1

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. ShahCo- Chairperson: Dr. Nitin K. Shah

Convener: Dr.Shyam Kukreja

Members: Dr. Rohit Agarwal

Dr. Indra Shekhar RaoDr. Shivananda

Dr. Nigam P NarainDr. Sangita Yadav

Ex-officio members: Dr. Deepak UgraDr. Tapan Kumar Ghosh

Dr. VN YewaleDr. Naveen Thacker

Dr AP Dubey

Dr Surjeet Singh

Address for correspondence:

Indian Academy of PediatricsKailas Darshan, Keneddy BridgeNear Nana ChowkMumbai India 400 007Tel: +91-22-3889565E-mail: iapcoff@bom5.vsnl.net.in

3

Preface

Immunization is the single most successful child survival s t rategy the world over. Immunization also reducesmorbidity to great extent. Due to progress in molecular biology and genetic engineering a number of new vaccineshave become available and many more are in the pipeline. Many of the developed countries have reduced theirvaccine 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 necessary in future as more informat ionabout the epidemiology of the disease becomes available. The inclusion of any new vaccine in the universalimmunization program of a country depends on disease epidemiology, availability of safe vaccine, economicconstraints and logistic problems. Unfortunately the limiting factor most of the times in developing countries likeIndia is the affordability.

There is always a need to update knowledge and concep ts es pecially in the field of immunization as there iscontinuous flow of new knowledge. Also one must try to objectively understand a difference between a publichealth measure paid for by the government and a personal safety measure instituted by the individual at one's owncost 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 matterof great concern to all of us. This has been one of the major obstacles in polio eradication program. There is anurgent need to reinforce quality immunization services and our academy has always been at the forefront of thisinitiative.

We are sure this updated guidebook will continue to serve as ready reckoner on issues concerning vaccines andimmunization in our country.

Dr. Raju C Shah

Chairperson, IAPCOI 2005- 2006

President IAP 2005

Dr. Nitin K. Shah

Co-Chairperson, IAPCOI2005-2006

President IAP 2006

Dr. Shyam Kukreja

Convener, IAP COI 2005- 2006

4

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

Contents

5

Introduction

Protect ion from preventable diseases, disabilities anddeath through immunization is the birth right of everychild. Immunization is one of the most cos t-effectivehealth interventions known to mankind Over the lastthree decades, a lot of progress has been made globallyas far as protection against the eight important vaccinepreventable diseases is concerned - from less than 5%children who were protected against these diseases inthe early 1970s, to as many as 75% being protectednow. Small pox has been eradicated and we are at thethreshold of eliminating polio.

An effective National Immunization strategy can helpdecrease childhood morbidity and mortality, especiallyin developing countries. It must, however, be clear thatimmunization strategies may vary from country tocountry depending on the local requ irements. Thisguide book represents the collective effo rts of themembers of the Indian Academy of PediatricsCommittee on Immunization (IAP COI). We are awarethat unanimity may not always be possible as far as theneed and timing of certain newer vaccines areconcerned, but we have made efforts to arrive at a

consensus based on the current evidence from theliterature. The IAP Immunization Time Tablerepresents the 'best individual practices schedule' for agiven child and would necessarily be at some variancefrom the National Immunization Schedule of theGovernment of India, which is meant for the public atlarge. With the availability of many newer vaccines, itis necessary that some of these should be considered forroutine immunization and the immunization schedulehas to be changed accordingly.

Unfortunately, there is lack of authentic data onepidemiology of most infectious diseases in our country.However that should not deter us from using some ofthese vaccines till such data is generated. Manydecisions on incorporation of new vaccines in theimmunization program have, therefore, to be based ondata from other parts of the world. This may appearunscientific to some, but is a reality and is the only wayout at present.

6

Historical Aspects

Though Dhanvantri, the father of IndianMedicine, spoke of preventing certain infectiousdiseases th rough immunization, the first successfulvaccine in the modern era was developed by EdwardJenner in 1796 when he used cowpox inoculation(vaccination) to protect against smallpox. LouisPasteur developed a h igh ly effective vaccine againstrabies, which was used for post-exposure prophylaxis.It was first given to a child in 1885. Since then manyother vaccines have been developed in rapid succession.

Experience with smallpox eradicat ion p rogramconvinced the health policymakers that immunizationwas the most powerful and cost-effective measure forcontrol of vaccine preventable diseases. At the globallevel, an organized immunization program came intoexis tence in the year 1974 under the banner of theWorld Health Organization (WHO). This waschristened as the 'Expanded Program on Immunization'(EPI). The term "Expanded" referred to the provisionof adding more antigens to vaccination s chedules,extending coverage to all corners of a country andspreading services to reach the less privileged sectionsof the society. The EPI program focused on childrenbelow 5 years of age and pregnant women. Thevaccines included were BCG, DTP, OPV, Measles andTT. The primary health care concept as enunciated inthe 1978 Alma Ata Declaration included immunizationas one of the strategies for reaching the goal of 'Healthfor All' by the year 2000. The Government of Indiaadopted the EPI in 1978 with the twin objectives ofreducing the mortality and morbidity resulting fromvaccine preventable diseases of childhood, and toachieve self-sufficiency in the production of vaccines.The program started with BCG, DTP and Typhoidvaccines - it did not include measles vaccine. OPV wasadded only in 1979 and measles later on. Typhoidvaccine continued to be a part of our nationalimmunization schedule until 1985. Program coverageof 85% was envisaged, but this could not be achievedfor several years and independent evaluations showedvery low coverage rates in many parts of our country.Therefore, a change of strategy was considerednecessary.

In 1985, the EPI was s upplanted by the UniversalImmunizat ion Program (UIP). The main objectives ofUIP were: i) universal immunization and reduction inmortality and morbidity due to vaccine preventablediseases ii) self-sufficiency in vaccine production iii)establishment of a functional cold chain system, and iv)the introduction of district level monitoring system. Inthis program the emphasis was s hifted from theunder-five to under-one age group, thereby reducing thenumber of potential beneficiaries. It considerab lyreduced the denominator for percentage coverage. Thevaccines recommended were BCG, DTP, OPV andMeasles for infants and TT for pregnant women. Itshould be noted that UIP envisaged 100% coverage ofpregnant women with 2 doses of tetanus toxoid (or abooster dose, as applicable) and at least 85% coverageof infants. Under the UIP, the government also aimedto establish logistics of vaccine production and supplyas well as training of medical and paramedicalpersonnel. The Government of India subsequently setup a " Technology Mission on Vaccination andImmunization of Vulnerable Population, especiallyChildren" to cover all aspects of the immunizationactivity from research and development to actualdelivery of services to the target population.

Since switching over to UIP in India there has been asignificant decline in many of the vaccine preventablediseases, such as poliomyelitis, neonatal tetanus,diphtheria, whooping cough and measles. The UIPbecame an integral component of Child Survival andSafe Motherhood Program (CSSM) in 1992 and thenpart of Reproductive and Child Health Program (RCH)in 1997. Supplementary immunization activitiesagainst poliomyelit is were started in 1995-96. In 2002,Hepatitis B vaccination was initiated in selected areastargeting the urban poor.

The WHO also endorsed global efforts at immunizationthrough Universal Childhood Immunization (UCI) in1990 - the name given to a declaration sponsored byUNICEF as part of the 40th anniversary of the UnitedNations in October 1985. Efforts were undertaken toinitiate research for the development of newer vaccines,to improve vaccine product ion technologies and to

7

understand the epidemiology of diseases. Thesedevelopments were highlighted in 1990 at the Summitfor Children, where it was claimed that EPI had indeedbeen a global success with 80% reported coverage withthe six vaccines. In 1992, the WHO also set a target foruniversal Hepatitis B immunization. It aimed toincorporate Hepatitis B vaccine in the immunizationschedules o f all member countries by 1997. Howeverunfortunately less than 50% of the countries haveactually introduces Hepatitis B vaccine in theirNational Schedule. India has recently accepted itsinclusion in National schedule and the coverage willexpand in a phased manner.

These global efforts at immunization were launchedunder the banner "Children Vaccine Initiative" (CVI)in 1991 with support from several in ternationalagencies like the WHO, UNICEF, World Bank and theRockefeller Foundation. CVI aimed at development ofnewer vaccines, improvement in vaccine productiontechnolog ies and vaccine quality. These efforts werefurther consolidated under the "Global Program onVaccines and Immunization" (GPV) in 1993 reflectingthe EPI and UCI init iative and combining these withthe CVI. The focus of GPV is on sustaining highvaccine coverage, developing global surveillancenetwork and evolving eradication strategies. The"Global Alliance for Vaccines and Immunization"(GAVI) was set up in 1999 as an international coalitionof multinational funding agencies (e.g. Bill andMelinda Gates Foundation, Rockefeller Foundation),vaccine manufactu re r s , n o n - g o vernmentalorganizations and the governments of 74 developingnations. GAVI organizes its activities through avaccine fund. The main objectives of GAVI are asfollows: i) improv ing acces s to s us tainableimmunization services ii) expanding use of all existingsafe and effective vaccines iii) accelerat ing thedevelopment and introduction of new vaccines iv)

augmenting research and development on vaccinesagainst HIV, malaria and tuberculosis v) makingimmunization coverage an integral part of internationaldevelopment initiatives. The GAVI Ind ia Project hasbeen instrumental in launching free Hepatitis Bimmunization in some of the urban slums. It has alsoendeavored to promote safe injection practices and useof auto-disable syringes for immunization as part of acountrywide initiative.

A survey conducted in 2002 under the RCH showedthat immunization coverage rates in India have beendeclining, since 1999. The Government of India hasrecently launched an Immunization StrengtheningProject with the objectives of i) strengthening routineimmunization with the aim of raising the percentage offully immunized children to above 80% ii) eliminatingpolio and achieving polio eradication iii) reviewing anddeveloping a new vision of the immunization programin the medium term keep ing in view the developmentof new epidemiological patterns, availability of newvaccines and delivery mechanisms and advances in coldchain technologies iv) improving surveillance andmonitoring mechanisms. The National Institute ofHealth and Family Welfare has been identified as thenodal institute for coordination and implementation ofthe program and the training shall be carried outthrough five regional inst itu tes. Training of mid-levelmanagers, including persons actively involved inimmunization program at the district and state level, isan integral component of this project. The project wasstarted in 50 poorly performing districts of 8 prioritystates of Uttar Pradesh, Bihar, Madhya Pradesh,Rajasthan, Oriss a, Gujarat, Assam and West Bengal.These newer initiatives have improved overall coveragein these districts. Unfortunately last report of Nationalfamily and health survey released in 3rd week of Nov'06 do not confirm this improvement.

8

Basic Immunology

The Greek work "immune" means "to be protected".Protection offered by the introduction of variousantigens or ready-made antibodies is called acquiredimmunity. The process by which th is acquiredimmunity is obtained is known as 'immunization'. Thisis of two types, active and passive. When specificantigens evoke the required immune response in thesystem it is called active immunization, and whenantibodies are supplied readymade in the form ofimmune g lobu lins and sera it is known as passiveimmunization.

Pathogenic infectious agen ts induce disease and thehost immune system responds with immunity , first toensure recovery and then to offer protection fromdisease if the same pathogen were to be encounteredagain. A vaccine is composed of one or more antigensof the pathogen, which will induce a protective immuneresponse without suffering from the disease.

Vaccines consist of attenuated live organisms (eg. oralpolio vaccines, oral typhoid vaccine, varicella vaccine,measles vaccine), whole inactivated organisms (e.g.pertusis vaccine, whole cell typhoid vaccine, rabiesvaccine, inactivated polio vaccine), modified exotoxinscalled "toxoids" (e.g. diphtheria toxoid, tetanus toxoid),or subunits (e.g. polysaccharide antigens of Salmonellatyphi or Haemophilus influenzae type b and the surfaceproteins of hepatitis B virus).

Vaccines mimic infection with the respective pathogen,but without the associated risk of developing thedisease. The consequent immune response may bemanifested through humoral (i.e. antibody) immunityor cell mediated immunity (CMI) or both. If the antigenpreferentially stimulates Th1 series of T helperlymphocytes, a strong lymphocytic respons e isobtained; if Th2 series is preferentially stimulated, theultimate express ion of immunity is predominantlyhumoral. Carbohydrate antigens are T cell independent;hence they stimulate B cells directly without T helpercell modulation. This results predominan t ly in a IgMresponse without IgG production or induction ofimmunological memory. BCG elicits CMI without aneasily demonstrable humoral component.

BCG, oral polio vaccine and Hepatitis B vaccines canbe given soon after birth as the maternally derivedimmunity apparently does not interfere with the vaccine"take" On the other hand, live measles vaccine may beinhibited in the presence of detectable maternalantibody in the infant's circu lation. Measles vaccine,therefore, should only be given after at least 9 monthsof age ; similarly, MMR vaccine is given only after 12months of age.

Timing of vaccination depends upon the age at whichthe disease is anticipated as well as on the feasibility ofadministering the vaccine at that time. For instance,neonatal tetanus can only be preven ted throughmaternal immunization by ensuring adequate titers oftransplacental antibodies and not by immunization ofthe baby at birth.

Vaccines are selected based on three important criteriaviz. necessity, safety and efficacy. All vaccines aresubjected to the following trials before being licensed:

Phase I Trial: Human volunteers - for tolerance, safety

Phas e II Trial: Human volunteers - for immuneresponse, safety

Phase III Trial: For field efficacy, safety

Further, before a vaccine is actually marketed itundergoes sterility, purity and potency tests at the levelof the manufacturer and the Drugs Controller Generalof India.

Most of the currently used childhood vaccines do notinterfere with the vaccine "take" of one another. Thesecan be, therefore, given simultaneously and severalantigens can be g iven the same day, if required. Ingeneral, the interval between two doses of the samevaccine, say for instance DTP, should be at least 4weeks; preferably 8 weeks. An interval of 4 weekswould obviously result in completion of the primaryschedule at an earlier age and may perhaps make iteasier for the parents to remember their follow-upappointments. Th is way the drop out rates may alsodecrease. BCG and OPV can be given from the day of

9

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

birth until 2 weeks of age, s o that there would be 4weeks gap until the next contact for immunization at 6weeks. If the opportunity to give BCG / Hepatitis B wasnot available in the neonatal period, it may be given at6 weeks, s imultaneously with DTP and OPV. Some ofthe viral vaccines (e.g. measles, varicella) may beassociated with possible short lasting suppression of the

immune system and it may be advisab le to avoidadministration of other vaccines within 4 weeks ofthese. There is, however, very little objective evidenceto show that this immunosuppression is clinicallysignificant.

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 roup o f ind ividuals [usually titer from those who haveseroconverted (GMT)]

Each time a vaccine is given the doctor should explainto the mother the nature of vaccine, the number ofdoses needed, the disease likely to be prevented,

anticipated adverse reactions and due date for the nextsession of immunization.

Types of Vaccines

10

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

National Immunization Schedule

*A second dos e of DT vaccine should be given at an interval of one month if there is no clear history ordocumented evidence of previous immunization with DTPw.

** A second dose of TT vaccine should be g iven at an interval of one month if there is no clear history ordocumented evidence of previous immunization with DTPw, DT or TT vaccines

(Source: Govt. of India (1994) National Child Survival and Safe Motherhood Program, Min is t ry of Health andFamily Welfare, New Delhi)

11

Commonly Used Vaccines

A. Vaccines Against Diseases Covered Under EPI

BCG Vaccine

Bacillus Calmette Guerin vaccine is derived from thebovine tuberculosis strain and was first developed in1921. It was the result of painstaking efforts by theFrench microbiologist Albert Calmette and theveterinary surgeon Camille Guerin who performed 231repeated subcultures over 13 years. It continues to bethe only effective vaccine against tuberculosis The twocommon strains in use are Copenhagen (Danish 1331)and Pasteur of which the former was produced in Indiaat the BCG Laboratories, Guindy, Tamil Nadu tillrecently.

BCG induces cell-mediated immunity but theprotective efficacy is a matter of debate and is verydifficult to quan t ify BCG vaccine is more effectiveagainst the development of hematogenous spread ofMycobacterium tuberculosis (which results in milliaryand meningeal forms of the disease against which ithas a protective efficacy of 50-80%), than against thedevelopment of pulmonary tuberculosis where it has aprotective efficacy of less than 50%.

The vaccine contains 0.1-0.4 million live viable bacilliper dose. It is supplied as a lyophilized (freeze-dried)preparation in vacuum sealed multi-dose dark coloredampoules. The long necked BCG ampoule should becut carefully by gradual filing at the junction of its neckand body, as sudden gush of air in the vacuum sealedampoule may lead to spillage of the contents. Thevaccine is light and heat sensitive and deteriorates onexposure to ult ra violet rays. Sterile normal salineshould be used for reconstitution. As the vaccinecontains no preservative, bacterial contamination mayoccur with repeated use. Therefore, once reconstituted,the vaccine should be used within 4 hours with theleft-over being discarded after the session.

In lyophilized form it can be stored at 2-80 C for up to12 months, without losing its potency. One should

ensure maintenance of cold chain during transport andstorage. The recommended dose is 0.1 ml ofreconstituted vaccine irrespective of the age and weightof the baby. Injection of BCG should be strictlyintradermal, using a Tuberculin syringe and a 26Gneed le. The convex aspect of the left shoulder ispreferred for easy visualization of the BCG scar. Theselected site may be swabbed clean using sterile saline- local antiseptics are unnecessary.

A wheal of 5 mm. at the injection site indicatessuccessful intradermal administrat ion of the vaccine.Subcutaneous administration of BCG is associated withan increased incidence of BCG aden it is . The injectedsite usually shows no visible change for several daysSubsequently, a papule develops after 2-3 weeks, whichincreases to a size of 4-8 mm. by the end of 5-6 weeks.This papule often heals with ulceration and results in as car after 6-12 weeks. Although the preferred time ofvaccination is soon after birth, it could be given up tothe age of 5 years. If no reaction is seen at the local siteeven after 12 weeks, it is an indication to repeat BCGpresuming that BCG has not taken up.

Adverse reactions - The ulcer at vaccination site maypersist for a few weeks before formation of the finalscar. No treatment is required for this condition.Secondary infection at the vaccination site may requirean t imicrob ia ls . I p s i la teral axillary /cerv icallymphadenopathy may develop a few weeks/monthsafter BCG vaccination. Antitubercular therapy is of nobenefit in such situations and should not beadministered. The nodes regress spontaneously after afew months. It should also be noted that if fine needleaspiration cytology of the nodes is carried out, stain foracid-fast bacilli may be positive. These are bovinevaccine bacilli and should not be misconstrued as beingsuggestive of tuberculous disease. In some children the

12

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

s ituat ion also. Disseminated BCG infection isextremely unusual but may occur in children withcellular immunodeficiency.

Oral Polio Vaccine

Oral polio vaccine (OPV) remains the vaccine of choicefor polio eradication in India. It is a suspension of over1 million particles of poliovirus types 1, 2 and 3. It issupplied with a stabilizing agent, namely magnesiumchloride. The vaccine, therefore, is quite stable underrefrigeration.

When OPV is given by mouth , the vaccine virusesreach the intestines where they must establish infection(vaccine virus "take") before an immune response mayoccur. A high level of gut immunity ensures thatvaccinated children would not participate in the chainof transmission of wild (pathogenic) polioviruses. Forreasons that are not clearly understood, OPV "take"rates may be somewhat variable. Seroconversion ratesafter three doses of OPV average 73%, 90% and 70%for Types I, II and III respectively. It is for this reasonthat multiple doses of OPV are necessary before90-95% of children develop immune responses to allthree poliovirus types . IAP recommends at least 5routine doses of OPV, during infancy and 2 morerepeat doses; at 16-18 months and 5 years. In additionto the routine OPV doses , " Pulse OPV doses" everyyear on Nat ional Immunization Days (NIDs) andsub-National Immunization Days (sNIDs) until the ageof 5 years are also mandatory.

Polio eradication is defined as no case of paralyticpoliomyelitis by wild poliovirus in last three calendaryears along with absence of wild poliovirus in thecommunity, when excellent clinical and virologicalsurveillance exists and the coverage of routine OPV ismore than 80%. Polio elimination is defined as no caseof paralytic poliomyelitis by the wild poliovirus in onecalendar year with other criteria being the s ame as ineradication . Adequate immunizat ion , clinicalsurveillance and appropriate virological investigationsin all children with acute flaccid paralys is (AFP) arethe cornerstones of polio eradication.

OPV should be stored at -200 C at the state and districtlevel and in the freezer at the clinic level. The vaccine

must reach the outreach facility at 2-80 C in vaccinecarriers with ice packs. Breastfeeding and mildd iarrhea are no con traind icat ion to OPVadminis t rat ion. If a substantial amount of OPV isvomited or regurgitated within 5-10 minutes ofadministration, the dose should be given again. If thisrepeat dose is also not retained, neither of the dosess hould be counted and the vaccine shou ld bere-administered at a later visit.

Adverse reactions - OPV is an excellent vaccine andthe WHO Global Polio Eradicat ion Initiative is at thethreshold of achieving its goal of eradicating wildpolioviruses. By mid-2006 polio has been eliminatedfrom all countries other than India, Pakistan,Afghanstan, Nigeria, Niger and Egypt. For developingcountries OPV is still the vaccine of choice foreradicating wild poliovirus and would continue to beused until wild poliovirus circulation ceases. However,like any other vaccine its use is associated with certainrisks.

OPV has been associated with occurrence of VaccineAssociated Paralytic Poliomyelitis (VAPP) Today, aswe move towards po lio eradication, VAPP is morecommon than paralysis due to wild polioviruses andhas, therefore, become an increasingly contentiousissue for all pediatricians . The risk of VAPP wouldcontinue to be there as long as we are using OPV as thepreferred vaccine against poliomyelitis. It has beenestimated that the global VAPP burden is in the rangeof 250-800 cases annually. Nearly 50 cases of VAPPare reported to occur in India annually. Approximatelyhalf of all VAPP cases are associated with the Type 2OPV strain.

The second major problem with us e of OPV is theemergence of circulating Vaccine Derived PolioViruses (cVDPVs), which are mutants that re-acquirewild virus-like properties and have been associated withoutbreaks of paralytic polio. cVDPVs usually aris e incommunities with low population immunity especially

13

when polio vaccine coverage rates decline but OPV usecontinues. The duration and extent of spread ofcVDPVs are dependent on the magnitude of theimmunity gap. As long as OPV is in use it ismandatory that very high immunization coverage ismaintained so as to decrease the risk of emergence ofcVDPV. W hereas VAPP occurs in individual cases,cVDPV can result in large outbreaks. It has been

suggested that mass OPV campaigns should bes ynchronized with the cessation of OPV use onceeradication of wild poliovirus has been achieved, so asto eliminate the risk of VAPP and the emergence o fcVDPVs. At the same time, a gradual transition to IPVshould be encouraged.

Polio Eradication

Why do we need pulse immunization against polio?

Simultaneous administration OPV to all susceptibleinfants and children interferes with circulation of wildpoliovirus in the community. It is, therefore, importantto ensure complete coverage with OPV during NIDs sothat no wild poliovirus remains in circulation.

Core strategies for eradication of polio include:

• Maintaining high routine infantimmunization coverage with OPV.

• Conducting mass campaigns (i.e. pulseimmunization against polio).

• Development of sensitive surveillance.• Organization of mop-up campaigns.

Inactivated Polio Vaccine (IPV)

IPV is formaldehyde killed poliovirus grown in monkeykidney cell/human diploid cells. Old IPV contained 20,8 and 32 D antigen units of types 1, 2 and 3polioviruses respectively. All curren tly used IPVvaccines are enhanced potency IPV (elIPV) whichcotains 40, 8 and 32 D antigen units of type 1, 2 and 3respectively. Currently term IPV means eIPV. It ishighly immunogenic. Seroconversion rates are 90-95%after two doses given after the age of 2 months and at2 months interval and 99% after three doses given evenwhen it is started at 6 weeks of age and given an 4weeks interval It produces excellent humoral immunityas well as local pharyngeal and, possible in testinalimmunity. The vaccine is very safe. It is now licensedto be used in India by Drug controller of India.

IPV can be used in combination with DTwP and Hibvaccines without compromising seroconversion orincreasing side effects. Ideal age to give first dose ofIPV is 8 weeks and the interval between two dosesshould also be 8 weeks. However if 3 primary doses aregiven, vaccine could be started at 6 weeks of age and

could be given at 4 weeks interval without anycompromise in the seroconversion rates.

Scientifically and immunologically schedule of givingtwo doses of IPV starting at 2 months of age and givenat 2 months interval followed by a booster at around 15months is similar to a schedule of giving 3 dosesstarting from 6 weeks of age and given at 4 weeksinterval followed by a booster at 15 months (even indeveloping countries). However in our country the laterschedule of 3 primary doses is better logistically as itcan be given along with DTP at 6, 10 and 14 weeksfollowed by a booster at 15 months. In any case theb irth dose of OPV must be given and all the OPVdoses on the days of NIDs / SIAs should be given to allthe children.

As the number of wild poliovirus cases in the countrydecreases, it is inevitable that one would have to shiftfrom OPV to IPV in the next few years. Thegovernment should, therefore, consider incorporatingIPV in the national immunization schedule in a phased

14

manner. IPV can also be an additional tool to eradicatewild polio from last few high risk difficult districts.

IPV is also the vaccine of choice in patients withimmunodeficiency and the preferred vaccine inchildren with symptomatic HIV infection.

Post-polio eradication scene and polio immunization:IAP believes that it will be unsafe and unethical tocontinue to use OPV in post-po lio eradication era.Following concepts should be kept in mind whiledeciding India specific guidelines for post-polioeradication immunization.

1. It will be unethical and unsafe to continue touse OPV after zero wild polio case and zerotransmission status is achieved due to risk ofVAPP following OPV.

2. It will be unwise to discontinue use of polioimmunization altogether after zero poliostatus is achieved due to fear of cVDPV andiVDPV. Past experience from somecountries has shown that countries whichhave eradicated wild polio virus and haveslackened in their routine polioimmunization programs have experiencedcVDPV outbreaks. These outbreaks ofcVDPV were curtailed by strengtheningroutine immunization and giving 2 or more

rounds of SIAs using OPV. However inpost-polio eradication era, it will beunethical and unsafe to reintroduce OPV insuch areas. It will force us to depend on thestocks of WHO or any such agency for OPVvaccine should out-break of wild polio orcVDPP occur. Hence India should preemptthe emergence of cVDPV and has to becomeself sufficient in stock-piling enough poliovaccine now to meet any such unforeseeneventuality in future.

3. Looking at the above problems, IAPrecommends that India should switch over toIPV, preferably as IPV-DTP, in its routineimmunization program gradually inpost-polio eradication era. India shouldencourage indigenous manufacturer toproduce enough IPV so that it becomesaffordable so that is will be possible toswitch to IPV in due course, looking at thehuge requirement of the number of doses.

Adverse reactions - The vaccine is very safe. As IPVcontains trace amounts of streptomycin, neomycin andpolymyxin B, allerg ic reactions may be seen inind iv iduals with hypersens it iv ity to thes eantimicrobials.

DTPw Vaccine

The combination of diphtheria toxoid, tetanus toxoidand whole cell killed pertussis vaccine (DTPw) ispopularly known as the "triple antigen" DTP is the corevaccine in all childhood immunization services. It isone of the oldest combination vaccines and has been incontinuous use for more than 55 years. Tetanus anddiphtheria toxoids are adsorbed on insoluble aluminiumsalts which act as adjuvants and enhance the antitoxinresponses to both the antigens. While the two toxoidsare highly immunogenic (95-100%), the pertussisvaccine (even after 3 doses) has a protective efficacy ofabout 70-90% only.

Adverse reactions - Local (pain and redness) andsystemic (fever) side-effects of the DTPw vaccine arealmost entirely due to the pertussis component. Wholecell pertus s is vaccine has been incriminated in the

induction of a neurological reaction in very rareinstances; however, there has been no conclusive prooffor this and the vaccine should not be denied tochildren with seizure disorders or stab le neurologicalconditions (e.g. Cerebral palsy, developmental delay).The results of the National Childhood EncephalopathyStudy (NCES) in the United Kingdom clearly show thatthere is no causal relationship between administrationof DTPw vaccine and development of chronicneurological disease in children. Convulsions followingDTPw vaccine are distinctly rare, and may onlyrepresent no th ing more sinister than fever triggeredseizures. Progressive/evolving neurological illnesses,however, are a relative contraindication to first dose ofDTPw immunization. For children who developpersistent inconsolable cry of more than 3 hours

15

duration, hyperpyrexia - fever > 40.50 C or hypotonic- hypo responsive episode HHE (collapse/shock likestage) within 48 hours of DTPw admin is t ration,seizures with or without fever within 72 hours ofadmin is tration of DTPw, the decision to administerfurther doses of DTPw should be carefully evaluatedand discussed with the parents These events wereregarded as absolute contraindications in the past. Theyare now considered mere precaut ions because theseevents generally do not recur with the next dose andthey have not been proven to cause permanent sequelaeIf a similar adverse reaction recurs with the subsequent

dose only then pertussis vaccine is contraindicated forfuture administration.

DTP and DT vaccines need to be stored at 2-80C. Thesevaccines s hould never be frozen, and if frozenaccidentally, it should be discarded. DTP must beinjected intramuscularly and the preferred site is theanterolateral as pect of the thigh. The IAP COIrecommends 5 doses of DTP - three in infancy with twoboosters at 18 months and 5 years. The DTPw or DTPavaccines 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 thenumber of constituent components viz. two componentDTPa containing pertussis toxin (PT) and filamentoushaemagglutinin (FHA); three component DTPacontaining pertact in in addition to PT and FHA; fivecomponent DTPa containing agglutinogens 2 and 3 inadd ition to PT, FHA and pertactin. Though a fivecomponent DTPa vaccine may be expected to elicit amore robust immune response as compared to two andthree component DTPa vaccines, the overall efficacy ofDTPa vaccines is comparable to the DTPw vaccine.

Dose: 0.5 ml by intramuscular injection.

• If parents are not willing for DTPwadministration after the adverse reaction withthe previous dose, DTaP can be recommendedin such circumstances as this vaccine is lessreactogenic.

• If encephalopathy (major alteration ofsensorium or illness with seizures lasting > 24hours) occurs within 7 days of DTPwadministration, further doses of DTPw and

DTaP are contraindicated. Pertussis vaccineshould not be given in such cases and insteadDT should be administered in the future.

• In case immediate anaphylaxis occurs afterDTwP administration, further DTwP/DTPashould be avoided because of uncertainty aboutwhich component of these vaccines has causedthe reaction, as is true with any vaccine.

The IAP COI unequivocally endorses the continued useof DTPw vaccine because of its proven efficacy andsafety. DTPa Vaccine may undoubtedly have fewerminor side-effects (like fever, local reactions atinjection site and irritability) but this minor advantagecan not justify the inord inate costs involved in theroutine use of this vaccine. DTPa vaccines are also byno means more effective than the whole cell pertussisvaccine. These are, therefore, not recommended foruniversal immunization in our country at present.There is, however, no bar to offering these vaccines tochildren from families who opt for the slight advantageof fewer minor side-effects.

16

Tetanus Toxoid

This vaccine contains Tetanus Toxoid 5 LF. It is ahighly heat stable and effective vaccine. Boos ters ofthis vaccine may be given at 10 and 16 years andthereafter every 10 years. After completing the fullcourse of seven doses, there is no need for additionaldoses during pregnancy at least for the next 10 years.Thereafter a single booster every 10 years would bes ufficient 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 bediscouraged.

For pregnant women who have not been previously

immunized, two doses of TT at least one month apartshould be given during pregnancy so that protectiveantibodies in adequate titers are transferred to thenewborn for prevention of neonatal tetanus. The seconddose of TT should be administered at least 2 weeksbefore delivery. A single dose of TT would suffice forsubsequent pregnancies that occur in the next 5 years;thereafter, 2 doses of TT would again be necessary. Forpreviously unimmunized schoo l age children, primaryTT immunization consists of two doses given 4 weeksapart.

Tetanus Immunoglobulin (TIG)

It is a liquid preparation containing immunoglobulins,mainly IgG, obtained from the plasma of healthydonors.

Indications: Unimmunised or inadequately immunizedindividuals with burns, roadside injuries and compoundfractures.

Adverse reactions: Local pain, fever, flush ing ,headache and chills may occur.

Dose: for Prophylaxis: 250-500 IU IM.

Therapeutic: tetanus neonatorum: 500-1000 IU IM or250 IU intrathecal.

In children and adults: 500-1000 IU IM and/or 250-500IU intrathecal.

Td Vaccine (Tetanus Toxoid, Reduced Dose Diphtheria)

Td contains the usual dose of tetanus toxoid and only 2units of diphtheria toxoid. It is recommended for use inchildren above 7 years of age IAP COI recommends theroutine use of Td at the age of 10 and 16 yrs (in other

words Td should replace TT boosters at 10 and 16years).

17

18

Measles Vaccine

Measles vaccine used in our country is derived from thelive attenuated Edmons ton Zagreb strain grown inhuman dip lo id cell culture. Other strains, which havebeen used for vaccination, include Schwarz, Moratenand Edmonston B. It is supplied freeze-dried and has ashelf life of 1-2 years, or even longer. The vaccine maybe stored frozen or refrigerated. After reconstitution thevaccine is very heat-labile and should be used within 4hours, with the unused vaccine being discarded.Reconstituted vaccine should not be frozen . Measlesvaccine does not contain any preservative, thereforestrict asepsis should be maintained while diluting andaspirating contents from the multi-dose vial. Somecases of staphylococcal sepsis/toxic shock syndromeassociated with use of this vaccine have occurred frombacterial contamination of the vaccine. The vaccineshould be injected subcutaneously, preferably over theupper arm / anterolateral thigh.

Being a live attenuated virus vaccine, it resu lts insub-clinical or attenuated infection and multiplication

of virus within the body. This infection mimics wildmeasles virus infection but is usually asymptomatic.Some children may develop a short lasting fever 7-10days after vaccination often accompanied by a macularrash. Paracetamol may be given to control/reduce fever.Vaccinees do not shed the virus.

Most infants are protected from measles by thematernally acquired antibodies until about 6-8 monthsof life. If measles vaccine is given in the presence ofmeasurable titers of maternal antibody, the vaccineefficacy may be reduced. In order to achieve the bestbalance between these competing demands o f earlyprotection and high seroconversion, completed 9months of age has been recommended as theappropriate age for measles vaccination in India. Incase of an outbreak, however, the vaccine can be givento infants as young as 6 months with a recommendationfor an additional MMR/Measles at 12-15 months.

B. Vaccines Recommended Against Diseases Not Covered Under EPI

MMR Vaccine

Globally, most coun tries use MMR instead of singleantigen measles vaccine. MMR vaccine contains 1000TCID50 of measles, 5000 TCID50 of mumps and 1000TCID50 of rubella v irus . It is administeredsubcutaneously in the upper arm/anterolateral thigh. Itis dispensed in single as well as multi-doseformulations; the diluent is available separately. Thevaccine is given as a 0.5 ml dose. Measles and MMRvaccines are supplied in lyophilized formulation andshould be frozen for long-term storage. In the clinicthese vaccines can be stored between 2 to 80C. Thevaccines should be p rotected from light. Oncereconstituted, vaccine should be used within 4 hours.

The IAP COI recommends administration of MMR to

all children. It should als o be given to all adolescentg irls not previously immunized and to hospital stafflikely to come in contact with pregnant mothers. Thereis no upper age limit for this vaccine. It may be notedthat the states like Delhi, Goa have included and fewstates like Tamilnadu, Maharashtra, etc. are likely toinclude MMR in its universal immunization program.

For infants given measles vaccine at 9-12 months,MMR vaccine may be given between 15-18 months ofage. If measles vaccine was missed altogether ininfancy, one dose of MMR can be given at or after 12months. The vaccine can be given along with othervaccines like DTP, OPV and Hib.

19

Mumps Vaccine

The mumps component in MMR vaccine contains liveattenuated mumps virus not less than 5000 TCID50 perdose. Vaccines are derived from Leningrad-Zagreb,Jerryl Lynn, RIT 4385 or Urabe AM9 strains and aregrown in chick embryo/human diploid cell cultures.Vaccinees do not shed the virus. There is no evidencethat mumps vaccination is associated with developmentof either au t is m or Crohn's Disease. There is nodifference in efficacy between various strains of mumpsvaccine.

Aseptic meningitis is known to occur following mumpsvaccine, though the incidence quoted is as rare as 1 in10,000 to 1 in 100,000 doses of vaccines used. Theclinical s everity of the vaccine induced asepticmeningitis is very mild and often may go unnoticed andall the cases recover without any permanent sequelae.Hence all the mumps vaccines are equally safe.Monovalent mumps vaccine or combination withrubella as MR vaccine is not available in our country.

Rubella Vaccine

Rubella vaccine currently available commercially isderived from RA 27/3 vaccine strain grown in humandiploid/chick embryo cell cultures. It is availableeither as a monovalent vaccine as a part ofcombination vaccine - MMR. It contains liveattenuated virus not less than 1000 TCID50. It is ahighly immunogenic vaccine with seroconversionrates of 95% It provides long term and probably lifelong protection; vaccine failures are uncommon.Vaccinees do not shed the virus.As a pediatrician one should be aware that rubellavaccination is mainly directed at preventing congenitalrubella syndrome (CRS) and not at preventing rubellainfection per se, as the latter is usually benign andinconsequential. By controlling the incidence of rubellainfections, CRS can be significantly reduced. There ispaucity of reliable data on occurrence of CRS in India.On the basis of what ever information is available CRSincidence is qu ite low in India. This is suggestive ofwide circulation of wild rubella virus in youngchildren. Seroprevalence of rubella antibodies inmajority of pregnant women in few studies in Indiasupport this view.

Haphazard use of rubella vaccine (monovalent or as a

constituent of MMR) in young children through publichealth measure with sub-optimal coverage of the targetpopulation may be counter-productive as it may shiftthe epidemiology of rubella to the righ t with moreclinical cases occurring in young adu lts leading toparadoxical increase in cases of CRS. This has beenshown to occur using mathematical models. Directevidence from some Latin American countries als ocorroborates these concerns.

Normally use of rubella vaccine (monovalent or as aconstituent of MMR) in young ch ildren throughindividual p ract itioners alone would not lead shift ofepidemiology in adolescents and adults as the coverageof target populat ion is miniscule by privatepractitioners In case MMR is incorporated in universalprogram and adequate coverage is not achieved, a shiftin epidemiology of rubella is quite possible. HenceMMR though a cos t effective vaccine should not beintroduced through public health facilities in areaswhere coverage fo r routine immunization isconsistently less than 80%.

20

Hepatitis B Vaccine

In India, 1-4% of individuals are found to be chroniccarriers of Hepatitis B Virus (HBV). Infection withHBV may occur perinatally (vertical transmission),during early childhood (the so-called horizontalspread), through sexual contact or nosocomially. Itshould be noted that 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 ofhepatitis B.

Younger the age of acquisition of HBV infection,higher the chances of becoming a chronic carrier. It isbelieved that as many as 90% of those who are infectedat birth go on to become chronic carriers. In fect ionwith HBV is one of the most important causes ofchronic hepatitis, cirrhosis of liver and hepatocellularcarcinoma. 30% of the chronic carriers go on todevelop chronic liver disease. These are all preventableby early childhood immunization. It is for this reasonthat the World Health Organization has recommendeduniversal Hepatitis B vaccination. As many as 150countries have now included HBV in their nationalimmunization schedu les . In June 2002, theGovernment of India also initiated the incorporation ofHB vaccine as a universal vaccine through a pilotprogram which will be scaled up in a phased manner.

HB vaccine is a highly purified recombinant DNAvaccine produced in the yeast species Hansenulapolymorpha, Saccharomyces cerevisiae or Pichiapastoris. It is adjuvanted with aluminium salts andshould be stored at 2-80 C. The vaccine should not befrozen - if frozen accidentally, the it should bediscarded. It should be injected intramuscularly in theanterolateral thigh. The usual pediatric dose (< 12years o f age) is 0.5 ml corresponding to 10µg of theantigenic component. Adult dose is twice the pediatricdose. The vaccine is high ly immunogenic andseroconversion rates are greater than 95% after a threedose schedule. Antibody titers greater than 10 mIU/mlare considered protective. The dose may be increasedwhen vaccinating immunocompromized individualse.g. patients on chemotherapy for malignant conditionsor those with chronic renal failure awaitinghemodialysis.

HB vaccine may be given in any of the following

schedules:

1. Birth, 1 and 6 months2. Birth, 6 and 14 weeks3. 6, 10 and 14 weeks

Immunologically 0 - 1 - 6 months schedule of hepatitisB immunization has been most widely used and provento be ideal with high antibody titers at the end of thevaccination. However now that HB vaccination isintegrated into the existing immunization program(UIP) in India, due to operational issues at a nationallevel one has to piggy back on the available contacts forroutine immunization i.e. DTP which is given at 6, 10and 14 weeks of age. At the same time birth dose has tobe given to cover for the vertical route. Hence IAP COIrecommends 0 - 6 - 14 wks schedule for publicmeasure. In case birth dose has been missed, 6 - 10- 14wks schedu le can be followed. In office practice, onecan still use 0 - 6wks - 6 months schedule. As on now,from the data available, none of the above schedulesneeds a booster.

The purpose of Hepatitis B vaccination is to preventchronic in fection and development of chronic liverdisease / hepatocellular carcinoma later in life. An idealHB vaccine schedule should, therefore, address verticalas well as horizontal modes of transmission of thevirus.

Pregnant women should be counseled and encouragedto opt for HBsAg screening. If the mother is known tobe HBsAg negative, HB vaccine can be g iven alongwith DTP at 6, 10 and 14 weeks/6 months as there is nospecial requirement to start vaccinat ion at birth itself.This 6-10-14 wks schedule may be easier to implementin the context of the national immunization program ashigher vaccination coverage may be achieved withearlier administration of vaccines.

If the mother's HBsAg status is not known, it isimportant that HB vaccination should begin within afew hours of birth so that perinatal transmission can beprevented. Any one of the following schedules may beused for this purpose; birth, 6 and 14 weeks or birth, 6wks and 6 months.

If the mother is HBsAg positive (and especially HBeAg

21

positive), the baby should be given Hepatitis B ImmuneGlobulin (HBIG) within 24 hours of birth, along withHB vaccine (at birth, 6 and 14 weeks or birth, 6 weeksand 6months) using two separate syringes and separatesites for injection. If HBIG is not available (o r isunaffordable), HB vaccine may be given at 0, 1 and 2months with an additional dose between 9-12 months.

It has been suggested by many authorities that ininfancy the third dose of HB vaccine should be given atleast 16 weeks after the firs t dose & at least 8 weeksafter the second dose and not before 6 months ofchronological age, as it presumably gives longer lastingimmunity. However this view is being challenged asHB vaccine is a T-cell dependent vaccine, the titers atthe end of immunization schedule may not beimportant so far as it is well above the protective level.There would occur anamnestic response with the titersgoing up should there occur contact with the v irusagain in future. As logistically, it is easier to combineHB vaccine program with the DTP vaccine, it can begiven in 0-6-14 weeks schedule too The vaccinationschedule need not be changed for preterm andsmall-for-dates babies; in the case of extremely pretermbabies, however, vaccination should commence only

after initial stabilization.

For older children and adults the preferred schedule is0, 1 and 6 months, '0' being the elected date for the firstdose.

In immunocompetent individuals HB vaccine inducesan effective immunological memory that lasts life-longand protects against symptomatic acute illness anddevelopment of chronic HB infection on exposure to thevirus. Boosters of HB vaccine are, therefore, notnecessary under usual circumstances.

HB vaccination is now being integrated into theexisting immunization program in India. It wasintroduced in 15 cities and 32 districts in the initialphase; selection of districts was based on achievementof targets of 80% or more DTPw-3 coverage underroutine immunization based on evaluation surveys.Under this program, the vaccine is being provided freeof cost to infants living in u rban slums. The programwill be expanded to include additional cities anddistricts within a certain timeframe. It is envisaged thatHB vaccination will be introduced in all districts ofIndia by 2007.

Hepatitis B Immunoglobulin (HBIG)

HBIG provides immediate passive immunity and isrecommended in situations wherein there has beenacute expos ure to HBsAg infected material e.g. by aneedle-stick injury. Clinical trials have demonstrated90% reduction in risk of transmis s ion following suchexposure if HBIG is used along with Hepatitis Bvaccine. HBIG does no t interfere with antibodyresponse to simultaneous HB vaccine. It is for th isreason that individuals who have had recent accidentalexposure to hepatitis B virus should be given combinedpassive-active immunization. It is also useful inprevention of mother to child transmission andtransmission following sexual expos ure like in rapecases. Lastly HBIG is indicated in oncology patientswho may not respond adequately to Hepatitis B vaccineas they are immune compromised following themalignancy as well its therapy.

Adverse Reactions: Transient, mild pain at the site ofinjection and itching may be seen in a small proportionof recipients.

Special Precautions : HBIG should never beadministered intravenously.

Dose: Adults : 1000-2000 IU; Children:- 32-48 IU/kgbody wt . This should be administered as soon asfollowing exposure, preferably within 48 hours thoughit can be administered even if the patient reports late upto 7 days after exposure. Neonates: 100-200 IU. Thefirst dose should be administered as soon as after birthup to within 5 days of birth. An additional dose of32-48 IU/kg of body weight may also be given between2-3 months after initial dose.

22

Typhoid Vaccines

Enteric fever is endemic in India and is a major publichealth problem. Three vaccines were available forclinical use till recently. However now only Vi typhoid

vaccine is available commercially.

The Whole Cell Inactivated Typhoid Vaccine (TA/TAB)

Heat-killed, phenol-preserved or the acetone inactivatedlyophilized whole cell Salmonella typhi vaccines wereinexpensive products that have been in use in India fora long time. The p rotective efficacy of acetoneinactivated preparation is more than that of the phenolpreserved vaccine but the former is more difficult toprepare and is associated with more side-effects. Bothvaccines contain Salmonella typhi 1000 millionorganisms per ml. Protection begins 4 weeks aftervaccination. Use of these vaccines may be associatedwith fever, local pain and malaise due to the endotoxinsin bacterial cell wall. A pure S. typhi vaccine is lessreactogenic than the combined TA/TAB vaccines. Thevaccine is very safe and is reasonably effective ifrevaccination can be carried out on a regular basis. Thevaccine efficacy has been estimated to be 50-70% in ameta-analysis of the randomized controlled trialsavailable.

The vaccine appears to be protective through theinduction of antibodies against cell wall somatic (O)and flagellar (H) antigens- these antibodies can act asa biological marker of the vaccine. It may interfere withthe interpretation of the Widal test. It is effective evenin child ren below 2 years of age and can be given toinfants > 6 months of age Primary vaccination requirestwo dos es , 4 o r more weeks apart, givensubcutaneously. Pediatric dose of the vaccine is 0.25 mlin children aged 6 months -10 years and 0.5 ml inorder children. The vaccine should be stored at 2-80 C.It should never be frozen. Revaccination is necessaryevery 2-3 years to sustain an optimum immuneresponse and should be done preferably before the onsetof summer.

Unfortunately, this vaccine is not being manufacturedin India at present

The Vi-Capsular Polysaccharide Vaccine

The vaccine consists of purified Vi-caps u larpolysaccharide, which during natural infection inhibitsphagocytosis and serum bactericidal activity and isresponsible for virulence of the bacteria. It hasreasonable efficacy o f 50-60% in children and lowreactogenicity. Protection begins within two weeks ofvaccination and the biological marker is anti-Viantibodies. It is not very effective in children below twoyears of age because it is an unconjugated

polysaccharide vaccine as available in our country atpresent. Cost of the vaccine though a limiting factor inpast, is now reasonably priced. The vaccine is availableas an isotonic phenolated buffer solution; the dose is0.5 ml. containing 25µg of the polysaccharide. It can begiven intramuscularly or subcutaneously. The vaccines hould be stored at 2-80 C. It should never be frozen.Adverse effects are mild and include pain and swellingat injection site.

Oral Live Attenuated Ty21a Vaccine:

23

Salmonella typhi Ty21a is a live attenuated strain witha mutation in gal E gene and lacks the enzymeUDP-gal 4 epimerase. It is genetically stable and is notknown to revert to virulence. The efficacy has beenshown to 50-60% with the capsule form and near 90%with the liquid form (not available commercially). Itprovides protection by inducing local gut immunity butthere is no biological marker of this vaccine. Thevaccine is supplied in an enteric coated formulation asthe bacteria are acid labile. It can be given to childrensix years of age and above as the capsules have to beswallowed intact.

The vaccine is given on an empty stomach in three

sittings, on alternate days. The capsule should never beopened before ingestion. Protection begins within aweek after completion of the course and the protectiveefficacy 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. Antimicrobialsactive against S. Typhi should not be used 3 days beforeand 7 days after oral typhoid vaccine administration asthese may interfere with the vaccine "take".Unfortunately this vaccine is also not available now inour country.

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

Hib Conjugate Vaccines

Haemophilus influenzae type b (Hib) is an importantinvasive pathogen causing invasive diseases likepneumonia, meningitis and bacteremia. Majority ofcases occur in children below 2 years of age. Hibvaccination is given routinely in the developedcountries for last many years. Countries with sensitivedisease surveillance systems have shown significantdeclines in invasive Hib disease following theincorporation o f this vaccine in their nationalimmunization programs. Recently published data of theInvasive Bacterial Infections Surveillance (IBIS) groupfrom six referral hospitals in India (Lancet, 2003) showthat Hib is a common cause of meningit is in ourcountry.

Hib capsular polysaccharide vaccine is a very effectiveand safe vaccine. A number of PRP conjugate Hibvaccines are available of which two are available inIndia viz. HbOC (with CRM 197 mutant diph theriatoxin as conjugate) and PRP-T (with tetanus toxoid asconjugate). PRP-OMP (with meningococcal outermembrane protein as conjugate) is no t available inIndia HbOC and PRP-T vaccines show only a marginalincrease in antibody levels after the first dose with amarked increase after the second and even better

response after the third dose. On the other hand,PRP-OMP shows an increase in antibody level after thefirst dose itself with only marginal increases after thesecond and third doses. It is for this reason that while3 doses of HbOC and PRP-T are recommended forprimary vaccination, only 2 doses of PRP-OMP arerecommended for this purpose. In spite of theseapparent differences, these three vaccines when used inthe recommended doses have similar efficacy.

The vaccination schedule for Hib consists of three doseswhen initiated below 6 months, 2 doses between 6-12months and 1 dose between 12-15 months , with abooster at 18 months. The interval between two dosesshould be at least 4 weeks. If vaccination is delayeduntil 15 months, a single dose may suffice. It is highlyefficacious vaccine, the protective efficacy being 95%.As Hib d isease is essentially confined to infants andyoung children, the vaccine is not necessary forchildren above 5 years. Hib vaccine is stored at 2-80 C.

The IAP COI recommends use of Hib vaccine for allchildren . It is particularly recommended to be givenprior to splenectomy and in patients with sickle celldisease.

24

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

Varicella Vaccine

Chicken pox is usually a self limiting and generallybenign disease affecting mostly children and youngadults. Complications of varicella may be morecommonly seen in immunocompromised individuals,adults and pregnant women. Takahashi et al developeda live attenuated vaccine from the Oka strain in Japanin the early seventies. The vaccine has been in clinicaluse in Japan since 1989 and in the United States since1995. The vaccine can be administered to any healthyindividual above the age of 12 months who has not hadvaricella previously.

Varicella vaccines in use today are all derived from theoriginal Oka strain but the virus contents may varyfrom one manufacturer to another. The recommendeddose is 0.5 ml and the minimum infectious viruscontent should be 1000 Plaque Forming Units. Thevaccine is administered subcutaneously. A single doseis sufficient below 13 years of age, after which twodoses (at 4-8 weeks interval) are required. The vaccineis not recommended for ch ild ren below 12 months ofage. Though vaccine manufacturers recommend to usethis vaccine at 12 months, breakthrough infections canbe less if used after 15 months of age. Hence IAP COIrecommends to use this vaccine after the age o f 15months. It is a highly effective vaccine and protectiveimmunity, humoral as well as cellular, develops in95-99% individuals. The immunity appears to be longlasting.

The IAP COI opines that varicella vaccine is notrecommended fo r universal immunization in India atpresent. One has to emphasize the generally benignnature of and rarity of complications with varicellainfection in young children. It may be offered tochildren from h igh socio-economic strata of societyafter explaining the pros and cons to the parents on aone-to-one "named child" basis. It may be prescribed toadolescents who have not had varicella in past (or areknown to be varicella IgG negative) especially if they

are leaving home for studies in a residentialschool/college. It is indicated in children with chroniclung/heart disease, humoral immunodeficiencies, HIVinfection (but with C4 counts above 15% of the agerelated norms), leukemia (but in remission and offchemotherapy for atleast 3-6 months) and those on longterm salicylates/high dose lone term oral steroids.Varicella vaccine is also recommended in householdcontacts of immunocompromised children. It may alsobe considered in children attending crèches and daycare centers. When used for post-exposure prophylaxisit should be administered within 72 hours of varicellaexposure - it should be noted, however, that the efficacyof the vaccine in preventing varicella under suchcircumstances is not very clear. Varicella vaccine isalso indicated in susceptible adolescents and adults ifthey are inmates of or working in the ins t itutional setup e.g. s chool teachers, day care center workers,military personnel and health care professionals.

The vaccine is stored at 2-80C and can be administeredsubcutaneously or intramuscularly. It should beprotected from light and needs to be used within 30minutes of its reconstitution.

Adverse reactions - It includes fever, vaccineass ociated rash, pain redness and swelling atvaccination site. When used in adult females,pregnancy should be avoided for at least 4 weeks aftervaccination.

Varicella zoster immunoglobulin (VZIG) is used forpassive post-exposure prophylaxis in immunodeficientindividuals who have been exposed to varicella orherpes zoster and are unlikely to have detectableantibody levels. It should be given to the neonate if themother develops varicella 5 days before to 2 days afterdelivery. It has to be given by intramuscular injectionand the dose is 125 units/10 kg body weight.

25

Hepatitis A Vaccine

Hepatitis A virus (HAV) infection is a relatively benigninfection in young ch ildren as many of them havecompletely asymptomatic sub-clinical infection Forinstance as many as 50% of children between 2-5 yearsand 85% of those below 2 years who acquire HAVinfection, may continue to remain anicteric and maydevelop non-specific symptoms like any other viralin fection. In adults hepatitis A is frequentlysymptomatic and mortality is much higher than inchildren. The disease severity increases irrespective ofage, in those with underlying chronic liver disease.

Inactivated HA vaccines derived from HM 175/GBMstrains and g rown on MRC5 human diploid cell linesare now available. The virus is formalin inactivated andadjuvanted with aluminimum hydroxide. It has beensuggested that the vaccine can be used any time after18 months of age when the maternally derived antibodylevels have declined; It is given in a two dose schedule,6 months apart. The adult formulation should be usedafter the recommended cut-off age of 15 yearsaccording to one manufacturer and 18 years accordingto the other The vaccine is given intramuscularly andthe protective efficacy is 94-100% Immunity appears tobe long lasting and boosters are not recommended atpresent.

The IAP COI op ines that HA vaccine is not

recommended for universal immunization in India atpresent. One has to emphasize the generally benignnature of disease and very small number of childrendeveloping complications with Hepatitis A infection inyoung children. It may be offered to children from highs ocio-economic strata of society after explaining thepros and cons to the parents on a one-to one "namedchild" basis. It may be prescribed to adolescents whohave not had viral hepatitis in past (or are known to beHAV-IgG negative), especially those who are leav inghome for further studies. It is recommended in allpatients with chronic liver d isease (who are HAVseronegative) and family contacts of patients withchronic liver disease. It may be offered to householdcontacts of patients with acute HA virus infection - inthe latter case the vaccine must be given within 10days; however, it may not always be effective undersuch circumstances when the contact has had the samesource of infection as the index patient. It may also beconsidered in children attending crèches and day carecenters and in travelers from abroad (e.g. non-residentIndians) visiting endemic areas.

The vaccine is stored at 2-80C.

Adverse reactions: It includes local pain and localinduration.

Pneumococcal Vaccines

Streptococcus pneumoniae is a common caus e ofinvasive bacterial diseases responsible for a significantproportion of potentially fatal cond it ions likepneumonia and meningitis in children. It also leads toconditions like otitis media and sinusitis, which mayhave morbidity but little or no mortality. In developingcountries, this organism is believed to be thecommonest cause of bacterial pneumonia. Peakincidence of pneumococcal disease is between 2 to 24months of age. Based on the capsular polysaccharideantigen, pneumococci are classified into 85 differentserotypes. Of these, about 10 serotypes account for most

infections. The common pathogenic stereotypesreported in children in Western countries are 1, 4, 5, 6,9, 11, 14, 15, 18, 19 and 23. It appears that theserotypes causing invasive disease in developedcountries are different from the ones which are foundin developing countries. According to results of theInvasive Bacterial Infection Surveillance (IBIS) study,the common serotypes responsible for invasive diseasein children below five years of age in India include 6,1, 19, 14, 4, 5 and 7. Serotypes 1& 5 accounted for29% of disease in India. Though prevalence ofpenicillin resistance is almost negligible at present

26

there is some evidence that the prevalence of resistanceto penicillin amongst the pneumococci may begradually increasing, thereby highlighting the need foran effective vaccine.

Two types of pneumococcal vaccines are currentlyavailable - the 23-valent unconjugated polysaccharidevaccine and the 7-valent conjugate polysaccaharidevaccine. Immunity is serotype specific.

The 23-valent polysaccharide vaccine contains thefollowing 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 almos t 85% ofinvasive disease (pneumonia, mening it is andbacteremia) caused by pneumococci. Immunization,however, is not effective for prevention of otitis media.Each dose is 05 ml containing 25ug polysaccharide ofeach of the 23 serotypes con tained in the vaccines.However, as it is an unconjugated polysaccharidevaccine it does not result in immunological memory.This vaccine is poorly immunogenic in children belowtwo years of age i.e. children who are at highest risk ofinvasive disease. The dose is 0.5 ml and the vaccine isgiven intramuscularly or subcutaneously. This vaccinemay be us ed in h igh-risk groups above the age of 2years. Revaccination is recommended after 5 years. Itis recommended for children with asplenia, sickle celld isease and nephrotic syndrome. It is als orecommended for HIV infected children. It may beoffered to those with underlying chronic illnesses likerenal diseases, cardiovascular diseases or diabetes.

The heptavalent conjugate vaccine (PCV-7) containsthe following sero types -4, 6B, 9V, 14, 18C, 19F, and23F. It is coupled with a non-toxic variant of diphtheriatoxin (CRM197) and has aluminium phosphate as theadjuvant. Conjugation of polysaccharide with proteinCRM197 makes it immunogenic below 2 years of age.In February 2000 this vaccine (PCV-7 Prevnar) waslicensed in US fo r administration to children below 5yrs of age. The development of this vaccine wasprompted by the observation that young children below2yrs of age are dis proportionately affected by theserious pneumococcal infection and recognition of thefact that available 23 valent polysaccharide vaccine wasnon immunogenic in th is age group 2 yrs. Conjugatevaccine is used in a 3-dose schedule in infancy at 4-8weeks interval followed by a booster at 15-18 months ofage and has protective efficacy of 95-99% against

invasive pneumococcal disease caused by the serotypescovered by the vaccine. The dose is 0.5 ml. and thevaccine is given intramuscularly. Pneumococcalvaccines are s tored at 2- 80 C. Conjugate vaccineshould not be frozen.

Since the introduct ion of PCV-7 in the childhoodvaccine schedule in US, there has been a dramaticreduction in the incidence of invasive pneumococcaldisease not only in the children who are vaccinated butalso non-vaccinated young children in their contact anda milder but statistically sign ificant decrease ininvasive disease in their adult contacts, suggestings trong herd effect. Similar herd effect was seen in theform of overall reduction in the disease caused by drugresistant serotypes in the community. Though there hasbeen replacement of the vaccine serotypes bynon-vaccine serotypes in the nasal carriage studies,fortunately this has not been seen significantly in theinvasive diseases studies. However there is a need forcontinuous surveillance for the serotype involved ininvasive cases from time to time.

Healthy children: The IAP COI does not recommendus e o f this vaccine for universal immunization in ourcountry at present. PCV - 7 covers approximately 50 to55% percent of pneumococcal serotypes responsible forinvasive pneumococcal disease in India offering about50 to 55% protection in infants & ch ild ren in India.The vaccine may be offered to healthy children abovethe age of 6 weeks t ill 2 years after explaining theparents on one to one "named child" basis.

High risk group: There are certain children who are athigh risk of severe invasive pneumococcal disease withhigh mortality. This includes children with Sickle celld is eas e, as p len ia, primary immunodeficiencys yndrome s , HI V, c h i ld r e n w i th s everecardio-respiratory illness and children with chronicillnes ses like renal diseases, diabetes etc., nephroticsyndrome, cerebrospinal fluid rhinorrhea etc. For suchchildren IAP COI recommends age appropriate dosesof 7 valent conjugated pneumococcal vaccine routinelytill 5 years of age. For children above 2 years, a dose of23 valent unconjugated pneumococcal vaccine is alsorecommended to be given after one priming dose ofconjugated vaccine.

Adverse reactions - Injection site so reness, malaise,low grade fever.

27

D. Vaccines Used in Special Circumstances

Meningococcal Vaccines

Neisseria meningitides accounts for 30-40% cases ofmeningitis in children up to the age 15 years. It is theonly bacterium capable of causing large scale epidemicsof meningitis. There are 12 known serogroups butmajority of the disease causing is o lates belong toserogroups A, B, C, Y and W135. Epidemic disease istypically associated with type A (occasionally type C)and usually occurs in cycles every 7-14 years, especiallyin the African meningitis belt which extends acros sAfrica from Senegal to Ethiopia. In India also almos tall epidemics were of type A Such group A epidemicsare usually due to a single strain of the pathogen. Someof the recent outbreaks in Western Asia have been dueto W135. Endemic disease occurs worldwide and ismostly caused by serogroups B, A, or C although groupY has been increasingly incriminated in recent reports.In India endemic cases are mainly due to type B. As arule, endemic disease occurs primarily in children andadolescents, with highest attack rates in infants aged3-12 months. Severe meningococcal disease occursprimarily in children and adolescents, with highestattack rates in infants aged 3-12 months. Severemeningococcal disease is associated with highcase-fatality rates (5-15%) even where adequatemedical facilities are available. Chemoprophylacticmeasures are in general insufficient for the control ofthis disease because secondary cases comprise only 1-2% of all meningococcal cases.

Immunity following meningococcal infection iss erogroup specific. Unconjugated meningococcalvaccines are based on combinations of group-specificcapsular polysaccharides - either bivalent (A and C) ortetravalent (A, C, Y and 135). The recommendedsingle dose of the reconstituted vaccine contains 50 µgof each of the individual polysaccharides. A conjugategroup C vaccine has also been marketed in developedcountries.

Unconjugated meningococcal vaccines, like all otherpolysaccharide vaccines, do not induce immunological

memory. The group C, Y, and W135 components,moreover, are not very immunogenic in children below2 years of age. Meningococcal group C conjugatevaccine, on the other hand, is efficacious even in theyoungest children.

Meningococcal vaccine is indicated fo r use (as anadjunct along with chemoprophylaxis) in close contactsof patients with the d isease. It may be considered inchild ren with complement deficiency, prior tosplenectomy and those asplenia and sickle cell anemia.It is also recommended during disease outbreaks(caused by serogroups included in the vaccine) andprior to travel to the high endemicity meningococcalbelt in the African continent. Meningococcal vaccine ismandatory for all Haj pilgrims and is necessary forresidential students in some of the universities abroad.

The IAP COI does not recommend th is vaccine foruniversal immunization in our country at present. Itcan be given to children above 2 years of age duringdisease epidemic and is administered subcutaneously orintramuscularly. In special circumstances (e.g. duringgroup A epidemic to close household contacts , closehousehold contact) it may be offered to even youngerinfants but the protective efficacy is likely to be low inthis age group. The dose is 0.5 ml. Revaccination maybe considered after 3-5 years if the individual is still atrisk. The vaccine is stored at 2-80C.

A conjugate meningococcal serogroup C vaccine hasbeen part of rou t ine immunization in the UnitedKingdom since Novemer 1999 as it is the commonestcause of meningococcal disease in children there - threedoses are g iven at 4-8 weeks interval along with theroutine childhood immunizations. Two doses of thevaccine suffice for children in age group 6-12 monthsand one dose in older children.

Adverse reactions - Fever and pain at injection site.

28

Japanese Encephalitis Vaccines

Japanese encephalitis (JE) is one of the most importantcauses of viral encephalitis in Asia. In India, JE isbelieved to be responsible for approximately 2000-3000clinical cases and 500-600 deaths every year. As thereis no anti-viral drug treatment, JE vaccination remainsthe single most important control measure. Contrary topopular belief JE vaccine should not be used as an"outbreak response vaccine" It should rather be givento all children 1-15 years of age living in highlyendemic areas (e.g. Andhra Pradesh, Ut tar Pradesh,Karnataka). The vaccine may also be offered to visitorsto endemic areas if the duration of stay is likely toexceed four weeks.

Currently three types of JE vaccines are available e.g.(a) mouse brain-derived and inactivated NakayamaStrain vaccine (b) cell culture-derived inactivatedvaccine and (c) cell culture-derived live attenuatedvaccine.

Mouse Brain-Derived Inactivated JE Vaccine

This vaccine is produced in Ind ia at the CentralResearch Institute, Kasauli. Commercially availablevaccine is imported. It is given subcutaneously - 0.5 mlin ch ildren 1-3 years, and 1 ml in older children.Primary immunization consists of three doses given on0, 7 and 30 days - 0 being the elected date. A boosterdose is recommended after 1 year and subsequently atthree year intervals.

Adverse reactions: Include fever, malaise, localtenderness and redness in 20% of recipients. In recentyears, several cases of acute encephalitis temporallylinked to JE vaccinat ion have also been reported.Anaphylactic reactions are known to occur with thisvaccine. This vaccine was also produced by s omeinternational vaccine manufacturers like AventisPasteur (now Sanoffi Aventis), however they havestopped manufacturing of this vaccine recently and aretrying to switch over to vero cell cultured vaccine.

Inactivated Primary Hamster Kidney Cell derived

Vaccine

This vaccine made from Primary Hamster Kidney cellline was used in China in millions o f doses. Howeverwith the availability of the Sa-14-14-2 live vaccine, this

vaccine has been given up.

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

This vaccine is based on a stable neuro-attenuatedstrain of JE virus (SA-14-14-2). It was firs licensed foruse in 1988 in People's Republic of China and oversixty million doses per year are being used there. Nowit is also licensed for use in Nepal, S. Korea and IndiaThis live attenuated vaccine constitutes to over 50% ofglobal production of all JE vaccine. Dose is 0.5ml at allages. It is given by subcutaneous route. Initial studiesdone on this vaccine demonstrated an efficacy of about80% 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 seriousadverse effects (other than anaphylaxis) have beenreported over 20-year period (1979 - 1998). Thisvaccine is not available in commercial market in India,however it has been used for public health by Govt. ofIndia in 2006.

Use of Sa-14-14-2 live JE vaccine in India in 2006:Recognizing the need to control JE in high ly endemicdistricts, GOI has initiated a pilot project ofimmunizing children from hyperendemic districtsagainst JE in 2006. 7 d is t ricts in UP, 2 in Assam andone each in West Bengal and Karnataka were targetedthis year. SA-14-14-2 live JE vaccine was usedmanufactured by Chengdu institute of BiologicalProducts, Chengdu, China. It was given in a campaignmode to children aged 1-15 years. It was g iven assingle dose subcutaneously using AD syringe. Thewhole campaign was carried out from 15th May to 15thJuly 2006. 11 million children were targeted asbeneficiaries and 9 million children actually receivedthe vaccine i.e. nearly 86% of the target was achieved.UP recorded 96% coverage against all expectations.There were 504 adverse effects following the campaignof which 482 were minor adverse effects. 22 deathswere reported but none were causally related to thevaccine as cleared by an expert committee set up tomonitor the adverse effects. Based on the success andsafety of this year, similar campaign is planned forother areas in coming years. From next year thisvaccine will be included in the routine immunizationschedule for the new birth cohorts in these areas.

29

Influenza Vaccine

Influenza virus is an orthomyxovirus. There are threeantigenic types (A, B and C) with several subtypes ofeach based on two surface an t igens - hemagglutininand neuraminidase Influenza virus, especially type A,is characterized by frequent mutations - antigenic driftsand antigen ic shifts. It is of the utmost importance,therefore, that the vaccine should incorporate thecurrent strain p revalent during that time. Currentinactivated influenza vaccines are produced from virusgrown in embryonated hen's eggs, and are of threetypes : whole v irus , s p lit -p roduct , s ubunitsurface-antigen formulations. Whole-virus vaccines areassociated with increased adverse reactions, especiallyin children, and are currently not used. Most influenzavaccines are split-product vaccines, p roduced fromdetergent treated , highly purified influenza virus, ors urface-an t igen vaccines containing purifiedhemagglutinin and neuraminidase.

Vaccines are usually trivalent, containing 15 µg each oftwo influenza A subtypes (H1N1 and H3N2) and oneinfluenza B strain. The present vaccine contains 15 µgof hemagglutinin o f each of the three WHOrecommended strains (Northern Hemisphere) for theseason 2004-2005.

1) A/New Caledonia/20/99 (H1N1) like strain [variantA/New Caledonia/20/99 (IVR - 116)];

2) A/Fujian/411/2002 (H3N2) - like strain [varian tA/Wyoming/3/2003 (X-147)];

3) B/ Shanghai/361/2002 - like strain [variantB/Jingsu/10/2003].

Vaccines elicit a relatively strain-specific humoralresponse, have reduced efficacy against antigenicallydrifted viruses and are ineffective against unrelatedstrains. The influenza vaccine is therefore unique as theprecise composition has to be changed periodically inanticipation of the prevalent influenza strain expectedto circulate in a given year. The vaccine is effective foronly a short period, usually 6 months to 1 year and anew vaccine is brought every year. The WHO reviewsvaccine composition biannually and updates antigeniccontent depend ing on prevalent circulating subtypesbased on the data obtained from its chain of referencelaboratories from world over to provide antigenicallywell-matched vaccines.

Influenza vaccine is highly immunogenic and isassociated with minimal side effects. When used for thefirst time the vaccine is given in 2 doses in children 6months to 8 years of age; only one dose is sufficientabove 8 years. Revaccination is done with a singleannual dose, which is given before the peak influenzaseason. The vaccine is administered intramuscularly,the dose being 0.25 ml. in ch ildren below three yearsand 0.5 ml thereafter. This vaccine is currentlyrecommended for us e only in high-risk children andadolescents e.g . individuals with chronic pulmonaryand card iac d is eas e, s ickle cell d is eas e,immunodeficiency, HIV infection, s ys temic lupuserythematosus, diabetes mellitus and those on longterm aspirin therapy. Influenza vaccine is alsorecommended to be given for severe cases of asthmawho need oral corticosteroids frequently.

30

Combination Vaccines

A combination vaccine consists of two or more separateimmunogens that have been physically combined in asingle preparation. These immunogens may pertain tothe many antigens/ serotypes of the given pathogen(e.g. poliovirus vaccines) or of multiple pathogens (e.g.DTP vaccine). This concept differs from that ofsimultaneous vaccines, which, although administeredconcurrently, are physically separate. The combining ofmultiple related o r unrelated antigens into a singlevaccine is not a new concept. The first combinationvaccine was trivalent influenza vaccine, which wasdeveloped as far back as 1945. This was followed byhexavalent pneumococcal vaccine in 1947 and DTPvaccine in 1948. Combination vaccines in common useinclude diphtheria and tetanus toxoid, available alone(DT, dT) or with pertussis vaccine (DTP); inactivated(IPV) or live oral (OPV) trivalent polio vaccine andMMR vaccine.

The number of vaccines in the immunization scheduleis increasing every year with the result that theseschedules are getting increasingly more complex. Manyparents opt for one single injection of combinationvaccines at a given visit, rather than getting a largenumber of simultaneous injections. Use of combinationvaccines is also likely to result in logistic advantages -reduced burden on the cold chain and reduced storagerequirements and syringes/needles apart from easierrecord keeping. A number of combination vaccines arenow available in the Indian market. The IAP COIendorses the use of combination vaccines, but with thefollowing cautionary statements:

• The manufacturer's recommendations shouldbe adhered to strictly

• “Mixing" of vaccines in the same syringe (priorto injection) should not be done as far aspossible, unless specifically recommended bythe manufacturer; in the latter case themanufacturer's instructions should be followedstrictly.

• Combination vaccines should not be viewed asbeing more effective than vaccines givenseparately.

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

31

Day of Vaccination D0 D3 D7 D14 D28 D90

Thai Red Cross Regime 2 2 2 0 1 1

Updated TRC Regime 2 2 2 0 2 0

Rabies Vaccines

The disease is caused by a single stranded RNA virusbelonging to the family Rhabdoviridae. It is almostalways fatal. Rab ies is caused by the bite of a rabidanimal, which is usually a dog in our country.Scratches or licks on mucous membranes by affectedanimals have also been known to transmit the virus.The incubation period averages 4-6 weeks but can bevery variable and may range from five days to morethan one year. Rabies is endemic in our country - Indiaaccounts for almost 50% of mortality in the world

There are two types of vaccines available in India

Modern tissue culture vaccines (MTCV)

• Purified Chick Embryo Cell (PCEC) vaccine -1 ml per dose.

• Human Diploid Cell Vaccine (HDCV) - 1 mlper dose.

• Purified Vero Cell Vaccine (PVRV) - 0.5 mlper dose.

• Purified Duck Embryo Vaccine (PDEV) - 1 mlper dose.

All tissue culture vaccines have almost equal efficacyand any one of these can be used.

Nerve tissue vaccine

This is no longer recommended because of its poorefficacy and life threatening adverse effects in the formof neuroparalytic reactions.

Post exposure prophylaxis

In order to remove as much of the rabies virus aspossible, immediately cleanse the wound with soap andflush thoroughly under running water for 10 minutes .Then treat with 70% alcohol or tincture iodine orpovidone iodine. Rabies immunoglobulin (RIG) shouldbe infiltrated in and around the wound in case of all

severe b ites or bites in the upper extremities, trunk,head and face (wound category 3). Intramuscularinjection of RIG is not recommended. The dose ofhuman rabies immunoglobulin (HRIG) is 20 U/kgwhile that of equine rabies immunoglobulin (ERIG) is40 U/kg. Skin testing is recommended before usingERIG but is not necessary when using HRIG. Anysuturing of wound should be avoided. When suturing isunavoidab le for purpose of hemostasis, it must beinsured that RIG has been infiltrated in the wound priorto suturing.

Rabies vaccine is administered intramuscularly inanterolateral thigh on days 0, 3, 7, 14 and 30 as per theEssen protocol, with day '0' being the day ofcommencement of vaccination. A sixth dose on day 90is optional and may be offered to patients with severedebility or those who are immunosuppressed. Childrenare given the same dose as adults. Rabies vaccineshould never be injected in the gluteal region.

Several other schedules of rabies vaccination have beenproposed. These include the 2-1-1 intramuscularschedule (Zagreb schedule) - two IM doses on day 1,one IM dose on day 7 and one IM dose on day 21; the2-2-2-1-1 intradermal schedule (Thai Red CrossTRC-ID schedule) in which two ID doses are given ondays 1, 3 and 7, followed by one ID dose on days 30and 90 - ID dose is 1/5th the IM dos e; the 8-4-1-1intradermal schedule (Oxford schedule) - 0.1 ml ofPCEC vaccine is given ID at eight sites on day 0, atfour sites on day 7 and at one site only on days 30 and90. The intradermal schedules have the obviousadvantage of being inexpensive and have been usedsuccessfully in Thailand, Philippines and Sri Lanka.

Based on the recommendations of the expert group aswell as WHO, the Drug Controller General of India(DCGI) has recently decided to allow ID routeadministration o f tissue culture based anti rabiesvaccine fo r post exposure prophylaxis in a phasedmanner. The following schedules as recommended by

32

ICMR are permitted in the 1st phase (Table below)

Vaccines recommended in the first phase of ID routeadministration are purified verocell rabies vaccine(Senofi Pasteur) and purified chick embryo cell vaccine(Chiron Behring). The unit dose of 0.1ml for ID shouldhave at leas t 0.25 units. The criteria for selection ofAntirabies centre for ID use are

• Attendance of minimum 50 patient per day forpost exposure prophylaxis

• Have adequately trained staff to give IDinoculation

• Can maintain cold chain and ensure adequate supply of disposable syringes and needles.

This ID administration is not recommended inindividual practice. Also it does not make economicsense to practice it for individual cases.

Pre-exposure prophylaxis

Pre-exposure prophylaxis became a reality only afterthe availability of MTCVs. This should be offered toind iv iduals in high risk occupations (e.g. veterinarysurgeons, wildlife workers, dog breeders, postmen).Any of the tissue culture vaccines can be given for thispurpose - three doses are given intramuscularly on days0, 7 and 28. A booster is given one year after primaryimmunization and every five years thereafter.

The vaccine is stored at 2-80C. Side-effects includelocal pain and induration.

For Re-Exposure after completed (and documented) preor post exposure prophylaxis two doses are given ondays 0 and 3. Antirabies antibody titers > 0.5 IU/ml areconsidered protective.

Rabies Immunoglobulin (RIG)

There are 2 types of RIG:

(1) Human rabies immunoglobulin (HRIG - dos e is 20U/kg body weight)

(2) Equine rab ies immunoglobulin (ERIG - dose is 40U/kg body weight).

RIG is indicated in all cases of category three woundswhere it should be infiltrated thoroughly into andaround the wound. The remaining part if any is to beinjected IM into the deltoid region or anterolateralaspect of thigh away from the site o f vaccineadministration to avoid vaccine neutralization. Itcontains specific an t irabies antibodies that neutralizethe rabies virus and provide passive protection. In caseRIG dos e (quantity) is insufficient for adequateinfiltration of extensive or multiple wound, it may bediluted with equal volume of normal saline so that allthe wounds can be thoroughly infiltrated.

If RIG could not be given when antirabies vaccinationwas began , it should be administered as early aspossible but no later than the seventh day after the firstdose of vaccine was given. From the eight day onwards,RIG is not indicated since an antibody response to thevaccine is presumed to have occurred.

HRIG is a liquid or freeze-dried preparation containingimmunoglobulins (mainly IgG) and is obtained fromthe p las ma of donors immunized against. In case ofERIG, skin testing is recommended prior to use.

Adverse reactions: Tenderness/stiffness at theinjection site, low grade fever; sensitization may occurafter repeated injections.

33

CategoryType of contact with suspectedor confirmed domestic or wildanimals* or animalunavailable for observation

Recommended treatment

I Touching or feeding of animals,licks on intact skin

None if reliable case history isavailable

II Nibbling of uncovered skin,minor scratches or abrasionswithout bleeding, licks onbroken skin

Administer vaccine immediatelyStop treatment if animal remains healthy throughout anobservation period of 10 days, or,if the animal is euthanised andfound to be negative for rabies byappropriate laboratory technique

III Single or multiple transdermalbites or scratches, contaminationof mucous membrane with saliva(i.e., licks)

Administer rabies immunoglobulins and vaccineimmediately Stop treatment ifanimal remains healthythroughout an observation periodof 10 days, or, if the animal iseuthanised and found to benegative for rabies byappropriate laboratory technique

WHO Recommendations for Management of Animal Bites

34

Age Vaccine

Birth BCG, OPV0, Hepatitis B1

6 weeks DTPw1 / DTPa1, OPV1, Hepatitis B2, Hib1

10 weeks DTPw2 / DTPa2, OPV2, Hib2

14 weeks DTPw3 / DTPa3, OPV3, Hepatitis B3*, Hib3

9 months Measles

15- 18 months DTPw B1 / DTPa B1, OPV B1 , Hib B1, MMR

2 years Typhoid+

5 years DTPw B2 / DTPa B2, OPV B2

10 years Td# / TT

16 years 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 Varicella vaccine#

More than 18 months Hepatitis A vaccine+

More than 6 weeks Pneumococcal conjugate vaccine*

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

IAP Immunization Time Table

35

It should be noted that the IAP ImmunizationTime-Table is, in effect, the 'Best IndividualPractices' schedule for a given child and may besomewhat different from the National ImmunizationSchedule. This is because of the fact that the formeris meant to be used for an individual, rather than forthe pediatric community as public health measure atlarge The two schedules are, however, not in conflictwith each other. Also, as pediatricians we must beconscious of the fact that the immunization needs ofchildren in a country are quite dynamic - a vaccinewhich may not be considered important today maybecome necessary in future as more informationabout the epidemiology of the disease becomesavailable. Further, in developing countriesaffordability of the vaccines is a critical issue and anydecision on incorporation of a new vaccine in theimmunization schedule has to take this fact intoconsideration. The IAP COI has based itsrecommendations based on the best availableevidence at present. It is heartening to note that someof the recommendations of the IAP COI in the pasthave been instrumental in changing governmentalpolicies and also the immunization schedules beingfollowed by some states.

Notes on the Time Table

1. The IAP endorses the continued use of wholecell pertussis vaccine because of its provenefficacy and safety. Acellular pertussis vaccinesmay undoubtedly have fewer side-effects (likefever, local reactions at injection site andirritability), but this minor advantage does notjustify the inordinate cost involved in theroutine use of this vaccine.

2. If the mother is known to be HBsAg negative,

HB vaccine can be given along with DTP at 6,10, 14 weeks/ 6 months. If the mother's HBsAgstatus is not known, it is advisable to startvaccination soon after birth to prevent perinataltransmission of the disease. If the mother isHBsAg positive (and especially HBeAgpositive), the baby should be given Hepatitis BImmune Globulin (HBIG) within 24 hours ofbirth, along with HB vaccine.

3. For Non EPI and Newer Vaccines, Varicella,Hepatitis A and Congujate Pneumococcalvaccines should be offered only after one to onediscussion with parents. Also refer to theindividual vaccines notes for recommendations.

4. Combination vaccines can be used to decreasethe number of pricks being given to the babyand to decrease the number of clinic visits. Themanufacture's instructions should be followedstrictly whenever "mixing" vaccines in thesame syringe prior to injection.

5. At present, the only typhoid vaccine availablein our country is the Vi Polysaccharide vaccine.Revaccination may be carried out every 3-4years.

6. Under special circumstances (e.g. epidemics),measles vaccine may be given earlier than 9months followed by MMR at 12-15 months.

7. During pregnancy, the interval between the twodoses of TT should be at least one month.

8. Continue using OPV till we eradicate polio inour country. IPV can be used additionally forindividual protection.

9. OPV must be given to children < 5 years of ageat the time of each supplementaryimmunization activity.

36

Immunization in Special Circumstances

Immunization in preterm infants

In general, all vaccines may be administered as perschedule according to the choronological ageirrespective of birth weight or period of gestation.

Very low birth weight / preterm babies can be givenimmunizations after initial stabilization.

Children receiving corticosteroids

Children receiving oral corticosteroids in high doses(e.g. Prednisolone 1-2 mg/kg/day) for more than 14days should not receive live virus vaccines until thesteroid has been discontinued for at least one month.

Killed vaccines are safe but may be incompletelyeffective in such situations. Patients on topical orinhaled steroid therapy should not be denied their ageappropriate vaccines.

Children awaiting splenectomy

Children with loss of splenic function are at high riskof serious infections with encapsulated organisms. Ifsurgical splenectomy is being planned, immunization

with pnueumococcal, Hib and meninggococcalvaccines should be initiated a few weeks prior tosplenectomy.

Vaccination in children in children with HIV infection

Children infected by HIV are particularly vulnerableto severe, recurrent, or unusual infections by vaccinepreventable pathogens. It must be emphasized thatroutine immunizations seem to be generally safe insuch children, but the immune response followingvaccination would depend upon the degree ofimmunodeficiency at that point of time. Immune

attrition associated with viral replication mayparticularly interfere with memory responses.Consideration should be given to readministeringchildhood immunizations to such children when theirimmune status has improved following anti-retroviraltherapy.

37

Vaccine Asymptomatic HIV Infection Symptomatic HIV Infection

BCG Yes (at birth) No

DTPw / DTPa Yes (at 6, 10, 14 weeks) Yes

OPV Yes (at 6, 10, 14 weeks) Yes / IPV

Measles Yes (at 6 and 9 weeks) Yes

MMR Yes Yes (CD4% >15%)

Hepatitis B Yes (as for uninfectedchildren)

Yes (double each dose)

Hib Yes Yes

Typhoid Vi Yes Yes

Pneumococcal Yes Yes

Influenza Yes ( > 6 months of age) Yes

Varicella Yes (2 doses at 6-8 weeksinterval)

Yes (2 doses at 6-8 weeksinterval, CD4% > 15%)

Hepatitis A Yes Yes

IAP Recommendations for Immunization of HIV Infected Children

Vaccination schedule for children not immunized in time

It may be noted that vaccination catch-up regimensmay be difficult to construct for older children andmust necessarily de individualized. The following

table depicts the suggested schedule which may befollowed in cases of children who have not beenoffered any immunization.

38

Age Less than 7 years More than 7 years

First visiit BCG*, OPV*, DTPw / DTPa,HB

Td, HB

Second visit (one month later) OPV*, DTPw / DTPa, HB Td, HB

Third visit (one month later) Measles / MMR, Typhoid MMR, Typhoid

Fourth visit (6 months after firstvisit)

DTPw / DTPa, HB HB

Every 3 years Typhoid Typhoid

Vaccination Schedule for an Unimmunized Child

* 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 onlyafter 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 the othervaccines) if compliance is likely to be a problem. However it is preferable to give it at a later visit if pat ientcompliance is not a problem.

Lapsed immunization

There is no need to restart a vaccine series regardlessof the time that has elapsed between individual doses.Immunizations should be given at the next visit as ifthe usual interval had elapsed and the immunization

scheduled should be completed at the next availableopportunity. In case of unknown or uncertainimmunization status, however, it is appropriate tostart the schedule as for an unimmunized child.

Missed opportunity for immunization

This is defined as a situation when a child visits ahealth care facility and is not immunized. Minorillness (e.g. fever, diarrhea, respiratory infections)and malnutrition should not be construed as

contradictions to immunization. Any dose not givenat the recommended age should be given at anysubsequent visit when indicated and feasible.

39

Vaccine Age

Td Booster at 10 and 16 years

MMR vaccine One dose if not given earlier

Hepatitis B 3 doses (20 mcg) 0, 1, and 6 months, if not given earlier

Typhoid vaccine Vi Polysaccharide vaccine every 3 years

Varicella vaccine* One dose up to 13 years and 2 doses (at 4 to 8 weeks interval) after 13years of age if not given

earlier.

Hepatitis A vaccine* Two doses 0 and 6 months if not given earlier

Simultaneous administration of multiple vaccines

Both killed and live vaccine can be administeredsimultaneously without decreasing the efficacy of the

individual vaccines. However, prudence demandsthat 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 trationof certain vaccines which may not have been indicated earlier. However, this should always be done aftercareful counseling.

Vaccination Schedule in Adolescents

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

Immunization for travelers

The risk of travelers contracting infectious d is easedepends on the region/country to be visited, duration oftrip and nature and conditions of t ravel. Uniformrecommendations are not possible because theepidemiology o f d is eas es d iffers in variousgeographical areas. The physician should try andupdate routine immunizat ion and also providedestination specific immunizations. For instance,vaccines commonly recommended for Indian travelers

include yellow fever vaccine for those intending to goto destinations in South America and SubsaharanAfrica (except in infants les s than 9 months andpregnant ladies) and meningococcal vaccine for thoseintending to go on a Haj pilgrimage. Similarly, visitorscoming to India from Western Europe/North Americaare usually advised vaccination against typhoid andHepatitis A, especially if the stay is likely to beprolonged.

40

Vaccination of children with bleeding disorders or those receiving anticoagulants

Needles less than 23G should be used for injection andthe 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 immunizationand is, therefore, not a con traindication for anyvaccine. Neither inactivated nor live vaccinesadministered to a lactating woman affects the safety ofbreas t -feeding for infants. There is no risk of

transmission of Hepatitis B virus from an HBsAgcarrier mother to her baby through breast milk if HBvaccination is started at birth.

41

Injection Safety Issues

Injection s afety is an important issue for anyimmunization program Wash or disinfect hands prio rto preparing injection material. Avoid giving injectionsif skin is infected or compromised by a local infection(such as a skin lesion or weeping dermatitis ). Evensmall cuts should be covered. Always use a sterilesyringe and needle for each injection and to reconstituteeach unit of medication. If single use syringes andneedles are not available, use equipment designed forsteam sterilization. Document the quality of thes terilizat ion process using time, Steam andTemperature (TST) spot indicators.

Prepare each injection in a clean designated area whereblood or body fluid contamination is unlikely. Cleanskin prior to injection with a disinfectant and wait forit to dry. Do not use cotton balls stored wet in amulti-use container. If multi-dose vials are used, alwayspierce the septum with a sterile needle but do not leavethe needle in place in the stopper of the vial. If using anampoule that requires a metal file to open, protectfingers with a small gauze pad when opening theampoule. Anticipate and take measures to preventsudden patient movement during and after injection.

All in t ramuscular injections in children should begiven only on the anterolateral aspect of thigh at thejunction o f the middle and lower third - the gluteal

region must be avoided as sciatic nerve injury is a realrisk especially in neonates, malnourished andstruggling children. It is not often appreciated that thenerve is within the reach of the standard needle evenwhen the injection is given in the upper outer quadrantof the buttock. It is also know that the immuneresponse 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 con tained in a 'sharps'box. The needle must not be recapped or manuallymutilated after use. To prevent reuse, the syringe maybe cut and the needle defanged using a syringe/needledestroyer. Syringes and needles should be disposed ofcarefully in leak-proof and puncture proof containersand needles and waste management should be givendue attention.

Auto-disable (AD) syringes are single-use, self-lockingsyringes designed in such a way that these are renderedunusable after single use. These are made fromclean-burning plastics and emit very low levels of toxicfumes. These are now being promoted for rou tineimmunization and may well become the norm in yearsto come. The Government of India has decided to useAD syringes in Immunization program.

42

Adverse Reactions Following Immunization

Adverse reactions following immunization can bebroadly classified as local and systemic. Although suchoccurrences are uncommon, every physician who isdealing with immunization should anticipate and beprepared to manage these events whenever they occurIt is mandatory for every immunization clinic to havean emergency kit for resuscitation.

Local reactions are especially common after theadsorbed vaccines (e.g. DTPw/DT) - no treatment otherthan symptomatic management is necessary. Whole cellkilled typhoid vaccines are also ass ociated withparticularly significant local reactions. Ulcer formationafter BCG vaccination is normal and no intervention isusually required - the ulcers may sometimes take manyweeks to heal.

Anaphylactic reactions are distinctly unusual but havebeen reported following Measles, MMR, Hib andHepatitis 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 Poliovaccines) or thiomerosal (e.g. DTP, TT vaccines).

It should be noted that it might often be difficult toprove a definite cause-effect relationship between avaccine and a given complication. It may be prudentnot to ascribe all adverse reactions to a vaccine, whichhas been given in the recent past before ascertaining allfacts about the case. Many adverse effects may resultfrom inappropriate vaccination technique or storage ofthe product.

Each member of the Academy is requested to reportany case of suspected adverse reaction followingimmunization to IAP committee on immunizationthrough IAP office.

43

AdverseReaction

Vaccine Symptoms Management

Anaphylaxis Any vaccine Within minutes

• Acute decompensation of circulatoryshock

• Hypovolemic shock• Laryngospasm /edema• Acute respiratory distress

• Adrenaline• Cardiopulmonary

resuscitation• IV volume expanders• Hysrocortisone• Dopamine/

Dobutamine

Hy p oten s iv ehyporesponsiveepisode

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 withTriclofos 50 mg/ Kg

• Paracetamol 10-15mg/ Kg per dose

• Feeding advice

T o xic ShockSyndrome

Measles vaccinecontamination

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

• IV fluids• Antimicrobials

cloxacillin 50-100mg? Kg per day

• Steroids• Supportive therapy

Lymphadenitis BCG • Within 2 to 6 months• Firm to soft axillary lymphadenitis

1.5- 3 cms size

• If firm, no treatment• If soft or fluctuant,

aspiration/ surgicalexcision

• ATT not indicated

B a c t e r i a labscess

Any vaccine After days to weeks

fluctuant to firm

• Antibiotics• Antipyretics• Drainage

Modera te tos evere lo c alreaction

Any vaccine Non fluctuant swelling / redness 3-10cms in size at the injection site

Paracetamol

Seizures withfever (rare)

DTP

Measles

Always generalised • Anticonvulsants• IV fluids (if need be)

Adverse Reactions Following Immunization

44

Vaccines damaged by freezing Vaccines that can be frozen without harm

DTP OPV

DT Measles/ MMR

TT BCG (before reconstitution)

Hepatitis B

Hib

Td

Typhoid (whole cell killed vaccine)

Hepatitis A

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, storingand distributing vaccines in a potent state at therecommended temperature from the point ofmanufacture to the point of use. In es s ence, it isconsidered to play a crucial role in the success of anyimmunization program However potent a vaccine maybe, if the cold chain is not maintained from the sourceof vaccine manufacture to the place of vaccination, thevaccine efficacy will suffer. Vaccine potency once lostcannot be restored. The essential components of a coldchain include:

1. Personnel responsible for vaccine distribution2. Appropriate equipment to store and transport

vaccines 3. Appropriate transport facilities4. Maintenance of equipment5. 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

45

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

Equipment

a) Walk- in freezers (WIF): are established in allthe states ; are used for bulk storage of OPV andmeasles vaccines and for preparing frozen ice packs atstate s tores; maintain a temperature of -200C and areavailable in 2 sizes - 16.5 & 32 CU Mt; freezers areprovided with two identical cooling units and standbygenerator sets.

b) Walk in cold rooms (WIC): are used fo r bulkstorage of vaccines at the manufacturer, state andregional levels which store vaccines for abou t 4-5districts; maintain a temperature recorders and alarmsystems.

c) Deep freezers: are used for storage of OPV/Measles//MMR vaccines and preparation of ice-packs;DTP/DT/TT/Hepatitis B vaccines should not be storedin deep freezers; have a top opening lid and areavailab le in 2 models -140 & 300 liters; cabinettemperature is maintained between -18 to -200C; incase of power failure these freezers can maintaincabinet temperature for 18 - 26 hours, if no t opened.All districts have been provided 2-5 large freezerswhereas most of the PHCs have one small deep freezer.About 25-30 ice packs (8-10 kg ice) and 35-40 icepacks (12-14 kg ice) can be frozen in one day in 140Land 300L deep freezers respectively.

d) Ice lined refrigerators (ILR): may have eitherice tubes or ice packs filled with water upto 90% oftheir volumes; on freezing there is formation of aninner lining of ice; this enables the temperature to staywithin a safe range even when there is electricitysupply for only 8-12 hours in a day; are available in 2sizes (140 & 300 liters) - the former is supplied todistrict headquarters while the latter is supplied toPHCs; in top opening ILRs the temperatures is least atthe bottoms - th is should be used for storingOPV/Measles/MMR; DTP / DT/ TT/ Hepatitis Bvaccines should be kept near the top in a s eparatecontainer to avoid accidental freezing. The Electroluxtype of ILR (Model TCW 1151) can also be used as afreezer by a changeover switch inside the compressor

chamber in situations where OPV is to be stored forlong duration (at -200C) or there is increased demandof ice-packs.

e) Domestic refrigerators: meant for vaccinestorage should not be used for any other purpose;should be kept away from heat and direct sun light;should have ice-packs fo r freezer compartment andwater bottles in the shelves; these help in maintaininglow temperatures in case of power failure; no vaccineshould be stored in the baffle tray or the door shelves;periodic defrosting is necessary; this is generally donewhenever the layer of ice exceeds 5-6 mms. The usualtemperature within the main compartment of adomestic refrigerator is between 4-100C while that ofthe 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

f) Cold boxes or isothermic boxes: are wellinsulated, solid and thermetically (air tight) sealedboxes packed with frozen ice packs at the bottom, sidesand at the top; available in 2 sizes - 5 & 20L; these aresupplied to all peripheral centers and are used fortransportation of large amounts of vaccines to outreachfacilities - 1500 vaccine doses can be carried in a 5Lbox and 6000 doses in a 20L box; vaccines should beplaced in cartons or polythene bags and then placed indirect contact with frozen ice packs; in emergencysituations, can also be used to store vaccines and frozenice packs for up to 5 days; the hold over time is morethan 90 hours for a 5L, and 6 days for a 20L, cold boxat 430C ambient temperature, if the cold box is notopened at all. In general a cold box of 5L canaccommodate one month's supply of a PHC (30,000population), while a cold box of 20L capacity canaccommodate one month's supply for a CHC (100,000population).

Cold boxes can also be used in health centers forstorage of vaccines and ice packs in case of electricityfailure or breakdown of other cold chain equipment. Icepacks should be made from tap water - water should befilled in the icepack up to the level marked.

g) Vaccine carriers: are s maller versions of cold

46

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 temperaturesfor 2 days if the packs are frozen and lid is kept tightlyclosed. DTP/DT/TT/Hepatitis B vials should bewrapped in plastic to avoid direct contact with ice.

h) Day carriers: are smaller versions of vaccinecarriers and are used to carry still small quantities ofvaccines (e.g. 6-8 vials) of vaccine; have provision foronly 2 frozen ice-packs; can be used to store vaccinesfor 6-8 hours; vaccines in day carrier should be issuedon the day of immunization only; presently, the use ofday carriers is not encouraged.

i) Ice packs: are made of polyethylene and weighapproximately 80 gm; the dimensions are 163 x 90 x33 mms; contain 0.36L of water; never add salt to thewater. Ice packs are used to line the sides of cold boxes,vaccine carriers and day carriers.

Storage of vaccines

All vaccines are safe at temperatures between 2-80C forat least 6 months. If a freezer is available, it should beused for storage of OPV and Measles/MMR vaccines.The latter vaccines should be kept frozen at -200Cwhen stored fo r the long term - at this temperaturethese vaccines have a shelf life of 2 years. Even thesevaccines, however, can be kept at 2-80C for shorterperiods e.g. 6- 12 months for OPV and 18-24 monthsfor measles.

DTP / DT / TT / Typhoid (T-series vaccines), HB andHep A vaccines should never be frozen. The freezingpoint for adsorbed DTP vaccine is between -5 to 10oC.Freezing time depends on the number of doses in thevial and the temperature. It takes about 110 to 130minutes at -10oC. The "Shake Test" can be used todetermine if these vaccine has been frozen at any time:shake the vial so that the sediments, if any, arecompletely mixed ; wait for 15 minutes; if the vaccineis not uniformly mixed or the sediments/ flocculationsare still found settled at the bottom, the vaccine is likelyto have been frozen at some time. Such vials should bediscarded.

At a temperature of 2-8oC, DTP/DT/TT/ HepatitisB/Hepatitis A/Varicella and Hib vaccines have a shelf

life of 24 months. Diluents should be stored at 2-8oC -these should not be us ed beyond 4 hours. Vaccinesshould be transported on ly in cold boxes or vaccinecarriers - vacuum flasks should never be used for thispurpose.

It is recommended that vaccines should not be storedfor more than 3 months at the district level and formore than 1 month at the level of primary healthcenter. No vaccines should ever be stored at thesub-centers. Expiry dates of vials shou ld be checkedonce a week. While storing vaccines fo llow the"First-In-First-Out (FIFO)" and "First to ExpireFirst-Out (FEFO)" rules.

During shipment and transportat ion, temperature andtime sensitive monitor marks are used to check the coldchain. Dial thermometers are used to monitor thetemperature in refrigerators/ice-lined refrigerators(ILRs) and are kept in every unit. Alcohol stemthermometers are much more sensitive and accuratethan dial thermometers and can record temperaturesfrom - 50oC to +50oC. These can be used for deepfreezers and ILRs . Temperature monitoring should bedone twice a day in the case of ILRs and deep freezerand once a day in the case of walk-in coolers, wherevaccines are stored in bulk for longer periods. A breakin the cold chain is indicated if temperature rises above+8oC or falls below +2oC in the case of ILR and otherrefrigerators and above -180C in the case of deepfreezers.

The Vaccine Vial Monitor

(VVM) is a time and temperature sensitive coloredlabel that provides an indication of the cumulative heatto which the vial has been exposed. VVMs were firstintroduced on OPV vials supplied to UNICEF andWHO in 1996. The VVM warns the end user whenexposure to heat is likely to have degraded the vaccinebeyond an acceptable level. It is used especially fortemperatures monitoring of OPV, which is the mostthermo lab ile of all vaccines. If the VVM indicatesproper storage of OPV in a given center, it can bepresumed that other vaccines would also be potent.VVMs increas e the flexibility in handling of vaccinesin the field.

Interpretation of the colour change of VVM is asfollows:

47

1. Inner square is lighter than outer circle: If theexpiry date has not passed, vaccine can be used.

2. Inner square matches colour of outer circle or isdarker than outer circle: vaccine should be discarded.

The VVM provides in formation about the heatexposure of the vial over a period of time - the changein colour is gradual but irreversible. However there maybe other factors which can also affect the potency ofvaccine (e.g. storage beyond the expiry date) and thesemay not be reflected in the VVM. Loss of potencydepends upon the degree of temperature elevation aswell as duration of exposure. Tetanus toxoid is the leastheat sensitive vaccine.

The manufacturer's instructions regarding shelf life ofa given vaccine must be rigorously followed. Measlesvaccine loses viability quickly if kept at temperaturesabove 400C. Reconstituted measles vaccine should bekept protected from heat and light during animmunization session and the left-over discarded afterthe session. OPV would lose viability if kept at 22-25oCfor more than a day . Opened vials of OPV, however,may be used in subsequent sessions at a given healthfacility if it has been p reserved at 2-8oC. OPV vialsused in the field setting or an outreach facility o rduring a pulse immunization session must be discardedat the end of the day. Vaccine vials (single/multi-dose)should be gently shaken before use to ensure that thecon ten ts are clear and not granular or flaky. Vaccinevials should not be taken out to the field more than 3times - after that these are best discarded irrespective ofwhether these have been opened or not.

When using multidose vials it may be adv isable toschedule all immunizations to a fixed day every week.This reduces wastage o f vaccine and minimizes therisks of contamination/loss of potency. One can sendOPV vials for viab ility test with the help of the localhealth authorities. OPV has been taken as an indicatorof quality of cold chain as th is vaccine is more heatlabile than other vaccines and is easier to test. The testtakes only 7 days. Open vials can also be sen t and ,ideally, 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. Testingfacilities are available at the Central Research Institute

(Kasauli), National Institute of Communicable Disease(Delhi), Enterovirus Research Centre (Mumbai),School of Trop ical Medicine (Kolkata) and othercenters. Samples from different immunization sitesshould be collected in vaccine/day carriers with fullyfrozen ice packs and transported to the headquarters byobs erv ing "reverse cold chain" If delays intransportation are anticipated, the samples should bekept in a deep freezer/ILR before these are sent to thetesting laboratory. The WHO recommends that incountries where VVM is being used for monitoringcold chain, OPV sample testing is not required.Recen tly Government of India is following thisrecommendation.

The Future

Advances in sugar-glass drying technology now allowmanufacturing of vaccines which can be stored andtrans ported at tropical room temperatures. Trehalose,a disaccharide, has long term stabilizing ability and canbe effectively used for this purpose. Dried measlesvaccine stabilized with trehalose has been found viableafter 2 months at room temperature while DTPa canwithstand a temperature of 600C for 12 weeks . Oralpolio vaccine, however, has failed to 'dry' successfully.If all vaccines can be successfully 'dried', there will nolonger be a need for maintenance of co ld chain - thiswill also result in substantial cost savings.

Supply of vaccines

All UIP vaccines are available free of cost to allpractitioner from local health authorities. One isallowed to collect profes s ional fees for the servicesrendered. However, the utilization report should besubmitted periodically.

When buying from market individual practitionersshould ensure that vaccines are procured directly froma stockist with appropriate cold chain facilities, ratherthan off the shelf from a nearby retailer. Vaccum flasksshould never be used for an outreach activity.

48

Vaccine Temperature in oC

2- 8 22- 25 35- 37 > 37

D T / T T ( a sm o n o v a l e n tvaccines or ascomponents ofcombined vaccine)

3-7 years Many months At least 6 weeks 2 weeks at 45OC

Pertussis vaccine 18- 24 months ,but there is asteady decrease inpotency

Variable, but doesno t e xceed 2weeks

Variable 10% lo s s o fpotency per day

Freeze dried BCGvaccine

1 year 2 0 - 3 0 % o fviability after 3months

Variable Unstable

Re c o n s t i t u te dBCG vaccine

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 ie dmeasles vaccine

2 years 1 month 1 week 5 0 % l o s s o fviab ility in 2-3days at 41OC

Rec o n s t i t u t e dmeasles vaccine

Should be usedwithin 4 hours

OPV 6- 12 months 5 0 % l o s s o fviability after 3weeks

Very uns tab le.Significant loss ofviability within 1-3 days

Very un s tab le.Significant loss ofviability within 1day at 41OC

Inactivated PolioVaccine (IPV)

1- 4 years D e c l i n e o fD-antigen contentfor Type I after 20days

Variable P r e c i s e d a t alacking

Hepatitis B 2- 4 years Many months Many weeks St a b le fo r manydays at 45OC

Rabies HDCV 3- 5 years 3 months 4 weeks No dataavailable

Stability of Vaccines at Different Temperatures

49

Surveillance for Vaccine Preventable Disease (VPDS)

Surveillance is a French word, which means "watchingwith attention, suspicion and authority" Diseasesurveillance under the Universal ImmunizationProgram refers to the collection, analysis and use ofdata on VPD to improve action to p revent thesediseases As higher levels of vaccination coverage areachieved, the role of disease surveillance becomesincreas ingly important to document the impact of agiven immunization program. A sensitive surveillancesystem is required to direct program resources to areasof greatest need and to ident ify areas for special ormore intensive interventions. A good surveillancesystem can detect program failures and impendingoutbreaks and can also be used to assess vaccineefficacy.

Any sat isfactory national immunization programshould result in gradual decline of the VPDs. All casesof VPDs should be reported to the local health authoritywithin 48-72 hours for taking prompt action at the fieldlevel.

The WHO had declared 3 district objectives for the year2000 A.D.

1) Polio eradication

2) Neonatal tetanus elimination

3) Measles reduction

It is a pity that none of these targets have been met sofar. The revised target for certification of polioeradication and neonatal tetanus elimination is the year2007. The nomenclatu re used for control of the threediseases is rather specific because while it is possible toeradicate poliov irus from the planet, it may not befeasible to eradicate the tetanus bacilli, which areubiquitous. However, by immunizing all mothers withtetanus toxoid it is possible to at least eliminateneonatal tetanus. Similarly while it may be possible toeradicate measles in the future, at the present time onecan only hope to preven t measles mortality bypreventing measles in the vast majority of immunizedchildren.

Acute Flaccid Paralysis (AFP) surveillance is anessential component of polio eradication. A min imumAFP rate of 1/100,000 children below 15 years o f ageis required to ensure that adequate surveillance existsat the ground level. At present most of the parts of thecountry have excellent and adequate surveillance.Every case of AFP should be reported to local healthauthority.

50

Vaccination in Current Millenium

The future holds lot of promise as far as prevention ofdisease through vaccination is concerned. We are likelyto witness more refined vaccination techniques,improved antigens and safe vaccines.We are likely toget many new combo vaccines also. "Naked" DNAvaccines and administration of antigens through viralvectors/edible plants may completely revolutionizechildhood vaccination programs. Some vaccines whichmay soon become available for clin ical use are asfollows:

Bacterial vaccines

Enterotoxicogenic E. coli vaccine

Shigella vaccine

Cholera vaccine

Streptococcal vaccine for rheumatic fever

Helicobacter pylori vaccine

Viral Vaccines

Rotaviurs vaccine

Respiratory Syncitial Virus vaccine

Dengue fever vaccines

HIV vaccine

Hepatitis C vaccine

Protozoal vaccines

Malaria vaccine

Websites for additional information

The following websites may provide useful information-

www.who.int/vaccines; www.immunizationinfo.org;

www.vaccines .o rg ; www.inejc t ions afety .o rg ;www.vaccinealliance.org;

www.aap .o rg ; www.cdc.gov/nip; www.path.org;www.childrensvaccine.org

www.unicef.org

51

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 Academy of Pediatrics Committee onImmunization (IAP COI) conducted its deliberationsand reviewed its stand on various policies, guidelinesand recommendations pertaining to childhoodimmunization. As has been enunciated earlier,"policies" are the decisions taken by the Academy inrelation to the scientific principles and practice ofimmunization. "Policies" are expected to be pract icedby all members of Academy. 'Guidelines" relate to

those items which are outside the purview of policy,and for which guidance is necessary. Guidelines usuallypertain to newer vaccines or issue related to them."Recommendations" are, in general, what the academyin its role of advocacy on behalf of children, requestsother agencies, the Government of India or otherprofessional bodies.

IAP Policies on Immunization, 2006

On NTAGI

The IAP welcomes the establis hment of the NationalTechnical Advisory Group on Immunization (NTAGI)by the Government o f India. This followed a formalrecommendation from the IAP, given a couple of yearsago. The Secretary, Department of Family Welfare isthe Chairperson of the committee while the AssistantCommissioner, Immunization Program is its MemberSecretary. The IAP COI appreciates that the IAP isrepresented on this important committee by itsincumbent President and recommends that theChairperson/Convener of the IAP COI .should also beinvited as a member of this committee.

On Universal Immunization Program (UIP)

The IAP continues to endorse and reiterate its supportto the nat ional immunization schedule whilerecognizing the fact that much more needs to be donefor meeting the current immunization requirements ofthe children of our country. It is a fact that except forthe recent phased introduction in Hepatitis B vaccine in

a few districts, no new vaccine has been introduced inthe national program in the last 25 years. All vaccinesunder UIP shou ld continue to be available free ofcharge to all eligible children.

On Polio Eradication Goals and SIAs

The Academy fully supports the Government of Indiain the use o f oral polio vaccine (OPV) for the pulseimmunization program against polio. It is ourconsidered opinion that, in sp ite of some operationalhiccups, we must continue with this program and bringit to its logical conclusion, i.e. till wild polio virus iseradicated from our country. IAP advocates that somesteps are required to be taken to overcome the lasthurdles in achieving the goals of polio eradication asfast as possible. These include operationalization ofbirth dose of OPV all over the country, at least in areaswith wild polio virus transmission continuing;strengthening of routine immunization; better qualityof SIAs and role of IPV in difficult areas where wildpolio virus circulation is still continuing.

52

Inactivted Polio Vaccine (IPV)

(Role of IPV vis a vis OPV)

OPV is cheaper & being given orally and so moreacceptable. However it is less efficacious in tropicalcountry like India due to in terference with otherenteroviruses and other unknown factors It also needsstrict co ld chain maintenance. Where as IPV is moreefficacious, less thermolab ile and has no chance ofinducing vaccine induced paralysis. Of late IPV hasbeen shown to induce local gu t immunity as well asherd effect. Coverage of children less than 2 years inhigh risk areas with 2-3 doses of IPV can be anadditional tool to eradicate polio from our country. Thecost and availability of vaccine can be a problem.

Post-polio eradication scene and polio immunization:IAP believes that it will be unsafe and unethical tocontinue to use OPV in post-po lio eradication era.Following concepts should be kept in mind whiledeciding India specific guidelines for post-polioeradication immunization..

• It will be unethical and unsafe to continue touse OPV after zero wild polio case and zerotransmission status is achieved due to risk ofVAPP and cVDPV following OPV.

• It will be unwise to discontinue use of polioimmunization altogether after zero polio statusis achieved due to fear of cVDPV, iVDPV. Pastexperience from some countries has shown thatcountries which have eradicated wild poliovirus and have slackened in their routine polioimmunization programs have experiencedcVDPV outbreaks. These outbreaks of cVDPVwere curtailed by strengthening routineimmunization and giving 2 or more rounds ofSIAs using OPV. However in post-polioeradication era, it will be unethical and unsafeto reintroduce OPV in such areas. It will forceus to depend on the stocks of WHO or any suchagency for OPV vaccine, should out-break ofwild polio or cVDPP occur. Hence India should

preempt the emergence of cVDPV and has tobecome self sufficient in stock-piling enoughpolio vaccine now to meet any such unforeseeneventuality in future.

• Looking at the above problems, IAPrecommends that India should switch over toIPV, preferably as IPV-DTP, in its routineimmunization program in post-polioeradication era. India should encourageindigenous manufacturer to produce enoughIPV so that it becomes affordable so that it willbe possible to switch to IPV in due course,looking at the huge requirement of the numberof doses.

Practitioner keen to use this vaccine may use thevaccine as 3 primary doses followed by one boosterdose with DTwP / DTaP. OPV must be given to thesechildren as birth dose and on the NIDs and SIAs.

On number of routine DTP/OPV doses

The IAP COI endorses the use of five dos es ofDTP/OPV at 6, 10 and 14 weeks and thereafter at15-18 months and 5 years respectively. An additionaldose of OPV is to be given at birth to all where possibleand one more additional dose along with measlesvaccine. It should be noted that we continue to endorsethe use of DTP (rather than DT as in the nationalprogram) and OPV at 5 years.

On Vaccines not covered in EPI

The IAP COI suggests that the UIP s hould besupplemented by the following vaccines: Hepatitis B(HB), HIB, MMR and typhoid. Td should replace TT at10 and 16 years. Parents, however, should be madeaware of the availability and need of these vaccines.Varicella and Hepatitis A vaccines are still notrecommended for routine use. Pneumococcal PCV-7,live attenuated SA-14-14-2 Japanese EncephalitisVaccines are the new vaccines which have becomeavailable in India. Tdap and Rota virus are the vaccineswhich are likely to be available in near future.

53

IAP COI stand on RECOMMENDED vaccines not covered under EPI

Hepatitis B vaccine

HB vaccine may be given in any of the followingschedules:

(i) Birth, 1 and 6 months

(ii) Birth, 6 and 14 weeks/6 months

(iii) 6, 10 and 14weeks/6 months

Immunologically 0 - 1 - 6 months schedule of hepatitisB immunization has been most widely used and provento be ideal. HB vaccination is now been integrated intothe existing immunization program (UIP) in India. Dueto operational issues at a national level one has to piggyback on the available contacts for routineimmunization, hence 0 - 6 - 14 wks schedule isrecommended. 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 preventchronic infection and development o f chronic liverdisease / hepatocellular carcinoma later in life. Anideal HB vaccine schedule should, therefore, addressvertical as well as horizontal modes of transmission ofthe virus.

If the mother is HBsAg positive (and especially HBeAgpositive), the baby should be given Hepatitis B ImmuneGlobulin (HBIG) as soon as possible after birth,preferably within 24 Hours of birth, along with HBvaccine. The injections should be given at two separatesites. If HBIG is not available (or is unaffordable), HBvaccine may be given at 0, 1 and 2 months with anadditional optional dose between 9-12 months.

Boosters of HB vaccine are no t necessary inimmunocompentent individuals. The vaccinationschedule need not be changed for preterm babies, in thecase of extremely preterm babies, however, vaccinationshould commence only after initial stabilization.

The IAP COI recommends universal immunization

against Hepatitis B.

MMR Vaccine

MMR should be promoted as a universal vaccine. Itshould be given at around 15-18 months of age and atleast 3 months after the measles vaccine. It should alsobe given to all adolescent girls and young women notpreviously immunized, as also to hospital staff likely tocome in con tact with pregnant mothers. There is noupper age limit for this vaccine.

Typhoid Vaccine

The IAP COI strongly recommends the use of typhoidvaccine for all children. Of the 3 types of vaccines (viz.Vi-polys acharide, whole cell inactivated and oralTy-21a), only the Vi-polysacharide vaccine is freelyavailable in our country at present. It is recommendedto be given after the age of 2 years followed byrevaccination every 3-5 years. The government shouldexplore the possibility of manufacturing this vaccine inthe public sector on large scale so that the costs arebrought down.

Hib Vaccine

Hib vaccine should be offered to all children and maybe given at 6, 10 and 14 weeks along with DTP. Abooster is given at 15-18 months. If vaccination iss tarted after 6 months of age, only two doses (at 4-8weeks interval) need be given as primary schedule witha booster at 15-18 months. If vaccination is startedbetween 12-15 months of age, only one dose need begiven, with a booster at around 18 months. After 15months of age only one dose of the vaccine needs to begiven- no boosters are required under suchcircumstances. The vaccine need not be given after 5years of age. Hib vaccine is also recommended for allhigh risk children, irrespect ive of age, prior tosplenectomy and also in patients with sickle celldisease. IAP COI strongly recommends GOI to include

54

this vaccine in UIP.

IAP COI stand on vaccines that are given after discussion with parents:

Hepatitis A Vaccine

Hepatitis A (HA) vaccine is not recommended foruniversal immunization in India at present. One has toemphasize the generally benign nature of and rarity ofcomplications with Hepatitis A infection in youngchildren. It may be offered to children from highsocio-economic strata of society after explaining thepros and cons to the parents on a one-to one "namedchild" basis. It may be prescribed to adolescents whohave not had viral hepatitis in past (or are known to beHAV-IgG negative) especially if they are leaving homefor studies in a residential school/college.

HA vaccine is indicated fo r all patients with chronicliver disease as well as household contacts of patientswith chronic liver disease as well as household contactsof patients with HA virus infection - in the latter casethe vaccine must be given within 10 days; it may,however, be not always effective under suchcircumstances if the contact has the same source ofinfection as the index patient. It may also be consideredin children attending crèches and day care centers andin travelers from abroad (e.g. non-resident Indians)visiting endemic areas.

It is given in a 2-dose schedule, 6 months apart afterthe age of 18 months The adult formulation should beused after the recommended cut-off age: 15 yearsaccording to one manufacturer and 18 years accordingto the other. The vaccine is given intramuscularly andthe protective efficacy is 94-100%. Boosters are notrecommended at present.

Live attenuated Hepatitis A Vaccine

The live attenuated Hepatitis A Vaccine has beenlicensed for use in China since 1992. The manufacturerclaims 92 to 100 percent seroconversion with single

dose administered by subcutaneous route. This vaccinehas recently been licensed for use in India. There isonly one Indian study conducted at Pune on thisvaccine showing 95% seroconversion. The vaccine hasnot been studied extensively outside China. Thisvaccine should be subjected to post marketingsurveillance for efficacy and adverse reactions in India.However, for 100% seroconversion second dose after 6months needs to be considered as recommended inChina.

Varicella Vaccine

The IAP COI opines that varicella vaccine is notrecommended for universal immunization in India atpresent. One has to emphasize the generally benignnature of and rarity of complications with, varicellain fection in young children. It may be offered tochildren after age o f 15 months from highsocio-economic strata of society after explaining thepros and cons to the parents on a one-to-one "namedchild" basis. It may be prescribed to adolescents whohave not had varicella in past (o r are known to bevaricella IgG negative) especially if ther are leavinghome for studies in a residential school/college.

It is indicated in children with chronic lung/heartdisease, humoral immunodeficiency, HIV infection (butwith CD 4 counts above 15% of the age related norms),leukemia (but in remission and off chemotherapy for atleas t 6-12 weeks) and those on long terms alicy lates/steroids. Varicella vaccine is als orecommended in hous e h o ld c o n tacts o fimmunocompromised children. It may also beconsidered in children attending crèches and day carecenters.

Varicella vaccine is also indicated in susceptibleadolescents and adults if they inmates of or working in

55

the institutional set up e.g. school teachers, day carecenter workers, military personnel and health careprofessionals.

A single dose suffices between the ages of 1-13 years,after which a 2-dose schedule (4-8 weeks apart) isrecommended.

Acellular Pertussis Vaccine

The IAP COI endorses the continued use of whole cellpertussis vaccine (as DTPw) because of its provenefficacy and safety. Acellular pertussis vaccines mayundoubtedly have fewer minor side-effects (like fever,local reactions at injection site and irritability), but thissmall advantage dose not justify the inordinate costsinvolved in the routine us e of this vaccine. It is ,therefore, no t recommended for un ivers alimmunization in our country at present. There is ,however, no bar to offering these vaccines to childrenfrom families who opt for the vaccine for the slightadvantage of fewer minor side-effects.

Use of acellular pertussis vaccine should, however, beconsidered in children who have had s ign ificant

reactions to a previous dose of whole cell pertussisvaccine. These include:

1. Convulsions with/without fever occurring within 3days

2. Persistent inconsolable crying for 3 or more hourswithin 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 does not recommend use of this vaccinefor universal immunization for healthy children in ourcountry at present. PCV - 7 covers only 50 to 55percent of pneumococcal serotypes responsible forserious invasive pneumococcal diseas e in infants &children in India. The vaccine may be offered afterexplaining the parents on one to one "named child"basis. However it is recommended routinely in h ighrisk group children up to the age of 5 years.

IAP Stand on vaccines for special circumstances

Live Japanese Encephalitis (JE) Vaccine

(SA-14-14-2)

This vaccine is bas ed on a stable neuro-attenuatedstrain of JE virus (SA-14-14-2). It was firs licensed foruse in 1988 in People's Republic of China and oversixty million doses per year are being used there. Nowit is also licensed for use in Nepal, S. Korea and IndiaThis live attenuated vaccine constitutes to over 50% ofglobal production of all JE vaccine. Dose is 0.5ml at allages. It is given by subcutaneous route.

Init ial studies done on this vaccine demonstrated anefficacy of about 80% with single dose and 98% with 2doses. However, more recent studies have shown

efficacy reaching 99% even with single dose. As per aW HO report no serious adverse effects (other thananaphylaxis) have been reported over 20 year period(1979 - 1998). This vaccine is not availablecommercially in India; it has been used this year inseven endemic districts after importing it fromChengdu Institute of Biologicals, China. From theavailable safety data, the vaccine was found to beextremely safe.

Meningococcal Vaccines

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

56

with the disease. It is also indicated in high riski n d i v i d u a l s ( e . g . t h o s e w i t hhyposplenia/asplenia,complement deficiency) and

during epidemics It is recommended for those who aregoing for Haj pilgrimage.

IAP COI stand on future vaccines:

Tdap

In the western world it is being felt that there is a needto vaccinate adolescents and adults with pertussisvaccine. There the epidemiology has undergone amarked shift since the introduction of mass childhoodvaccination programs, the proportion of pertussis casesin older children, adolescents and adults though no tgreat in numbers have relatively increas ed, makingthem the source of transmission to very young infantswho are unimmunized or partially immunized and thisage group is more vulnerable to dis eas e relatedcomplications and mortality.

The Tdap vaccine has been incorporated as boosterdose during adolescence in the immunization scheduleof few developed countries. This provides booster towaning immunity in adolescents thus leading toindividual protection and prevention of transmission ofdisease to susceptible infants and children.

In India the epidemiology of pertuss is is not wellknown and there is lack of information regardingepidemiological shift. So the Tdap vaccine is notrecommended for universal use at present. This vaccinemay be of particular use for children who have missedtheir 2nd booster of the DPT and are more than 7 yearsof age.

Rota Virus Vaccine

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

developing countries 53% of rotavirus deaths occur inAfrica & 42% in Asia. It is estimated that 100,000children d ie each year in India due to rotavirusdiarrhea.

As rotavirus d iarrhea occurs in spite of higheststandards of hygiene it cannot be prevented by publichealth measures like s afe water supply and goodsanitations. For prevention universal immunizationappears to be the only answer.

The first vaccine against rotavirus was tetravalentrhesus-human rotavirus vaccine (RRV-TV vaccine,Rotashield: Wyeth Lederle). This vaccine licensed inUSA in 1998 and recommended for universal use hadto be withdrawn when an increased rate ofintussusceptions was shown to occur after vaccineadministration.

Recently a new Pentavalent bovine-human reassortantvaccine from Merck (Rotateq) has been licensed inUSA. Another Rotavirus vaccine - a live at tenuatedhuman (G1P8) monovalent vaccine from GSK (RIX4414 Rotarix) has recently been licensed in LatinAmerican countries and some As ian Countries. Boththese vaccines have been found to be safe and highlyefficacious.

Trials of these vaccines have not been initiated in Indiaso far. There is a great diversity of Rotavirus strainsprevalent in India. There is need to know the efficacyof these vaccines in India before any recommendationscan be made on the use of existing vaccines. OtherRotavirus vaccine being developed are LLR vaccine inChina which is in phase II / III trials and the newbornstrain vaccine in India.

57

Combination Vaccines

The number of vaccines in the immunization scheduleis increasing every year and this trend is likely tocontinue for the next few years. Many parents opt forone single injection of combination vaccines at a givenvisit, rather than come repeatedly for the variousindividual vaccines or take multiple pricks on a singleday for vaccines that are now included in theimmunization time- table. A number of combinationvaccines are now available in the Indian market. TheIAP COI endorses the use of combination vaccines, butwith the following cautionary statements:

1. The manufacture's recommendations should be

adhered to strictly

2. Extemporaneous " mixing" of vaccines in the samesyringe (prior to injection) should not be done as far aspossible, unless specifically recommended by themanufacturer; in the latter case the manufacture'sinstructions should be followed strictly

3. The advantage of a combination vaccine is theconvenience of fewer clinic visits for the parents andfewer pricks for the child

4. Combination vaccines should not be viewed as beingmore effective than vaccines given separately

On Adolescent Vaccination

The Academy endorses the continued use of Td/tetanustoxoid at 10 and 16 years and thereafter every 10 years.HB vaccine may be offered in the 0, 1 and 6 monthsschedu le as mentioned earlier under individualvaccines, if the child has not received it earlier. MMRvaccine should be offered to all children who have notreceived it earlier - there is no upper age limit for thisvaccine. The Academy encourages the use of typhoidvaccine for all adolescents. Hepatitis A and varicellavaccines should be used in selected cases as mentionedabove.

On Immunization Records

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

Immunization card to be used for this purpose. Parentsmust be instructed to keep the document safely andpresent it to their doctor whenever required.

On Advertisements in the Lay Media

Some of the multinational companies have been usingthe lay media (television, electronic media andnews papers/magazines) for placing advertisementspertaining to optional/combination vaccines. We opinethat this is uneth ical. The IAP placed a formalcomplaint before the Drug Controller General of Indiaand the Union Health Ministry. This led to the issuanceof a letter by the Drug Controller to the concernedcompanies requesting them for the withdrawal of theseadvertisements. We are hopeful the companies wouldsee reason and refrain from lay advertising.

58

IAP 2006 Recommendations for other agencies including Ministry of Health and Family

Welfare, Govt of India

The IAP COI has formulated several specificrecommendations to other agencies pertaining toimmunization.

• The IAP recommends that the Academy should berepresented on NTAGI by incumbent President andthe Chairperson/Convener of IAP COI

• At 5 years of age booster immunization should bedone with DTP rather than DT.

• The Academy recommends that inactivated polio

vaccine should be introduced in the routineimmunization in a phased manner, now that it islicensed in the country.

• The Academy strongly recommends that Hepatitis B,HIB and MMR Vaccines should be included in thenational immunization schedule with immediateeffect.

• The Government should actively consider inclusionof typhoid vaccine in the national immunizationschedule. The Academy suggests use of

Vi-polysaccharide vaccine for this purpose.

• The Academy supports the decision of the

Government to discontinue production of animalbrain rabies vaccine. However we need to ensureadequate supplies of indigenously produced chickembryo/tissue culture vaccines at affordable costs.Intradermal route of cell cultured vaccine as per therecent approval and the guidelines of the DrugController General of India should be encouragedand the minimum number of vaccinees stipulated inthe guidelines should be brought down to 10 (thenumber of doses obtained from one vial of vaccine).

• The Academy again reiterates its previousrecommendation to the Federation of Obstetric andGynecologic Societies of India to adopt a policy ofroutine testing of all pregnant women for HBVinfection. If the mother is HBsAg positive, the babyshould be given HBIG plus HB vaccine soon afterbirth.

59