiological Unit, Ministry of Health, nutrition& Welfare, Sri Lanka, Immunization Handbook, National Extended Programme on Immunization, Sri Lanka-2002, Funded by World Health Organization.

Rare Vaccine Reactions.      

While there is some similarity between the common reactions caused by all vaccines, the rare more serious reactions tend to be more specific to each vaccine. Most of the rare and more serious vaccine reactions (e.g. seizures, thrombocytopaenia, hypotonic hypo-responsive episodes, persistent inconsolable screaming) do not lead to long-term problems. Anaphylaxis, while potentially fatal, is treatable without leaving any long-term effects. Although encephalopathy is included as a possible rare reaction to measles or DTP vaccine, it is not certain that these vaccines in fact cause encephalopathy (brain inflammation).

Approximately 90% of those receiving a second dose are already immune. Reactions do not occur if the child/women are already immune. This is not the case for anaphylaxis where this type of reaction is more likely on the second or subsequent doses.

The risk of VAPP is higher after the first dose (1.4-3.4 Per Million Doses) compared with the second and third doses (0.17 Per Million Doses)

 Seizures mostly febrile and risk depends on age, with much lower risk in infants under the age of 4 months.

Reference: Epidemiological Unit, Ministry of Health, nutrition& Welfare, Sri Lanka, Immunization Handbook, National Extended Programme on Immunization, Sri Lanka-2002,Funded by World Health Organization.

Program Errors.      

Programme errors result from errors and accidents in vaccine preparation, handling, or administration. They are preventable with good practice, appropriate facilities and equipment.  Vaccinator technique in choosing the site for the injection, the depth of the injection, and the speed of injection may affect the rate and extent of local reactions. A programme error may lead to a cluster of events associated with a particular provider, health facility, or even a single vial of vaccine that has been inappropriately prepared or contaminated. Programme errors can also affect many vials (e.g. by freezing vaccine during transport, leading to an increase in local reactions and loss of effect). Globally, the most common programme errors are non-sterile injections leading to bacterial or viral infections. Injection technique can also lead to increased local reactions for example giving intramuscular injections too superficially.

Program Errors Leading to Adverse Events:

Failure to comply with strict procedures to assure sterility of injections may lead to cross-infections such as hepatitis B and C and HIV. Vaccines used in national immunization programs are extremely safe and effective, although adverse events can occur following immunization. In addition to the vaccines themselves, the process of immunization (program error) can be a potential cause of an adverse event.

Non-sterile injection:

a. Reuse of disposable syringe or needle

b. Improperly sterilized syringe or needle

c. Contaminated vaccine or diluents

d. Reuse of reconstituted vaccine at subsequent sessionInfection (local suppuration at injection site, abscess, cellulites, systemic infection, sepsis, toxic shock syndrome,

transmission of blood borne virus like HIV, hepatitis B or hepatitis C)

Vaccine prepared incorrectly:

a. Vaccine reconstituted with incorrect diluents.

b. Drugs or other substance substituted for vaccine or diluents.

Local Reaction or abscess from inadequate shaking

Effect of incorrect diluents or drug, e.g, muscle relaxation, insulin.Immunization injected in wrong site:

a. Subcutaneous instead of intradermal for BCG

b. Too superficial for toxoid vaccine (DPT, DT, TT)

c.  Buttocks

Local reaction or injection site abscess

Sciatic nerve damage ( and ineffective vaccine)Vaccine transported or stored

incorrectlyIncreased local reaction from frozen vaccine (and ineffective vaccine)Contraindications ignoredAvoidable severe vaccine reaction e.g., anaphylaxis in case of known history of

allergy.

 Reference: Epidemiological Unit, Ministry of Health, nutrition& Welfare, Sri Lanka, Immunization Handbook, National Extended Programme on Immunization, Sri Lanka-2002,Funded by World Health Organization.

Injection Reactions.

Individuals can react in anticipation and as a result of the pain of any injection. This reaction is unrelated to the content of the vaccine. Some individuals may be ‘needle-phobic,’ aggravating such reactions.  The injection reaction can lead to a group event.  The event is essentially a psychological reaction that spreads between individuals of the group (who are usually primed for this by high levels of anxiety), when a member of the group suffers a reaction such as a faint or other vaccine reaction.

• Fainting (vaso-vagal reactions) is a relatively common injection reaction, but usually only affects children aged over five years. Fainting does not require any management beyond placing the patient in a recumbent position, preferably the recovery position.
  The likelihood of faints can be anticipated when immunising older children, and reduced by minimising stress in those awaiting injection through short waiting times, comfortable room temperatures, preparation of vaccine out of recipient’s view, and privacy during the procedure. Avoiding injury from the fall is important, and those at particular risk should be immunised while lying down; the faint however can occur many minutes after the immunization.
• Hyperventilation as a result of anxiety about the immunization leads to specific symptoms of light-headedness, dizziness, tingling around the mouth and in the hands, and sometimes chest pain.
• Younger children tend to react in a different way, with vomiting a common anxiety symptom. Breath-holding may occur, which can end in a brief period of unconsciousness during which breathing resumes. They may also scream to prevent the injection or run away.  Clear explanations about the immunization and calm, confident delivery will decrease the level of anxiety about the injections and thus reduce the likelihood of an injection reaction.

It is important to be able to distinguish the loss of consciousness resulting from a fainting (vasovagal) injection reaction to that of anaphylaxis.

Table:  Vasovagal Injection to Anaphylaxis

Distinguishing anaphylaxis from a faint (vasovagal reaction)

Source: “Immunization Safety Surveillance: guidelines for managers of immunization programmes on reporting and investigating adverse events following immunization. Manila: World Health Organization, 1999.”

Coincidental Events.

This is probably the most important type of AEFI, in terms of impact on immunization program.  It is the main cause for the continuing controversy about immunization safety.  The distinction between the event happening after immunization and being caused by immunization is not easy to make, and many people find it hard to understand.  The automatic assumption is that when B follows A, it is that A caused B. Because large numbers of immunizations are given every day, it is inevitable that in the days following immunization many people will suffer major health events.  Most vaccines are given early in life, when infections and other illnesses are common, including manifestations of an underlying congenital or neurological condition.  The health event is likely to be blamed on the immunization, simply because of the temporal association between the events that, in fact, reflect chance and coincidence and not a real causal relationship.

Examples of false allegations caused by coincidental events

• One good example is the association between immunization and Sudden Infant Death Syndrome (SIDS or cot death).  The incidence of SIDS peaks around the age when infant immunizations are delivered. So, many SIDS cases will occur in children who have been recently immunized. Inevitably, when a previously healthy child dies a cause is sought.  In some cases there will, purely by chance, have been an immunization, shortly before the death.  The only way to clarify if such an event is in fact due to a chance association is through careful studies.  In the case of SIDS, controlled studies have shown that the association of SIDS and immunization is purely coincidental and not causal.
• More recently, there has been much concern around MMR vaccine causing autism that started from a report of 12 cases with a variable temporal association.  Despite many controlled studies that have failed to find a link, many parents remain convinced that their child’s autism was due to the vaccine.  This association has arisen because MMR is usually given early in the second year of life – at a time when autism is recognized.

Anticipating Coincidental Events.               It is possible to predict how often one would expect to see a coincidental association between a health event and immunization.  Using the expected incidence (number of cases per population to be vaccinated per time period) of the health event. For example, assume that one million children aged 1-15 years are immunized in a mass campaign and the background mortality rate for this population is 3 per 1000 per year. Then, 250 deaths can be expected in the month after immunization and 8 deaths on the day of the immunization, simply by coincidence. These deaths will be temporally associated with, even though entirely unrelated to, immunization.

A similar calculation is shown in the Table below for infant (aged under one-year) deaths in selected Western Pacific countries for the number of deaths temporally associated with routine DTP immunization (calculated in 1999).

Table : Routine DTP Immunization⁴⁵

Coincidental deaths temporally linked to DPT immunization

NOTE: Assumes uniform distribution of deaths and children who are near to death will still be immunized.
Infant mortality and births from 1998 Western Pacific Region Health Data Bank.
IMR= Infant mortality rate per live birth (can substitute for rate of any event).
N = Number in population (births used as proxy for numbers aged under one year).
nv = number of immunization doses: assumed here to be three visits.
ppv = proportion of population vaccinated: assumed here to be 90% for each dose.
Note: in calculation of deaths the first line of equation shows number of total deaths in period, second line adjusts for exposure to vaccine within that period, multiplied by the number of periods in the year.

Errors which can lead to AEFI

a.         Too much vaccine given in one dose.

b.         Improper immunization site or route.

c.         Syringes and needles improperly sterilized.

d.         Vaccine reconstituted with incorrect diluent.

e.         Wrong amount of diluent used.

f.          Drug inadvertently substituted for vaccine or diluent (can result from inattention when reading labels on vials resulting in mistaking content).

g.         Vaccine prepared incorrectly for use e.g. an absorbed vaccine not being shaken properly before use.

h.         Vaccine or diluent contaminated.

i.          Vaccine stored incorrectly.

j.          Contraindications ignored e.g. a child who experienced a serious reaction after a previous dose of a vaccine is immunized with the same vaccine.

k.         Reconstituted vaccine used beyond six hours after reconstitution or not thrown out at the end of an immunization session and used at a subsequent one.

 Cold Chain⁹:       The “cold chain” is the name given to a system of people and equipment which ensure that the correct quantity of potent vaccine reaches the women and children who need it from the point of production. The cold chain system is necessary because vaccines are delicate substances that lose potency if they are exposed to temperatures that are too warm or too cold. High levels of immunization coverage are useless if the vaccine that was used is not potent.

Figure 2 illustrates the entire cold chain system. There are many steps between the manufacturer of the vaccine and the woman or child in need of immunization. Vaccine must stay at the correct temperature throughout the entire cold chain system – when it is transported, when it is stored in a refrigerator or cold store, and when it is used at an immunization session

Essential Elements.       The two essential elements of the cold chain system are:

a.   People to manage vaccine distribution;

b.   Equipment to store and transport vaccine.

The basic cold chain equipment includes:

• Refrigerators, freezers and cold rooms

• Cold boxes, Vaccine carriers, Day-carriers and Thermos flasks;

• Thermometers;

• Vehicles.

Cold Chain and Logistics (CCL) System⁴⁵.            UNICEF supports national immunization programs in several ways. One critical area is CCL system, as vaccines are biological products that must be kept within a narrow temperature range, usually 2-8 degrees Centigrade (36-45º F). The cold chain refers to the storage and transport equipment that enables vaccine to be kept at this temperature from the point of manufacture to the point of use in an immunization session or a clinic. The CCL system includes:

(1) A management information system capable of collecting and reporting data;

(2) A stock inventory control system to ensure proper management of all supplies;

(3) Storage and warehousing of adequate capacity and quality to ensure their integrity;

(4) A distribution/maintenance system for efficient transport to every immunization session; and

(5) Sufficient number of trained personnel at every level, with adequate supervision.

Storage of Vaccine Maintaining the Cold Chain⁹: Vaccines should be stored in cold rooms and/or in refrigerators and deep-freezers maintained at +2⁰C–8⁰ C and –20⁰C – (depending on the type of vaccine).

a.   If the temperature is maintained above +8^0C:

1. Bottles of water (or ice packs filled with water) should be stored in every spare space in the refrigerator, except for one-half of the volume which is needed for air circulation. This helps to stabilize the temperature and prevent wide fluctuations during the day.

2. Ensure that the door of the refrigerator/freezer is opened as few times as possible.

The ice packs should be pre-cooled at night in the refrigerator before inserting them in the freezer (except for solar refrigerators, where ice packs should be inserted in the morning).

b.   If the temperature is maintained below 0⁰ C:

1.         Bottles of water (or ice packs filled with water) should be stored in every spare space in the refrigerator, except for one-half of the volume which is needed for air circulation. This helps to stabilize the temperature and stops it from fluctuating widely during the day.

2.         Temperature could be adjusted by turning the temperature control switch button (Thermostat) in the equipment.

3. Windows or ventilators should be kept closed at night to keep the store-room warmer if necessary.

4. If these actions do not ensure that the internal temperature is maintained correctly, the refrigerator should be replaced.

c.   Storage of different vaccines

1. It is best to store the different vaccines in different cold-rooms/freezers/refrigerators.

2. The maximum stock of vaccine, diluents and water bottles (if used) should only take up one-half of the total space available in the refrigerator/freezer. If more than half the space is used, air will not circulate around the vaccine to maintain the correct temperature in all parts of the refrigerator/freezer.

3. Bottles of water (or ice packs filled with water) should be stored in the refrigerator to keep the refrigerator cool specially if there is frequent interruptions to the energy/power supply.

Maintenance of Refrigerators/Freezers     At the stores, if there are more than one refrigerator/freezer it is better to house them in one room or a separate part of a room. A person should be identified to be responsible for the day to day maintenance of these.

He/she should observe the following:

a. The room is well ventilated;

b. Each refrigerator/freezer is protected from outside heat;

c. Direct rays of the sun do not fall on the refrigerator/freezer;

d. Each refrigerator/freezer has a different plug point and care should be taken to ensure that the plug is not accidentally disconnected;

e. Refrigerator/freezer doors and lids are kept firmly closed;

f.    Each refrigerator/freezer is defrosted regularly and kept clean. Whenever a layer of ice measuring several millimeters (5 at most) forms on the freezer compartment, the refrigerators should be defrosted;

g. Each refrigerator/freezer has a maintenance chart – Refrigerator Record;

h.   Any problems should be brought to the notice of the relevant officers immediately. A note should be prominently displayed as to whom to be contacted;

i.    An alternate place to store vaccine during an emergency (an emergency plan) should be identified and prominently displayed. This place should be identified at the onset in consultation with the DPDHS/RE/MO (MCH)/MOH depending on the stores involved;

j. Inventory of equipment is checked annually.

During Transport.   

a.         Vaccine stocks should be distributed to the clinic centres packed in vaccine carriers/day carriers/flasks – Figure 5 (do not take excess stocks).

b.         These should be used even when the clinic is held in a room adjoining the storage point.

c.         The correct number of cold packs or the correct amount of ice should be used to maintain the cold life of the vaccine during transport to and from the clinic and duration of the clinic.

d.         The vaccine carrier/day carrier/flask should be taken close to the refrigerator/deep freezer.

Packing of Vaccines in Cold boxes/Day Carriers/Thermos flasks

Health workers should:

a.    Remove the ice packs from the freezer;

b.   Wait for them to be free of frost (approximately 10-15 minutes);

c.   Place fully frozen ice packs around the inside walls of the the carrier;

d.   If pieces of ice are used they should be packed in a bag. Amount of ice should be sufficient to ensure cold life of the vaccine carrier/day carrier/thermos flask;

e.   Stack vaccine and diluents in the vaccine carrier/day carrier/thermos flask;

f.    Place two layers of frozen ice packs/pieces of ice on top;

g.   Take precautions to prevent vulnerable vaccines from being frozen (for example, keep them in their packaging/wrap a paper around them);

h.   Secure the lid tightly.

CCL Taskforce at New York.   UNICEF has convened a CCL Taskforce of partners involved in immunization to enhance and coordinate the collective support provided to national governments. The CCL Taskforce Workshop held in New York from 2-4 November 2009  sought to reach a consensus on the approach and key actions needed to address CCL needs over the next year or so. Workshop members adopted the vision, goals and outcomes articulated at the first CCL Taskforce meeting, held in November 2007. The CCL Taskforce has established four subgroups to advance the work program, viz.

(1) Guidance,

(2) Monitoring,

(3) Advocacy, and

(4) Integration. 

Vision of the CCL Taskforce.   “The capacity of National Immunization Programs is strengthened so that every individual can benefit from vaccines of assured quality delivered in the right amount at the right time through efficient logistics, proper vaccine management, and a well-functioning cold chain system”.

Outcomes of the Taskforce.     

1. Adequate number of vaccines are available for every immunization session
2. Vaccine wastage is minimized without affecting coverage
3. Vaccines are stored and transported without temperature damage
4. New vaccine introduction is not constrained by lack of storage/transport capacity
5. There is greatly increased coordination and a commitment towards effective integration with procurement and management of other priority health commodities.

Reasons for Reporting about AEFI:  Following are the causes for reporting about AEFI:

a.         To ensure that the vaccines used in our country are safe

b.         To maintain public confidence in immunization programs

c.         It is a health care professional responsibility

d.         It is a legal requirement in many Bangladeshi’s jurisdictions

WHO should Report:  Following personnel may report:

a.   All vaccine providers

b.   All health care professionals caring for patients who may have had an AEFI

c.   All vaccine manufacturers to whom an AEFI report is submitted

WHEN to Report:      When an AEFI is severe (death, hospitalization for > 3 days, congenital abnormality, life threatening), unexpected (in terms of type or frequency)  and of concern (to the patient, his/her caregiver(s) or AEFI reporter).  When an AEFI occurs within a timeframe that is generally consistent with one or more of the following:

a.         immunizing agent: 30 days after live vaccine/7 days after killed or subunit vaccine

b.   plausible biologic mechanism: up to 8 weeks for immune-mediated events

c.   reporter suspects the AEFI may be linked to immunization .

WHAT to Report⁵: Following should be reported in details:

a.         Patient – unique identifier, date of birth and sex

b.         Immunization Event – province/territory where given, date, all vaccines given including name, manufacturer, lot number, administration site and route, as well as the number in series of vaccine doses if relevant

c.         Adverse Event – description, including time of first onset following immunization, duration, health care utilization, treatment and outcome

d.         Relevant Medical History – underlying disease, known allergies, prior AEFI

e.         Associated Event – acute illness, current medication, injury, exposure to environmental toxins.

f.          Reporter details.

When an AEFI form needs to be completed: An AEFI form should only be completed for reportable events that are:

a.         serious in nature; OR

b.         required an urgent medical attention (not resulting in hospitalization); OR

c.         unusual / unexpected (regardless of severity) .

 Major Adverse Events:  Any reaction that requires immediate medical intervention and/or hospitalization, which may include:

1. Anaphylaxis
2. Acute Encephalopathy
3. Paralysis
4. Guillian Barre Syndrome

It is normally reported within one working day.

Moderate Adverse Events⁶:  It is normally reported within 5 working days.

1. Fever as high as 40⁰C
2. Chills/Shivers
3. Hives
4. Pronounced Drowsiness
5. Prolonged Crying or irritability
6. Significant nodules/lumps
7. Abscesses at injection site

What not to Report: It is not required to report the following minor adverse events that occur frequently following immunization:

1. Local redness and/or induration at the injection site
2. Local Tenderness
3. Painful limb
4. Crying, fretfulness, drowsiness, irritability, loss of appetite
5. Swelling of lymph nodes near injection site, fever, arthralgia, myalgia
6. With live vaccines (MMR, vericella), the reaction may resemble a mild form of disease with a fever and rash 5-14 days following immunization

Events that should be reported after immunization:

Table shows the events that should be reported after immunization.

ü  Anaphylaxis

ü  Persistent (more than 3 hours) inconsolable screaming

ü  Hypotonic hyporesponsive episode (HHE)

ü  Toxic shock syndrome (TSS)¹Occurring within 5 days of immunization

• Severe local reaction
•  Sepsis¹
• Injection site abscess (bacterial/sterile)¹

Occurring within 15 days of immunizationv  Seizures, including febrile seizures (6-12 days for measles/MMR; 0-2 days for DTP)

v  Encephalopathy (6-12 days for measles/MMR; 0-2 days for DTP)Occurring within 3 month of immunization

• Acute flaccid paralysis (4-30 days for OPV recipient; 4-75 days for contact)
• Brachial neuritis (2-28 days after tetanus containing vaccine)
• Thrombocytopaenia (15-35 days after measles/ MMR)

Occurring between 1 and 12 month after BCG immunization     #   Lymphadenitis¹

#   Disseminated BCG infection

#   Osteitis/OsteomyelitisNo time limitü  Any death, hospitalisation, or other severe and unusual events that are thought by health¹

Limit reporting to those events if only limited reporting capacity

Reference: Epidemiological Unit, Ministry of Health, nutrition& Welfare, Sri Lanka, Immunization Handbook, National Extended Programme on Immunization, Sri Lanka-2002,Funded by World Health Organization.

Management of an immediate AEFI. There are four steps of the management of AEFI and prevention of crisis. They are:

a.         Anticipate:      Do not wait until crisis occurs. Prepare for unavoidable.

b.         Train vaccination personnel at all levels to respond adequately.

c.         Confirm the all facts before making any public statement.

d.         Prepare a plan to react to a crisis when it occurs.

Why to monitor AEFI?

1. No vaccines are 100% safe and without any risks
2. It is important to know the risks and how to handle such an event when it occurs
3. Informing people correctly on AEFI helps keep public’s confidence in the immunization programmes
4. Monitoring AEFI also helps improve the quality of service

Advice to Parents on Common Adverse Events.    Vaccine injections may result in soreness, redness, itching, swelling or burning at the injection site for 1 to 2 days. Paracetamol might be required to ease the discomfort.

Managing Fever after Vaccination. Routine use of paracetamol at the time of vaccination is no longer recommended. If an infant or child has a fever of >38.5ºC following vaccination, paracetamol can be given. The dose of paracetamol is 15 mg/kg/dose of paracetamol liquid, up to a maximum daily dose of 90 mg/kg per day in 4 to 6 divided doses for up to 48 hours.

Preventing AEFI. The key to preventing uncommon or rare adverse events is to screen each person to be vaccinated using pre-vaccination screening to ensure that the person does not have a condition which either increases the risk of an adverse event or is a contraindication to vaccination. The correct injection technique is also important.

Observation after vaccination. Recipients of vaccines should remain under observation for a short interval to ensure that they do not experience an immediate adverse event. It is recommended that recipients remain in the vicinity of the place of vaccination for at least 15 minutes. Severe anaphylactic reactions usually have a rapid onset; most life-threatening adverse events begin within 10 minutes of vaccination.

The most serious immediate AEFI is anaphylaxis. However, in adults and older children, the most common immediate adverse event is a vasovagal episode (fainting), either immediately or soon after vaccination. Because fainting after vaccination can lead to serious consequences, anyone who complains of giddiness or light-headedness before or after vaccination should be advised to lie down until free of symptoms. Most faints following vaccination occur within 5 minutes, and 98% occur within 30 minutes. Adults should, therefore, be warned of the risk of driving or operating machinery for at least 30 minutes after vaccination. Children who have had a serious adverse event (other than a contraindication, such as anaphylaxis) to a previous vaccine may subsequently be vaccinated under close medical supervision.

Anaphylaxis and Vasovagal Episodes. Anaphylaxis following routine vaccination is very rare, but can be fatal. All immunization service providers must be able to distinguish between anaphylaxis, convulsions and fainting.

Fainting (vasovagal episode) is relatively common after vaccination of adults and adolescents, but infants and children rarely faint. Sudden loss of consciousness in young children should be presumed to be an anaphylactic reaction, particularly if a strong central pulse is absent. A strong central pulse (eg. carotid) persists during a faint or convulsion.

The features listed in Table 9 may be useful in differentiating these 2 conditions. If the diagnosis is unclear and anaphylaxis is considered, management for this should be instituted with the prompt administration of adrenaline.

Hypotension – usually transient and corrects in supine position.Tachycardia, weak/absent peripheral and carotid pulse.

Hypotension – sustained and no improvement without specific treatment.NeurologicalFeels faint, light-headed.

Loss of consciousness – improves once supine or head down position.Sense of severe anxiety and distress.

Loss of consciousness – no improvement once supine or head down position.

Immunization service providers should be able to recognize all the following symptoms and signs of anaphylaxis:

1. Cutaneous, such as the rapid development of widespread urticarial lesions (circumscribed, intensely itchy weals with erythematous, raised edges and pale, blanched centres) and/or erythema and/or angioedema (soft tissue swelling usually affecting the face and/or limbs),
2. Upper airway obstruction, such as hoarseness and stridor, resulting from angioedema of the hypopharynx, epiglottis and larynx,
3. Lower airway obstruction, such as subjective feelings of retrosternal tightness, and dyspnoea with audible expiratory wheeze from bronchospasm,
4. Limpness and pallor, which are signs of hypotension in infants and young children,
5. Profound hypotension in association with other signs of cardiovascular disturbance, such as sinus tachycardia or severe bradycardia, absent central pulses and reduced peripheral circulation, and/or
6. Abdominal cramps, diarrhoea and/or vomiting.

Signs of Anaphylaxis.         Anaphylaxis is a severe adverse event of rapid onset, characterised by sudden respiratory compromise and/or circulatory collapse. Early signs include involvement of the skin, eg. generalised erythema, urticaria and/or angioedema (swelling), and/or gastrointestinal tract, eg. diarrhoea, vomiting. In severe cases, there is circulatory collapse with alteration in the level of consciousness, hypotension and weak or absent pulses, and/or marked respiratory compromise from upper airway oedema or bronchospasm.

Signs and symptomsSeverity of attack Mild, early warning signs

Life Threatening  SymptomsItching of the skin, rash and swelling around injection site. Dizziness, general feeling of warmthMildPainless swellings in part of the body e.g. face or mouth. Flushed, itching skin, nasal congestion, sneezing, tears.Mild to moderateHoarseness, feeling sick, vomitingModerate to severeSwelling in the throat, difficulty in breathing, abdominal painModerate to severeWheezing, noisy, difficulty in breathing, collapse, low blood pressure, irregular or weak pulseSevere

Reference: Epidemiological Unit, Ministry of Health, nutrition& Welfare, Sri Lanka, Immunization Handbook, National Extended Programme on Immunization, Sri Lanka-2002,Funded by World Health Organization.

Management of Anaphylaxis.Rapid IM administration of adrenaline is the cornerstone of treatment of anaphylaxis. Anaphylaxis occurs without warning, usually within 15 minutes of giving a vaccine. A protocol for the management of anaphylaxis, adrenaline, and 1 mL syringes must always be immediately at hand whenever vaccines are given.

If the patient is unconscious, lie him/her on the left side and position to keep the airway clear. If the patient is conscious, lie supine in ‘head down and feet up’ position (unless this results in breathing difficulties).

b.   Give adrenaline by IM injection (see below for dosage) for any signs of anaphylaxis with respiratory and/or cardiovascular symptoms or signs. Adrenaline is not required for generalised non-anaphylactic reactions (such as skin rash or angioedema). If in doubt, IM adrenaline should be given.

c.   If there is no improvement in the patient’s condition by 5 minutes, repeat doses of adrenaline every 5 minutes until improvement occurs.

d.   If oxygen is available, administer by facemask at a high flow rate.

e.   Call for assistance. Never leave the patient alone.

f.    Begin expired air resuscitation for apnoea, check for a central pulse. If pulse is not palpable, commence external cardiac massage (ECM).

g.   All cases should be admitted to hospital for further observation and treatment.

h.   Document the time and dose of adrenaline given.

Experienced practitioners may choose to use an oral airway if the appropriate size is available, but its use is not routinely recommended unless the patient is unconscious. Antihistamines and/or hydrocortisone are not recommended for the emergency management of anaphylaxis.

Adrenaline Dose.Adrenaline 1:1000 contains 1 mg of adrenaline per mL of solution in a 1 mL glass vial. Adrenaline 1 in 10 000 is no longer recommended for the treatment of anaphylaxis. The use of 1:1000 adrenaline is recommended because it is universally available. Use a 1 mL syringe to improve the accuracy of measurement when drawing up small doses.

The recommended dose of 1:1000 adrenaline is 0.01 mL/kg body weight (equivalent to 0.01 mg/kg or 10 µg/kg) up to a maximum of 0.5 mL, given by deep IM injection (not the deltoid). Adrenaline 1:1000 must not be administered intravenously. Table 11 lists the dose of 1:1000 adrenaline to be used if the exact weight of the individual is not known.

Table : Doses of Intramuscular 1:1000 (one in one thousand) Adrenaline for Anaphylaxis⁴

The dose of 1:1000 (one in one thousand) adrenaline may be repeated every 5 minutes as necessary until there is clinical improvement.

IMMUNIZATION PROCEDURES.   Following are the procedures to be following during immunization:

a.         Pre-vaccination questionnaire.         Before vaccination, the doctor, the nurse, the public health inspector or the public health midwife should make sure that the individual to be vaccinated does not have a condition (or a history of a previous condition) which could increase the risk of a severe reaction. One way to do this is to routinely inquire about such conditions. The following information is needed to assess the fitness of a person for vaccination. (Inform the parents, that the conditions listed below do not necessarily mean that their child cannot be vaccinated today. But they should inform the doctor if any of the following conditions are presents:

The person to be vaccinated:

• is unwell today;
• is having treatment which lowers immunity (e.g. steroids such as cortisone and prednisolone, radiotherapy, or chemotherapy);
• has had a severe reaction to any vaccine;
• has any severe allergies to vaccine components (e.g. neomycin);
• has a disease which lowers immunity (e.g. leukaemia, cancer);
• has had a vaccine containing live viruses within the last month (e.g. measles, poliomyelitis, yellow fever or rubella vaccines), or an injection of immunoglobulin or a blood transfusion within the last three months;
• has a disease of the brain or the spinal cord

e.       Standard vaccination procedure

(1)   Before administering vaccines, the following procedures should be followed:

(a) Check whether preparations have been made to respond immediately to adverse reactions;

(b)  Read the product information;

(c) Ensure that valid consent is given;

(d) Provide the parent or guardian with a pre-immunization questionnaire;

(e) Check whether there are any contra-indications to vaccination from the pre-vaccination assessment;

(f) Check the identity of the recipient;

(g) Check the identity of the vaccine to be administered;

(h) Ensure that vaccines have been stored correctly;

(i) Check the vaccine to be administered for obvious signs of deterioration (check expiry date and note any particular matter or colour change that may indicate damage to the vaccine);

(j) Ensure that the correct vaccines are being administered according to the schedule;

(k) Administer the vaccine, using the correct technique (see details below on needle selection, needle angle, injection location, and position of the subject).

(2)   After administering the vaccine, do the following:

(a) Give instructions, preferably in writing, to the parent or guardian regarding what to do in the event of common reactions or serious adverse reactions;

(b) Record the vaccination in the child health development record and in the clinical notes.

c.   Storage.Vaccines that are not stored and transported correctly will lose potency. The instructions of the product leaflet should be followed. The general rule for most vaccines is that they should be refrigerated at +2^oC to +8^oC and NOT FROZEN. Some vaccines such as DTP, Hib, hepatitis B and hepatitis A vaccines are inactivated by freezing.

d.   Reconstitution.   The vaccines should be used within the recommended time period (with gentle shaking the dried cake/power is easily dissolved). They should be kept under proper cold chain conditions and protected from heat and sunlight. Note that reconstituted measles vaccine deteriorates rapidly at room temperature. A sterile 21 gauge needle should be used for reconstitution and a separate 23 gauge needle 25 mm in length should be used for administration of the vaccine.

e.  Cleaning of Skin.The injection site should be cleaned. After cleaning, alcohol and other disinfecting agents must be allowed to evaporate before injection of vaccine since they can inactivate live vaccine preparations. Clean water could be used, if other cleaning agents are not available.

f.   Route of Administration. Almost all vaccines are given by intramuscular or deep subcutaneous injection. The two major exceptions are Oral Polio Vaccine (OPV), which is given by mouth and never injected and BCG, which is given by intradermal injection. Although intramuscular or deep subcutaneous injection route can be used for most vaccines, the intramuscular route is generally recommended because of the difficulties that some health professionals experience with subcutaneous injection of vaccines.

g. Standard Technique and Needle size for Injection of Vaccines.   Persons administering vaccines should observe standard health and safety guidelines given by the Department of Health Services in order to minimize the risk of spread of infection and needle stick injury.  A sterile reusable syringe and needle or a new, sterile, auto-disable syringe and needle should be used for each injection. A syringe or needle which has been used to inject a person should never come in contact with the vial. Auto-disable needles and syringes should be discarded into a safety box. The standard needle for vaccine injection is 23 gauge and 25 mm in length. Intra-dermal immunization (for BCG vaccination) should be given with a 25 gauge and 10 mm long needle.

h. Needle angle for Intramuscular Injection.   The needle should be inserted at an angle of 45 to 60 degrees into the vastus lateralis or deltoid muscle. For the vastus lateralis, the needle should point towards the knee and for the deltoid, the needle should point towards the shoulder. Neural and vascular damage are more likely if the needle is inserted at a 90 degree angle. Insertion at 45 to 60 degrees may result in less tissue resistance as the needle penetrates the muscle.

i. Recommended Sites of Injection for Vaccination.   The anterolateral thigh is the preferred site for vaccination in infants and children under 12 months of age. The deltoid region is an alternative site for vaccination in older children and adults. The hepatitis B and rabies vaccines are less immunogenic if injected into the buttock. Therefore, these vaccines should not be injected into the buttock in subjects of any age.

j.   Drawing up Vaccines from Ampoules.       For vaccines that are drawn through rubber bung, or are reconstituted, a new needle should be used for administration. A needle or syringe, that has been used to inject a person, must never be used to draw vaccine from vaccine vial because of the risk of cross-contamination.

k.  Administration of two or more Vaccines on the Same Day. Administration of different antigens/vaccines on the same day is recommended. Inactivated vaccines and live attenuated virus vaccines, particularly those in the national EPI schedule (childhood schedule) can generally be given during the same visit. Vaccines that should be administered by injections should be given at different sites (e.g. DPT, M, MR and hepatitis B). More than one live attenuated virus vaccine may be given on the same day; but if only one is given, a second live attenuated vaccine should not be given within 4 weeks of the first vaccine because the response to the second vaccine may be diminished. In addition there is a specific interaction between some vaccines (e.g. yellow fever and cholera vaccines) and they should not be given within 4 weeks of each other. It is also recommended that a three week interval should be allowed between the administration of live virus vaccines (except O.P.V.) and BCG vaccine. Different vaccines should not be mixed in the same syringe unless it is clearly stated in the instructions of the manufacturer (given in the information schedule supplied by the vaccine supplier). Different vaccines given to a person on the same day should be injected at different sites using different syringes.

l.   Consent.Prior to vaccination, parents/guardian should be given adequate information including type of vaccine, disease protected, number of doses needed for protection, contraindications, adverse events and what to do if adverse events occur to make an informed decision

m. Consent in Special Programs/mass Vaccination/school Programmes. In large scale school programs a valid consent from the parent or guardian should be obtained before administration of vaccine. Prior to vaccination, parents or guardian should be given adequate information in a leaflet to make an informed decision. If a child’s health status or suitability for vaccination cannot be established, vaccination should be postponed.

n.  Recording of Vaccination.    Each vaccination provider should record all relevant vaccination data on the child health development card or other immunization card. Parents and guardians should be encouraged to present the record at every time their child is seen by a health professional. The following should be recorded:

(1)The date of vaccination;

(2)Details of the vaccine given, including batch number

(3)The name/signature of the person providing the vaccination

(4)Any severe or moderate adverse event;

(5)Date the next vaccination is due

o.Immunization Registers.       The health staff conducting the immunization clinic (health unit, other clinics or hospital clinics) should enter the necessary information in the relevant registers according to the instructions given by the Department of Health Services.

p.  Adverse Events Following Immunization (AEFI). Recipients of vaccines should remain under observation until they are seen to be in good health and not be experiencing an immediate adverse reaction. It is not possible to specify an exact length of time for post-vaccination observations but it is recommended that recipients should remain in the clinic/hospital for about 15 minutes. Parents or guardian should be provided with the necessary information before leaving the clinic on how to act if the child develops an adverse event following immunization. Children who have had a serious adverse event following vaccination may be subsequently vaccinated under close medical supervision in a hospital.

q.  Anaphylaxis.  In infants and children, the most important immediate reaction to vaccination is anaphylaxis. The incidence of anaphylaxis reactions varied with the type of vaccine. But the incidence of true anaphylaxis is only 1-3 cases per million vaccinations. Any member of the health staff carrying out vaccination procedures must be able to distinguish between anaphylaxis, convulsions and fainting.

r.  Reporting of AEFI.   Adverse events following immunization with EPI vaccines including MR, and adult Td vaccines should be reported to the respective hospitals.

Barriers for Immunization.  Despite the availability of safe and effective vaccines, and enormous progress in reducing vaccine-preventable diseases, the effective delivery and acceptance of vaccinations continue to be challenges for healthcare providers and healthcare systems. The growing number of vaccines, the complexity of the vaccination schedule, and the increasing focus to the public on vaccine safety add to the increasing difficulty of achieving and maintaining age-appropriate vaccinations. Overcoming these challenges is essential to further reduce and eliminate vaccine-preventable causes of morbidity and mortality in the country. It is clear that high national immunization rates should not cause complacency. Even with our currently high vaccination rates, vaccine-preventable diseases among children and adolescents remain important continuing causes of morbidity and mortality. Barriers that result in a lack of community or individual demand for immunizations include a weak public health policy (eg, one that does not require or enforce vaccination requirements for school entry) and misinformation or incomplete information about vaccines and the diseases they prevent.

Barrier 2: Limited Access to Vaccination Services in Traditional Venues. Normally hospitals are ideal place for vaccinations. But in some area, due to geographical locations the hospitals are quite far and communication to hospital is not always that good. So sometimes, people are not willing to go. At the same time, it is very difficult to carry all accessories to provide vaccination. Because, some vaccine requires to keep in control temperature. Obviously, ensuring communication with hospital is essential.

Barrier 3: Vaccine Shortages and Delays. Sometimes vaccine shortage, hinder the immunization program. For instances, Beginning in 2000, the U.S. experienced vaccine supply disruptions of unprecedented scope and magnitude. Although the early supply disruptions have been resolved, new problems have evolved. It appears that a fragile vaccine supply will be part of the immunization environment in the U.S. for the foreseeable future. There is no single reason for the supply disruptions. Four factors, which are somewhat interrelated, play a role: 1) business decisions to leave the market; 2) production problems; 3) adherence to requirements for current Good Manufacturing Practices; and 4) recommendations to remove thimerosal as a preservative. In 2002 and 2005, the National Vaccine Advisory Committee (NVAC) organized workshops to identify the reasons for vaccine shortages and develop strategies and solutions to prevent shortages in the future. The NVAC workshops, consisting of members of the various constituencies involved in vaccine supply, identified 5 general issues that need to be addressed to strengthen the vaccine supply in the U.S.: 1) providing incentives to maintain current vaccine manufacturers and encourage new manufacturers to enter the market; 2) streamlining regulatory authority; 3) strengthening liability protections for consumers, manufacturers, and providers; 4) implementing a more comprehensive program of vaccine stockpiles; and 5) developing an educational program that provides information to parents and vaccine recipients about the use and value of vaccines.

Barrier 4: Lack of Public Health Policy Requiring Immunizations. Enactment and enforcement of state immunization laws requiring immunization before school entry helped achieve the current high vaccination rates of school-age children. The effectiveness of school entry requirements is demonstrated by the higher percentages of children with up-to-date vaccinations when entering kindergarten compared to younger children, and the substantial increase in hepatitis B and second measles immunizations in states with middle school vaccination requirements. Childcare, school, and college entry vaccination requirements are beneficial for children and young adults and appear to be effective nationwide, regardless of race, ethnicity, and/or socioeconomic status.

Barrier 5: The community or individuals in the community are uninformed or misinformed about the safety and importance of vaccinations. Community vaccine education programs can provide most or all of a population or subpopulation in a geographic area with knowledge and information that may change their behavior in favor of acceptance of vaccines. Education strategies include mailings, messages delivered through the schools and media, telephone calls, and posters. These interventions have the potential to reduce disparities in immunization rates between inner-city and suburban children, and among racial and ethnic minority populations.

Barrier 6: Lack of specific information about what vaccines are needed or were given. Supplying patient-held medical records is an intervention that provides personal medical records to members of a target population or their families. Such records show which vaccinations have been received. State and local health departments and many providers have encouraged the use of patient-held medical records to varying degrees. Patient-held medical records could result in increases in vaccination coverage by increasing knowledge about and demand for vaccinations among parents, by reducing missed opportunities to vaccinate in healthcare settings, or a combination of the two.

Training. Training is always one kind of welfare. Because it builds confidence among the trainees. Even periodical training also play significant role in gaining confidence.

1. A national core committee for training in immunization should continue to oversee and contribute to development of materials and methods for training in immunization.
2. Performance indicators and expected performance for basic healthcare workers should be defined.
3. Pre-service/in-service training curricula should be re-designed to be relevant to the expected performances of these cadres. This training should be competency-based, hands-on, practical, preferably including coached sessions in the field, before certification. There is an urgent need to train health workers on:

(1)   Micro planning for routine immunization

(2)   Injection safety and waste disposal

(3) Immunization of children not immunized as per the schedule.

1. Refresher training should be designed to meet the performance needs of the basic healthcare workers.
2. A team of master trainers should be trained at the national and regional health training centres, who are not only knowledgeable and skilful in the subject matter but also competent in delivering competency-based training. All the available resources (government training centres, public and private schools of health professionals, NGOs, UN organizations, etc.) should be utilized to form such a team.

Different International Workshop regarding Immunization

Workshop at Nepal.

The Global Training Network Workshop on AEFI was held in Kathmandu, Nepal, from 4-10 November 2001. The objectives of the workshop were:

(1) To provide participants with the skills, awareness and information needed to develop or strengthen national and sub-national vaccine safety systems, and

(2) To encourage collaboration between national immunization programs, National Regulatory Authorities and with other key players to minimize and prevent risk of harm associated with immunization or perceived to be associated with immunization. The occasional severe adverse event or cluster of adverse events associated with the use of vaccines may rapidly become a serious threat to public health programs, if not handled correctly. In addition, as vaccine preventable diseases become less visible through effective immunization programs, the public tends to focus more on AEFIs than on the disease threat. It is essential that national monitoring and reporting systems for vaccine safety are efficient and adequately coordinated to deal with such events and that public concerns are addressed through sound communication strategy at national as well as community levels. The cornerstone of an AEFI system is rapid investigation and identification of causal factors. This becomes even more crucial during mass immunization campaigns.

The objectives of the training were as follows:

a. To develop an appreciation for the importance of a national immunization safety program

b. To develop or strengthen the detection and reporting system for AEFI within a country

c. To investigate an AEFI or cluster of AEFIs

d. To analyze and assess data on AEFIs

e. To assess the need and carry out corrective action in response to an AEFI or cluster of AEFIs

f. To evaluate actions taken in response to AEFIs

g. To understand the importance and the respective roles of NRA and national immunization programs and other role players in ensuring the safety of vaccines used in immunization programs

h. To promote collaboration and communication between NRA, national immunization programs, the Ministry of Health, health professionals, the media, patients and parents and the public.

i. To consider and present a draft plan of action by each country for strengthening the national immunization safety program for implementation.

The workshop used various techniques to encourage participant interaction, learning, and sharing experiences. These include facilitator presentations, small group discussions, small group work sessions, case studies, role-playing, and individual country presentations.

AEFI Reported Cases in Bangladesh⁵⁵:      Bangladesh has developed the surveillance system for AEFI in 1998-99 (CES 2000). In this regard preparation of AEFI surveillance manual, format development and training for fields staffs of several districts and upazilla level have completed. Regardless of the type of AEFI, national EPI authority have selected 6 types of events which are reportable and require further investigation. Those are called trigger events. Officially, surveillance and reporting of AEFI have been started in several districts and upazillas from April 2003.

In 2004, there were following reported four cases :

a. Three suspected polio  cases. In Rangpur (Rajshahi division) , Khulna (Khulna division) and Bandarban (Chittagong division) districts)

b.One death of boy aged six in Khulna (Khulna Division)

One boy dies after administration of Vitamin-A capsule in Munshiganj (Dhaka division) during NID

In 2003, there were following cases reported

a.  3 deaths in Jamalpur (Dhaka division) after measles vaccination

b.  Six more fell ill, later recovered

c.  All deceased were 10-month old

d. Two girls, one boy

Another part of the post:

Immunization Among Infants in an Urban Slum (Part-2)