IAP Guidebook on immunization 2007


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IAP Guidebook on immunization 2007

  1. 1. 1
  2. 2. IAP GUIDEBOOK ON IMMUNIZATION Editors Dr. Raju C Shah Dr. Nitin K Shah Dr. Shyam Kukreja IAP Committee on Immunization 2005-2006 Chairperson: Dr. Raju C. Shah Co- Chairperson: Dr. Nitin K. Shah Convener: Dr.Shyam Kukreja Members: Dr. Rohit Agarwal Dr. Indra Shekhar Rao Dr. Shivananda Dr. Nigam P Narain Dr. Sangita Yadav Ex-officio members: Dr. Deepak Ugra Dr. Tapan Kumar Ghosh Dr. VN Yewale Dr. Naveen Thacker Dr AP Dubey Dr Surjeet Singh Address for correspondence: Indian Academy of Pediatrics Kailas Darshan, Keneddy Bridge Near Nana Chowk Mumbai India 400 007 Tel: +91-22-3889565 E-mail: iapcoff@bom5.vsnl.net.in 2
  3. 3. Preface Immunization is the single most successful child survival s t rat egy the world over. Immunization also reduces morbidity to great extent. Due to progress in molecular biology and genetic engineering a number of new vaccines have become available and many more are in the pipeline. Many of the developed countries have reduced their vaccine preventable disease burden by using this tool very effectively. As Pediatricians we must be conscious of the fact that the immunization needs of the children are quite dynamic. A vaccine which may not be considered important today may become n ecessary in future as more informat ion about the epidemiology of the disease becomes available. The inclusion of an y n ew v accine in the universal immunization program of a country depends on disease epidemiology, availability of safe vaccine, economic constraints and logistic problems. Unfortunately the limiting factor most of the times in developing countries like India is the affordability. There is always a need to update knowledge and co n cep t s es pecially in the field of immunization as there is continuous flow of new knowledge. Also one must try to objectively understand a difference between a public health measure paid for by the government and a personal safety measure instituted by the individual at one's own cost due to certain limitations. To get the most benefits for any vaccine (herd effect), adequate immunization coverage is required. Unfortunately, in our country the routine immunization coverage rates have slipped down over the last few years. This is a matter of great concern to all of us. This has been one of the major obstacles in polio eradication program. There is an urgent need to reinforce quality immunization services and our academy has always been at the forefront of this initiative. We are sure this updated guidebook will continue to serve as ready reckoner on issues concerning vaccines and immunization in our country. Dr. Raju C Shah Dr. Nitin K. Shah Dr. Shyam Kukreja Chairperson, IAPCOI 2005- 2006 Co-Chairperson, IAPCOI Convener, IAP COI 2005- 2006 2005-2006 President IAP 2005 President IAP 2006 3
  4. 4. Contents Introduction 5 Historical aspects 6 Basic immunology 8 National immunization schedule 10 Commonly used vaccines 11 Newer vaccines 24 Vaccines used in special circumstances 27 Combination vaccines 30 IAP Immunization Time-Table 34 Immunization in special circumstances 36 Adverse reactions following immunization 42 The cold chain 44 Surveillance for vaccine preventable diseases 49 Vaccination in the current millenium 50 IAP COI meeting report and policy updates 51 4
  5. 5. Introduction Protect ion from preventable diseases, disabilities and consensus based on the current evidence from the death through immunization is the birth right of every literature. The IAP Immunization Time Table child. Immunization is one of the most co s t-effective represents the 'best individual practices schedule' for a health intervention s known to mankind Over the last given child and would necessarily be at some variance three decades, a lot of progress has been made globally from the National Immu n ization Schedule of the as far as protection against the eight important vaccine Government of India, which is meant for the public at preventable diseases is concerned - from less than 5% large. With the availability of many newer vaccines, it children who were protected against these diseases in is necessary that some of these should be considered for the early 1970s, to as many as 75% being protected routine immunization and the immu nization schedule now. Small pox has been eradicated and we are at the has to be changed accordingly. threshold of eliminating polio. Unfortunately, there is lack of authentic data on An effective National Immunization strateg y can help epidemiology of most infectious diseases in our country. decrease childhood morbidity and mortality, especially However that should not deter us from using some of in developing countries. It must, however, be clear that these vaccines till such data is generated. Many immunization strategies may vary from co u n try to decisions on incorporation of new vaccines in t he country depending on the local req u irements. This immunization program have, therefore, to be based on guide book represents the collective effo rts of the data from other parts of t h e world. This may appear members of the Indian A cademy of Pediatrics unscientific to some, but is a reality and is the only way Co mmittee on Immunization (IAP COI). We are aware out at present. that unanimity may not always be possible as far as the need and timing of certain newer vaccines are concerned, but we have made efforts t o arriv e at a 5
  6. 6. Historical Aspects Though Dhanvantri, t h e father of Indian In 1985, the EPI was s upplanted by the Universal Medicine, sp o ke of preventing certain infectious Immunizat ion Program (UIP). The main objectives of diseases t h rough immunization, the first successful UIP were: i) universal immunization and reduction in vaccine in the modern era was developed b y Edward mortality and morbidity due to vaccine prev entable Jenner in 1796 when he used cowpo x inoculation diseases ii) self-sufficiency in vaccine production iii) (vaccination) to protect against smallpox. Louis establishment of a functional cold chain system, and iv) Pasteur developed a h ig h ly effective vaccine against the introduction of district level monitoring system. In rabies, which was used for post-exposure prophylaxis. this program the emphasis was s hifted from the It was first given to a child in 1885. Since then many under-five to under-one age group, thereby reducing the other vaccines have been developed in rapid succession. number of potential beneficiaries. It considerab ly reduced the denominator for percentage coverage. The Experience with smallpox eradicat io n p ro g ram vaccines recommen d ed were BCG, DTP, OPV and convinced the health policy makers that immunization Measles for infant s an d TT for pregnant women. It was the most powerful and cost-effective measure for should be noted that UIP envisaged 100% coverage of control of vaccine preventable diseases. At the global pregnant women with 2 doses of tetanus toxoid (or a level, an organized immunization program came into booster dose, as applicable) and at least 85% coverage exis tence in the year 1974 under the banner of the of infants. Under the UIP, the govern ment also aimed World Health Organization (WHO). This was to establish logistics of vaccine production and supply christened as the 'Expanded Program on Immunization' as well as training of medical and p aramedical (EPI). The term "Exp anded" referred to the provision personnel. The Government of India subsequently set of adding more antigens to vaccinatio n s chedules, up a " Technology Mission on Vaccination and extending coverage to all corners of a country and Immunization of Vulnerable Po pulation, especially spreading services to reach the less privileged sections Children" to cover all asp ect s of the immunization o f the society. The EPI program focused on children activity from research and development to actual below 5 years of age and pregnant women. The delivery of services to the target population. vaccines included were BCG, DTP, OPV, Measles and TT. The primary health care concept as enunciated in Since switching over to UIP in India there has been a the 1978 Alma Ata Declaration in cluded immunization significant decline in many of the vaccine preventable as one of the strategies for reaching the goal of 'Health diseases, such as poliomy elitis, neonatal tetanus, for All' by the y ear 2000. The Government of India diphtheria, wh o o p ing cough and measles. The UIP adopted the EPI in 1978 with the t win objectives of became an integral component of Child Survival and reducing the mortality and morbidity resulting from Safe Motherhood Program (CSSM) in 1992 and then vaccine preventable diseases of childhood, and to part of Reproductive and Child Health Program (RCH) achieve self-sufficiency in the production of vaccines. in 1997. Supplemen t ary immunization activities The program started with BCG, DTP and Typhoid against poliomyelit is were started in 1995-96. In 2002, vaccines - it did not include measles vaccine. OPV was Hepatitis B vaccination was initiated in selected areas added only in 1979 and measles later on. Ty p h oid targeting the urban poor. vaccin e continued to be a part of our national The WHO also endorsed global efforts at immunization immunization schedule until 1985. Program coverage through Universal Childhood Immunization (UCI) in of 85% was envisaged, but this could not be achieved 1990 - the name given to a declaration sponsored by for several years and independent evaluations showed UNICEF as part of the 40th anniversary of the United very low coverage rates in many parts of our country. Th erefore, a change of strategy was considered Nations in October 1985. Efforts were undertaken to initiate research for the development of newer vaccines, necessary. to improve vaccine product ion technologies and to 6
  7. 7. u n d erstand the epidemiology of diseases. These augmenting research and d ev elopment on vaccines developments were highlighted in 1990 at the Summit against HIV, malaria and tuberculosis v) making for Children, where it was claimed that EPI had indeed immunization coverage an integral part of international been a global success with 80% reported coverage with development initiatives. The GAVI Ind ia Project has the six vaccines. In 1992, the WHO also set a target for been instrumental in launching free Hepatitis B universal Hepatitis B immunization. It aimed to immunizatio n in some of the urban slums. It has also incorporate Hepatitis B vaccine in the immunization endeavored to promote safe injection practices and use schedules o f all member countries by 1997. However of auto-disable syringes for immunization as part of a unfortunately less than 50% of t h e countries have countrywide initiative. actually introduces Hepatitis B vaccine in their A surv ey conducted in 2002 under the RCH showed National Schedule. India has recently accepted its that immunization coverage rates in India have been inclusion in National schedule and the coverage will d eclining, since 1999. The Government of India h as expand in a phased manner. recently lau n ched an Immunization Strengthening These global efforts at immunization were launched Project with the objectives of i) strengthening routine under the banner "Children Vaccine Initiative" (CVI) immunization with the aim of raising the percentage of in 1991 with support from several in t ernational fully immunized children t o ab ove 80% ii) eliminating agencies like the WHO, UNICEF, World Bank and the polio and achieving polio eradication iii) reviewing and Rockefeller Foundation. CVI aimed at development of developing a new vision of the immunization program newer vaccines, improvement in vaccine production in the medium term keep in g in view the development technolo g ies and vaccine quality. These efforts were of new epidemiological patterns, availability of new further co nsolidated under the "Global Program on vaccines and delivery mechanisms and advances in cold Vaccines and Immunization" (GPV) in 1993 reflecting chain technologies iv) improving surveillance and the EPI and UCI init iative and combining these with monitoring mechanisms. The National Institute of the CVI. The focus of GPV is on sustaining high Health and Family Welfare has been identified as the vaccine coverage, developing global surv eillance nodal institute for coordination and implementation of network and evolving eradication strategies. The the program an d the training shall be carried out "Global Alliance for Vaccines and Immunization" through five regional inst it u tes. Training of mid-level (GAVI) was set up in 1999 as an international coalition managers, including persons actively involved in of multination al funding agencies (e.g. Bill and immunization program at the district and state level, is Melinda Gates Foundation, Rockefeller Foundation), an integral component of this project. The project was v accin e man u fact u re r s , n o n - g o v ern men t al started in 50 poorly performing districts of 8 priority organizations and the governments of 74 d ev eloping states of Uttar Pradesh, Bihar, Madhya Pradesh, nations. GAVI organizes its activities through a Rajasthan, Oriss a, Gujarat, Assam and West Bengal. vaccin e fund. The main objectives of GAVI are as These newer initiatives have improved overall coverage follows: i) impro v in g acces s t o s u s t ainable in these districts. Unfortunately last report of National immunization services ii) expanding use of all existing family and health survey released in 3rd week of Nov safe and effective vaccines iii) accelerat ing the '06 do not confirm this improvement. development and introduction of new vaccines iv) 7
  8. 8. Basic Immunology The Greek work "immune" means "to be protected". BCG, oral polio v accine and Hepatitis B vaccines can Protection offered by the introduction of various be given soon after birth as the maternally derived antigens or ready-made antibodies is called acquired immunity apparently does not interfere with the vaccine immunity. The process by which t h is acquired "take" On the other hand, live measles vaccine may be immunity is obtained is known as 'immunization'. This inhibited in the presence of detectable maternal is of two types, active and passive. When specific antibody in the infant's circu lation. Measles vaccine, antigens evoke the required immune response in the therefore, should only be given after at least 9 months system it is called active immunization, and when of age ; similarly, MMR vaccine is given only after 12 antibodies are supplied readymade in th e form of months of age. immune g lo b u lins and sera it is known as passive Timing of vaccination depends upon the age at which immunization. the disease is anticipated as well as on the feasibility of Pathogenic infectious ag en t s induce disease and the administering the vaccine at that time. For instan ce, host immune system responds with immunity , first to neonatal tetanus can only be prev en t ed through ensure recovery and then to offer protection from maternal immunization by ensuring adequate titers of disease if the same patho gen were to be encountered transplacent al antibodies and not by immunization of again. A vaccine is composed of one or more antigens the baby at birth. of the pathogen, which will induce a protective immune Vaccines are selected based on three important criteria response without suffering from the disease. viz. necessity, safety and efficacy. All vaccines are Vaccines consist of attenuated live organisms (eg. oral subjected to the following trials before being licensed: polio vaccines, oral typhoid vaccine, varicella vaccine, Phase I Trial: Human volunteers - for tolerance, safety measles vaccine), whole inactivated org anisms (e.g. pertusis vaccine, whole cell typhoid vaccine, rabies Ph as e II Trial: Human volunteers - for immu n e vaccine, inactivated polio vaccine), modified exotoxins response, safety called "toxoids" (e.g. diphtheria toxoid, tetanus toxoid), or subunits (e.g. polysaccharide antigens of Salmonella Phase III Trial: For field efficacy, safety typhi or Haemophilus influenzae type b and the surface Further, before a vaccine is act u ally marketed it proteins of hepatitis B virus). undergoes sterility, purity and potency tests at the level Vaccines mimic infection with the respective pathogen, of the manufacturer and the Drugs Controller General but without the asso ciated risk of developing the of India. disease. The consequent immune response may be Most of the currently used childhood vaccines do not manifested through hu moral (i.e. antibody) immunity interfere with the vaccine "take" of one another. These or cell mediated immunity (CMI) or both. If the antigen can be, therefore, given simultaneously and several preferentially stimulates Th1 series of T helper antigens can be g iv en the same day, if required. In lymphocytes, a strong lymphocytic respons e is general, the interval between two doses of the same obtained; if Th2 series is preferentially stimulated, the v accine, say for instance DTP, should be at least 4 ultimate express ion of immunity is predominantly weeks; preferably 8 weeks. An interval of 4 weeks humoral. Carbohydrate antigens are T cell independent; would obviously result in completion of the primary hence they stimulate B cells directly without T helper schedule at an earlier age an d may perhaps make it cell modulation. This results predominan t ly in a IgM easier for the parents to remember their follo w-up response wit h out IgG production or induction of appointments. Th is way the drop out rates may also immunological memory. BCG elicits CMI without an decrease. BCG and OPV can be given from the day of easily demonstrable humoral component. 8
  9. 9. birth until 2 weeks of age, s o that there would be 4 immune system and it may be advisab le to avoid weeks gap until the next contact for immunization at 6 administratio n of other vaccines within 4 weeks of weeks. If the opportunity to give BCG / Hepatitis B was these. There is, however, very little objective evidence not available in the neonatal period, it may be given at to show t h at this immunosuppression is clinically 6 weeks, s imultaneously with DTP and OPV. Some of significant. the viral vaccines (e.g. measles, varicella) may be associated with possible short lasting suppression of the Terminology Vaccination: process of inoculating the vaccine/antigen. Immunization: process of inducing immune response which may be humoral or cellular. Seroconversion: change from antibody negative state to antibody positive state. Seroprotection: a stage of protection from disease, due to the presence of detectable antibody. Antibody titer: the reciprocal of the highest serum dilution at which antibody has been detected. Geometric mean: the mean antibody titer in a g ro u p o f in d ividuals [usually titer from those who have seroconverted (GMT)] Each time a vaccine is given the doctor should explain anticipated adverse reactions and due date for the next to the mother the nature of vaccine, t h e n umber of session of immunization. doses needed, the disease likely to be prevented, Types of Vaccines Type of Antigen Examples Live bacteria, attenuated BCG, Ty21a Live virus, attenuated OPV, MMR, varicella Inactivated bacteria Pertussis, whole cell killed typhoid Inactivated virus IPV, rabies, HAV Toxoid Tetanus, diphtheria, Td Capsular polysaccharide Typhoid Vi, Hib, meningococcal, pneumococcal Viral subunit HBsAg Bacterial subunit Acellular pertussis 9
  10. 10. National Immunization Schedule Age Vaccines Birth BGG, OPV0 for institutional deliveries 6 weeks DTP1, OPV1 (BCG if not given at birth) 10 weeks DTP2, OPV2 14 weeks DTP3, OPV3 9 months Measles 16-24 months DTP, OPV 5-6 years DT* 10 years TT** 16 years TT For pregnant women Early in pregnancy TT1 or booster One month after TT TT2 *A second d o s e of DT vaccine should be given at an interval of one month if there is no clear history or documented evidence of previous immunization with DTPw. ** A second dose of TT vaccine should b e g iv en at an interval of one month if there is no clear history or documented evidence of previous immunization with DTPw, DT or TT vaccines (Source: Govt. of India (1994) National Child Survival and Safe Motherhood Program, M in is t ry of Health and Family Welfare, New Delhi) 10
  11. 11. Commonly Used Vaccines A. Vaccines Against Diseases Covered Under EPI BCG Vaccine Bacillus Calmette Guerin vaccine is derived from the ensure maintenance of cold chain during transport and bovine tuberculosis strain and was first developed in storage. Th e recommended dose is 0.1 ml of 1921. It was the result of painstaking efforts by t h e reconstituted vaccine irrespective of the age and weight French microbiologist Albert Calmette and the of the baby. Injection of BCG should be strictly veterinary surgeon Camille Guerin who performed 231 intradermal, using a Tuberculin syringe and a 26G repeated subcultures over 13 years. It continues to be need le. The convex aspect of the left shoulder is the only effective vaccine against tuberculosis The two preferred for easy visualization of the BCG scar. The common strains in use are Copenhagen (Danish 1331) selected site may be swabbed clean using sterile saline and Pasteur of which the former was produced in India - local antiseptics are unnecessary. at the BCG Laboratories, Guindy, Tamil Nadu till A wheal of 5 mm. at the injection site indicates recently. successful intradermal administrat ion of the vaccine. BCG induces cell-mediated immunity but t h e Subcutaneous administration of BCG is associated with protective efficacy is a matter of debate and is very an increased incidence of BCG aden it is . The injected difficult to q u an t ify BCG vaccine is more effective site usually shows no visible change for several days against t h e development of hematogenous spread of Subsequently, a papule develops after 2-3 weeks, which Mycobacterium tuberculosis (which results in milliary increases to a size of 4-8 mm. by the end of 5-6 weeks. and meningeal forms of the disease against which it This papule often heals with ulceration and results in a has a protective efficacy of 50-80%), than against the s car after 6-12 weeks. Although the preferred time o f development of pulmonary tuberculosis where it has a vaccination is soon after birth, it could be given up to protective efficacy of less than 50%. the age of 5 years. If no reaction is seen at the local site even after 12 weeks, it is an in dication to repeat BCG The vaccine contains 0.1-0.4 million live viable bacilli presuming that BCG has not taken up. per dose. It is supplied as a lyophilized (freeze-dried) preparation in vacuum sealed multi-dose dark colored Adverse reactions - The ulcer at vaccination site may ampoules. The lon g n ecked BCG ampoule should be persist for a few weeks before formation of the final cut carefully by gradual filing at the junction of its neck scar. No treatment is required for this co ndition. and body, as sudden gush of air in the vacuum sealed Secondary infection at the vaccination site may require ampoule may lead to spillage of th e contents. The an t imicro b i a l s . I p s i l a t eral axillary / cerv ical vaccine is light and heat sensitive and deteriorates on ly mphadenopathy may develop a few weeks/months exposure to ult ra violet rays. Sterile normal saline after BCG vaccination. Antitubercular therapy is of no should be used for reconstitution. As t h e vaccine benefit in such situations and should not be contains no preservative, bacterial contamination may administered. The nodes regress spontaneously after a occur with repeated use. Therefore, once reconstituted, few months. It should also be noted that if fine needle the vaccine should be used within 4 hours with the aspiration cytology of the nodes is carried out, stain for left-over being discarded after the session. acid-fast bacilli may b e p o sitive. These are bovine vaccine bacilli and should not be misconstrued as being In lyophilized form it can be stored at 2-80 C for up to suggestive of tuberculous disease. In some children the 12 months, without losing its potency. One should 11
  12. 12. nodes may even liquefy and result in an ab s cess. s it u at ion also. Disseminated BCG infection is Surgical removal of the nodes or repeated needle extremely unusual but may occur in children with aspiration is the treatment of choice - again, cellular immunodeficiency. antitubercular therapy is not recommended in this Oral Polio Vaccine Oral polio vaccine (OPV) remains the vaccine of choice must reach the outreach facility at 2-80 C in vaccine for polio eradication in India. It is a suspension of over carriers with ice packs. Breastfeeding and mild 1 million particles of poliovirus types 1, 2 and 3. It is d iarrh ea are n o co n t rain d icat io n t o OPV supplied with a stabilizing agent, namely magnesium adminis t rat ion. If a substantial amount of OPV is chloride. The vaccine, therefore, is quite stable under vomited or regurgitated wit hin 5-10 minutes of refrigeration. administration, the dose should be given again. If this repeat dose is also not retained, neith er of the doses When OPV is given by mout h , t h e vaccine viruses s hould be counted and the vaccine shou ld b e reach the intestines where they must establish infection re-administered at a later visit. (vaccine virus "take") before an immune response may occur. A high level of gut immunity ensures that Adverse reactions - OPV is an excellent vaccin e and vaccinated children would not participate in the chain the WHO Global Polio Eradicat io n Initiative is at the of transmission of wild (pathogenic) polioviruses. For threshold of achieving its goal of eradicating wild reasons that are not clearly understood, OPV "take" polioviruses. By mid-2006 polio has been elimin ated rates may be somewhat variable. Seroconversion rates from all countries other than India, Pakistan, after three doses of OPV average 73%, 90% and 70% Afghanstan, Nigeria, Niger and Egypt. For developing for Types I, II and III respectively. It is for this reason cou n t ries OPV is still the vaccine of choice for that multiple doses of OPV are necessary before eradicating wild poliovirus and would continu e t o be 90-95% of children develop immune responses to all used until wild poliovirus circulation ceases. However, three poliovirus typ es . IAP recommends at least 5 like any other vaccine its use is associated with certain routine doses of OPV, d u ring infancy and 2 more risks. repeat doses; at 16-18 months and 5 years. In addition to the routine OPV doses , " Pulse OPV doses" every OPV has been associated with occurrence of Vaccine Associat ed Paralytic Poliomyelitis (VAPP) Today, as year on Nat io n al Immunization Days (NIDs) and sub-National Immunization Days (sNIDs) until the age we move towards p o lio eradication, VAPP is more common than paralysis due to wild polioviruses and of 5 years are also mandatory. has, therefore, become an increasingly contentious Polio eradication is defined as no case of paralytic issue for all pediatricians . The risk of VAPP would poliomyelitis by wild polioviru s in last three calendar continue to be there as long as we are using OPV as the years along with absence of wild poliovirus in the preferred vaccine against poliomyelitis. It has been community, when excellent clinical and virological estimated that the global VAPP burden is in the range surveillance exists and the coverage of routine OPV is of 250-800 cases an nually. Nearly 50 cases of VAPP more than 80%. Polio elimination is defined as no case are reported to occur in India annually. Approximately of paralytic poliomyelitis by the wild poliovirus in one half of all VAPP cases are associated with the Type 2 calendar year with other criteria being the s ame as in OPV strain. eradication . A d eq u at e immu n izat io n , clinical The second major problem with u s e of OPV is the surveillance and appropriate virological investigations in all children with acute flaccid paralys is (AFP) are emergence of circulating Vaccine Derived Polio Viruses (cVDPVs), which are mutants that re-acquire the cornerstones of polio eradication. wild virus-like properties and have been associated with OPV should be stored at -200 C at the state and district outbreaks of paralytic polio. cVDPVs usually aris e in level and in the freezer at the clinic level. The vaccine communities with low population immunity especially 12
  13. 13. when polio vaccine coverage rates decline but OPV use suggested that mass OPV campaigns should be continues. The duration and extent of spread of s ynchronized with the cessation of OPV use o n ce cVDPVs are dependent on the magnitude of the eradication of wild poliovirus has been achieved, so as immunity gap. As lo n g as OPV is in use it is t o eliminate the risk of VAPP and the emergence o f mandatory that very high immunization coverage is cVDPVs. At the same time, a gradual transition to IPV maintained so as to decrease the risk of emergence of should be encouraged. cVDPV. W hereas VAPP occurs in individual cases, cVDPV can result in large outbreaks. It has been Polio Eradication Why do we need pulse immunization against polio? • Maintaining high routine infant immunization coverage with OPV. Simultaneous administration OPV to all susceptible • Conducting mass campaigns (i.e. pulse infants and children interferes with circulation of wild immunization against polio). poliovirus in the community. It is, therefore, important • Development of sensitive surveillance. to ensure complete coverage with OPV during NIDs so • Organization of mop-up campaigns. that no wild poliovirus remains in circulation. Core strategies for eradication of polio include: Inactivated Polio Vaccine (IPV) IPV is formaldehyde killed poliovirus grown in monkey could be given at 4 weeks interval without any kidney cell/human diploid cells. Old IPV contained 20, compromise in the seroconversion rates. 8 and 32 D antigen units of types 1, 2 and 3 Scientifically and immunologically schedule of giving polioviruses respectively. All curren tly used IPV two doses of IPV starting at 2 months of age and given vaccines are enhanced potency IPV (elIPV) which at 2 months interval followed by a booster at around 15 cotains 40, 8 and 32 D antigen units of type 1, 2 and 3 mo n t h s is similar to a schedule of giving 3 doses respectively. Currently term IPV means eIPV. It is starting from 6 weeks of age and given at 4 weeks highly immunogenic. Seroconversion rates are 90-95% interval followed b y a booster at 15 months (even in after two doses given after the age of 2 months and at developing countries). However in our country the later 2 months interval and 99% after three doses given even schedule of 3 primary doses is better logistically as it when it is started at 6 weeks of age and given an 4 can be given along with DTP at 6, 10 and 14 weeks weeks interval It produces excellent humoral immunity followed b y a booster at 15 months. In any case the as well as local pharyngeal and, possible in testinal b irt h d o se of OPV must be given and all the OPV immunity. The vaccine is very safe. It is now licensed doses on the days of NIDs / SIAs should be given to all to be used in India by Drug controller of India. the children. IPV can be used in combination with DTwP and Hib As the number of wild poliovirus cases in the country vaccines without compromising seroconversion or decreases, it is inevitable that one would have to shift increasing side effects. Ideal age to give first dose of fro m OPV to IPV in the next few years. The IPV is 8 weeks an d the interval between two doses government sh o uld, therefore, consider incorporating should also be 8 weeks. However if 3 primary doses are IPV in the national immunization schedule in a phased given, vaccine could be started at 6 weeks of age and 13
  14. 14. manner. IPV can also be an additional tool to eradicate rounds of SIAs using OPV. However in wild polio from last few high risk difficult districts. post-polio eradication era, it will be unethical and unsafe to reintroduce OPV in IPV is also the vaccine of choice in patients with such areas. It will force us to depend on the immunodeficiency and th e preferred vaccine in stocks of WHO or any such agency for OPV children with symptomatic HIV infection. vaccine should out-break of wild polio or cVDPP occur. Hence India should preempt Post-polio eradication scene and polio immunization: the emergence of cVDPV and has to become IA P believes that it will be unsafe and unethical t o self sufficient in stock-piling enough polio continue to use OPV in post-p o lio eradication era. vaccine now to meet any such unforeseen Following concept s should be kept in mind while eventuality in future. deciding India specific guidelines for post-polio 3. Looking at the above problems, IAP eradication immunization. recommends that India should switch over to IPV, preferably as IPV-DTP, in its routine 1. It will be unethical and unsafe to continue to immunization program gradually in use OPV after zero wild polio case and zero post-polio eradication era. India should transmission status is achieved due to risk of encourage indigenous manufacturer to VAPP following OPV. produce enough IPV so that it becomes 2. It will be unwise to discontinue use of polio affordable so that is will be possible to immunization altogether after zero polio switch to IPV in due course, looking at the status is achieved due to fear of cVDPV and huge requirement of the number of doses. iVDPV. Past experience from some countries has shown that countries which Adverse reactions - Th e vaccine is very safe. As IPV have eradicated wild polio virus and have contains trace amounts of streptomycin, neomycin and slackened in their routine polio polymyxin B, allerg ic reactions may be seen in immunization programs have experienced in d iv id u als wit h hypersen s it iv it y t o t h es e cVDPV outbreaks. These outbreaks of antimicrobials. cVDPV were curtailed by strengthening routine immunization and giving 2 or more DTPw Vaccine The combination of diphtheria t o xoid, tetanus toxoid induction of a neurological reaction in v ery rare and whole cell killed pertussis vaccine (DTPw) is instances; however, there has been no conclusive proof popularly known as the "triple antigen" DTP is the core for this and the vaccine should not be denied to vaccine in all childhood immunization services. It is children with seizure disorders or st ab le neurological one of the oldest combination vaccines and has been in conditions (e.g. Cerebral palsy, developmental delay). continuous use for more than 55 years. Tetanus an d The results of the National Childhood Encephalopathy diphtheria toxoids are adsorbed on insoluble aluminium Study (NCES) in the United Kingdom clearly show that salts which act as adjuvants and enhance the antitoxin there is no causal relationship between administration responses to both the antigens. While the two toxoids of DTPw vaccine and development of chronic are highly immunogenic (95-100%), the pertussis neurological disease in children. Convulsions following vaccine (even after 3 doses) has a protective efficacy of DTPw v accine are distinctly rare, and may only about 70-90% only. represent n o t h ing more sinister than fever triggered seizures. Progressive/evolving n eurological illnesses, Adverse reactions - Local (pain and redness) and however, are a relative contraindication to first dose of systemic (fever) side-effects of the DTPw vaccine are DTPw immunization. For children who develop almost entirely due to the pertussis component. Whole persistent inconsolable cry of more t h an 3 hours cell pertus s is vaccine has been incriminated in the 14
  15. 15. duration, hyperpyrexia - fever > 40.50 C or hypotonic dose only then pertussis vaccine is contraindicated for - hypo responsive episode HHE (collapse/shock like future administration. stage) within 48 hours of DTPw admin is t ration, seizures with or without fever within 72 h ours of DTP and DT vaccines need to be stored at 2-80C. These vaccin es s hould never be frozen, and if frozen admin is tration of DTPw, the decision to administer further doses of DTPw should be carefully evaluated accidentally, it should be discarded. DTP must be injected intramuscularly and the preferred site is th e and discussed with the parents These events were regarded as absolute contraindications in the past. They anterolateral as p ect of the thigh. The IAP COI recommends 5 doses of DTP - three in infancy with two are now considered mere precaut ions because these boosters at 18 months and 5 years. The DTPw or DTPa events generally do not recur with the next dose and vaccines can be administered up to the age of 7 years. they have not been proven to cause permanent sequelae After the age of 7 years, Td should be given. If a similar adverse reaction recurs with the subsequent Acellular Pertussis Vaccine (DTPa) DTPa vaccines are of various types depending on the DTaP are contraindicated. Pertussis vaccine number of constituent components viz. two component should not be given in such cases and instead DTPa containing pertussis toxin (PT) and filamentous DT should be administered in the future. haemagglutinin (FHA); three co mponent DTPa • In case immediate anaphylaxis occurs after containing pertact in in addition to PT and FHA; five DTwP administration, further DTwP/DTPa component DTPa containing agglutinogens 2 and 3 in should be avoided because of uncertainty about which component of these vaccines has caused ad d ition to PT, FHA and pertactin. Though a five the reaction, as is true with any vaccine. component DTPa vaccine may be expected to elicit a more robust immune response as compared to two and The IAP COI unequivocally endorses the continued use three component DTPa vaccines, the overall efficacy of o f DTPw vaccine because of its proven efficacy an d DTPa vaccines is comparable to the DTPw vaccine. safety. DTPa Vaccine may u ndoubtedly have fewer Dose: 0.5 ml by intramuscular injection. minor side-effects (like fever, local reactions at injection site and irritability) but this minor advantage • If parents are not willing for DTPw can not justify the inord in at e costs involved in the administration after the adverse reaction with routine use of this vaccine. DTPa vaccines are also by the previous dose, DTaP can be recommended no means more effective than the whole cell pertussis in such circumstances as this vaccine is less vaccine. These are, therefore, not recommended for reactogenic. universal immunization in our country at present. • If encephalopathy (major alteration of sensorium or illness with seizures lasting > 24 There is, however, no bar to offering these vaccines to hours) occurs within 7 days of DTPw children from families who opt for the slight advantage administration, further doses of DTPw and of fewer minor side-effects. 15
  16. 16. Tetanus Toxoid This vaccine contains Tetanus Toxoid 5 LF. It is a immunized, two doses of TT at least one month apart highly heat stable and effective vaccine. Bo o s t ers of should b e given during pregnancy so that protective this vaccine may be given at 10 and 16 years and antibodies in ad equate titers are transferred to the thereafter every 10 years. After completing the full newborn for prevention of neonataltetanus. The second course of seven doses, there is no need for additional dose of TT should be administered at least 2 weeks doses during pregnancy at least for the next 10 years. before delivery. A single dose of TT would suffice for Thereafter a single booster every 10 years wo u ld be subsequent pregnancies that occur in the next 5 years; s u fficient to extend immunity for another 10 years - thereafter, 2 doses of TT would again be necessary. For boosters should not be given more frequently than this. previously unimmunized schoo l age children, primary The practice of giving TT after every injury should be TT immunization consists of two doses given 4 weeks discouraged. apart. For pregnant women who have not been previously Tetanus Immunoglobulin (TIG) It is a liquid preparation containing immunoglobulins, Dose: for Prophylaxis: 250-500 IU IM. mainly IgG, obtained from the plasma of healthy Therapeutic: tetanus neonatorum: 500-1000 IU IM or donors. 250 IU intrathecal. In dications: Unimmunised or inadequately immunized In children and adults: 500-1000 IU IM and/or 250-500 individuals with burns, roadside injuries and compound IU intrathecal. fractures. Adverse reactions: Local pain, fever, flush in g , headache and chills may occur. Td Vaccine (Tetanus Toxoid, Reduced Dose Diphtheria) Td contains the usual dose of tetanus toxoid and only 2 words Td should replace TT boosters at 10 and 16 units of diphtheria toxoid. It is recommended for use in years). children above 7 years of age IAP COI recommends the routine use of Td at the age of 10 and 16 yrs (in other 16
  17. 17. 17
  18. 18. Measles Vaccine Measles vaccine used in our country is derived from the of virus within the body. This infection mimics wild live attenuated Edmon s t o n Zagreb strain grown in measles virus infection but is usually asymptomatic. human dip lo id cell culture. Other strains, which have Some children may develop a short lasting fever 7-10 been used for vaccination, include Schwarz, Moraten days after vaccination often accompanied by a macular and Edmonston B. It is supplied freeze-dried and has a rash. Paracetamol may be given to control/reduce fever. shelf life of 1-2 years, or even longer. The vaccine may Vaccinees do not shed the virus. be stored frozen or refrigerated. After reconstitution the Most infants are protected fro m measles by the vaccine is very heat-labile and should be used within 4 maternally acquired antibodies until about 6-8 months hours, wit h the unused vaccine being discarded. of life. If measles vaccine is given in t h e presence of Reconstituted vaccine should not be frozen . Measles measu rable titers of maternal antibody, the vaccine v accine does not contain any preservative, therefore efficacy may be reduced. In order to achieve t he best strict asepsis should be maintained while diluting and balance between these competing deman d s o f early aspirating contents from the multi-dose vial. Some protection and high seroconversion, completed 9 cases of staphylococcal sepsis/toxic shock syndrome months of age has been recommended as the associated with use of this vaccine have occurred from appropriate age for measles v accination in India. In bacterial contamination of the vaccine. The v accine case of an outbreak, however, the vaccine can be given should be injected subcutaneously, preferably over the to infants as young as 6 months with a recommendation upper arm / anterolateral thigh. for an additional MMR/Measles at 12-15 months. Being a live attenuated virus vaccine, it resu lt s in sub-clinical or attenuated infection and multiplication B. Vaccines Recommended Against Diseases Not Covered Under EPI MMR Vaccine Globally, most co u n t ries use MMR instead of single all children. It should als o b e given to all adolescent antigen measles vaccine. MMR vaccine contains 1000 g irls not previously immunized and to hospital staff TCID50 of measles, 5000 TCID50 of mu mp s and 1000 likely to come in contact with pregnant mothers. There TCID50 of ru b ella v iru s . It is administered is no upper age limit for this vaccine. It may be noted subcutaneously in the upper arm/anterolateral thigh. It that the states like Delhi, Goa h ave included and few is dispensed in single as well as multi-dose states like Tamilnadu, Mah arashtra, etc. are likely to formulations; the diluent is available separately. The include MMR in its universal immunization program. vaccine is given as a 0.5 ml dose. Measles and MMR For infants given measles vaccine at 9-12 months, vaccines are supplied in lyophilized formulation and MMR vaccine may be given between 15-18 months of should be frozen for long-term storage. In the clinic age. If measles vaccine was missed altogether in these vaccines can be stored between 2 to 8 0 C. Th e vaccines should be p rotected from light. Once infancy, one dose of MMR can be given at or after 12 months. The vaccine can be given along with other reconstituted, vaccine should be used within 4 hours. vaccines like DTP, OPV and Hib. The IAP COI recommend s administration of MMR to 18
  19. 19. Mumps Vaccine The mumps component in MMR vaccine contains live Aseptic meningitis is known to occur following mumps attenuated mumps virus not less than 5000 TCID50 per vaccine, though the incidence quoted is as rare as 1 in dose. Vaccines are derived from Leningrad-Zagreb, 10,000 to 1 in 100,000 d o ses of vaccines used. The Jerryl Lynn, RIT 4385 or Urab e A M9 strains and are clinical s everity of the vaccine induced aseptic grown in chick embryo/human diploid cell cultures. meningitis is very mild and often may go unnoticed and Vaccinees do not shed the virus. There is no evidence all the cases recover without any permanent sequelae. that mumps vaccination is associated with development Hence all the mumps vaccines are equally safe. of either au t is m or Crohn's Disease. There is no Monovalent mumps vaccine or combination with difference in efficacy between various strains of mumps rubella as MR vaccine is not available in our country. vaccine. Rubella Vaccine Rubella vaccine currently available commercially is constituent of MMR) in young children through public derived from RA 27/3 vaccine strain grown in human health measure with sub-optimal coverage of the target diploid/chick embryo cell cultures. It is available population may be counter-productive as it may shift either as a monovalent vaccine as a part of the epidemiology of rubella to the rig h t with more combination vaccine - MMR. It contains live clinical cases occurring in young adu lt s leading to attenuated virus not less than 1000 TCID50. It is a paradoxical increase in cases of CRS. This has been highly immunogenic vaccine with seroconversion shown to occur using mathematical models. Direct rates of 95% It provides long term and probably life long protection; vaccine failures are uncommon. evidence from some Latin American countries als o Vaccinees do not shed the virus. corroborates these concerns. As a pediatrician one should be aware that rubella Normally use of rubella vaccine (monovalent or as a vaccination is mainly directed at preventing congenital constituent of MMR) in young ch ildren through rubella syndrome (CRS) and not at preventing rubella individual p ract itioners alone would not lead shift of infection per se, as the latter is usually benign an d epidemiology in adolescents and adults as the coverage inconsequential. By controlling the incidence of rubella of target populat io n is miniscule by private infections, CRS can be significantly reduced. There is practitioners In case MMR is incorporated in universal paucity of reliable data on occurrence of CRS in India. program and adequate coverage is not achieved, a shift On the basis of what ever information is available CRS in epidemiology of rubella is quite possible. Hence incidence is qu it e low in India. This is suggestive of MMR though a co s t effective vaccine should not be wide circulation of wild rubella virus in yo u n g introduced through public health facilities in areas children. Seroprevalence of ru bella antibodies in wh ere co v erag e fo r routine immunization is majority of pregnant women in few studies in India consistently less than 80%. support this view. Haphazard use of rubella vaccine (monovalent or as a 19
  20. 20. Hepatitis B Vaccine In India, 1-4% of individuals are found to be chronic schedules: carriers of Hepatitis B Virus (HBV). Infection with 1. Birth, 1 and 6 months HBV may occur perinatally (v ertical transmission), 2. Birth, 6 and 14 weeks during early childhood (the so-called horizontal 3. 6, 10 and 14 weeks spread ), through sexual contact or nosocomially. It should be noted t h at in our country horizontal route Immunologically 0 - 1 - 6 months schedule of hepatitis (e.g. ch ild to child) route and the vertical route (i.e. B immunization has been most widely used and proven mother to child) are the major routes of transmission of to be ideal with high antibody titers at the end of the hepatitis B. v accination. However now that HB vaccination is Younger the age of acquisitio n of HBV infection, integrated into the existing immun ization program higher the chances of becoming a chronic carrier. It is (UIP) in India, d u e to operational issues at a national believed that as many as 90% of those who are infected level one has to piggy back on the available contacts for at birth go on to become chronic carriers. In fect ion routine immunization i.e. DTP wh ich is given at 6, 10 with HBV is one of the most important causes of and 14 weeks of age. At the same time birth dose has to chronic hepatitis, cirrhosis of liver and hep atocellular be given to cover for the vertical route. Hence IAP COI carcinoma. 30% of the chronic carriers go on to recommends 0 - 6 - 14 wks schedule for public develop chronic liver disease. These are all preventable measure. In case birth dose has been missed, 6 - 10- 14 by early childhood immunization. It is for this reason wks sched u le can be followed. In office practice, one that the World Health Organization has recommended can still use 0 - 6wks - 6 months schedule. As on now, u niversal Hepatitis B vaccination. As many as 150 from the d ata available, none of the above schedules countries have n ow included HBV in their national needs a booster. immunization sch ed u les . In Ju n e 2002, the Th e p urpose of Hepatitis B vaccination is to prevent Government of India also initiated the incorporation of chronic in fection and development of chronic liver HB vaccine as a univ ersal vaccine through a pilot disease / hepatocellular carcinoma later in life. An ideal program which will be scaled up in a phased manner. HB vaccine schedule should, therefore, address vertical HB v accine is a highly purified recombinant DNA as well as h orizontal modes of transmission of the vaccine produced in the yeast species Hansenula virus. polymorpha, Saccharomyces cerevisiae or Pichia Pregnant women should be counseled and encouraged pastoris. It is adjuvanted with aluminiu m salts and to opt for HBsAg screening. If the mother is known to should be stored at 2-80 C. The vaccine should not be be HBsAg negative, HB vaccine can be g iv en along frozen - if frozen accidentally, the it should be with DTP at 6, 10 and 14 weeks/6 months as there is no discarded. It should be injected intramuscularly in the special requirement to start vaccinat ion at birth itself. anterolat eral thigh. The usual pediatric dose (< 12 This 6-10-14 wks schedule may be easier to implement years o f ag e) is 0.5 ml corresponding to 10µg of the in the context of the national immunization program as antigenic component. Adult dose is twice the pediatric higher vaccination coverage may be achieved with dose. The vaccine is hig h ly immunogenic and earlier administration of vaccines. seroconversion rates are greater than 95% after a three dose schedule. Antibody titers greater than 10 mIU/ml If the mother's HBsAg stat u s is not known, it is are considered protective. The dose may be increased important that HB v accination should begin within a when vaccinating immunocompromized individuals few hours of birth so that perinatal transmission can be e.g. patients on chemotherapy for malignant conditions prevented. Any one of the following schedules may be or those with chronic ren al failure awaiting used for this purpose; birth, 6 and 14 weeks or birth, 6 hemodialysis. wks and 6 months. HB vaccine may be given in any of the follo win g If the mother is HBsAg positive (and especially HBeAg 20
  21. 21. positive), the baby should be given Hepatitis B Immune after initial stabilization. Globulin (HBIG) within 24 hours of birth, along with For older children and adults the preferred schedule is HB vaccine (at birth, 6 and 14 weeks or birth, 6 weeks and 6months) using two separate syringes and separate 0, 1 and 6 months, '0' being the elected date for the first dose. sites for injection. If HBIG is not available (o r is unaffordable), HB vaccine may be given at 0, 1 and 2 In immunocompetent individuals HB vaccine induces months with an additional dose between 9-12 months. an effective immunological memory that lasts life-long and protects against symptomatic acute illness and It has been suggested by many authorities that in development of chronic HB infection on exposure to the infancy the third dose of HB vaccine should be given at virus. Boosters of HB vaccine are, therefore, not least 16 weeks after the firs t d ose & at least 8 weeks necessary under usual circumstances. after the second dose and not before 6 months of chronological age, as it presumably gives longer lasting HB vaccination is now being integrated into t he immunity. However this view is being challenged as existing immunization program in India. It was HB vaccine is a T-cell dependent vaccine, the titers at introduced in 15 cities an d 32 districts in the initial the end of immunization schedule may not be phase; selection of districts was based on achievement important so far as it is well above the protective level. of targets of 80% or more DTPw-3 coverage under There would occur anamnestic response with the titers routine immunization based on evaluation surveys. going up should there occur contact with th e v irus Under this program, the vaccine is being provided free again in future. As logistically, it is easier to combine of cost to infants living in u rb an slums. The program HB vaccine program with the DTP vaccine, it can be will be expanded to include additional cities and given in 0-6-14 weeks schedule too The vaccination districts within a certain timeframe. It is envisaged that schedule need not be changed for preterm and HB vaccination will be introd u ced in all districts of small-for-dates babies; in the case of extremely preterm India by 2007. babies, ho wev er, vaccination should commence only Hepatitis B Immunoglobulin (HBIG) HBIG provides immediate passive immunity and is Adverse Reactions: Transient, mild pain at the site of recommended in situations wherein there has been injection and itching may be seen in a small proportion acute expos u re t o HBsAg infected material e.g. by a of recipients. needle-stick injury. Clinical trials h ave demonstrated 90% reduction in risk of transmis s ion following such Special Precauti ons : HBIG should never be exposure if HBIG is used alon g wit h Hepatitis B administered intravenously. vaccine. HBIG does n o t interfere with antibody Dose: Adult s : 1000-2000 IU; Children:- 32-48 IU/kg response to simultaneous HB vaccine. It is for t h is bod y wt . This should be administered as soon as reason that individuals who have had recent accidental following exposure, preferably within 48 hours though exposure to hepatitis B virus should be given combined it can be administered even if the patient reports late up passive-active immunization. It is also useful in to 7 day s after exposure. Neonates: 100-200 IU. The prevention of mo t her to child transmission and first dose should be administered as soon as after birth transmission following sexual exp o s u re like in rape up to within 5 days of birth. An additional d o se of cases. Lastly HBIG is indicated in o ncology patients 32-48 IU/kg of body weight may also be given between who may not respond adequately to Hepatitis B vaccine 2-3 months after initial dose. as they are immune compromised follo win g the malignancy as well its therapy. 21
  22. 22. Typhoid Vaccines Enteric fever is endemic in India and is a major public vaccine is available commercially. health problem. Th ree vaccines were available for clinical use till recently. However now only Vi typhoid The Whole Cell Inactivated Typhoid Vaccine (TA/TAB) Heat-killed, phenol-preserved or the acetone inactivated The vaccine appears to be protective through the lyophilized whole cell Salmonella t yphi vaccines were induction of antibodies against cell wall somatic (O) inexpensive products that have been in use in India for and flagellar (H) antigens- these antibodies can act as a long time. The p rotective efficacy of acetone a biological marker of the vaccine. It may interfere with inactivated preparation is more than that of the phenol the interpretation of the Widal test. It is effective even preserved vaccine but the former is more difficult to in child ren below 2 years of age and can be given to prepare and is associated with more side-effects. Both infants > 6 months of age Primary vaccination requires vaccin es contain Salmonella typhi 1000 million two d o s es , 4 o r more weeks apart, given organisms per ml. Protection begins 4 weeks after subcutaneously. Pediatric dose of the vaccine is 0.25 ml vaccination. Use of these vaccines may be associated in children aged 6 month s -10 years and 0.5 ml in with fever, local pain and malaise due to the endotoxins order children. The vaccine should be stored at 2-80 C. in bacterial cell wall. A pure S. typhi vaccine is less It should never be frozen. Revaccination is necessary reactogenic than the combined TA/TAB vaccines. The every 2-3 years to sustain an o ptimum immune vaccin e is very safe and is reasonably effective if response and should be done preferably before the onset revaccination can be carried out on a regular basis. The of summer. vaccine efficacy has been estimated to be 50-70% in a Unfortunately, this vaccine is not being manufactured meta-analysis of the randomized co ntrolled trials in India at present available. The Vi-Capsular Polysaccharide Vaccine Th e vaccine consists of purified Vi-cap s u lar polysaccharide vaccine as available in our country at polysaccharide, which during natural infection inhibits present. Cost of the vaccine though a limiting factor in p hagocytosis and serum bactericidal activity an d is past, is now reasonably priced. The vaccine is available responsible for virulence of the bacteria. It h as as an isotonic phenolated buffer solution; the dose is reasonable efficacy o f 50-60% in children and low 0.5 ml. containing 25µg of the polysaccharide. It can be reactogenicity. Protection begins within two weeks of given intramuscularly or subcutaneously. The vaccine vaccination and the biological marker is anti-Vi s h ould be stored at 2-80 C. It should never be frozen. antibodies. It is not very effective in children below two Adverse effects are mild and include pain and swelling years of age because it is an unconjugated at injection site. Oral Live Attenuated Ty21a Vaccine: 22
  23. 23. Salmonella typhi Ty21a is a live attenuated strain with sittings, on alternate days. The capsule should never be a mutation in gal E gen e and lacks the enzyme op en ed before ingestion. Protection begins within a UDP-gal 4 epimerase. It is genetically stable and is not week after completion of the course and the protective known to revert to virulence. The efficacy has been efficacy is as good as other available typhoid vaccines. shown to 50-60% with the capsule form and near 90% Immunization needs to be repeated every 3-5 years with th e liquid form (not available commercially). It The vaccine should be stored at 2-80C. Antimicrobials provides protection by inducing local gut immunity but there is no biological marker of this vaccine. The active against S. Typhi should not be used 3 days before and 7 days after oral typhoid vaccine administration as vaccine is supplied in an enteric coated formulation as these may interfere with the v accin e "take". the bacteria are acid labile. It can be given to children Unfortunately this vaccine is also not available now in six years of age and above as the capsules have to be our country. swallowed intact. The vaccine is given on an empty stomach in three The efficacy of all typhoid vaccines at best is 50-70% Hib Conjugate Vaccines Haemophilus influenzae type b (Hib) is an important response after the third dose. On the other hand, invasive pathogen cau sing invasive diseases like PRP-OMP shows an increase in antibody level after the pneumonia, meningitis and bacteremia. Majority of first dose itself with only marginal increases after the cases occur in children below 2 years of ag e. Hib second and third doses. It is for this reason that while vaccination is given routinely in the d eveloped 3 doses of HbOC and PRP-T are recommended for countries for last many years. Countries with sensitive primary vaccination, only 2 doses of PRP-OMP are disease surveillan ce systems have shown significant recommended for this purpose. In spite of these declines in in v asive Hib disease following the apparent differences, these three vaccines when used in incorporation o f this vaccine in their national the recommended doses have similar efficacy. immunization programs. Recently published data of the The vaccination schedule for Hib consists of three doses Invasive Bacterial Infections Surveillance (IBIS) group when initiated below 6 months, 2 doses between 6-12 from six referral hospitals in India (Lancet, 2003) show months and 1 dose between 12-15 mon t h s , with a that Hib is a common cause of meningit is in our booster at 18 months. The interval between two doses country. should b e at least 4 weeks. If vaccination is delayed Hib capsular polysaccharide vaccine is a very effective until 15 months, a single dose may suffice. It is highly and safe vaccine. A number of PRP conjugate Hib efficacious vaccine, the protective efficacy being 95%. vaccines are available of which t wo are available in As Hib d isease is essentially confined to infants and India viz. HbOC (with CRM 197 mutant diph t h eria young children, the vaccine is not necessary for toxin as conjugate) and PRP-T (with tetanus toxoid as children above 5 years. Hib vaccine is stored at 2-80 C. conjugate). PRP-OMP (wit h meningococcal outer The IAP COI reco mmen d s use of Hib vaccine for all membrane protein as conjugate) is no t available in children . It is particularly recommended to be given India HbOC and PRP-T vaccines show only a marginal increase in antibody levels aft er the first dose with a p rior to splenectomy and in patients with sickle cell disease. marked increase after the secon d and even better 23
  24. 24. C) Vaccines That Need to Be Given After Discussion With Parents Varicella Vaccine Chicken pox is usually a self limiting and generally are leaving h o me for studies in a residential b enign disease affecting mostly children and youn g school/college. It is indicated in children with chronic adults. Complications of varicella may be mo re lung/heart disease, humoral immunodeficiencies, HIV commonly seen in immunocompromised individuals, infection (but with C4 counts above 15% of the age adults and pregnant women. Takahashi et al developed related norms), leukemia (but in remission and off a live attenuated vaccine from the Oka strain in Japan chemotherapy for atleast 3-6 months) and those on long in the early seventies. The vaccine has been in clinical term salicylates/high dose lone t erm oral steroids. use in Japan since 1989 and in the United States since Varicella vaccin e is also recommended in household 1995. The vaccine can be administered to any healthy contacts of immunocompromised children. It may also individual above the age of 12 months who has not had be considered in children attendin g crèches and day varicella previously. care centers. When used for post-exposure prophylaxis it should be administered within 72 hours of varicella Varicella vaccines in use today are all derived from the exposure - it should be noted, however, that the efficacy original Oka strain but the virus contents may vary of the vaccine in preventing varicella under such from one manufacturer to anoth er. The recommended circumstances is not very clear. Varicella vaccine is dose is 0.5 ml and the minimum infectious virus also indicated in susceptible adolescents and adults if content should be 1000 Plaque Forming Units. The they are inmates of or working in the ins t itutional set vaccine is administered subcutaneously. A single dose up e.g. s ch o ol teachers, day care center workers, is sufficient b elo w 13 years of age, after which two military personnel and health care professionals. doses (at 4-8 weeks interval) are required. The vaccine is not recommended for ch ild ren below 12 months of The vaccine is stored at 2-80C and can be administered age. Though vaccine manufacturers recommend to use subcutaneously or intramuscularly. It should be this vaccine at 12 months, breakthrough infections can protected from light and needs to be used within 30 be less if used after 15 months of age. Hence IAP COI minutes of its reconstitution. recommends to use this vaccine after the age o f 15 months. It is a highly effective vaccine and protective Adverse reactions - It includes fever, vaccine ass o ciated rash, pain redness and swelling at immunity, humoral as well as cellular, develops in 95-99% individuals. The immunity appears to be long vaccination site. When used in adult females, pregnancy should be avoided for at least 4 weeks after lasting. vaccination. The IAP COI opines that varicella vaccine is not recommended fo r universal immunization in India at Varicella zoster immunoglobulin (VZIG) is used for passive post-exposure prophylaxis in immunodeficient present. One has to emphasize the generally benign nature of an d rarity of complications with varicella individuals who have been exposed to varicella or herpes zoster and are unlikely to have d et ectable infection in young children. It may be offered to children fro m h igh socio-economic strata of society antibody levels. It should be given to the neonate if the mother develops varicella 5 days before to 2 days after after explaining the pros and cons to the parents on a one-to-one "named child" basis. It may be prescribed to delivery. It has to be given by intramuscular injection adolescents who have not had varicella in past (or are and the dose is 125 units/10 kg body weight. known to be varicella IgG neg ative) especially if they 24
  25. 25. Hepatitis A Vaccine Hepatitis A virus (HAV) infection is a relatively benign recommended for universal immunization in India at infection in young ch ildren as many of them have present. One has to emphasize the generally benign completely asymptomatic sub-clinical infection For nature of disease and very small number of children instance as many as 50% of children between 2-5 years developing complications with Hepatitis A infection in and 85% of those below 2 years who acquire HAV young children. It may be offered to children from high infection, may continue t o remain anicteric and may s o cio-economic strata of society after explaining the develop non-specific symptoms like any other viral pros and cons to the parents on a one-to one "named in fection. In adults hepatitis A is frequently child" basis. It may be prescribed to adolescents who symptomatic and mortality is much higher than in have not had viral hepatitis in past (or are known to be children. The disease severity increases irrespective of HAV-IgG negative), especially those who are leav ing age, in those with underlying chronic liver disease. home for further studies. It is recommended in all patients with chronic liver d isease (who are HAV Inactivated HA vaccines d eriv ed from HM 175/GBM seronegative) and family contacts of patients with strains and g ro wn on MRC5 human diploid cell lines chronic liver disease. It may be offered to household are now available. The virus is formalin inactivated and contacts of patients with acute HA virus infection - in adjuvanted with aluminimum hydroxide. It has been t h e latter case the vaccine must be given within 10 suggested that the vaccine can be used any time after days; however, it may not always be effective under 18 months of age when the maternally derived antibody such circumstances when the contact has had the same levels have declined; It is given in a two dose schedule, source of infection as the index patient. It may also be 6 months apart. The adult formulation should be used considered in children attending crèches and day care after t h e recommended cut-off age of 15 years centers and in travelers from abroad (e.g. non-resident according to one manufacturer and 18 years according Indians) visiting endemic areas. to the other The vaccine is given intramuscularly and the protective efficacy is 94-100% Immunity appears to The vaccine is stored at 2-80C. be long lasting and boosters are not recommended at present. Adverse reactions: It includes local pain and local induration. The IAP COI o p ines that HA vaccine is not Pneumococcal Vaccines Streptococcus pneumoniae is a common cau s e of infections. The common pathogenic stereotypes invasive bacterial diseases responsible for a significant reported in children in Western countries are 1, 4, 5, 6, proportion of potentially fatal con d it io n s like 9, 11, 14, 15, 18, 19 and 23. It appears that the pneumonia and meningitis in children. It also leads to serotypes causing invasive disease in developed conditions like otitis media and sinusitis, which may countries are different from the ones which are found have morbidity but little or no mortality. In developing in developing countries. According to results of the countries, this organism is believ ed to be the Invasive Bacterial Infection Surveillance (IBIS) study, commonest cause of bacterial pneumonia. Peak the common serotypes responsible for invasive disease incidence of pneumococcal disease is between 2 to 24 in children below five y ears of age in India include 6, months of age. Based on the capsular polysaccharide 1, 19, 14, 4, 5 and 7. Serotypes 1& 5 accounted for antigen, p neumococci are classified into 85 different 29% of disease in India. Thou g h prevalence of serotypes. Of these, about 10 serotypes account for most penicillin resistance is almost negligible at present 25
  26. 26. there is some evidence that the prevalence of resistance invasive pneumococcal disease caused by the serotypes to penicillin amongst the p neumococci may be covered by the vaccine. The dose is 0.5 ml. and the gradually increasing, thereby highlighting the need for vaccine is given intramu scularly. Pneumococcal an effective vaccine. vaccines are s tored at 2- 80 C. Conjugate vaccine should not be frozen. Two types of pneumococcal vaccines are currently available - the 23-valent unconjugated polysaccharide Since the introdu ct io n of PCV-7 in the childhood v accine and the 7-valent conjugate polysaccaharide vaccine schedule in US, there has been a dramatic vaccine. Immunity is serotype specific. reduction in the in cidence of invasive pneumococcal disease not only in the children who are vaccinated but The 23-valent polysaccharide vaccine contains the also non-vaccinated young children in their contact and following serotypes - 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, a milder but statistically sign ificant decrease in 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, invasive disease in their adult contacts, suggesting 23F, 33F. It is capable of preventing almo s t 85% of s trong herd effect. Similar herd effect was seen in the in vasive disease (pneumonia, men in g it is an d form of overall reduction in the disease caused by drug bacteremia) caused by pneumococci. Immunization, resistant serotypes in the community. Though there has however, is not effective for prevention of otitis media. been replacement of t h e vaccine serotypes by Each dose is 05 ml containing 25ug polysaccharide of non-vaccine serotypes in the nasal carriage studies, each of the 23 serotypes co n tained in the vaccines. fortunately this has not been seen significantly in the However, as it is an unconjugated polysaccharide invasive diseases studies. However there is a need for vaccine it does not result in immunological memory. continuous surveillance for the serotype involved in This vaccine is poorly immunogenic in children below invasive cases from time to time. two years of age i.e. children who are at highest risk of invasive disease. The dose is 0.5 ml and the vaccine is Healthy children: Th e IAP COI does not recommend given intramuscularly or subcutaneously. This vaccine u s e o f this vaccine for universal immunization in our may be us ed in h igh-risk groups above the age of 2 country at present. PCV - 7 covers approximately 50 to years. Revaccination is recommended after 5 years. It 55% percent of pneumococcal serotypes responsible for is recommended for children with asplenia, sickle cell invasive pneumococcal disease in India offering about d isease and nephrotic syndrome. It is als o 50 to 55% protection in infants & ch ild ren in India. recommen d ed for HIV infected children. It may be The vaccine may be offered to healthy children above offered to those with underlying chronic illnesses like the age of 6 weeks t ill 2 years after explaining the renal diseases, cardiovascular diseases or diabetes. parents on one to one "named child" basis. The heptavalent conjugate vaccine (PCV-7) contains High risk group: There are certain children who are at the following sero t y p es -4, 6B, 9V, 14, 18C, 19F, and high risk of severe invasive pneumococcal disease with 23F. It is coupled with a non-toxic variant of diphtheria high mortality. This includes children with Sickle cell toxin (CRM197) and has aluminium phosphate as the d is eas e, as p len ia, primary immu n o d eficien cy adjuvant. Conjugation of polysaccharide with protein s y n d ro me s , H I V, c h i l d r e n w i t h s ev ere CRM197 makes it immunogenic below 2 years of age. cardio-respiratory illness and children with chro nic In February 2000 this vaccine (PCV-7 Prevnar) was illn es ses like renal diseases, diabetes etc., nephrotic licensed in US fo r ad ministration to children below 5 syndrome, cerebrospinal fluid rhinorrhea etc. For such yrs of age. The development of this v accine was children IAP COI recommends age appropriate doses prompted by the observation that young children below of 7 valent conjugated pneumococcal vaccine routinely 2yrs of age are dis p ro p ortionately affected by the till 5 years of age. For children above 2 years, a dose of serious pneumococcal infection and recognition of the 23 valent unconjugated pneumococcal vaccine is also fact that available 23 valent polysaccharide vaccine was recommended to be given after one priming dose of non immunogenic in t h is age group 2 yrs. Conjugate conjugated vaccine. vaccine is used in a 3-dose schedule in infancy at 4-8 weeks interval followed by a booster at 15-18 months of Adverse reactions - Injection site so reness, malaise, age and has protective efficacy of 95-99% ag ain st low grade fever. 26