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IAP GUIDEBOOK ON IMMUNIZATION

Editors

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

IAP Committee on Immunization 2005-2006

Chairperson: Dr. Raju C. Shah Co- Chairperson: Dr. Nitin K. Shah Convener: Dr.Shyam Kukreja Members: Dr. Rohit Agarwal Dr. Indra Shekhar Rao Dr. Shivananda Dr. Nigam P Narain Dr. Sangita Yadav Ex-officio members: Dr. Deepak Ugra Dr. Tapan Kumar Ghosh Dr. VN Yewale Dr. Naveen Thacker Dr AP Dubey Dr Surjeet Singh
Address for correspondence:

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

Immunization is the single most successful child survival s t rat egy the world over. Immunization also reduces morbidity to great extent. Due to progress in molecular biology and genetic engineering a number of new vaccines have become available and many more are in the pipeline. Many of the developed countries have reduced their vaccine preventable disease burden by using this tool very effectively. As Pediatricians we must be conscious of the fact that the immunization needs of the children are quite dynamic. A vaccine which may not be considered important today may become n ecessary in future as more informat ion about the epidemiology of the disease becomes available. The inclusion of an y n ew v accine in the universal immunization program of a country depends on disease epidemiology, availability of safe vaccine, economic constraints and logistic problems. Unfortunately the limiting factor most of the times in developing countries like India is the affordability. There is always a need to update knowledge and co n cep t s es pecially in the field of immunization as there is continuous flow of new knowledge. Also one must try to objectively understand a difference between a public health measure paid for by the government and a personal safety measure instituted by the individual at one's own cost due to certain limitations. To get the most benefits for any vaccine (herd effect), adequate immunization coverage is required. Unfortunately, in our country the routine immunization coverage rates have slipped down over the last few years. This is a matter of great concern to all of us. This has been one of the major obstacles in polio eradication program. There is an urgent need to reinforce quality immunization services and our academy has always been at the forefront of this initiative. We are sure this updated guidebook will continue to serve as ready reckoner on issues concerning vaccines and immunization in our country.

Dr. Raju C Shah

Dr. Nitin K. Shah

Dr. Shyam Kukreja

Chairperson, IAPCOI 2005- 2006 President IAP 2005

Co-Chairperson, IAPCOI 2005-2006 President IAP 2006

Convener, IAP COI 2005- 2006

Contents

Introduction Historical aspects Basic immunology National immunization schedule Commonly used vaccines Newer vaccines Vaccines used in special circumstances Combination vaccines IAP Immunization Time-Table Immunization in special circumstances Adverse reactions following immunization The cold chain Surveillance for vaccine preventable diseases Vaccination in the current millenium IAP COI meeting report and policy updates

5 6 8 10 11 24 27 30 34 36 42 44 49 50 51

Introduction

Protect ion from preventable diseases, disabilities and death through immunization is the birth right of every child. Immunization is one of the most co s t-effective health intervention s known to mankind Over the last three decades, a lot of progress has been made globally as far as protection against the eight important vaccine preventable diseases is concerned - from less than 5% children who were protected against these diseases in the early 1970s, to as many as 75% being protected now. Small pox has been eradicated and we are at the threshold of eliminating polio.

consensus based on the current evidence from the literature. The IAP Immunization Time Table represents the 'best individual practices schedule' for a given child and would necessarily be at some variance from the National Immu n ization Schedule of the Government of India, which is meant for the public at large. With the availability of many newer vaccines, it is necessary that some of these should be considered for routine immunization and the immu nization schedule has to be changed accordingly.

An effective National Immunization strateg y can help decrease childhood morbidity and mortality, especially in developing countries. It must, however, be clear that immunization strategies may vary from co u n try to country depending on the local req u irements. This guide book represents the collective effo rts of the members of the Indian A cademy of Pediatrics Co mmittee on Immunization (IAP COI). We are aware that unanimity may not always be possible as far as the need and timing of certain newer vaccines are concerned, but we have made efforts t o arriv e at a

Unfortunately, there is lack of authentic data on epidemiology of most infectious diseases in our country. However that should not deter us from using some of these vaccines till such data is generated. Many decisions on incorporation of new vaccines in t he immunization program have, therefore, to be based on data from other parts of t h e world. This may appear unscientific to some, but is a reality and is the only way out at present.

Historical Aspects

Though Dhanvantri, t h e father of Indian Medicine, sp o ke of preventing certain infectious diseases t h rough immunization, the first successful vaccine in the modern era was developed b y Edward Jenner in 1796 when he used cowpo x inoculation (vaccination) to protect against smallpox. Louis Pasteur developed a h ig h ly effective vaccine against rabies, which was used for post-exposure prophylaxis. It was first given to a child in 1885. Since then many other vaccines have been developed in rapid succession. Experience with smallpox eradicat io n p ro g ram convinced the health policy makers that immunization was the most powerful and cost-effective measure for control of vaccine preventable diseases. At the global level, an organized immunization program came into exis tence in the year 1974 under the banner of the World Health Organization (WHO). This was christened as the 'Expanded Program on Immunization' (EPI). The term "Exp anded" referred to the provision of adding more antigens to vaccinatio n s chedules, extending coverage to all corners of a country and spreading services to reach the less privileged sections o f the society. The EPI program focused on children below 5 years of age and pregnant women. The vaccines included were BCG, DTP, OPV, Measles and TT. The primary health care concept as enunciated in the 1978 Alma Ata Declaration in cluded immunization as one of the strategies for reaching the goal of 'Health for All' by the y ear 2000. The Government of India adopted the EPI in 1978 with the t win objectives of reducing the mortality and morbidity resulting from vaccine preventable diseases of childhood, and to achieve self-sufficiency in the production of vaccines. The program started with BCG, DTP and Typhoid vaccines - it did not include measles vaccine. OPV was added only in 1979 and measles later on. Ty p h oid vaccin e continued to be a part of our national immunization schedule until 1985. Program coverage of 85% was envisaged, but this could not be achieved for several years and independent evaluations showed very low coverage rates in many parts of our country. Th erefore, a change of strategy was considered necessary. 6

In 1985, the EPI was s upplanted by the Universal Immunizat ion Program (UIP). The main objectives of UIP were: i) universal immunization and reduction in mortality and morbidity due to vaccine prev entable diseases ii) self-sufficiency in vaccine production iii) establishment of a functional cold chain system, and iv) the introduction of district level monitoring system. In this program the emphasis was s hifted from the under-five to under-one age group, thereby reducing the number of potential beneficiaries. It considerab ly reduced the denominator for percentage coverage. The vaccines recommen d ed were BCG, DTP, OPV and Measles for infant s an d TT for pregnant women. It should be noted that UIP envisaged 100% coverage of pregnant women with 2 doses of tetanus toxoid (or a booster dose, as applicable) and at least 85% coverage of infants. Under the UIP, the govern ment also aimed to establish logistics of vaccine production and supply as well as training of medical and p aramedical personnel. The Government of India subsequently set up a " Technology Mission on Vaccination and Immunization of Vulnerable Po pulation, especially Children" to cover all asp ect s of the immunization activity from research and development to actual delivery of services to the target population. Since switching over to UIP in India there has been a significant decline in many of the vaccine preventable diseases, such as poliomy elitis, neonatal tetanus, diphtheria, wh o o p ing cough and measles. The UIP became an integral component of Child Survival and Safe Motherhood Program (CSSM) in 1992 and then part of Reproductive and Child Health Program (RCH) in 1997. Supplemen t ary immunization activities against poliomyelit is were started in 1995-96. In 2002, Hepatitis B vaccination was initiated in selected areas targeting the urban poor. The WHO also endorsed global efforts at immunization through Universal Childhood Immunization (UCI) in 1990 - the name given to a declaration sponsored by UNICEF as part of the 40th anniversary of the United Nations in October 1985. Efforts were undertaken to initiate research for the development of newer vaccines, to improve vaccine product ion technologies and to

u n d erstand the epidemiology of diseases. These developments were highlighted in 1990 at the Summit for Children, where it was claimed that EPI had indeed been a global success with 80% reported coverage with the six vaccines. In 1992, the WHO also set a target for universal Hepatitis B immunization. It aimed to incorporate Hepatitis B vaccine in the immunization schedules o f all member countries by 1997. However unfortunately less than 50% of t h e countries have actually introduces Hepatitis B vaccine in their National Schedule. India has recently accepted its inclusion in National schedule and the coverage will expand in a phased manner. These global efforts at immunization were launched under the banner "Children Vaccine Initiative" (CVI) in 1991 with support from several in t ernational agencies like the WHO, UNICEF, World Bank and the Rockefeller Foundation. CVI aimed at development of newer vaccines, improvement in vaccine production technolo g ies and vaccine quality. These efforts were further co nsolidated under the "Global Program on Vaccines and Immunization" (GPV) in 1993 reflecting the EPI and UCI init iative and combining these with the CVI. The focus of GPV is on sustaining high vaccine coverage, developing global surv eillance network and evolving eradication strategies. The "Global Alliance for Vaccines and Immunization" (GAVI) was set up in 1999 as an international coalition of multination al funding agencies (e.g. Bill and Melinda Gates Foundation, Rockefeller Foundation), v accin e man u fact u re r s , n o n - g o v ern men t al organizations and the governments of 74 d ev eloping nations. GAVI organizes its activities through a vaccin e fund. The main objectives of GAVI are as follows: i) impro v in g acces s t o s u s t ainable immunization services ii) expanding use of all existing safe and effective vaccines iii) accelerat ing the development and introduction of new vaccines iv)

augmenting research and d ev elopment on vaccines against HIV, malaria and tuberculosis v) making immunization coverage an integral part of international development initiatives. The GAVI Ind ia Project has been instrumental in launching free Hepatitis B immunizatio n in some of the urban slums. It has also endeavored to promote safe injection practices and use of auto-disable syringes for immunization as part of a countrywide initiative. A surv ey conducted in 2002 under the RCH showed that immunization coverage rates in India have been d eclining, since 1999. The Government of India h as recently lau n ched an Immunization Strengthening Project with the objectives of i) strengthening routine immunization with the aim of raising the percentage of fully immunized children t o ab ove 80% ii) eliminating polio and achieving polio eradication iii) reviewing and developing a new vision of the immunization program in the medium term keep in g in view the development of new epidemiological patterns, availability of new vaccines and delivery mechanisms and advances in cold chain technologies iv) improving surveillance and monitoring mechanisms. The National Institute of Health and Family Welfare has been identified as the nodal institute for coordination and implementation of the program an d the training shall be carried out through five regional inst it u tes. Training of mid-level managers, including persons actively involved in immunization program at the district and state level, is an integral component of this project. The project was started in 50 poorly performing districts of 8 priority states of Uttar Pradesh, Bihar, Madhya Pradesh, Rajasthan, Oriss a, Gujarat, Assam and West Bengal. These newer initiatives have improved overall coverage in these districts. Unfortunately last report of National family and health survey released in 3rd week of Nov '06 do not confirm this improvement.

Basic Immunology

The Greek work "immune" means "to be protected". Protection offered by the introduction of various antigens or ready-made antibodies is called acquired immunity. The process by which t h is acquired immunity is obtained is known as 'immunization'. This is of two types, active and passive. When specific antigens evoke the required immune response in the system it is called active immunization, and when antibodies are supplied readymade in th e form of immune g lo b u lins and sera it is known as passive immunization. Pathogenic infectious ag en t s induce disease and the host immune system responds with immunity , first to ensure recovery and then to offer protection from disease if the same patho gen were to be encountered again. A vaccine is composed of one or more antigens of the pathogen, which will induce a protective immune response without suffering from the disease. Vaccines consist of attenuated live organisms (eg. oral polio vaccines, oral typhoid vaccine, varicella vaccine, measles vaccine), whole inactivated org anisms (e.g. pertusis vaccine, whole cell typhoid vaccine, rabies vaccine, inactivated polio vaccine), modified exotoxins called "toxoids" (e.g. diphtheria toxoid, tetanus toxoid), or subunits (e.g. polysaccharide antigens of Salmonella typhi or Haemophilus influenzae type b and the surface proteins of hepatitis B virus). Vaccines mimic infection with the respective pathogen, but without the asso ciated risk of developing the disease. The consequent immune response may be manifested through hu moral (i.e. antibody) immunity or cell mediated immunity (CMI) or both. If the antigen preferentially stimulates Th1 series of T helper lymphocytes, a strong lymphocytic respons e is obtained; if Th2 series is preferentially stimulated, the ultimate express ion of immunity is predominantly humoral. Carbohydrate antigens are T cell independent; hence they stimulate B cells directly without T helper cell modulation. This results predominan t ly in a IgM response wit h out IgG production or induction of immunological memory. BCG elicits CMI without an easily demonstrable humoral component. 8

BCG, oral polio v accine and Hepatitis B vaccines can be given soon after birth as the maternally derived immunity apparently does not interfere with the vaccine "take" On the other hand, live measles vaccine may be inhibited in the presence of detectable maternal antibody in the infant's circu lation. Measles vaccine, therefore, should only be given after at least 9 months of age ; similarly, MMR vaccine is given only after 12 months of age. Timing of vaccination depends upon the age at which the disease is anticipated as well as on the feasibility of administering the vaccine at that time. For instan ce, neonatal tetanus can only be prev en t ed through maternal immunization by ensuring adequate titers of transplacent al antibodies and not by immunization of the baby at birth. Vaccines are selected based on three important criteria viz. necessity, safety and efficacy. All vaccines are subjected to the following trials before being licensed: Phase I Trial: Human volunteers - for tolerance, safety Ph as e II Trial: Human volunteers - for immu n e response, safety Phase III Trial: For field efficacy, safety Further, before a vaccine is act u ally marketed it undergoes sterility, purity and potency tests at the level of the manufacturer and the Drugs Controller General of India. Most of the currently used childhood vaccines do not interfere with the vaccine "take" of one another. These can be, therefore, given simultaneously and several antigens can be g iv en the same day, if required. In general, the interval between two doses of the same v accine, say for instance DTP, should be at least 4 weeks; preferably 8 weeks. An interval of 4 weeks would obviously result in completion of the primary schedule at an earlier age an d may perhaps make it easier for the parents to remember their follo w-up appointments. Th is way the drop out rates may also decrease. BCG and OPV can be given from the day of

birth until 2 weeks of age, s o that there would be 4 weeks gap until the next contact for immunization at 6 weeks. If the opportunity to give BCG / Hepatitis B was not available in the neonatal period, it may be given at 6 weeks, s imultaneously with DTP and OPV. Some of the viral vaccines (e.g. measles, varicella) may be associated with possible short lasting suppression of the

immune system and it may be advisab le to avoid administratio n of other vaccines within 4 weeks of these. There is, however, very little objective evidence to show t h at this immunosuppression is clinically significant.

Terminology Vaccination: Immunization: process of inoculating the vaccine/antigen. process of inducing immune response which may be humoral or cellular.

Seroconversion: change from antibody negative state to antibody positive state. Seroprotection: a stage of protection from disease, due to the presence of detectable antibody. Antibody titer: the reciprocal of the highest serum dilution at which antibody has been detected.

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

Each time a vaccine is given the doctor should explain to the mother the nature of vaccine, t h e n umber of doses needed, the disease likely to be prevented,

anticipated adverse reactions and due date for the next session of immunization.

Types of Vaccines

Type of Antigen

Examples

Live bacteria, attenuated Live virus, attenuated Inactivated bacteria Inactivated virus Toxoid Capsular polysaccharide Viral subunit Bacterial subunit

BCG, Ty21a OPV, MMR, varicella Pertussis, whole cell killed typhoid IPV, rabies, HAV Tetanus, diphtheria, Td Typhoid Vi, Hib, meningococcal, pneumococcal HBsAg Acellular pertussis

National Immunization Schedule

Age Birth 6 weeks 10 weeks 14 weeks 9 months 16-24 months 5-6 years 10 years 16 years For pregnant women Early in pregnancy One month after TT TT1 or booster TT2

Vaccines BGG, OPV0 for institutional deliveries DTP1, OPV1 (BCG if not given at birth) DTP2, OPV2 DTP3, OPV3 Measles DTP, OPV DT* TT** TT

*A second d o s e of DT vaccine should be given at an interval of one month if there is no clear history or documented evidence of previous immunization with DTPw. ** A second dose of TT vaccine should b e g iv en at an interval of one month if there is no clear history or documented evidence of previous immunization with DTPw, DT or TT vaccines (Source: Govt. of India (1994) National Child Survival and Safe Motherhood Program, M in is t ry of Health and Family Welfare, New Delhi)

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Commonly Used Vaccines

A. Vaccines Against Diseases Covered Under EPI

BCG Vaccine Bacillus Calmette Guerin vaccine is derived from the bovine tuberculosis strain and was first developed in 1921. It was the result of painstaking efforts by t h e French microbiologist Albert Calmette and the veterinary surgeon Camille Guerin who performed 231 repeated subcultures over 13 years. It continues to be the only effective vaccine against tuberculosis The two common strains in use are Copenhagen (Danish 1331) and Pasteur of which the former was produced in India at the BCG Laboratories, Guindy, Tamil Nadu till recently. BCG induces cell-mediated immunity but t h e protective efficacy is a matter of debate and is very difficult to q u an t ify BCG vaccine is more effective against t h e development of hematogenous spread of Mycobacterium tuberculosis (which results in milliary and meningeal forms of the disease against which it has a protective efficacy of 50-80%), than against the development of pulmonary tuberculosis where it has a protective efficacy of less than 50%. The vaccine contains 0.1-0.4 million live viable bacilli per dose. It is supplied as a lyophilized (freeze-dried) preparation in vacuum sealed multi-dose dark colored ampoules. The lon g n ecked BCG ampoule should be cut carefully by gradual filing at the junction of its neck and body, as sudden gush of air in the vacuum sealed ampoule may lead to spillage of th e contents. The vaccine is light and heat sensitive and deteriorates on exposure to ult ra violet rays. Sterile normal saline should be used for reconstitution. As t h e vaccine contains no preservative, bacterial contamination may occur with repeated use. Therefore, once reconstituted, the vaccine should be used within 4 hours with the left-over being discarded after the session. In lyophilized form it can be stored at 2-80 C for up to 12 months, without losing its potency. One should 11 ensure maintenance of cold chain during transport and storage. Th e recommended dose is 0.1 ml of reconstituted vaccine irrespective of the age and weight of the baby. Injection of BCG should be strictly intradermal, using a Tuberculin syringe and a 26G need le. The convex aspect of the left shoulder is preferred for easy visualization of the BCG scar. The selected site may be swabbed clean using sterile saline - local antiseptics are unnecessary. A wheal of 5 mm. at the injection site indicates successful intradermal administrat ion of the vaccine. Subcutaneous administration of BCG is associated with an increased incidence of BCG aden it is . The injected site usually shows no visible change for several days Subsequently, a papule develops after 2-3 weeks, which increases to a size of 4-8 mm. by the end of 5-6 weeks. This papule often heals with ulceration and results in a s car after 6-12 weeks. Although the preferred time o f vaccination is soon after birth, it could be given up to the age of 5 years. If no reaction is seen at the local site even after 12 weeks, it is an in dication to repeat BCG presuming that BCG has not taken up. Adverse reactions - The ulcer at vaccination site may persist for a few weeks before formation of the final scar. No treatment is required for this co ndition. Secondary infection at the vaccination site may require an t imicro b i a l s . I p s i l a t eral axillary / cerv ical ly mphadenopathy may develop a few weeks/months after BCG vaccination. Antitubercular therapy is of no benefit in such situations and should not be administered. The nodes regress spontaneously after a few months. It should also be noted that if fine needle aspiration cytology of the nodes is carried out, stain for acid-fast bacilli may b e p o sitive. These are bovine vaccine bacilli and should not be misconstrued as being suggestive of tuberculous disease. In some children the

nodes may even liquefy and result in an ab s cess. Surgical removal of the nodes or repeated needle aspiration is the treatment of choice - again, antitubercular therapy is not recommended in this

s it u at ion also. Disseminated BCG infection is extremely unusual but may occur in children with cellular immunodeficiency.

Oral Polio Vaccine Oral polio vaccine (OPV) remains the vaccine of choice for polio eradication in India. It is a suspension of over 1 million particles of poliovirus types 1, 2 and 3. It is supplied with a stabilizing agent, namely magnesium chloride. The vaccine, therefore, is quite stable under refrigeration. When OPV is given by mout h , t h e vaccine viruses reach the intestines where they must establish infection (vaccine virus "take") before an immune response may occur. A high level of gut immunity ensures that vaccinated children would not participate in the chain of transmission of wild (pathogenic) polioviruses. For reasons that are not clearly understood, OPV "take" rates may be somewhat variable. Seroconversion rates after three doses of OPV average 73%, 90% and 70% for Types I, II and III respectively. It is for this reason that multiple doses of OPV are necessary before 90-95% of children develop immune responses to all three poliovirus typ es . IAP recommends at least 5 routine doses of OPV, d u ring infancy and 2 more repeat doses; at 16-18 months and 5 years. In addition to the routine OPV doses , " Pulse OPV doses" every year on Nat io n al Immunization Days (NIDs) and sub-National Immunization Days (sNIDs) until the age of 5 years are also mandatory. Polio eradication is defined as no case of paralytic poliomyelitis by wild polioviru s in last three calendar years along with absence of wild poliovirus in the community, when excellent clinical and virological surveillance exists and the coverage of routine OPV is more than 80%. Polio elimination is defined as no case of paralytic poliomyelitis by the wild poliovirus in one calendar year with other criteria being the s ame as in eradication . A d eq u at e immu n izat io n , clinical surveillance and appropriate virological investigations in all children with acute flaccid paralys is (AFP) are the cornerstones of polio eradication. OPV should be stored at -200 C at the state and district level and in the freezer at the clinic level. The vaccine 12 must reach the outreach facility at 2-80 C in vaccine carriers with ice packs. Breastfeeding and mild d iarrh ea are n o co n t rain d icat io n t o OPV adminis t rat ion. If a substantial amount of OPV is vomited or regurgitated wit hin 5-10 minutes of administration, the dose should be given again. If this repeat dose is also not retained, neith er of the doses s hould be counted and the vaccine shou ld b e re-administered at a later visit. Adverse reactions - OPV is an excellent vaccin e and the WHO Global Polio Eradicat io n Initiative is at the threshold of achieving its goal of eradicating wild polioviruses. By mid-2006 polio has been elimin ated from all countries other than India, Pakistan, Afghanstan, Nigeria, Niger and Egypt. For developing cou n t ries OPV is still the vaccine of choice for eradicating wild poliovirus and would continu e t o be used until wild poliovirus circulation ceases. However, like any other vaccine its use is associated with certain risks. OPV has been associated with occurrence of Vaccine Associat ed Paralytic Poliomyelitis (VAPP) Today, as we move towards p o lio eradication, VAPP is more common than paralysis due to wild polioviruses and has, therefore, become an increasingly contentious issue for all pediatricians . The risk of VAPP would continue to be there as long as we are using OPV as the preferred vaccine against poliomyelitis. It has been estimated that the global VAPP burden is in the range of 250-800 cases an nually. Nearly 50 cases of VAPP are reported to occur in India annually. Approximately half of all VAPP cases are associated with the Type 2 OPV strain. The second major problem with u s e of OPV is the emergence of circulating Vaccine Derived Polio Viruses (cVDPVs), which are mutants that re-acquire wild virus-like properties and have been associated with outbreaks of paralytic polio. cVDPVs usually aris e in communities with low population immunity especially

when polio vaccine coverage rates decline but OPV use continues. The duration and extent of spread of cVDPVs are dependent on the magnitude of the immunity gap. As lo n g as OPV is in use it is mandatory that very high immunization coverage is maintained so as to decrease the risk of emergence of cVDPV. W hereas VAPP occurs in individual cases, cVDPV can result in large outbreaks. It has been

suggested that mass OPV campaigns should be s ynchronized with the cessation of OPV use o n ce eradication of wild poliovirus has been achieved, so as t o eliminate the risk of VAPP and the emergence o f cVDPVs. At the same time, a gradual transition to IPV should be encouraged.

Polio Eradication Why do we need pulse immunization against polio? Simultaneous administration OPV to all susceptible infants and children interferes with circulation of wild poliovirus in the community. It is, therefore, important to ensure complete coverage with OPV during NIDs so that no wild poliovirus remains in circulation. Core strategies for eradication of polio include:

Maintaining high routine infant immunization coverage with OPV. Conducting mass campaigns (i.e. pulse immunization against polio). Development of sensitive surveillance. Organization of mop-up campaigns.

Inactivated Polio Vaccine (IPV) IPV is formaldehyde killed poliovirus grown in monkey kidney cell/human diploid cells. Old IPV contained 20, 8 and 32 D antigen units of types 1, 2 and 3 polioviruses respectively. All curren tly used IPV vaccines are enhanced potency IPV (elIPV) which cotains 40, 8 and 32 D antigen units of type 1, 2 and 3 respectively. Currently term IPV means eIPV. It is highly immunogenic. Seroconversion rates are 90-95% after two doses given after the age of 2 months and at 2 months interval and 99% after three doses given even when it is started at 6 weeks of age and given an 4 weeks interval It produces excellent humoral immunity as well as local pharyngeal and, possible in testinal immunity. The vaccine is very safe. It is now licensed to be used in India by Drug controller of India. IPV can be used in combination with DTwP and Hib vaccines without compromising seroconversion or increasing side effects. Ideal age to give first dose of IPV is 8 weeks an d the interval between two doses should also be 8 weeks. However if 3 primary doses are given, vaccine could be started at 6 weeks of age and 13 could be given at 4 weeks interval without any compromise in the seroconversion rates. Scientifically and immunologically schedule of giving two doses of IPV starting at 2 months of age and given at 2 months interval followed by a booster at around 15 mo n t h s is similar to a schedule of giving 3 doses starting from 6 weeks of age and given at 4 weeks interval followed b y a booster at 15 months (even in developing countries). However in our country the later schedule of 3 primary doses is better logistically as it can be given along with DTP at 6, 10 and 14 weeks followed b y a booster at 15 months. In any case the b irt h d o se of OPV must be given and all the OPV doses on the days of NIDs / SIAs should be given to all the children. As the number of wild poliovirus cases in the country decreases, it is inevitable that one would have to shift fro m OPV to IPV in the next few years. The government sh o uld, therefore, consider incorporating IPV in the national immunization schedule in a phased

manner. IPV can also be an additional tool to eradicate wild polio from last few high risk difficult districts. IPV is also the vaccine of choice in patients with immunodeficiency and th e preferred vaccine in children with symptomatic HIV infection. Post-polio eradication scene and polio immunization: IA P believes that it will be unsafe and unethical t o continue to use OPV in post-p o lio eradication era. Following concept s should be kept in mind while deciding India specific guidelines for post-polio eradication immunization.

3.

1.

2.

It will be unethical and unsafe to continue to use OPV after zero wild polio case and zero transmission status is achieved due to risk of VAPP following OPV. It will be unwise to discontinue use of polio immunization altogether after zero polio status is achieved due to fear of cVDPV and iVDPV. Past experience from some countries has shown that countries which have eradicated wild polio virus and have slackened in their routine polio immunization programs have experienced cVDPV outbreaks. These outbreaks of cVDPV were curtailed by strengthening routine immunization and giving 2 or more

rounds of SIAs using OPV. However in post-polio eradication era, it will be unethical and unsafe to reintroduce OPV in such areas. It will force us to depend on the stocks of WHO or any such agency for OPV vaccine should out-break of wild polio or cVDPP occur. Hence India should preempt the emergence of cVDPV and has to become self sufficient in stock-piling enough polio vaccine now to meet any such unforeseen eventuality in future. Looking at the above problems, IAP recommends that India should switch over to IPV, preferably as IPV-DTP, in its routine immunization program gradually in post-polio eradication era. India should encourage indigenous manufacturer to produce enough IPV so that it becomes affordable so that is will be possible to switch to IPV in due course, looking at the huge requirement of the number of doses.

Adverse reactions - Th e vaccine is very safe. As IPV contains trace amounts of streptomycin, neomycin and polymyxin B, allerg ic reactions may be seen in in d iv id u als wit h hypersen s it iv it y t o t h es e antimicrobials.

DTPw Vaccine The combination of diphtheria t o xoid, tetanus toxoid and whole cell killed pertussis vaccine (DTPw) is popularly known as the "triple antigen" DTP is the core vaccine in all childhood immunization services. It is one of the oldest combination vaccines and has been in continuous use for more than 55 years. Tetanus an d diphtheria toxoids are adsorbed on insoluble aluminium salts which act as adjuvants and enhance the antitoxin responses to both the antigens. While the two toxoids are highly immunogenic (95-100%), the pertussis vaccine (even after 3 doses) has a protective efficacy of about 70-90% only. Adverse reactions - Local (pain and redness) and systemic (fever) side-effects of the DTPw vaccine are almost entirely due to the pertussis component. Whole cell pertus s is vaccine has been incriminated in the 14 induction of a neurological reaction in v ery rare instances; however, there has been no conclusive proof for this and the vaccine should not be denied to children with seizure disorders or st ab le neurological conditions (e.g. Cerebral palsy, developmental delay). The results of the National Childhood Encephalopathy Study (NCES) in the United Kingdom clearly show that there is no causal relationship between administration of DTPw vaccine and development of chronic neurological disease in children. Convulsions following DTPw v accine are distinctly rare, and may only represent n o t h ing more sinister than fever triggered seizures. Progressive/evolving n eurological illnesses, however, are a relative contraindication to first dose of DTPw immunization. For children who develop persistent inconsolable cry of more t h an 3 hours

duration, hyperpyrexia - fever > 40.50 C or hypotonic - hypo responsive episode HHE (collapse/shock like stage) within 48 hours of DTPw admin is t ration, seizures with or without fever within 72 h ours of admin is tration of DTPw, the decision to administer further doses of DTPw should be carefully evaluated and discussed with the parents These events were regarded as absolute contraindications in the past. They are now considered mere precaut ions because these events generally do not recur with the next dose and they have not been proven to cause permanent sequelae If a similar adverse reaction recurs with the subsequent

dose only then pertussis vaccine is contraindicated for future administration. DTP and DT vaccines need to be stored at 2-80C. These vaccin es s hould never be frozen, and if frozen accidentally, it should be discarded. DTP must be injected intramuscularly and the preferred site is th e anterolateral as p ect of the thigh. The IAP COI recommends 5 doses of DTP - three in infancy with two boosters at 18 months and 5 years. The DTPw or DTPa vaccines can be administered up to the age of 7 years. After the age of 7 years, Td should be given.

Acellular Pertussis Vaccine (DTPa) DTPa vaccines are of various types depending on the number of constituent components viz. two component DTPa containing pertussis toxin (PT) and filamentous haemagglutinin (FHA); three co mponent DTPa containing pertact in in addition to PT and FHA; five component DTPa containing agglutinogens 2 and 3 in ad d ition to PT, FHA and pertactin. Though a five component DTPa vaccine may be expected to elicit a more robust immune response as compared to two and three component DTPa vaccines, the overall efficacy of DTPa vaccines is comparable to the DTPw vaccine. Dose: 0.5 ml by intramuscular injection. If parents are not willing for DTPw administration after the adverse reaction with the previous dose, DTaP can be recommended in such circumstances as this vaccine is less reactogenic. If encephalopathy (major alteration of sensorium or illness with seizures lasting > 24 hours) occurs within 7 days of DTPw administration, further doses of DTPw and DTaP are contraindicated. Pertussis vaccine should not be given in such cases and instead DT should be administered in the future. In case immediate anaphylaxis occurs after DTwP administration, further DTwP/DTPa should be avoided because of uncertainty about which component of these vaccines has caused the reaction, as is true with any vaccine.

The IAP COI unequivocally endorses the continued use o f DTPw vaccine because of its proven efficacy an d safety. DTPa Vaccine may u ndoubtedly have fewer minor side-effects (like fever, local reactions at injection site and irritability) but this minor advantage can not justify the inord in at e costs involved in the routine use of this vaccine. DTPa vaccines are also by no means more effective than the whole cell pertussis vaccine. These are, therefore, not recommended for universal immunization in our country at present. There is, however, no bar to offering these vaccines to children from families who opt for the slight advantage of fewer minor side-effects.

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

Tetanus Immunoglobulin (TIG) It is a liquid preparation containing immunoglobulins, mainly IgG, obtained from the plasma of healthy donors. In dications: Unimmunised or inadequately immunized individuals with burns, roadside injuries and compound fractures. Adverse reactions: Local pain, fever, flush in g , headache and chills may occur. Dose: for Prophylaxis: 250-500 IU IM. Therapeutic: tetanus neonatorum: 500-1000 IU IM or 250 IU intrathecal. In children and adults: 500-1000 IU IM and/or 250-500 IU intrathecal.

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

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

B. Vaccines Recommended Against Diseases Not Covered Under EPI

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

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

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

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Hepatitis B Vaccine In India, 1-4% of individuals are found to be chronic carriers of Hepatitis B Virus (HBV). Infection with HBV may occur perinatally (v ertical transmission), during early childhood (the so-called horizontal spread ), through sexual contact or nosocomially. It should be noted t h at in our country horizontal route (e.g. ch ild to child) route and the vertical route (i.e. mother to child) are the major routes of transmission of hepatitis B. Younger the age of acquisitio n of HBV infection, higher the chances of becoming a chronic carrier. It is believed that as many as 90% of those who are infected at birth go on to become chronic carriers. In fect ion with HBV is one of the most important causes of chronic hepatitis, cirrhosis of liver and hep atocellular carcinoma. 30% of the chronic carriers go on to develop chronic liver disease. These are all preventable by early childhood immunization. It is for this reason that the World Health Organization has recommended u niversal Hepatitis B vaccination. As many as 150 countries have n ow included HBV in their national immunization sch ed u les . In Ju n e 2002, the Government of India also initiated the incorporation of HB vaccine as a univ ersal vaccine through a pilot program which will be scaled up in a phased manner. HB v accine is a highly purified recombinant DNA vaccine produced in the yeast species Hansenula polymorpha, Saccharomyces cerevisiae or Pichia pastoris. It is adjuvanted with aluminiu m salts and should be stored at 2-80 C. The vaccine should not be frozen - if frozen accidentally, the it should be discarded. It should be injected intramuscularly in the anterolat eral thigh. The usual pediatric dose (< 12 years o f ag e) is 0.5 ml corresponding to 10g of the antigenic component. Adult dose is twice the pediatric dose. The vaccine is hig h ly immunogenic and seroconversion rates are greater than 95% after a three dose schedule. Antibody titers greater than 10 mIU/ml are considered protective. The dose may be increased when vaccinating immunocompromized individuals e.g. patients on chemotherapy for malignant conditions or those with chronic ren al failure awaiting hemodialysis. HB vaccine may be given in any of the follo win g schedules: 1. 2. 3. Birth, 1 and 6 months Birth, 6 and 14 weeks 6, 10 and 14 weeks

Immunologically 0 - 1 - 6 months schedule of hepatitis B immunization has been most widely used and proven to be ideal with high antibody titers at the end of the v accination. However now that HB vaccination is integrated into the existing immun ization program (UIP) in India, d u e to operational issues at a national level one has to piggy back on the available contacts for routine immunization i.e. DTP wh ich is given at 6, 10 and 14 weeks of age. At the same time birth dose has to be given to cover for the vertical route. Hence IAP COI recommends 0 - 6 - 14 wks schedule for public measure. In case birth dose has been missed, 6 - 10- 14 wks sched u le can be followed. In office practice, one can still use 0 - 6wks - 6 months schedule. As on now, from the d ata available, none of the above schedules needs a booster. Th e p urpose of Hepatitis B vaccination is to prevent chronic in fection and development of chronic liver disease / hepatocellular carcinoma later in life. An ideal HB vaccine schedule should, therefore, address vertical as well as h orizontal modes of transmission of the virus. Pregnant women should be counseled and encouraged to opt for HBsAg screening. If the mother is known to be HBsAg negative, HB vaccine can be g iv en along with DTP at 6, 10 and 14 weeks/6 months as there is no special requirement to start vaccinat ion at birth itself. This 6-10-14 wks schedule may be easier to implement in the context of the national immunization program as higher vaccination coverage may be achieved with earlier administration of vaccines. If the mother's HBsAg stat u s is not known, it is important that HB v accination should begin within a few hours of birth so that perinatal transmission can be prevented. Any one of the following schedules may be used for this purpose; birth, 6 and 14 weeks or birth, 6 wks and 6 months. If the mother is HBsAg positive (and especially HBeAg 20

positive), the baby should be given Hepatitis B Immune Globulin (HBIG) within 24 hours of birth, along with HB vaccine (at birth, 6 and 14 weeks or birth, 6 weeks and 6months) using two separate syringes and separate sites for injection. If HBIG is not available (o r is unaffordable), HB vaccine may be given at 0, 1 and 2 months with an additional dose between 9-12 months. It has been suggested by many authorities that in infancy the third dose of HB vaccine should be given at least 16 weeks after the firs t d ose & at least 8 weeks after the second dose and not before 6 months of chronological age, as it presumably gives longer lasting immunity. However this view is being challenged as HB vaccine is a T-cell dependent vaccine, the titers at the end of immunization schedule may not be important so far as it is well above the protective level. There would occur anamnestic response with the titers going up should there occur contact with th e v irus again in future. As logistically, it is easier to combine HB vaccine program with the DTP vaccine, it can be given in 0-6-14 weeks schedule too The vaccination schedule need not be changed for preterm and small-for-dates babies; in the case of extremely preterm babies, ho wev er, vaccination should commence only

after initial stabilization. For older children and adults the preferred schedule is 0, 1 and 6 months, '0' being the elected date for the first dose. In immunocompetent individuals HB vaccine induces an effective immunological memory that lasts life-long and protects against symptomatic acute illness and development of chronic HB infection on exposure to the virus. Boosters of HB vaccine are, therefore, not necessary under usual circumstances. HB vaccination is now being integrated into t he existing immunization program in India. It was introduced in 15 cities an d 32 districts in the initial phase; selection of districts was based on achievement of targets of 80% or more DTPw-3 coverage under routine immunization based on evaluation surveys. Under this program, the vaccine is being provided free of cost to infants living in u rb an slums. The program will be expanded to include additional cities and districts within a certain timeframe. It is envisaged that HB vaccination will be introd u ced in all districts of India by 2007.

Hepatitis B Immunoglobulin (HBIG) HBIG provides immediate passive immunity and is recommended in situations wherein there has been acute expos u re t o HBsAg infected material e.g. by a needle-stick injury. Clinical trials h ave demonstrated 90% reduction in risk of transmis s ion following such exposure if HBIG is used alon g wit h Hepatitis B vaccine. HBIG does n o t interfere with antibody response to simultaneous HB vaccine. It is for t h is reason that individuals who have had recent accidental exposure to hepatitis B virus should be given combined passive-active immunization. It is also useful in prevention of mo t her to child transmission and transmission following sexual exp o s u re like in rape cases. Lastly HBIG is indicated in o ncology patients who may not respond adequately to Hepatitis B vaccine as they are immune compromised follo win g the malignancy as well its therapy. Adverse Reactions: Transient, mild pain at the site of injection and itching may be seen in a small proportion of recipients. Special Precauti ons : HBIG should never be administered intravenously. Dose: Adult s : 1000-2000 IU; Children:- 32-48 IU/kg bod y wt . This should be administered as soon as following exposure, preferably within 48 hours though it can be administered even if the patient reports late up to 7 day s after exposure. Neonates: 100-200 IU. The first dose should be administered as soon as after birth up to within 5 days of birth. An additional d o se of 32-48 IU/kg of body weight may also be given between 2-3 months after initial dose.

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Typhoid Vaccines Enteric fever is endemic in India and is a major public health problem. Th ree vaccines were available for clinical use till recently. However now only Vi typhoid
The Whole Cell Inactivated Typhoid Vaccine (TA/TAB)

vaccine is available commercially.

Heat-killed, phenol-preserved or the acetone inactivated lyophilized whole cell Salmonella t yphi vaccines were inexpensive products that have been in use in India for a long time. The p rotective efficacy of acetone inactivated preparation is more than that of the phenol preserved vaccine but the former is more difficult to prepare and is associated with more side-effects. Both vaccin es contain Salmonella typhi 1000 million organisms per ml. Protection begins 4 weeks after vaccination. Use of these vaccines may be associated with fever, local pain and malaise due to the endotoxins in bacterial cell wall. A pure S. typhi vaccine is less reactogenic than the combined TA/TAB vaccines. The vaccin e is very safe and is reasonably effective if revaccination can be carried out on a regular basis. The vaccine efficacy has been estimated to be 50-70% in a meta-analysis of the randomized co ntrolled trials available.

The vaccine appears to be protective through the induction of antibodies against cell wall somatic (O) and flagellar (H) antigens- these antibodies can act as a biological marker of the vaccine. It may interfere with the interpretation of the Widal test. It is effective even in child ren below 2 years of age and can be given to infants > 6 months of age Primary vaccination requires two d o s es , 4 o r more weeks apart, given subcutaneously. Pediatric dose of the vaccine is 0.25 ml in children aged 6 month s -10 years and 0.5 ml in order children. The vaccine should be stored at 2-80 C. It should never be frozen. Revaccination is necessary every 2-3 years to sustain an o ptimum immune response and should be done preferably before the onset of summer. Unfortunately, this vaccine is not being manufactured in India at present

The Vi-Capsular Polysaccharide Vaccine Th e vaccine consists of purified Vi-cap s u lar polysaccharide, which during natural infection inhibits p hagocytosis and serum bactericidal activity an d is responsible for virulence of the bacteria. It h as reasonable efficacy o f 50-60% in children and low reactogenicity. Protection begins within two weeks of vaccination and the biological marker is anti-Vi antibodies. It is not very effective in children below two years of age because it is an unconjugated polysaccharide vaccine as available in our country at present. Cost of the vaccine though a limiting factor in past, is now reasonably priced. The vaccine is available as an isotonic phenolated buffer solution; the dose is 0.5 ml. containing 25g of the polysaccharide. It can be given intramuscularly or subcutaneously. The vaccine s h ould be stored at 2-80 C. It should never be frozen. Adverse effects are mild and include pain and swelling at injection site.

Oral Live Attenuated Ty21a Vaccine:

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Salmonella typhi Ty21a is a live attenuated strain with a mutation in gal E gen e and lacks the enzyme UDP-gal 4 epimerase. It is genetically stable and is not known to revert to virulence. The efficacy has been shown to 50-60% with the capsule form and near 90% with th e liquid form (not available commercially). It provides protection by inducing local gut immunity but there is no biological marker of this vaccine. The vaccine is supplied in an enteric coated formulation as the bacteria are acid labile. It can be given to children six years of age and above as the capsules have to be swallowed intact. The vaccine is given on an empty stomach in three

sittings, on alternate days. The capsule should never be op en ed before ingestion. Protection begins within a week after completion of the course and the protective efficacy is as good as other available typhoid vaccines. Immunization needs to be repeated every 3-5 years The vaccine should be stored at 2-80C. Antimicrobials active against S. Typhi should not be used 3 days before and 7 days after oral typhoid vaccine administration as these may interfere with the v accin e "take". Unfortunately this vaccine is also not available now in our country.

The efficacy of all typhoid vaccines at best is 50-70%

Hib Conjugate Vaccines Haemophilus influenzae type b (Hib) is an important invasive pathogen cau sing invasive diseases like pneumonia, meningitis and bacteremia. Majority of cases occur in children below 2 years of ag e. Hib vaccination is given routinely in the d eveloped countries for last many years. Countries with sensitive disease surveillan ce systems have shown significant declines in in v asive Hib disease following the incorporation o f this vaccine in their national immunization programs. Recently published data of the Invasive Bacterial Infections Surveillance (IBIS) group from six referral hospitals in India (Lancet, 2003) show that Hib is a common cause of meningit is in our country. Hib capsular polysaccharide vaccine is a very effective and safe vaccine. A number of PRP conjugate Hib vaccines are available of which t wo are available in India viz. HbOC (with CRM 197 mutant diph t h eria toxin as conjugate) and PRP-T (with tetanus toxoid as conjugate). PRP-OMP (wit h meningococcal outer membrane protein as conjugate) is no t available in India HbOC and PRP-T vaccines show only a marginal increase in antibody levels aft er the first dose with a marked increase after the secon d and even better response after the third dose. On the other hand, PRP-OMP shows an increase in antibody level after the first dose itself with only marginal increases after the second and third doses. It is for this reason that while 3 doses of HbOC and PRP-T are recommended for primary vaccination, only 2 doses of PRP-OMP are recommended for this purpose. In spite of these apparent differences, these three vaccines when used in the recommended doses have similar efficacy. The vaccination schedule for Hib consists of three doses when initiated below 6 months, 2 doses between 6-12 months and 1 dose between 12-15 mon t h s , with a booster at 18 months. The interval between two doses should b e at least 4 weeks. If vaccination is delayed until 15 months, a single dose may suffice. It is highly efficacious vaccine, the protective efficacy being 95%. As Hib d isease is essentially confined to infants and young children, the vaccine is not necessary for children above 5 years. Hib vaccine is stored at 2-80 C. The IAP COI reco mmen d s use of Hib vaccine for all children . It is particularly recommended to be given p rior to splenectomy and in patients with sickle cell disease.

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C) Vaccines That Need to Be Given After Discussion With Parents

Varicella Vaccine Chicken pox is usually a self limiting and generally b enign disease affecting mostly children and youn g adults. Complications of varicella may be mo re commonly seen in immunocompromised individuals, adults and pregnant women. Takahashi et al developed a live attenuated vaccine from the Oka strain in Japan in the early seventies. The vaccine has been in clinical use in Japan since 1989 and in the United States since 1995. The vaccine can be administered to any healthy individual above the age of 12 months who has not had varicella previously. Varicella vaccines in use today are all derived from the original Oka strain but the virus contents may vary from one manufacturer to anoth er. The recommended dose is 0.5 ml and the minimum infectious virus content should be 1000 Plaque Forming Units. The vaccine is administered subcutaneously. A single dose is sufficient b elo w 13 years of age, after which two doses (at 4-8 weeks interval) are required. The vaccine is not recommended for ch ild ren below 12 months of age. Though vaccine manufacturers recommend to use this vaccine at 12 months, breakthrough infections can be less if used after 15 months of age. Hence IAP COI recommends to use this vaccine after the age o f 15 months. It is a highly effective vaccine and protective immunity, humoral as well as cellular, develops in 95-99% individuals. The immunity appears to be long lasting. The IAP COI opines that varicella vaccine is not recommended fo r universal immunization in India at present. One has to emphasize the generally benign nature of an d rarity of complications with varicella infection in young children. It may be offered to children fro m h igh socio-economic strata of society after explaining the pros and cons to the parents on a one-to-one "named child" basis. It may be prescribed to adolescents who have not had varicella in past (or are known to be varicella IgG neg ative) especially if they are leaving h o me for studies in a residential school/college. It is indicated in children with chronic lung/heart disease, humoral immunodeficiencies, HIV infection (but with C4 counts above 15% of the age related norms), leukemia (but in remission and off chemotherapy for atleast 3-6 months) and those on long term salicylates/high dose lone t erm oral steroids. Varicella vaccin e is also recommended in household contacts of immunocompromised children. It may also be considered in children attendin g crches and day care centers. When used for post-exposure prophylaxis it should be administered within 72 hours of varicella exposure - it should be noted, however, that the efficacy of the vaccine in preventing varicella under such circumstances is not very clear. Varicella vaccine is also indicated in susceptible adolescents and adults if they are inmates of or working in the ins t itutional set up e.g. s ch o ol teachers, day care center workers, military personnel and health care professionals. The vaccine is stored at 2-80C and can be administered subcutaneously or intramuscularly. It should be protected from light and needs to be used within 30 minutes of its reconstitution. Adverse reactions - It includes fever, vaccine ass o ciated rash, pain redness and swelling at vaccination site. When used in adult females, pregnancy should be avoided for at least 4 weeks after vaccination. Varicella zoster immunoglobulin (VZIG) is used for passive post-exposure prophylaxis in immunodeficient individuals who have been exposed to varicella or herpes zoster and are unlikely to have d et ectable antibody levels. It should be given to the neonate if the mother develops varicella 5 days before to 2 days after delivery. It has to be given by intramuscular injection and the dose is 125 units/10 kg body weight.

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Hepatitis A Vaccine Hepatitis A virus (HAV) infection is a relatively benign infection in young ch ildren as many of them have completely asymptomatic sub-clinical infection For instance as many as 50% of children between 2-5 years and 85% of those below 2 years who acquire HAV infection, may continue t o remain anicteric and may develop non-specific symptoms like any other viral in fection. In adults hepatitis A is frequently symptomatic and mortality is much higher than in children. The disease severity increases irrespective of age, in those with underlying chronic liver disease. Inactivated HA vaccines d eriv ed from HM 175/GBM strains and g ro wn on MRC5 human diploid cell lines are now available. The virus is formalin inactivated and adjuvanted with aluminimum hydroxide. It has been suggested that the vaccine can be used any time after 18 months of age when the maternally derived antibody levels have declined; It is given in a two dose schedule, 6 months apart. The adult formulation should be used after t h e recommended cut-off age of 15 years according to one manufacturer and 18 years according to the other The vaccine is given intramuscularly and the protective efficacy is 94-100% Immunity appears to be long lasting and boosters are not recommended at present. The IAP COI o p ines that HA vaccine is not recommended for universal immunization in India at present. One has to emphasize the generally benign nature of disease and very small number of children developing complications with Hepatitis A infection in young children. It may be offered to children from high s o cio-economic strata of society after explaining the pros and cons to the parents on a one-to one "named child" basis. It may be prescribed to adolescents who have not had viral hepatitis in past (or are known to be HAV-IgG negative), especially those who are leav ing home for further studies. It is recommended in all patients with chronic liver d isease (who are HAV seronegative) and family contacts of patients with chronic liver disease. It may be offered to household contacts of patients with acute HA virus infection - in t h e latter case the vaccine must be given within 10 days; however, it may not always be effective under such circumstances when the contact has had the same source of infection as the index patient. It may also be considered in children attending crches and day care centers and in travelers from abroad (e.g. non-resident Indians) visiting endemic areas. The vaccine is stored at 2-80C. Adverse reactions: It includes local pain and local induration.

Pneumococcal Vaccines Streptococcus pneumoniae is a common cau s e of invasive bacterial diseases responsible for a significant proportion of potentially fatal con d it io n s like pneumonia and meningitis in children. It also leads to conditions like otitis media and sinusitis, which may have morbidity but little or no mortality. In developing countries, this organism is believ ed to be the commonest cause of bacterial pneumonia. Peak incidence of pneumococcal disease is between 2 to 24 months of age. Based on the capsular polysaccharide antigen, p neumococci are classified into 85 different serotypes. Of these, about 10 serotypes account for most 25 infections. The common pathogenic stereotypes reported in children in Western countries are 1, 4, 5, 6, 9, 11, 14, 15, 18, 19 and 23. It appears that the serotypes causing invasive disease in developed countries are different from the ones which are found in developing countries. According to results of the Invasive Bacterial Infection Surveillance (IBIS) study, the common serotypes responsible for invasive disease in children below five y ears of age in India include 6, 1, 19, 14, 4, 5 and 7. Serotypes 1& 5 accounted for 29% of disease in India. Thou g h prevalence of penicillin resistance is almost negligible at present

there is some evidence that the prevalence of resistance to penicillin amongst the p neumococci may be gradually increasing, thereby highlighting the need for an effective vaccine. Two types of pneumococcal vaccines are currently available - the 23-valent unconjugated polysaccharide v accine and the 7-valent conjugate polysaccaharide vaccine. Immunity is serotype specific. The 23-valent polysaccharide vaccine contains the following serotypes - 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F. It is capable of preventing almo s t 85% of in vasive disease (pneumonia, men in g it is an d bacteremia) caused by pneumococci. Immunization, however, is not effective for prevention of otitis media. Each dose is 05 ml containing 25ug polysaccharide of each of the 23 serotypes co n tained in the vaccines. However, as it is an unconjugated polysaccharide vaccine it does not result in immunological memory. This vaccine is poorly immunogenic in children below two years of age i.e. children who are at highest risk of invasive disease. The dose is 0.5 ml and the vaccine is given intramuscularly or subcutaneously. This vaccine may be us ed in h igh-risk groups above the age of 2 years. Revaccination is recommended after 5 years. It is recommended for children with asplenia, sickle cell d isease and nephrotic syndrome. It is als o recommen d ed for HIV infected children. It may be offered to those with underlying chronic illnesses like renal diseases, cardiovascular diseases or diabetes. The heptavalent conjugate vaccine (PCV-7) contains the following sero t y p es -4, 6B, 9V, 14, 18C, 19F, and 23F. It is coupled with a non-toxic variant of diphtheria toxin (CRM197) and has aluminium phosphate as the adjuvant. Conjugation of polysaccharide with protein CRM197 makes it immunogenic below 2 years of age. In February 2000 this vaccine (PCV-7 Prevnar) was licensed in US fo r ad ministration to children below 5 yrs of age. The development of this v accine was prompted by the observation that young children below 2yrs of age are dis p ro p ortionately affected by the serious pneumococcal infection and recognition of the fact that available 23 valent polysaccharide vaccine was non immunogenic in t h is age group 2 yrs. Conjugate vaccine is used in a 3-dose schedule in infancy at 4-8 weeks interval followed by a booster at 15-18 months of age and has protective efficacy of 95-99% ag ain st

invasive pneumococcal disease caused by the serotypes covered by the vaccine. The dose is 0.5 ml. and the vaccine is given intramu scularly. Pneumococcal vaccines are s tored at 2- 80 C. Conjugate vaccine should not be frozen. Since the introdu ct io n of PCV-7 in the childhood vaccine schedule in US, there has been a dramatic reduction in the in cidence of invasive pneumococcal disease not only in the children who are vaccinated but also non-vaccinated young children in their contact and a milder but statistically sign ificant decrease in invasive disease in their adult contacts, suggesting s trong herd effect. Similar herd effect was seen in the form of overall reduction in the disease caused by drug resistant serotypes in the community. Though there has been replacement of t h e vaccine serotypes by non-vaccine serotypes in the nasal carriage studies, fortunately this has not been seen significantly in the invasive diseases studies. However there is a need for continuous surveillance for the serotype involved in invasive cases from time to time. Healthy children: Th e IAP COI does not recommend u s e o f this vaccine for universal immunization in our country at present. PCV - 7 covers approximately 50 to 55% percent of pneumococcal serotypes responsible for invasive pneumococcal disease in India offering about 50 to 55% protection in infants & ch ild ren in India. The vaccine may be offered to healthy children above the age of 6 weeks t ill 2 years after explaining the parents on one to one "named child" basis. High risk group: There are certain children who are at high risk of severe invasive pneumococcal disease with high mortality. This includes children with Sickle cell d is eas e, as p len ia, primary immu n o d eficien cy s y n d ro me s , H I V, c h i l d r e n w i t h s ev ere cardio-respiratory illness and children with chro nic illn es ses like renal diseases, diabetes etc., nephrotic syndrome, cerebrospinal fluid rhinorrhea etc. For such children IAP COI recommends age appropriate doses of 7 valent conjugated pneumococcal vaccine routinely till 5 years of age. For children above 2 years, a dose of 23 valent unconjugated pneumococcal vaccine is also recommended to be given after one priming dose of conjugated vaccine. Adverse reactions - Injection site so reness, malaise, low grade fever.

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D. Vaccines Used in Special Circumstances Meningococcal Vaccines Neisseria meningitides accounts for 30-40% cases of meningitis in children up to the age 15 years. It is the only bacterium capable of causing large scale epidemics of meningitis. There are 12 kn o wn serogroups but majority of the disease causing is o lat es belong to serogroups A, B, C, Y and W135. Epidemic disease is typically associated with type A (occasionally type C) and usually occurs in cycles every 7-14 years, especially in the African meningitis belt which extends acro s s A frica from Senegal to Ethiopia. In India also almo s t all epidemics were of type A Such group A epidemics are usually due to a single strain of the pathogen. Some of the recent outbreaks in Western Asia have been due to W135. En d emic disease occurs worldwide and is mostly caused by serogroups B, A, or C although group Y has been increasingly incriminated in recent reports. In India endemic cases are mainly due to type B. As a rule, endemic disease occurs primarily in children and adolescents, with highest attack rates in infants aged 3-12 months. Severe meningococcal disease occurs p rimarily in children and adolescents, with highest attack rates in infants aged 3-12 months. Severe meningococcal disease is associated with high case-fat ality rates (5-15%) even where adequate medical facilities are available. Chemoprophylactic measures are in general insufficient for t he control of this disease because secondary cases comprise only 1-2 % of all meningococcal cases. Immu n ity following meningococcal infection is s erogroup specific. Unconjugated meningococcal vaccines are based on combinations of group-specific capsular polysaccharides - either bivalent (A and C) or tetrav alent (A, C, Y and 135). The recommended single dose of the reconstituted vaccine contains 50 g of each of the individual polysaccharides. A conjugate group C vaccine has also been marketed in developed countries. Unconjugated meningococcal vaccines, like all other polysaccharide vaccines, do not induce immunological memory. The group C, Y, and W135 components, moreover, are not very immunogenic in children below 2 years of age. Meningococcal group C conjug at e vaccine, on the other hand, is efficacious even in the youngest children. Meningococcal vaccine is indicated fo r use (as an adjunct along with chemoprophylaxis) in close contacts of patients with t h e d isease. It may be considered in child ren with complement deficiency, prior to splenectomy and those asplenia and sickle cell anemia. It is also recommended during disease outbreaks (caused by serogroups included in the vaccine) and prior to travel to the high endemicity meningococcal belt in the African continent. Meningococcal vaccine is mandatory for all Haj pilgrims and is necessary for residential students in some of the universities abroad. The IAP COI does not recommen d t h is vaccine for universal immunization in our country at present. It can be given to children ab ove 2 years of age during disease epidemic and is administered subcutaneously or intramuscularly. In special circumstances (e.g. during group A epidemic to close household contacts , close household contact) it may be offered to even younger infants but the protective efficacy is likely to be low in this age group. The dose is 0.5 ml. Revaccination may be considered after 3-5 years if the individual is still at risk. The vaccine is stored at 2-80C. A conjugate meningococcal serogroup C vaccine has been part of ro u t in e immunization in the United Kingdom since Novemer 1999 as it is t h e commonest cause of meningococcal disease in children there - three doses are g iven at 4-8 weeks interval along with the routine childhood immunizations. Two doses of the vaccine suffice for children in age group 6-12 months and one dose in older children. Adverse reactions - Fever and pain at injection site.

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Japanese Encephalitis Vaccines Japanese encephalitis (JE) is one of the most important causes of viral encephalitis in Asia. In India, JE is believed to be responsible for approximately 2000-3000 clinical cases and 500-600 deaths every year. As there is no anti-viral drug treatment, JE vaccination remains the single most important control measure. Contrary to popular belief JE vaccine should n ot be used as an "outbreak response vaccine" It should rather be given to all children 1-15 y ears of age living in highly endemic areas (e.g. Andhra Pradesh, Ut t ar Pradesh, Karnataka). The vaccine may also be offered to visitors to endemic areas if the duration of stay is likely to exceed four weeks. Currently three types of JE vaccines are available e.g. (a) mouse brain-derived and inactivated Nakayama Strain vaccine (b) cell culture-derived inactivated vaccine and (c) cell culture-derived live attenu at ed vaccine.
Mouse Brain-Derived Inactivated JE Vaccine

vaccine has been given up.

Cell culture derived live SA-14-14-2 vaccine

Th is v accine is based on a stable neuro-attenuated strain of JE virus (SA-14-14-2). It was firs licensed for use in 1988 in People's Republic of Ch in a and over sixty million doses per year are being used there. Now it is also licensed for use in Nepal, S. Korea and India This live attenuated vaccine constitutes to over 50% of global production of all JE vaccine. Dose is 0.5ml at all ages. It is given by subcutaneous route. Initial studies done on this vaccine demonstrated an efficacy of about 80% with single dose and 98% with 2 doses. However, more recent studies have shown efficacy reaching 99% even with single dose. As per a WHO report no serious adverse effects (other than anaphylaxis) have been reported over 20-y ear period (1979 - 1998). This vaccine is not available in commercial market in India, however it has been used for public health by Govt. of India in 2006. Use of Sa-14-14-2 live JE vaccine in India in 2006: Recognizing the need to control JE in high ly endemic districts, GOI has initiated a pilot project of immunizing children from h y perendemic districts against JE in 2006. 7 d is t rict s in UP, 2 in Assam and one each in West Bengal and Karnataka were targeted this year. SA-14-14-2 live JE vaccine was used man ufactured by Chengdu institute of Biological Products, Chengdu, China. It was given in a campaign mode to children aged 1-15 years. It was g iven as single dose subcutaneously usin g A D syringe. The whole campaign was carried out from 15th May to 15th July 2006. 11 million children were target ed as b eneficiaries and 9 million children actually received the vaccine i.e. nearly 86% of the target was achieved. UP recorded 96% coverag e ag ainst all expectations. There were 504 adverse effects following the campaign of which 482 were minor adverse effects. 22 deaths were reported but none were causally related to the vaccine as cleared by an expert committee set up to monitor the adverse effects. Based on the success and safety of this year, similar campaign is planned for ot h er areas in coming years. From next year this vaccine will be included in the routine immunization schedule for the new birth cohorts in these areas.

This vaccine is produced in In d ia at the Central Research Institute, Kasauli. Commercially available vaccine is imported. It is given subcutaneously - 0.5 ml in ch ildren 1-3 years, and 1 ml in older children. Primary immunization consists of three doses given on 0, 7 and 30 days - 0 being the elected date. A booster dose is recommended after 1 year and subsequently at three year intervals. Adverse reactions: Include fever, malaise, local tenderness and redness in 20% of recipients. In recent years, several cases of acute encephalitis temporally linked to JE vaccinat ion have also been reported. Anap h y lactic reactions are known to occur with this vaccine. This vaccine was also produced by s o me international vaccine manufacturers like A ventis Pasteur (now Sanoffi Aventis), however they have stopped manufacturing of this vaccine recently and are trying to switch over to vero cell cultured vaccine.
Inactivated Primary Hamster Kidney Cell derived Vaccine

This vaccine made from Primary Hamster Kidney cell line was used in China in millions o f doses. However with the availability of the Sa-14-14-2 live vaccine, this 28

Influenza Vaccine Influenza virus is an ortho my xovirus. There are three antigenic types (A, B and C) with several subtypes of each based on two surface an t ig ens - hemagglutinin and neuraminidase Influenza virus, especially type A, is characterized by frequent mutations - antigenic drifts and antig en ic shifts. It is of the utmost importance, therefore, that the vaccine should incorporate t h e current strain p revalent during that time. Current inactivated influenza vaccines are produced from virus grown in emb ryonated hen's eggs, and are of three types : wh o le v iru s , s p lit -p ro d u ct , s u b unit surface-antigen formulations. Whole-virus vaccines are associated with increased adverse reactions, especially in children, and are currently not used. Most influenza vaccines are split-product vaccines, p roduced from detergent treat ed , highly purified influenza virus, or s u rface-an t ig en v accin es containing purified hemagglutinin and neuraminidase. Vaccines are usually trivalent, containing 15 g each of two influen za A subtypes (H1N1 and H3N2) and one influenza B strain. The present vaccine contains 15 g of hemagglutinin o f each of the three WHO reco mmended strains (Northern Hemisphere) for the season 2004-2005. 1) A/New Caledonia/20/99 (H1N1) like strain [variant A/New Caledonia/20/99 (IVR - 116)]; 2) A/Fujian/411/2002 (H3N2) - like strain [varian t A/Wyoming/3/2003 (X-147)]; 3) B/ Sh anghai/361/2002 - like strain [variant B/Jingsu/10/2003]. Vaccines elicit a relatively strain-specific humoral response, have reduced efficacy against antigenically drifted viruses and are ineffective against unrelated strains. The influenza vaccine is therefore unique as the precise composition has to be changed periodically in anticipation of the prevalent influenza strain expected to circulate in a given year. The vaccine is effective for only a short period, usually 6 month s to 1 year and a new vaccine is brought every year. The WHO reviews vaccine composition biannually and updates antigenic content depen d ing on prevalent circulating subtypes based on the data obtained from its chain of reference laboratories from world over to provide antigenically well-matched vaccines. Influenza vaccine is highly immu n ogenic and is associated with minimal side effects. When used for the first time the vaccine is given in 2 doses in children 6 months to 8 years of age; only one dose is sufficient above 8 years. Revaccination is d o ne with a single annual dose, which is given before the peak influenza season. The vaccine is administered intramuscularly, the dose being 0.25 ml. in ch ildren below three years and 0.5 ml thereafter. This vaccine is cu rrently recommended for u s e only in high-risk children and adolescents e.g . individuals with chronic pulmonary an d card iac d is eas e, s ickle cell d is eas e, immunodeficiency, HIV infection, s y s temic lupus erythematosus, diabetes mellitus and t h o se on long term aspirin therapy. Influenza vaccine is also recommended to be giv en for severe cases of asthma who need oral corticosteroids frequently.

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Combination Vaccines A combination vaccine consists of two or more separate immunogens that have been physically combined in a single preparation. These immunogens may pertain to the many antigens/ serotypes of the given pat h o g en (e.g. poliovirus vaccines) or of multiple pathogens (e.g. DTP v accine). This concept differs from that of simultaneous vaccines, which, although ad ministered concurrently, are physically separate. The combining of multiple related o r unrelated antigens into a single vaccine is not a new concept. The first combination vaccine was trivalent influenza vaccine, which was developed as far back as 1945. This was followed by hexavalent pneumococcal vaccine in 1947 and DTP vaccine in 1948. Combination vaccines in common use include diphtheria and tetanus toxoid, available alone (DT, dT) or with pertussis vaccine (DTP); inactivated (IPV) or live oral (OPV) trivalent polio vaccine and MMR vaccine. The number of vaccines in the immunization schedule is increasing every year with the result that these schedules are getting increasingly more complex. Many parents opt for one single injection of combination vaccines at a given visit, rather than g etting a large number of simultaneous injections. Use of combination vaccines is also likely to result in logistic advantages reduced burden on the cold chain and reduced storage requirements and syringes/needles apart from easier record keeping. A number of combination vaccines are now available in the Indian market. The IA P COI endorses the use of combination vaccines, but with the following cautionary statements: The manufacturer's recommendations should be adhered to strictly Mixing" of vaccines in the same syringe (prior to injection) should not be done as far as possible, unless specifically recommended by the manufacturer; in the latter case the manufacturer's instructions should be followed strictly. Combination vaccines should not be viewed as being more effective than vaccines given separately.

Current status of new combination vaccines

Already developed DTPw + Hib DTPw + Hepatits B DTPw + IPV DTPw + IPV + Hib DTPw + Hib + Hepatits B DTPw + Hib + IPV DTPw + IPV DTPa + IPV DTPa + Hib DTPa + Hib + Hepatits B + IPV Hepatitis A + Hepatitis B MMR + Varicella

Under development DTPa + Hib + IPV + Hepatitis B + Hepatitis A

Available for use in India DTPw + Hib DTPw + HB DTPw + Hib + HB DTPa + Hib HA + HB

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Rabies Vaccines The disease is caused by a single stranded RNA virus belonging to the family Rhabdoviridae. It is almost always fat al. Rab ies is caused by the bite of a rabid animal, which is usually a dog in our country. Scratches or licks on mucous membranes by affected animals have also been kn o wn to transmit the virus. The incubation period averages 4-6 weeks but can be very variable and may range from five days to more than one year. Rabies is endemic in our country - India accounts for almost 50% of mortality in the world There are two types of vaccines available in India
Modern tissue culture vaccines (MTCV)

severe b it es or bites in the upper extremities, trunk, head and face (wound category 3). Intramuscular injection of RIG is not recommended. The dose of human rabies immunoglobulin (HRIG) is 20 U/kg while that of equine rabies immunoglobulin (ERIG) is 40 U/kg. Skin testing is recommended before using ERIG but is not n ecessary when using HRIG. Any suturing of wound should be avoided. When suturing is unavoid ab le for purpose of hemostasis, it must be insured that RIG has been infiltrated in the wound prior to suturing. Rabies vaccine is administered intramuscularly in anterolateral thigh on days 0, 3, 7, 14 and 30 as per the Essen protocol, with day '0' being the day of commencement of vaccination. A sixth dose on day 90 is optional and may be offered to patients with severe debility or those who are immunosuppressed. Children are given the same dose as ad ults. Rabies vaccine should never be injected in the gluteal region. Several other schedules of rabies vaccination have been proposed. These include the 2-1-1 intramuscular schedule (Zagreb schedule) - two IM doses on day 1, one IM dose on day 7 and one IM dose on day 21; the 2-2-2-1-1 intrad ermal schedule (Thai Red Cross TRC-ID schedule) in which two ID doses are given on days 1, 3 and 7, followed by one ID dose o n days 30 and 90 - ID dose is 1/5th the IM d o s e; the 8-4-1-1 intradermal schedule (Oxford schedule) - 0.1 ml of PCEC vaccine is given ID at eight sites on day 0, at four sites on day 7 and at one site only on days 30 and 90. The intradermal schedules have the obviou s advantage of being inexpensive and have b een used successfully in Thailand, Philippines and Sri Lanka. Based on the recommendations of the expert group as well as WHO, the Drug Controller General of India (DCGI) has recently decided to allow ID route administration o f tissue culture based anti rabies vaccine fo r post exposure prophylaxis in a phased manner. The following schedules as recommended by

Purified Chick Embryo Cell (PCEC) vaccine 1 ml per dose. Human Diploid Cell Vaccine (HDCV) - 1 ml per dose. Purified Vero Cell Vaccine (PVRV) - 0.5 ml per dose. Purified Duck Embryo Vaccine (PDEV) - 1 ml per dose.

All tissue culture vaccines have almost equal efficacy and any one of these can be used.
Nerve tissue vaccine

This is no longer recommended because of its poor efficacy and life threatening adverse effects in the form of neuroparalytic reactions.
Post exposure prophylaxis

In order to remove as much of the rabies virus as possible, immediately cleanse the wound with soap and flush thoroughly under running water for 10 minutes . Then treat with 70% alcohol or tincture iodine or povidone iodine. Rabies immunoglobulin (RIG) should be infiltrated in and around the wo u n d in case of all

Day of Vaccination Thai Red Cross Regime Updated TRC Regime

D0 2 2

D3 2 2
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D7 2 2

D14 0 0

D28 1 2

D90 1 0

ICMR are permitted in the 1st phase (Table below) Vaccines reco mmended in the first phase of ID route administration are purified verocell rabies vaccine (Senofi Pasteur) and purified chick embryo cell vaccine (Chiron Behring). The unit dose of 0.1ml for ID should have at leas t 0.25 units. The criteria for selection of Antirabies centre for ID use are Attendance of minimum 50 patient per day for post exposure prophylaxis Have adequately trained staff to give ID inoculation Can maintain cold chain and ensure adequate supply of disposable syringes and needles.
Rabies Immunoglobulin (RIG)

There are 2 types of RIG: (1) Human rabies immunoglobulin (HRIG - do s e is 20 U/kg body weight) (2) Equine rab ies immunoglobulin (ERIG - dose is 40 U/kg body weight). RIG is indicated in all cases of category three wounds where it should be infiltrated thoroughly into and around the wound. The remaining part if an y is to be injected IM into the deltoid region or anterolateral aspect of thigh away from the sit e o f vaccine administration to avoid vaccine neutralization. It contains specific an t irabies antibodies that neutralize the rabies virus and provide passive protection. In case RIG dos e (q uantity) is insufficient for adequate infiltration of extensive or multiple wound, it may be diluted with equal volume of normal saline so th at all the wounds can be thoroughly infiltrated. If RIG could not be given when antirabies vaccination was began , it should be administered as early as possible but no later than the seventh day after the first dose of vaccine was given. From the eight day onwards, RIG is not indicated since an antibody response to the vaccine is presumed to have occurred. HRIG is a liquid or freeze-dried preparation containing immunoglobulins (mainly IgG) and is obtained from the p las ma of donors immunized against. In case of ERIG, skin testing is recommended prior to use. Adverse reactions: Tenderness/stiffness at t h e injection site, low grade fever; sensitization may occur after repeated injections.

This ID administration is not recommended in individu al practice. Also it does not make economic sense to practice it for individual cases.
Pre-exposure prophylaxis

Pre-exposure prophylaxis became a reality only after the availability of MTCVs. This should be offered to in d iv iduals in high risk occupations (e.g. veterinary surgeons, wildlife workers, dog breeders, postmen). Any of the tissue culture vaccines can be given for this purpose - three doses are given intramuscularly on days 0, 7 and 28. A booster is given one year after primary immunization and every five years thereafter. The vaccine is stored at 2-80C. Side-effects include local pain and induration. For Re-Exposure after completed (and documented) pre or post exposure prophylaxis two doses are given o n days 0 and 3. Antirabies antibody titers > 0.5 IU/ml are considered protective.

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WHO Recommendations for Management of Animal Bites

Category

Type of contact with suspected or confirmed domestic or wild animals* or animal unavailable for observation

Recommended treatment

I II

Touching or feeding of animals, licks on intact skin Nibbling of uncovered skin, minor scratches or abrasions without bleeding, licks on broken skin

None if reliable case history is available Administer vaccine immediately Stop treatment if animal remains healthy throughout an observation period of 10 days, or, if the animal is euthanised and found to be negative for rabies by appropriate laboratory technique Administer rabies immunoglobulins and vaccine immediately Stop treatment if animal remains healthy throughout an observation period of 10 days, or, if the animal is euthanised and found to be negative for rabies by appropriate laboratory technique

III

Single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva (i.e., licks)

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IAP Immunization Time Table

Age

Vaccine

Birth 6 weeks 10 weeks 14 weeks 9 months 15- 18 months 2 years 5 years 10 years 16 years

BCG, OPV0 , Hepatitis B1 DTPw1 / DTPa1 , OPV1, Hepatitis B2, Hib1 DTPw2 / DTPa2 , OPV2, Hib2 DTPw3 / DTPa3 , OPV3, Hepatitis B3 *, Hib3 Measles DTPw B1 / DTPa B1, OPV B1 , Hib B1 , MMR Typhoid+ DTPw B2 / DTPa B2, OPV B2 Td# / TT Td# / TT

Pregnant women: 2 doses of Td # / TT * Third dose of Hepatitis B can be given at 6 months age +Revaccination every 3-4 years # Td preferred over TT

Vaccines that can be given after discussion with parents

Age

Vaccine

More than 15 months More than 18 months More than 6 weeks

Varicella vaccine# Hepatitis A vaccine+ Pneumococcal conjugate vaccine*

#

Below 13 years of age one dose, over 13 years of age 2 doses at 4-8 weeks interval + 2 doses at 6- 12 months interval * 3 primary doses at 6, 10, and 14 weeks, followed by a booster dose at 15 months

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It should be noted that the IAP Immunization Time-Table is, in effect, the 'Best Individual Practices' schedule for a given child and may be somewhat different from the National Immunization Schedule. This is because of the fact that the former is meant to be used for an individual, rather than for the pediatric community as public health measure at large The two schedules are, however, not in conflict with each other. Also, as pediatricians we must be conscious of the fact that the immunization needs of children in a country are quite dynamic - a vaccine which may not be considered important today may become necessary in future as more information about the epidemiology of the disease becomes available. Further, in developing countries affordability of the vaccines is a critical issue and any decision on incorporation of a new vaccine in the immunization schedule has to take this fact into consideration. The IAP COI has based its recommendations based on the best available evidence at present. It is heartening to note that some of the recommendations of the IAP COI in the past have been instrumental in changing governmental policies and also the immunization schedules being followed by some states.
Notes on the Time Table

3.

4.

5.

6.

1.

2.

The IAP endorses the continued use of whole cell pertussis vaccine because of its proven efficacy and safety. Acellular pertussis vaccines may undoubtedly have fewer side-effects (like fever, local reactions at injection site and irritability), but this minor advantage does not justify the inordinate cost involved in the routine use of this vaccine. If the mother is known to be HBsAg negative,

7. 8.

9.

HB vaccine can be given along with DTP at 6, 10, 14 weeks/ 6 months. If the mother's HBsAg status is not known, it is advisable to start vaccination soon after birth to prevent perinatal transmission of the disease. If the mother is HBsAg positive (and especially HBeAg positive), the baby should be given Hepatitis B Immune Globulin (HBIG) within 24 hours of birth, along with HB vaccine. For Non EPI and Newer Vaccines, Varicella, Hepatitis A and Congujate Pneumococcal vaccines should be offered only after one to one discussion with parents. Also refer to the individual vaccines notes for recommendations. Combination vaccines can be used to decrease the number of pricks being given to the baby and to decrease the number of clinic visits. The manufacture's instructions should be followed strictly whenever "mixing" vaccines in the same syringe prior to injection. At present, the only typhoid vaccine available in our country is the Vi Polysaccharide vaccine. Revaccination may be carried out every 3-4 years. Under special circumstances (e.g. epidemics), measles vaccine may be given earlier than 9 months followed by MMR at 12-15 months. During pregnancy, the interval between the two doses of TT should be at least one month. Continue using OPV till we eradicate polio in our country. IPV can be used additionally for individual protection. OPV must be given to children < 5 years of age at the time of each supplementary immunization activity.

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Immunization in Special Circumstances

Immunization in preterm infants In general, all vaccines may be administered as per schedule according to the choronological age irrespective of birth weight or period of gestation. Very low birth weight / preterm babies can be given immunizations after initial stabilization.

Children receiving corticosteroids Children receiving oral corticosteroids in high doses (e.g. Prednisolone 1-2 mg/kg/day) for more than 14 days should not receive live virus vaccines until the steroid has been discontinued for at least one month. Killed vaccines are safe but may be incompletely effective in such situations. Patients on topical or inhaled steroid therapy should not be denied their age appropriate vaccines.

Children awaiting splenectomy Children with loss of splenic function are at high risk of serious infections with encapsulated organisms. If surgical splenectomy is being planned, immunization with pnueumococcal, Hib and meninggococcal vaccines should be initiated a few weeks prior to splenectomy.

Vaccination in children in children with HIV infection Children infected by HIV are particularly vulnerable to severe, recurrent, or unusual infections by vaccine preventable pathogens. It must be emphasized that routine immunizations seem to be generally safe in such children, but the immune response following vaccination would depend upon the degree of immunodeficiency at that point of time. Immune attrition associated with viral replication may particularly interfere with memory responses. Consideration should be given to readministering childhood immunizations to such children when their immune status has improved following anti-retroviral therapy.

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IAP Recommendations for Immunization of HIV Infected Children

Vaccine

Asymptomatic HIV Infection

Symptomatic HIV Infection

BCG DTPw / DTPa OPV Measles MMR Hepatitis B Hib Typhoid Vi Pneumococcal Influenza Varicella Hepatitis A

Yes (at birth) Yes (at 6, 10, 14 weeks) Yes (at 6, 10, 14 weeks) Yes (at 6 and 9 weeks) Yes Yes (as for uninfected children) Yes Yes Yes Yes ( > 6 months of age) Yes (2 doses at 6-8 weeks interval) Yes

No Yes Yes / IPV Yes Yes (CD4% >15%) Yes (double each dose) Yes Yes Yes Yes Yes (2 doses at 6-8 weeks interval, CD4% > 15%) Yes

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

37

Vaccination Schedule for an Unimmunized Child Age Less than 7 years More than 7 years

First visiit

BCG*, OPV* , DTPw / DTPa, HB OPV*, DTPw / DTPa, HB Measles / MMR, Typhoid DTPw / DTPa, HB

Td, HB

Second visit (one month later) Third visit (one month later) Fourth visit (6 months after first visit) Every 3 years

Td, HB MMR, Typhoid HB

Typhoid

Typhoid

* OPV and BCG recommended up to 5 years of age. ** Varicella vaccine one dose up to 13 years and hepatitis A vaccine two doses 0 and 6 months to be offered only after discussing with parents on a one to one basis It may be noted that Measles/MMR vaccines may as well be given at the first visit itself (along with t he other vaccines) if compliance is likely to be a problem. However it is preferable to give it at a later visit if pat ient compliance is not a problem.

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

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

38

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

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

Vaccination Schedule in Adolescents Vaccine Age

Td MMR vaccine Hepatitis B Typhoid vaccine Varicella vaccine*

Booster at 10 and 16 years One dose if not given earlier 3 doses (20 mcg) 0, 1, and 6 months, if not given earlier Vi Polysaccharide vaccine every 3 years One dose up to 13 years and 2 doses (at 4 to 8 weeks interval) after 13 years of age if not given earlier.

Hepatitis A vaccine*

Two doses 0 and 6 months if not given earlier

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

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

39

Vaccination of children with bleeding disorders or those receiving anticoagulants Needles less than 23G should be used for injection and the parents should be asked to apply firm and sustained pressure, without rubbing, for at least 5 minutes.

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

40

Injection Safety Issues

Injectio n s afety is an important issue for any immunization program Wash or disinfect hands prio r to preparing injection material. Avoid giving injections if skin is infected or compromised by a local infection (such as a skin lesion or weeping dermatitis ). Ev en small cuts should b e co vered. Always use a sterile syringe and needle for each injection and to reconstitute each unit of medication. If single use syring es an d needles are not available, use equipment designed for steam st erilization. Document the quality of the s t erilizat ion process using time, St eam an d Temperature (TST) spot indicators. Prepare each injection in a clean designated area where blood or body fluid contamination is unlikely. Clean skin prior to injection with a disinfectant and wait for it t o dry. Do not use cotton balls stored wet in a multi-use container. If multi-dose vials are used, always pierce the septum with a sterile needle but do not leave the needle in place in the stopper of the vial. If using an ampoule that requires a metal file to open, protect fingers with a small gauze pad when opening the ampoule. Anticipate and take measures to prevent sudden patient movement during and after injection. All in t ramuscular injections in children should be given only on th e anterolateral aspect of thigh at the junction o f t h e middle and lower third - the gluteal

region must be avoided as sciatic nerve injury is a real risk especially in neonates, malnourished and struggling children. It is not often appreciated that the nerv e is within the reach of the standard needle even when the injection is given in the upper outer quadrant of the buttock. It is also know that the immune response of some of the vaccines (especially rabies) administered in the gluteal region is not optimum. It is important for health personnel to understand that 'sharps' must be immediately co n t ained in a 'sharps' box. The needle must not be recapped or manually mutilated after use. To prevent reuse, the syringe may be cut and the needle defanged using a syringe/needle destroyer. Syringes and needles should be disposed of carefully in leak-proof and puncture proof contain ers an d n eedles and waste management should be given due attention. Auto-disable (AD) syringes are single-use, self-locking syringes designed in such a way that these are rendered unusable after single use. These are made from clean-burning plastics and emit very low levels of toxic fumes. These are now being promoted for rou tine immunization and may well become the norm in years to come. The Government of India has decided to use AD syringes in Immunization program.

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Adverse Reactions Following Immunization

A d v erse reactions following immunization can be broadly classified as local and systemic. Although such occurrences are uncommon, every physician who is dealing with immunization should anticipate and be prepared to manage these events whenever they occur It is mandatory for every immunization clinic t o h ave an emergency kit for resuscitation. Local reactions are especially common aft er the adsorbed vaccines (e.g. DTPw/DT) - no treatment other than symptomatic management is necessary. Whole cell killed typhoid vaccines are also ass ociated with particularly significant local reactions. Ulcer formation after BCG vaccination is normal and no intervention is usually required - the ulcers may sometimes take many weeks to heal. Anaphylactic reactions are distinctly unusual but have been reported following Measles, MMR, Hib and Hepatitis vaccines. Such reactions may be secondary to

allergy to egg (e.g . Measles, MMR, yellow fever, influenza vaccines), gelatin (e.g. MMR, Varicella, Yellow fever vaccines), certain antimicrobials (e.g . Neomycin in MMR, Varicella and Inactivated Polio vaccines) or thiomerosal (e.g. DTP, TT vaccines). It should be noted that it might often be difficult to prove a definite cause-effect relationship between a vaccine an d a given complication. It may be prudent not to ascribe all adverse reactions to a vaccine, which has been given in the recent past before ascertaining all facts about the case. Many adverse effects may result from inappropriate vaccination technique or storage of the product. Each member of the Academy is requested to report any case of suspected adverse reaction follo wing immunization to IAP committee on immunization through IAP office.

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Adverse Reactions Following Immunization

Adverse Reaction

Vaccine

Symptoms

Management

Anaphylaxis

Any vaccine

Within minutes

Adrenaline
Cardiopulmonary resuscitation IV volume expanders Hysrocortisone Dopamine/ Dobutamine

Acute decompensation of circulatory

shock Hypovolemic shock Laryngospasm /edema Acute respiratory distress

H y p o t en s i v e hyporesponsive episode

DTP

Acute pallor
Transient decreased level or loss of consciousness Decrease or loss of muscle tone

IV fluids Oxygen

Incessant crying

DTP

Within 48-72 hours of immunization Excessive, inconsolable crying

Sedation with Triclofos 50 mg/ Kg Paracetamol 10-15 mg/ Kg per dose Feeding advice IV fluids Antimicrobials cloxacillin 50-100 mg? Kg per day Steroids Supportive therapy If firm, no treatment If soft or fluctuant, aspiration/ surgical excision ATT not indicated Antibiotics Antipyretics Drainage Paracetamol

T o xic Sh o ck Syndrome

Measles vaccine contamination

Within 30 minutes to few hours Mounting fever Vomiting Diarrhoea Septic Shock

Lymphadenitis

BCG

Within 2 to 6 months Firm to soft axillary lymphadenitis 1.5- 3 cms size

Ba c t e ria l abscess M o d era t e t o s ev ere l o c al reaction Seizures wit h fever (rare)

Any vaccine

After days to weeks fluctuant to firm

Any vaccine

No n fluctuant swelling / redness 3-10 cms in size at the injection site

DTP Measles

Always generalised

Anticonvulsants IV fluids (if need be)

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The Cold Chain

A vaccine has two characteristics - safety and potency. The potency of a vaccine is maintained by 'cold chain' This term refers to the system of transporting, storing and distributing vaccines in a potent state at the recommen d ed t emp erat ure from the point of manufacture to the point of use. In es s en ce, it is considered to play a crucial role in the success of any immunization program However potent a vaccine may be, if the cold chain is not maintained from the source of vaccine manufacture to the place of vaccination, the vaccine efficacy will suffer. Vaccine potency once lost cannot be restored. The essential components of a cold chain include: 1. 2. 3. 4. 5. Personnel responsible for vaccine distribution Appropriate equipment to store and transport vaccines Appropriate transport facilities Maintenance of equipment Monitoring

Order of sensitivity of vaccines to heat

Most sensitive BCG (after reconstitution) OPV Measles (both before and after reconstitution) Hepatitis B DTP DT BCG (before reconstitution) Least sensitive Tetanus toxoid

Sensitivity of vaccines to freezing

Vaccines damaged by freezing

Vaccines that can be frozen without harm

DTP DT TT Hepatitis B Hib Td Typhoid (whole cell killed vaccine) Hepatitis A

OPV Measles/ MMR BCG (before reconstitution)

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The cold chain involves two complementary aspects: a) the set chain represented by the walk-in cold rooms, deep freezers and refrigerators and b) the mobile chain represented by isothermic boxes and vaccine carriers.

chamber in situations where OPV is to be stored for long duration (at -200C) or there is increased demand of ice-packs. Domestic refrigerators: meant for vaccine e) storage should not be used for any ot h er p urpose; should be kept away from heat and direct su n lig ht; should have ice-packs fo r freezer compartment and water bottles in the shelves; these help in maintaining low temperatures in case of power failure; no vaccine should be stored in the baffle tray or the door shelves; periodic defrosting is necessary; this is generally done whenever the layer of ice exceeds 5-6 mms. The usual temperature within the main compartment of a domestic refrigerator is between 4-100C while t h at of the freezer compartment is between 0 to -40C. The vaccines can be placed as follows: Freezer compartment: OPV / Measles / MMR Top shelf: BCG / Measles / MMR Middle shelf: DTP / DT / TT/ Typhoid/ Hepatitis A / Hib Lower shelf: Hepatitis B / Varicella Crispator: Diluents Baffle tray: should be kept empty

Equipment Walk- in freezers (WIF): are established in all a) the states ; are u sed for bulk storage of OPV and measles vaccines and for preparing frozen ice packs at state s t ores; maintain a temperature of -200C and are available in 2 sizes - 16.5 & 32 CU Mt; freezers are provided with two identical cooling units and standby generator sets. Walk in cold rooms (WIC): are used fo r bulk b) storage of vaccines at the man ufacturer, state and regional levels which store vaccines for abou t 4-5 districts; maintain a temperature recorders and alarm systems. Deep freezers: are used for storage of OPV/ c) Measles//MMR vaccines and preparation of ice-packs; DTP/DT/TT/Hepatitis B vaccines should not be stored in deep freezers; have a top opening lid and are availab le in 2 models -140 & 300 liters; cabinet temperature is maintained between -18 to -200C; in case of power failure these freezers can maintain cabinet temperature for 18 - 26 hours, if n o t o p ened. All districts have been provided 2-5 large freezers whereas most of the PHCs have one small deep freezer. A b o u t 25-30 ice packs (8-10 kg ice) and 35-40 ice packs (12-14 kg ice) can be frozen in one day in 140L and 300L deep freezers respectively. d) Ice lined refrigerators (ILR): may have either ice tubes or ice packs filled wit h water upto 90% of their volumes; o n freezing there is formation of an inner lining of ice; this enables the temperature to stay within a safe range even when there is electricity supply for only 8-12 hours in a day; are available in 2 sizes (140 & 300 liters) - the former is supplied to district headquart ers while the latter is supplied to PHCs; in top opening ILRs the temperatures is least at the bottoms - t h is should be used for storing OPV/Measles/MMR; DTP / DT/ TT/ Hepatitis B vaccines should be kept near the top in a s ep arate container to avoid accidental freezing. The Electrolux type of ILR (Model TCW 1151) can also be used as a freezer by a changeover switch inside the compressor 45

f) Cold boxes or isothermic boxes: are well insulated, solid and thermetically (air tight) sealed boxes packed with frozen ice packs at the bottom, sides and at the top; available in 2 sizes - 5 & 20L; these are supplied to all peripheral centers and are used for transportation of large amounts of vaccines to outreach facilities - 1500 vaccine doses can be carried in a 5L box and 6000 doses in a 20L box; vaccines should be placed in cartons or polythene bags and then placed in direct contact with fro zen ice packs; in emergency situations, can also be used to store vaccines and frozen ice packs for up to 5 days; the hold over time is more than 90 hours for a 5L, and 6 days for a 20L, cold box at 430C ambient temperature, if the cold box is not opened at all. In general a cold box of 5L can acco mmo date one month's supply of a PHC (30,000 population), while a cold box of 20L capacity can accommodate one month's supply for a CHC (100,000 population). Cold boxes can also be used in h ealth centers for storage of vaccines and ice packs in case of electricity failure or breakdown of other cold chain equipment. Ice packs should be made from tap water - water should be filled in the icepack up to the level marked. g) Vaccine carriers: are s maller versions of cold

boxes and are used to carry small quantities of vaccines (e.g. 16-20 vials) for distribution to outreach facilities; these contain 4 fully frozen ice packs (0.36 liters each) and an inner plastic lining; can maintain temperatures for 2 days if the packs are frozen and lid is kept tightly clo sed. DTP/DT/TT/Hepatitis B vials should be wrapped in plastic to avoid direct contact with ice. Day carriers: are smaller versions of vaccine h) carriers and are used to carry still small quantities of vaccines (e.g. 6-8 vials) of vaccine; have provision for only 2 frozen ice-packs; can be used to store vaccines for 6-8 hours; vaccines in day carrier should be issued on the day of immunization only; presently, the use of day carriers is not encouraged. Ice packs: are made of polyethylene and weigh i) approximately 80 gm; t h e dimensions are 163 x 90 x 33 mms; co ntain 0.36L of water; never add salt to the water. Ice packs are used to line the sides of cold boxes, vaccine carriers and day carriers.

life of 24 months. Diluents should be stored at 2-8oC these should not be us ed b ey ond 4 hours. Vaccines should be transported o n ly in cold boxes or vaccine carriers - vacuum flasks should never be used for this purpose. It is recommended that vaccines should not be stored for more than 3 months at the district lev el and for more than 1 month at the level of primary health center. No vaccines sh o uld ever be stored at the sub-centers. Expiry dates of vials shou ld b e checked once a week. While storing vaccines fo llo w the "First-In-First-Out (FIFO)" and "First to Expire First-Out (FEFO)" rules. During shipment and transportat ion, temperature and time sensitive monitor marks are used to check the cold chain. Dial t h ermometers are used to monitor the temperature in refrigerators/ice-lined refrigerators (ILRs) and are kept in every unit. Alcohol stem t h ermometers are much more sensitive and accurat e t h an dial thermometers and can record temperatures fro m - 50oC to +50oC. These can be used for deep freezers and ILRs . Temperature monitoring should be done twice a day in the case of ILRs and deep freezer and once a day in the case of walk-in coolers, where vaccines are stored in bulk for longer periods. A break in the cold chain is indicated if temperature rises above +8oC or falls below +2oC in the case of ILR and other refrigerators and above -180C in the case of deep freezers.

Storage of vaccines All vaccines are safe at temperatures between 2-80C for at least 6 months. If a freezer is available, it should be used for storage of OPV and Measles/MMR vaccines. The latter vaccines should be kept frozen at -200C when stored fo r t h e long term - at this temperature these vaccines have a shelf life of 2 years. Even these v accines, however, can be kept at 2-80C for short er periods e.g. 6- 12 months for OPV and 18-24 months for measles. DTP / DT / TT / Typhoid (T-series vaccines), HB and Hep A vaccines should never be frozen. The freezing point for adsorbed DTP vaccine is between -5 to 10oC. Freezing time depends on the number of doses in the vial and the temperature. It takes about 110 to 130 minutes at -10oC. The "Shake Test" can be used to determine if these vaccine has been frozen at any time: shake the vial so t h at the sediments, if any, are completely mixed ; wait for 15 minutes; if the vaccine is not uniformly mixed or the sediments/ flocculations are still found settled at the bottom, the vaccine is likely to have been frozen at some time. Such vials should be discarded. At a temperature of 2-8oC, DTP/ DT/TT/ Hepatitis B/Hepatitis A/Varicella and Hib vaccines have a shelf 46

The Vaccine Vial Monitor (VVM) is a time an d temperature sensitive colored label that provides an indication of the cumulative heat to wh ich the vial has been exposed. VVMs were first introduced on OPV vials supplied to UNICEF and WHO in 1996. The VVM warn s t h e end user when exposure to heat is likely to have degraded the vaccine beyond an acceptable level. It is used especially for temperatures monitoring of OPV, which is the most thermo lab ile of all vaccines. If the VVM indicates proper storage of OPV in a given center, it can be presumed that oth er vaccines would also be potent. VVMs increas e the flexibility in handling of vaccines in the field. Interpretation of the colour change of VVM is as follows:

1. Inner square is lighter than outer circle: If the expiry date has not passed, vaccine can be used. 2. Inner square matches colour of outer circle or is darker than outer circle: vaccine should be discarded. The VVM provides in formation about the heat exposure of the vial over a period of time - the change in colour is gradual but irreversible. However there may be other factors which can also affect the potency of vaccine (e.g. storage beyond the expiry date) and these may not be reflected in the VVM . Loss of potency depends upon the degree of temperature elevation as well as duration of exposure. Tetanus toxoid is the least heat sensitive vaccine. The manufacturer's instructions regarding shelf life of a given vaccine must be rigorously followed. Measles vaccine loses viability quickly if kept at temperatures above 400C. Reconstituted measles vaccine should be kept protected from heat and light during an immunization session and the left-over discarded after the session. OPV would lose viability if kept at 22-25oC for more than a d ay . Opened vials of OPV, however, may be used in subsequent sessions at a given health facility if it has b een p reserved at 2-8oC. OPV vials u sed in the field setting or an outreach facilit y o r during a pulse immunization session must be discarded at the end of the day. Vaccine vials (single/multi-dose) should be gently shaken before use to ensure that the co n t en ts are clear and not granular or flaky. Vaccine vials should not be taken out to the field more than 3 times - after that these are best discarded irrespective of whether these have been opened or not. When using multidose vials it may be ad v isable to schedule all immunizations to a fixed day every week. This reduces wastage o f v accine and minimizes the risks of contamination/loss of potency. One can send OPV vials for viab ilit y test with the help of the local health authorities. OPV has been taken as an indicator of quality of cold chain as t h is v accine is more heat labile than other vaccines and is easier to test. The test t akes only 7 days. Open vials can also be sen t an d , id eally, the vials should be lifted from all levels - i.e. from the periphery after the immunization sess ion, PHC, CHC, district and reg ional stores. Testing facilities are available at the Central Research Institute

(Kasauli), National Institute of Communicable Disease (Delhi), Enterovirus Research Centre (Mumbai), School of Tro p ical Medicine (Kolkata) and other centers. Samples from different immunization sites should be collected in vaccine/day carriers with fully frozen ice packs and transported to the headquarters by o b s erv ing "reverse cold chain" If delays in transportation are anticipated, th e samples should be kept in a deep freezer/ILR before these are sent to the testing lab o ratory. The WHO recommends that in countries where VVM is being used for monitoring cold chain, OPV sample testing is not required. Recen tly Government of India is following this recommendation.

The Future

Advances in sugar-glass drying technology now allow manufacturing of vaccines which can be stored and tran s p orted at tropical room temperatures. Trehalose, a disaccharide, has long term stabilizing ability and can be effectively used for this purpose. Dried measles vaccine stabilized with trehalose has been found viable after 2 months at room temperature while DTPa can withstand a temperature of 600C for 12 weeks . Oral polio vaccine, however, has failed to 'dry' successfully. If all vaccines can be successfully 'dried', there will no longer be a need for maintenance of co ld chain - this will also result in substantial cost savings.
Supply of vaccines

A ll UIP vaccines are available free of cost to all practitioner from lo cal health authorities. One is allowed to collect profes s ional fees for the services rendered. However, the utilizatio n report should be submitted periodically. When buying from market individual practitioners should ensure that vaccines are procured directly from a stockist with appropriate cold chain facilities, rather than off the shelf from a nearby retailer. Vaccum flasks should never be used for an outreach activity.

47

Stability of Vaccines at Different Temperatures

Vaccine 2- 8

Temperature 22- 25

in oC 35- 37 > 37

D T / TT (a s mo n o v a le n t v accines or as co mp o n en ts of combined vaccine) Pertussis vaccine

3-7 years

Many months

At least 6 weeks

2 weeks at 45OC

18- 24 mo n t h s , but there is a steady decrease in potency 1 year

Variable, but does n o t e xceed 2 weeks

Variable

10% lo s s o f potency per day

Freeze dried BCG vaccine Re c o n s t it u te d BCG vaccine

2030% of viability after 3 months

Variable

Unstable

Should be used within 4 hours. This recommendation is based on the fact that: 1. There is a risk of contamination as BCG vaccine contains no bacteriostatic agent. 2. Concern over loss of viability.

F r e e ze d r i e d measles vaccine

2 years

1 month

1 week

50% lo s s o f viab ilit y in 2-3 days at 41OC

R ec o n s t i t u t e d measles vaccine OPV

Should be u sed within 4 hours 6- 12 months 50% lo ss o f viability after 3 weeks Very u n s t ab le. Significant loss of viability within 13 days Variable Very u n s t ab le. Significant loss of viability within 1 day at 41OC Pre c i s e lacking data

Inactivated Polio Vaccine (IPV)

1- 4 years

De c lin e o f D-antigen content for Type I after 20 days Many months

Hepatitis B

2- 4 years

Many weeks

St a b le fo r man y days at 45OC

Rabies HDCV

3- 5 years

3 months

4 weeks

No data available

48

Surveillance for Vaccine Preventable Disease (VPDS)

Surveillance is a French word, which means "watching with attentio n, suspicion and authority" Disease surveillan ce under the Universal Immunization Program refers t o the collection, analysis and use of data on VPD to improve action to p rev ent these diseases As higher levels of vaccination coverage are achieved, the role of disease surveillance becomes increas ingly important to document the impact of a giv en immunization program. A sensitive surveillance system is required to direct program resources to areas of greatest need and to ident ify areas for special or more intensive interventions. A g o o d surveillance system can det ect program failures and impending outbreaks and can also be used to assess vaccine efficacy. Any sat isfactory national immunization program should result in gradual decline of the VPDs. All cases of VPDs should be reported to the local health authority within 48-72 hours for taking prompt action at the field level. The WHO had declared 3 district objectives for the year 2000 A.D. 1) 2) 3) Polio eradication Neonatal tetanus elimination Measles reduction

It is a pity that none of these targets have been met so far. The revised target for certification of polio eradication and neonatal tetanus elimination is the year 2007. The nomenclat u re used for control of the three diseases is rather specific because while it is possible to eradicate polio v irus from the planet, it may not be feasible to eradicat e the tetanus bacilli, which are u biquitous. However, by immunizing all mothers wit h tetanus toxoid it is possible to at least eliminate neonatal tetanus. Similarly while it may be possible to eradicate measles in the future, at the present time one can only hope to preven t measles mortality by preventing measles in the vast majority of immunized children. Acute Flaccid Paralysis (AFP) surveillance is an essential component of polio eradication. A min imum AFP rate of 1/100,000 children below 15 years o f ag e is required to ensure that adequate surveillance exists at the ground level. At present most of the parts of the coun try have excellent and adequate surveillance. Every case of AFP should be reported to local health authority.

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Vaccination in Current Millenium

The future holds lot of promise as far as prevention of disease through vaccination is concerned. We are likely to witness more refined vaccination techniques, improved antigens and safe vaccines.We are likely to g et many new combo vaccines also. "Naked" DNA vaccines and administration of antigens through viral vectors/edible plants may completely revolutionize childhood vaccination programs. Some vaccines which may soon become available for clin ical use are as follows:
Bacterial vaccines

Viral Vaccines

Rotaviurs vaccine Respiratory Syncitial Virus vaccine Dengue fever vaccines HIV vaccine Hepatitis C vaccine
Protozoal vaccines

Enterotoxicogenic E. coli vaccine Shigella vaccine Cholera vaccine Streptococcal vaccine for rheumatic fever Helicobacter pylori vaccine

Malaria vaccine
Websites for additional information

The following websites may provide useful information www.who.int/vaccines; www.immunizationinfo.org; www.v accin es .o rg ; www.in ejc t io n s afet y .o rg ; www.vaccinealliance.org; www.aap .o rg ; www.cd c.g ov/nip; www.path.org; www.childrensvaccine.org www.unicef.org

50

Update of IAP Immunization Policies, Guidelines And Recommendations

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

The Indian A cademy of Pediatrics Committee on Immunization (IAP COI) conducted its deliberations and reviewed its stand on various policies, guidelines an d reco mmendations pertaining to childhood immu n ization. As has been enunciated earlier, "policies" are the decisions taken by the Academy in relation to the scientific principles and practice of immunization. "Policies" are expected to be pract iced by all members of Academy. 'Guidelines" relate to

those items wh ich are outside the purview of policy, and for which guidance is necessary. Guidelines usually pertain to newer vaccines or issue related to them. "Recommendations" are, in general, what the academy in its role of advocacy on behalf of children, requests other agencies, the Go v ernment of India or other professional bodies.

IAP Policies on Immunization, 2006 a few districts, no new vaccine has been introduced in the national program in the last 25 years. All vaccines under UIP sh o u ld continue to be available free of charge to all eligible children.
On Polio Eradication Goals and SIAs

On NTAGI

The IAP welcomes the establis h ment of the National Technical Advisory Group o n Immunization (NTAGI) by the Government o f India. This followed a formal recommendation from the IAP, given a couple of years ago. The Secretary, Department of Family Welfare is t he Chairperson of the committee while the Assistant Commissioner, Immunization Program is its Member Secretary. The IAP COI ap p reciates that the IAP is represented on this important committee by its incu mb ent President and recommends that the Chairperson/Convener of the IAP COI .should also be invited as a member of this committee.
On Universal Immunization Program (UIP)

The Academy fully supports the Government of India in the use o f oral polio vaccine (OPV) for the pulse immunization program against polio. It is our considered opinion that, in sp it e of some operational hiccups, we must continue with this program and bring it to its logical conclusion, i.e. till wild polio virus is eradicated from our country. IAP advocates that some st ep s are required to be taken to overcome the last hurdles in achieving the goals of polio eradication as fast as possible. These include operationalizatio n of birth dose of OPV all over the country, at least in areas with wild polio virus transmission continuing; strengthening of routine immunization; better quality of SIAs and role of IPV in difficult areas where wild polio virus circulation is still continuing.

The IAP continues to endorse and reiterate its support to th e n at io n al immunization schedule while recognizing the fact that much more needs to be done for meeting the current immunization requiremen t s of the children of our country. It is a fact that except for the recent phased introduction in Hepatitis B vaccine in

51

Inactivted Polio Vaccine (IPV) (Role of IPV vis a vis OPV)

preempt the emergence of cVDPV and has to become self sufficient in stock-piling enough polio vaccine now to meet any such unforeseen eventuality in future. Looking at the above problems, IAP recommends that India should switch over to IPV, preferably as IPV-DTP, in its routine immunization program in post-polio eradication era. India should encourage indigenous manufacturer to produce enough IPV so that it becomes affordable so that it will be possible to switch to IPV in due course, looking at the huge requirement of the number of doses.

OPV is cheaper & being given orally and so mo re acceptable. However it is less efficacious in tropical country like India due to in terference with other enteroviruses and other unknown factors It also needs strict co ld chain maintenance. Where as IPV is more efficacious, less thermolab ile and has no chance of inducing vaccine induced paralysis. Of late IPV h as been shown to induce local g u t immunity as well as herd effect. Coverage of children less than 2 years in high risk areas with 2-3 doses of IPV can b e an additional tool to eradicate polio from our country. The cost and availability of vaccine can be a problem. Post-polio eradication scene and polio immunization: IAP believes that it will be unsafe and u n et hical to continue to use OPV in post-po lio eradication era. Following concepts should be kept in mind while deciding India specific guidelines for post-polio eradication immunization.. It will be unethical and unsafe to continue to use OPV after zero wild polio case and zero transmission status is achieved due to risk of VAPP and cVDPV following OPV. It will be unwise to discontinue use of polio immunization altogether after zero polio status is achieved due to fear of cVDPV, iVDPV. Past experience from some countries has shown that countries which have eradicated wild polio virus and have slackened in their routine polio immunization programs have experienced cVDPV outbreaks. These outbreaks of cVDPV were curtailed by strengthening routine immunization and giving 2 or more rounds of SIAs using OPV. However in post-polio eradication era, it will be unethical and unsafe to reintroduce OPV in such areas. It will force us to depend on the stocks of WHO or any such agency for OPV vaccine, should out-break of wild polio or cVDPP occur. Hence India should

Practitioner keen to use this vaccine may use the vaccine as 3 primary doses followed b y o ne booster dose with DTwP / DTaP. OPV must be given to these children as birth dose and on the NIDs and SIAs.
On number of routine DTP/OPV doses

The IAP COI endorses the use of five d o s es of DTP/OPV at 6, 10 and 14 weeks and thereafter at 15-18 months and 5 years respectively. An additional dose of OPV is to be given at birth to all where possible and one more additional dose along with measles vaccine. It should be noted that we continue to endorse the use of DTP (rather than DT as in t h e national program) and OPV at 5 years.
On Vaccines not covered in EPI

The IAP COI suggests that the UIP s h o uld be supplemen ted by the following vaccines: Hepatitis B (HB), HIB, MMR and typhoid. Td should replace TT at 10 and 16 years. Parents, however, should b e made aware of the availabilit y an d need of these vaccines. Varicella an d Hepatitis A vaccines are still not recommended for routine use. Pn eu mococcal PCV-7, liv e attenuated SA-14-14-2 Japanese Encephalitis Vaccines are the new vaccines which have become available in India. Tdap and Rota virus are the vaccines which are likely to be available in near future.

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IAP COI stand on RECOMMENDED vaccines not covered under EPI against Hepatitis B.
MMR Vaccine

Hepatitis B vaccine

HB vaccine may be given in any of t h e following schedules: (i) (ii) (iii) Birth, 1 and 6 months Birth, 6 and 14 weeks/6 months 6, 10 and 14weeks/6 months

MMR should be promo t ed as a universal vaccine. It should be given at around 15-18 months of age and at least 3 months after the measles vaccine. It should also be given to all adolescent girls and young women not previously immunized, as also to hospital staff likely to come in co n tact with pregnant mothers. There is no upper age limit for this vaccine.
Typhoid Vaccine

Immunologically 0 - 1 - 6 months schedule of hepatitis B immunization has been most widely used and proven to be ideal. HB vaccination is now been integrated into the existing immunization program (UIP) in India. Due to operational issues at a national level one has to piggy back on the av ailable contacts for routine immunization, hen ce 0 - 6 - 14 wks schedule is recommended. In case birth dose has been missed, 6 10- 14 wks schedule can be followed. In office practice, one can still use 0 - 6wks - 6 months schedule. The purpose of Hepatitis B vaccination is to prevent chronic infection and development o f chronic liver disease / hepatocellular carcin o ma later in life. An ideal HB vaccine schedule should, therefore, address vertical as well as horizontal modes of transmission of the virus. If the mother is HBsAg positive (and especially HBeAg positive), the baby should be given Hepatitis B Immune Globulin (HBIG) as soon as possible after birth, preferably within 24 Hours of birth, along with HB vaccine. The injections should be given at two separate sites. If HBIG is not available (or is unaffordable), HB vaccine may be given at 0, 1 and 2 month s with an additional optional dose between 9-12 months. Boosters of HB vaccine are n o t n ecessary in immun o co mpentent individuals. The vaccination schedule need not be changed for preterm babies, in the case of extremely preterm babies, however, vaccination should commence only after initial stabilization. The IAP COI recommends universal immunization 53

The IAP COI strongly recommends the use of typhoid vaccine for all children. Of the 3 types of vaccines (viz. Vi-polys ach aride, whole cell inactivated and oral Ty-21a), only the Vi-polysacharide vaccine is freely available in our country at present. It is recommended to be given after the age of 2 years followed by revaccination every 3-5 years. The government should explore the possibility of manufacturing this vaccine in the public sector on large scale so that t h e costs are brought down.
Hib Vaccine

Hib vaccine should be offered to all children and may be given at 6, 10 an d 14 weeks along with DTP. A booster is given at 15-18 months. If vaccination is s t arted after 6 months of age, only two doses (at 4-8 weeks interval) need be given as primary schedule with a booster at 15-18 months. If vaccination is started between 12-15 months of age, only one dose need be given, with a booster at around 18 months. After 15 months of age only one dose of the vaccine needs to be given- no boosters are required u n d er such circumstan ces. The vaccine need not be given after 5 years of age. Hib vaccine is also recommended for all high risk children, irrespect ive of age, prior to splenectomy and also in patients with sickle cell disease. IAP COI strongly recommends GOI to include

this vaccine in UIP.

IAP COI stand on vaccines that are given after discussion with parents: dose administered by subcutaneous route. This vaccine has recently been licensed for use in India. There is only one Indian study con d u ct ed at Pune on this vaccine showing 95% seroconversion. The vaccine has not been studied extensively outside China. This vaccine should be subject ed to post marketing surveillance for efficacy and adverse reactions in India. However, for 100% seroconversion second dose after 6 months n eed s to be considered as recommended in China.
Varicella Vaccine

Hepatitis A Vaccine

Hepatitis A (HA) vaccine is not recommen d ed for universal immunization in India at present. One has to emphasize the generally benign nature of and rarity of complications with Hepatitis A infection in young children. It may be offered to children from high socio-economic strata of society after explaining the pros and cons to the parents on a one-to one "named child" basis. It may be prescribed to adolescents who have not had viral hepatitis in past (or are known to be HAV-IgG negative) especially if they are leaving home for studies in a residential school/college. HA vaccine is indicated fo r all patients with chronic liver disease as well as household contacts of patients with chronic liver disease as well as household contacts of patients with HA virus infection - in the latter case the vaccine must be given within 10 days; it may, however, be not always effective under such circumstances if the contact has the same source of infection as the index patient. It may also be considered in children attending crches and day care centers and in travelers from abroad (e.g. non-resident Indians) visiting endemic areas. It is given in a 2-dose schedule, 6 months apart after the age of 18 months The adult formulation should be used after the recommended cut-off age: 15 years according to one manufacturer and 18 years according to the other. The vaccine is given intramuscularly and the protectiv e efficacy is 94-100%. Boosters are not recommended at present.
Live attenuated Hepatitis A Vaccine

The IAP COI opines that varicella vaccine is not recommended for universal immunization in India at present. One has to emphasize the gen erally benign natu re of and rarity of complications with, varicella in fection in young children. It may be offered t o children after ag e of 15 months from high socio-economic strata of society after explaining the pros and cons to the parents on a one-to-one "named child" basis. It may be prescribed to adolescents who have not had varicella in past (o r are known to be varicella IgG negative) especially if ther are leaving home for studies in a residential school/college. It is indicated in children with ch ro nic lung/heart disease, humoral immunodeficiency, HIV infection (but with CD 4 counts above 15% of the age related norms), leukemia (but in remission and off chemotherapy for at leas t 6-12 weeks) and those on long term is als o of be in hous e h o ld c o n t act s s alicy lat es/steroids. Varicella vaccin e reco mmen d ed

immu n ocompromised children. It may also centers.

considered in children attending crches and day care

The live attenuated Hepatitis A Vaccine has been licensed for use in China since 1992. The manufacturer claims 92 to 100 percent seroconversion with single

Varicella vaccine is also indicated in susceptible adolescents and adults if they inmates of or working in 54

the institutional set up e.g. school teachers, day care center wo rkers, military personnel and health care professionals. A single dose suffices between the ages of 1-13 years, after which a 2-dose schedule (4-8 weeks apart) is recommended.
Acellular Pertussis Vaccine

reactions to a previous dose of whole cell pertussis vaccine. These include: 1. Convulsions with/without fever occurring within 3 days 2. Persistent inconsolable crying for 3 or more hours within 48 hours 3. Collapse or shock-like state within 48 hours 4. Temperature > 40.50C within 48 hours
Conjugate Pneumococcal Vaccines (PCV-7)

The IAP COI endorses the continued use of whole cell p ertussis vaccine (as DTPw) because of its pro v en efficacy and safety. Acellular pertussis vaccines may undoubtedly have fewer minor side-effects (like fever, local reactions at injection site and irritability), but this small advantage dose not justify the inordinate costs involved in the routine u s e of this vaccine. It is , t h erefo re, not reco mmen d ed for un iv ers al immunization in our country at present. There is , however, no bar to offering these vaccines to children from families who opt for the vaccine for the slight advantage of fewer minor side-effects. Use of acellular pertussis vaccine should, however, be considered in children who have had s ig n ificant

The IAP COI does not recommend use of this vaccine for universal immu n ization for healthy children in our country at present. PCV - 7 co v ers only 50 to 55 percent of pneumococcal seroty p es responsible for serious invasive pneumococcal diseas e in infants & children in India. The v accine may be offered after explaining the parents on o ne to one "named child" b asis. However it is recommended routinely in h ig h risk group children up to the age of 5 years.

IAP Stand on vaccines for special circumstances efficacy reaching 99% even with single dose. As per a W HO report no serious adverse effects (other than anaphylaxis) have been rep o rt ed over 20 year period (1979 - 1998). This vaccin e is not available commercially in India; it has been used this y ear in seven endemic districts after importing it from Chengd u Institute of Biologicals, China. From the av ailable safety data, the vaccine was found to be extremely safe.
Meningococcal Vaccines

Live Japanese Encephalitis (JE) Vaccine (SA-14-14-2)

This vaccine is bas ed on a stable neuro-attenuated strain of JE virus (SA-14-14-2). It was firs licensed for use in 1988 in People's Republic of China and over sixty million doses per year are being used there. Now it is also licensed for use in Nepal, S. Korea and India This live attenuated vaccine constitutes to over 50% of global production of all JE vaccine. Dose is 0.5ml at all ages. It is given by subcutaneous route. Init ial studies done on this vaccine demonstrated an efficacy of about 80% with single dose and 98% with 2 doses. However, more recent studies have shown 55

Meningococcal vaccine (bivalent A, C or tetravalent A, C, Y, W135) is indicated for use (as an adjunct along with chemoprophylaxis) in clos e co ntacts of patients

with the disease. It is also indicated in high risk in d iv id u als (e .g . t h o se with and hyposplenia/asplenia,complement deficien cy )

during epidemics It is recommended for those who are going for Haj pilgrimage.

IAP COI stand on future vaccines: developing countries 53% of rotavirus deaths occur in Africa & 42% in Asia. It is estimated that 100,000 children d ie each year in India due to rotavirus diarrhea. As rotavirus d iarrhea occurs in spite of highest standards of hygiene it cannot be prevented by public health measures like s afe water supply and good sanitations. For prevention universal immu n ization appears to be the only answer. The first vaccine against rotavirus was tetravalent rhesus-human rotavirus vaccine (RRV-TV vaccine, Ro t ashield: Wyeth Lederle). This vaccine licensed in USA in 1998 and recommend ed for universal use had to be withdrawn when an increased administration. Recently a new Pentavalent bovine-human reassortant vaccine from Merck (Rotateq) has been licensed in USA. Another Rotavirus vaccine - a live at t enuated human (G1P8) monovalent vaccine from GSK (RIX 4414 Rotarix) has recently been licensed in Latin American countries and some A s ian Countries. Both these vaccines have been found to be safe and highly efficacious. Trials of these vaccines have not been initiated in India so far. There is a great diversity of Ro t avirus strains
Rota Virus Vaccine

Tdap

In the western world it is being felt that there is a need to vaccinate adolescents and adult s with pertussis vaccine. There the epidemiology has undergone a marked shift since the introduction of mass childhood vaccination programs, the proportion of pertussis cases in older children, adolescents and adults though n o t great in numbers have relatively increas ed, making them the source of transmission to very young infants who are unimmunized or partially immunized and this age group is more vulnerable to dis eas e related complications and mortality. The Tdap vaccin e h as been incorporated as booster dose during adolescence in the immunization schedule of few developed countries. This provides booster to waning immunity in adolescents thus leading to individual protection and prevention of transmission of disease to susceptible infants and children. In India the epidemiology of pertuss is is not well known and there is lack of information reg arding epidemiological shift. So the Tdap vaccine is n ot recommended for universal use at present. This vaccine may be of particular use for children who have missed their 2nd booster of the DPT and are more than 7 years of age.

rate of

intussusceptions was shown to occur after vaccine

prevalent in India. There is need to know the efficacy of these vaccines in India before any recommendations can be mad e on the use of existing vaccines. Other Rotavirus vaccine being developed are LLR vaccine in China which is in phase II / III trials and the newborn strain vaccine in India.

Rotavirus is common cause of d iarrhea all over the world. Almost all children get infected by the age of 5 yrs. In India, of the children hospitalized for rotavirus diarrhea, 50% were < 6 months, 75% < 9 months and nearly 100% < 2 y rs. It is estimated that risk of death follo wing rotavirus diarrhea is 1 in 290 cases in 56

Combination Vaccines

adhered to strictly 2. Extemporaneous " mixing" of vaccines in the same syringe (prior to injection) should not be done as far as possible, unless specifically recommended b y the manufacturer; in the latter case the manufacture's instructions should be followed strictly 3. The advantage of a combination vaccin e is the convenience of fewer clinic visits for the parents and fewer pricks for the child 4. Combination vaccines should not be viewed as being more effective than vaccines given separately

The number of vaccines in the immunization schedule is increasing every year and this tren d is likely to continue for the next few years. Many parents opt for one single injection of combination vaccines at a given visit, rather than come repeatedly for the various individual vaccines or take multiple pricks on a single day for vaccines that are now in cluded in the immunization time- table. A number of combination vaccines are now available in the Indian market. The IAP COI endorses the use of combination vaccines, but with the following cautionary statements: 1. The manufacture's recommendations should be

On Adolescent Vaccination

Immunization card to be used for this purpose. Parents must be instructed to keep the document safely and present it to their doctor whenever required.
On Advertisements in the Lay Media

The Academy endorses the continued use of Td/tetanus toxoid at 10 and 16 years and thereafter every 10 years. HB vaccine may be offered in th e 0, 1 and 6 months sched u le as mentioned earlier under individual vaccines, if the child has not received it earlier. MMR vaccine should be offered to all children who have not received it earlier - there is no upper age limit for this vaccine. The Academy encourages the use of typhoid vaccin e for all adolescents. Hepatitis A and varicella vaccines should be used in selected cases as mentioned above.
On Immunization Records

Some of the multinational companies have been using the lay media (television, electronic media and news p apers/magazines) for placing advertisements pertaining to optional/combination vaccines. We opine that this is uneth ical. The IAP placed a formal complaint before th e Drug Controller General of India and the Union Health Ministry. This led to the issuance o f a letter by the Drug Controller to the concern ed companies requesting them for the withdrawal of these advertisements. We are hopeful the companies would see reason and refrain from lay advertising.

Every vaccine given to a child must be documented on a card/ booklet. We recommended the IAP Health and

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IAP 2006 Recommendations for other agencies including Ministry of Health and Family Welfare, Govt of India The IAP COI has formulated several specific recommendations to other agencies pertaining to immunization.
The IAP recommends that the Academy should be represented on NTAGI by incumbent President and the Chairperson/Convener of IAP COI At 5 years of age booster immunization should be done with DTP rather than DT. The Academy recommends that inactivated polio vaccine should be introduced in the routine immunization in a phased manner, now that it is licensed in the country. The Academy strongly recommends that Hepatitis B, HIB and M M R Vaccines should be included in the national immunization schedule with immediate effect. The Government should actively consider inclusion of typhoid vaccine in the national immunization schedule. The Academy suggests use of Vi-polysaccharide vaccine for this purpose. The Academy supports the decision of the Government to discontinue production of animal brain rabies vaccine. However we need to ensure adequate supplies of indigenously produced chick embryo/tissue culture vaccines at affordable costs. Intradermal route of cell cultured vaccine as per the recent approval and the guidelines of the Drug Controller General of India should be encouraged and the minimum number of vaccinees stipulated in the guidelines should be brought down to 10 (the number of doses obtained from one vial of vaccine). The Academy again reiterates its previous recommendation to the Federation of Obstetric and Gynecologic Societies of India to adopt a policy of routine testing of all pregnant women for HBV infection. If the mother is HBsAg positive, the baby should be given HBIG plus HB vaccine soon after birth.

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