The IAP Advisory Committee on Vaccines and Immunization Practices (ACVIP) has recently reviewed and revised the recommended immunization schedule for children aged 0 through 18 years to ensure that the schedule reflects recommendations based on recent evidences for licensed vaccines in the country. The first annual meeting of the IAP ACVIP was held on 19th and 20th April 2014 in New Delhi. IAP ACVIP members and invited experts who attended the meeting are listed in Annexure 1. The aim of the meeting was to discuss and debate recent developments in the field, to revise recommendations for the IAP Immunization Timetable for the year 2014, and to issue recommendations for available licensed vaccines in the country. Following the meeting, a draft of revised immunization schedule for the year 2014 was prepared and circulated among the meeting participants to arrive at a consensus.

The detailed process behind issuing IAP recommen-dations on immunization – primarily for the pediatricians in office practice has been described earlier [1]. These recommendations provide guidelines to a pediatrician on how best to utilize available licensed vaccines in their office-practice settings. The members may use their own discretion while using them in a given situation within the framework suggested [2]. The existing National immunization schedule and government policies are also taken into account while drafting recommendations.

To revise IAP Immunization Timetable for the year 2014, and review and issue recommendations on the available licensed vaccines.

The IAP ACVIP has issued recommendations for the IAP Immunization Timetable (Table I and Fig. 1) for the year 2014 that includes the following major changes from last year:

TABLE I IAP Immunization Timetable 2014

I. IAP recommended vaccines for routine use

Recommendation: The committee has revised its recommendations on Measles and MMR vaccination schedule. The new schedule will have a dose of MMR at 9 months instead of measles, and another dose (2nd) at 15 months of age. The earlier recommendation of 2nd dose of MMR at 4-6 years of age has been removed.

The need and justification: NTAGI Standing Technical Sub-Committee (STSC) recommended two doses of Measles – Rubella (MR) vaccines in the Universal immunization program (UIP) at 9 months and 16-24 months at the time of 1st booster of DTP vaccine. Since the Academy has argued very strongly in favor of MMR instead of MR vaccine in UIP schedule, the revised recommendations will facilitate inclusion of Mumps vaccine in the National immunization program in near future. Furthermore, it will be more in sync with the upcoming UIP schedule. The detailed reasons are discussed in another recent position paper from IAP publication [3].

The evidence: There are many studies both from India and from other countries demonstrating efficacy and safety of MMR vaccine given at 9 month of age [3-8].

Recommendation: The committee has revised its recommendations on administration schedule of live attenuated hepatitis A vaccine, based on the viral H2 strain (Chinese vaccine). Now a single dose of this vaccine is recommended at 12 months of age over-riding the previous recommendation [9] of two doses of the same vaccine.

The justification and evidence: The committee reviewed both published [11,12] and unpublished long term follow-up data on immunogenicity and safety of a single dose of this vaccine from trials in India. The data showed 79.3% of 121 children were seroprotected (anti-HAV titers >20 mIU/mL) up to 6 years follow-up in the pivotal single center study, whereas 97.3% of 111 children had shown seroprotection after 5 years of follow-up period in the multi-centric group. In the multi-centric study [12], the test subjects maintained good GMT levels even after 5 years of follow-up. The committee had earlier shown its concern on waning of seroprotection in a subgroup of individuals of original single-center study cohort [2]. However, it was later disclosed that only ten subjects had shown this phenomenon, and most of these subjects were of comparatively higher age groups than other study subjects. The decision was also facilitated by the SAGE/WHO recommendations of single dose of live attenuated hepatitis A vaccine [10].

The committee reviewed new data on administration schedule of RV1 (Rotarix) from Pakistan [13] and Ghana [14]. In both studies, the seroconversion and GMTs were higher at delayed (10 and 14 weeks) than early (6 and 10 weeks) schedule, though not statistically significant [13, 14]. In Ghana study, the seroconversion and GMTs were significantly higher in 3-dose (6, 10 and 14 week) schedule than 2-dose early (6 and 10 week) schedule [14]. As these studies are yet unpublished, full methodology and results are not available for scrutiny. The available results do not warrant any change in the existing schedule of RV1 vaccine that includes the first dose at 10 weeks of age instead of 6 weeks in order to achieve better immune response, and the second dose at 14 weeks to fit with existing National immunization schedule [9].

This vaccine developed by Bharat Biotech (Rotavac) is a live, naturally attenuated vaccine containing monovalent, bovine human reassortant strain characterized as G9 P [11], with the VP4 of bovine rotavirus origin, and all other segments of human rotavirus origin. The vaccine strain was isolated from asymptomatic infants with mild diarrhea by Indian researchers in 1985 at AIIMS, New Delhi. Follow up of these infants indicated that they were protected against severe rotavirus diarrhea for up to 2 years. This strain was sent for vaccine development to the National Institute of Health by Department of Biotechnology, India, and later transferred to Bharat Biotech International Limited in 2001 for further development.

A randomized, double-blind, placebo-controlled phase III clinical trial [16] amongst 6,799 infants was conducted at three sites in India. The first year efficacy against severe rotavirus diarrhea was 53·6% (95% CI 35·0-66·9; P=0·001) with protection continuing into the second year of life also. The vaccine also showed 20% efficacy against all-cause severe diarrhea admission. Six cases of intussusceptions (all occurring after administration of 3rd dose) were recorded in the vaccinees and two in the control group. This vaccine has already been licensed in India and would soon be available for use in Indian market.

The committee reviewed the evidence and opined it to be a moderately effective vaccine against rotavirus diarrhea in India. As this is the only vaccine that has undergone large scale field- efficacy trial in India, the level of evidence regarding its efficacy is rated higher by the committee. However, the committee stresses the need of having large scale studies, particularly post-marketing surveillance to monitor occurrence of acute intussusception amongst vaccinated children. There seems to be one excess case of intussusception for every 2000 children vaccinated. Apparently, the sample size was not adequately powered to look for statistical significance [16]. Regarding use of the vaccine in office-practice, it is not clear whether pediatricians would be able to use it in coming months since information about formulation and commercial availability of the vaccine is not yet available.

Recommendations for office practice: The committee has now recommended that practically all children need vaccination against rabies and following two situations to be included in high-risk category of children for rabies vaccination: (i) children having pets at home; and (ii) children perceived with higher threat of being bitten by dogs such as hostellers, and those with risk of stray dog bite while going outdoor. These children should be offered pre-exposure prophylaxis (Pre-EP) against rabies. This must be preceded by a one-to-one discussion with the parents. The Pre-EP is not included in the IAP immunization schedule for all children. Three doses are recommended to be given intramuscularly on days 0, 7 and 28 (day 21 may be used if time is limited, as with imminent travel, but day 28 is preferred). The intradermal schedule has been shown to be effective, but is not approved for this purpose in office practice.

There are studies to show that good antibody levels persist up to 10 years even after a 3 dose pre-exposure prophylaxis followed by a booster at one year. However, on account of the nature of the disease, for re-exposure at any point of time after completed and documented, pre-or post-exposure prophylaxis, two doses are to be given on days 0 and 3. Rabies immunoglobulins (RIG) are not needed in these children. There is no change in the IAP recommendations for post-exposure prophylaxis (PEP) of rabies.

Public use: The committee urges the Government of India (GoI) to urgently take remedial measures to address the huge burden of rabies in India [17]. These measures include public education campaigns, need to ensure the uninterrupted availability of vaccines and anti-rabies immunoglobulin in primary health care facilities and training of primary care providers (including pediatricians), vaccination of dogs, sterilization of stray dogs, and declaration of rabies as a notifiable disease. The committee reiterated its position that universal Pre-EP vaccination, especially for children, could reduce the number of human rabies dramatically. Use of intradermal vaccination would bring down the vaccine cost for universal vaccination program dramatically [2].

Justifications: The advantages of the Pre-EP include elimination of the need for RIG, reduction in the number of vaccine doses on exposure and provision of immunity to individuals whose post-exposure prophylaxis is delayed. Further, the likelihood of lack of documentation of a dog bite amongst young children who may not report scratches and small playful bites from dogs and cats are other reasons why Pre-EP would be useful. However, it was agreed upon that inclusion of Pre-EP in only IAP schedule for office practice would not serve the desired purpose since majority of deaths occur among children belonging to low socioeconomic strata and those living in remote areas [17]. WHO encourages the implementation of carefully designed studies on the feasibility, cost-effectiveness and long-term impact of incorporating ‘Cell Culture Vaccines and Embryonated egg-based vaccines’ (CCEEVs) into the immunization programs of infants and children where canine rabies is a public health problem [18].

Primary schedule: The committee has now created a new slot for typhoid conjugate vaccine for primary immunization at 9-12 months of age in the IAP Immunization schedule. There are currently two typhoid conjugate vaccines (Typbar-TCV and PedaTyph), available and licensed in the country. However, this recommendation would be applicable only to the former as the committee is awaiting more data on the latter. Only a single dose of the vaccine is recommended for primary series. An interval of at least 4 weeks with the measles/MMR vaccine should be maintained since the data on interference with the measles/MMR vaccine are not yet available.

Boosters: Those who received a dose of conjugate vaccine at 9-12 months can be prescribed booster of either Vi-polysaccharide (Vi-PS) or the conjugate vaccine at 2 years of age. Those who have received booster of Vi-PS vaccine will need revaccination every 3 years till the intended duration of protection. There is no evidence of hypo-responsiveness on repeated vaccination so far. The need of further boosters after conjugate vaccine is not yet determined since long term data are not yet available.

Catch-up schedule: Catch-up vaccination is recommended throughout the adolescent period, i.e. up to 18 years of age. Below 2 years, only conjugate vaccine is recommended while above 2 years of age any of the two can be employed. The details about further schedule should be followed as described above in the ‘boosters’ section.

The committee strongly urges the GoI to include universal typhoid vaccination in its UIP all over the country at the earliest.

Evidence and justification: The committee believes that considering the epidemiology of typhoid in the country, there is definite need of protection against typhoid fever below 2 years of age. The Vi-PS vaccines are ineffective below 2 years of age and provide modest and short lasting protection. There is definite need of typhoid conjugate vaccines, effective below 2 years of age and capable of providing superior long-lasting protection. The committee reviewed the published [19] and unpublished data of new typhoid conjugate vaccines, (BBIL’s Typbar-TCV, BioMed’s PedaTyph and Novartis’s Vi-CRM197). All these vaccines can be administered at and around 9 months of age. Only a single dose is sufficient for adequate seroconversion for primary immunization, and the second dose failed to show incremental effect on antibody titers (data after 2nd dose of PedaTyph are not yet available). In the published trial of Novartis’s Vi-CRM197 conjugate typhoid vaccine [19], a low response was noted to measles, hepatitis B and H influenza type b both in reference (PCV13) and test vaccine (conjugate typhoid vaccine) groups, with a non-significant reduction in the rate of measles seroconversion in the test vaccine group in one center. The committee has thus recommended maintaining an interval of at least 4 weeks with the measles/MMR vaccine while administering this vaccine. The committee has also asked the manufacturer to undertake a ‘measles/MMR interference study’ with vaccination at 9 months.

Regarding the need and timing of boosters, the data provided by the manufacturer of Typbar-TCV vaccine show almost 100% seroprotection (>7.2 EU/mL) of test vaccine in both the cohorts (6 mo-2 years and 2-45 years) till 18 months of follow-up, although both seroconversion (>4-fold rise of antibody level) and GMT levels waned significantly in both cohorts. Regarding comparison of Vi-PS non-conjugate vaccine with the Vi-PS conjugate vaccine, both fared equally well above 2 years of age as far as immediate and long-term seroconversion are concerned, although the latter had significantly higher GMTs and slightly better seroconversion rates than the former. The committee has thus recommended either of the vaccines as a booster at 2 years of age. The need of repeat doses/boosters for conjugate vaccine shall only be determined after long-term efficacy data are available.

Recommendations: Two doses of HPV vaccine are advised for adolescent/pre-adolescent girls aged 9-14 years; for girls 15 years and older, current 3 dose schedule will continue. For two-dose schedule, the minimum interval between doses should be 6 months. The interval between the first and second dose may be extended upto12 months, should this facilitate administration – say in school settings. For girls, primed before the age of 15 years, even if older at the time of second dose, a two-dose schedule will be applicable. However, for immuno-compromised individuals, including HIV-infected, the three-dose schedule is recommended, irrespective of age.

Evidence and justification: IAP had recommended use of HPV vaccine in its immunization schedule way back in 2007. Though there is no coverage data on uptake of this vaccine through private sector, the common perception is that acceptance is poor and the coverage still remains miniscule. The move to revise HPV vaccine immunization schedule for adolescent girls from existing three to two doses would not only be cost-saving, but would also simplify logistics like increased flexibility of the intervals, and annual doses for school-based delivery. Hence, the revised recommendations may help in improving acceptance, facilitating delivery, and enhancing coverage of the vaccine.

The WHO’s Strategic Advisory Group of Experts (SAGE) working group (WG) on HPV has recommended revision of vaccination schedule for pre-adolescent and adolescent girls from three primary doses to two in its April 2014 meeting [20]. The committee has reviewed the background material and various trials conducted in this regard so far [21]. The main source of evidence is provided by a systematic review commissioned by SAGE WG [22]. The other sources include review of the data from observational studies on 2 versus 3 dose schedule, and proceedings of an Ad hoc Expert Consultation on HPV vaccine schedules organized in Geneva, 2013 [21]. The European Medicines Agency (EMA) has also approved two doses for pre-adolescent and adolescent girls aged 9-14 years for the bivalent HPV vaccine and also offered positive opinion for a similar schedule for quadrivalent vaccine [23]. Many countries have either already adopted or are planning to adopt a two-dose schedule [21]. Few countries like Brazil, Mexico, Columbia and British Columbia are running an extended schedule (2+1, i.e. 0, 6, 60 months) where the last dose at 5 years depends on follow-up assessment of the need [21]. In Costa Rica, strong 4 year protection was reported in women who received just one dose of bivalent HPV vaccine [21].

The systematic review [22] has identified various studies that include both randomized and non-randomized trials of both the vaccines, bivalent and quadrivalent, from various high income group countries like Canada, Australia, Sweden, Denmark, Germany, and low and middle income (LMI) countries like Uganda, Mexico, and India. In randomized comparisons of two-dose and three-dose schedules (overall 3 RCTs), seroconversion and seropositivity were non-inferior or inconclusive at all-time points. In non-randomized comparisons, all available data for seroconversion and seropositivity showed non-inferiority of the 2-dose compared with the 3-dose schedule. The efficacy against virological endpoints in initially HPV-naïve subjects who received 2 doses of bivalent vaccine at 48th month indicates that the two-dose schedule prevents HPV-16/18 infection in subjects who did not receive a complete 3-dose vaccination course. The review also compared different intervals between doses of HPV vaccine. The 6-month interval resulted in superior GMCs compared with the 2-month interval one month after the last vaccine dose in all the age groups enrolled.

The mathematical models also support the two-dose schedule for girls aged 9-14 years. In one such model it was shown that in high-income settings (such as the UK and Canada), if it was documented that a 2-dose vaccination conferred more than 10-20 years protection then adding the third dose would not be cost-effective [21]. The cost-effectiveness of 2-dose vs. 3-dose vaccination in low/middle income settings still needs to be explored.

The committee’s recommendations are also facilitated by the evidence generated by an ongoing multi-centric RCT on alternative dosing schedule of quadrivalent HPV vaccine in India [24-26]. In this trial, comparisons favored the 2-dose schedule and the ratio of antibody levels was higher in the 2-dose group than in 3-dose group [25,26]. The GMCs for HPV18 in the 2-dose group were non-inferior to that in the 3-dose group. However, on clinical outcomes basis, the RCT provided only limited data, and incident infections with any of the vaccine types in the quadrivalent vaccine were more common in the 2-dose than in the 3-dose group [25,26].

The magnitude of the vaccine response is determined by the age at the first dose. The review of different trials have shown that 100% adolescents can be primed with a single dose of the vaccine and the second dose after 6 months results in higher (almost twice) peak titers in adolescents than in adults. These antibodies then plateau for about 12 months after the peak and decline very slowly providing a long lasting protection [21]. There are limited data from HIV-infected individuals receiving a 3-dose schedule and no data from HIV-infected individuals receiving a 2-dose schedule.

The committee concludes that two doses of HPV vaccine in girls 9-14 years of age are non-inferior in terms of immunogenicity when compared to three doses in girls 9-14 years or 15-24 years of age. A 2-dose vaccine schedule is likely to be as efficacious as three doses, even though long-term outcome and clinical efficacy data are not yet available. The committee stresses the need of long-term studies on efficacy/effectiveness of alternative schedules.

Recommendation: In lieu with its earlier recommendations on pertussis vaccination [9], the committee clarifies that there is no need of repeating or giving additional doses of whole-cell pertussis (wP) vaccine in order to boost immunity in children who have earlier completed their primary schedule with acellular pertussis (aP) vaccine-containing products. However, it should be ensured that all the remaining doses are wP vaccine-containing products. This is to be reiterated here that wP vaccine is permitted till 7 years of age.

Justification: Although it is reported that presence of even a single dose of wP vaccine in the primary infant series of pertussis immunization was found to be providing superior priming and more durable immunity than the schedule completed with only aP containing vaccines [9,27], nevertheless, the aP vaccines are also effective and do offer protection against the disease. Since no stand-alone preparation of wP vaccine is available in the market, it is not advisable to administer too many doses of pertussis-containing combo products (that usually also contain diphtheria and tetanus toxoids) that may inadvertently enhance the frequencies of undesirable adverse events associated with their use.

There are concerns amongst pediatricians related to the quality, suitability and preference of available different wP-vaccine containing pentavalent vaccines in the market since the publication of IAP recommendations on pertussis immunization [9]. Intensive marketing strategies of vaccine manufacturers have further aggravated this confusion. There are no data on either efficacy/effectiveness of individual wP product or comparative evaluation of different available wP combinations in Indian market. ACVIP has urged the National Regulatory Authority (NRA) to setup indigenous National guidelines to manufacture and market different pertussis vaccines in the country [27]. In this background, the committee reviewed the evidence related to available wP-based pentavalent combinations in the country. There are currently six different brands available in Indian market (Table II). All pentavalent vaccines, except Quinvaxem-TM contain PRP-T as carrier protein conjugated with Hib PRP antigen whereas CRM-197 is used in the latter. Both these carrier proteins are consistently highly immunogenic after completion of three primary doses in infants [28-31]. Similarly, no statistically significant difference was found in the safety profile of Hib vaccines containing these two carrier proteins after completion of three doses [28]. Regarding the adjuvant, all the pentavalent products contain Aluminium phosphate in a WHO-prescribed quantity (<1.25 mg) [32]. All the pentavalent combinations, except Quinvaxem, contain thiomersal as preservative. Even the latter also has traces of thiomersal as residue. The committee supports the WHO policy on this issue which continues to recommend the use of thiomersal in vaccines used for global immunization programs since the benefits of using such products far outweigh any theoretical risk of toxicity [32,33].

All the brands are approved by Indian National Regulatory Authority (NRA), Central Drugs Standard Control Organization (CDSCO), MoHFW, GoI after reviewing their phase III clinical immunogenicity and safety studies. However, only the trials of Pentavac, Shan5 and Quinvaxem are published in peer-reviewed journals and available in public domain [34-36]. Information about other brands (Easyfive-TT, Comvac-5, and ComBEfive) are obtained through clinical trial data submitted to CDSCO and package inserts [37-40].

Efficacy: Though direct comparisons are not possible – due to differences in data collection, assays used for evaluation of the immune response, and analysis methods – the seroconversion rates for all the five antigens except for pertussis antigen (which were found lower for Comvac5 and Easyfive-TT) were comparable for all the six brands (Table II). However, the seroconversion rates of Comvac5 and Easyfive-TT against pertussis were comparable to the comparator vaccines’ arms. It has to be noted that till date no known single correlate of protection for pertussis exists, nor any established protective antibody levels are known. Antibody responses to pertussis antigens are variable amongst wP vaccines, likely related to the variability of antigen content amongst them. Furthermore, many different assays are used by manufacturers for the assessment of the immunogenicity.

Reactogenicity: Regarding reactogenicity profile of available brands, a marked diversity was noted. Pentavac was found to be the most reactogenic while Quinvaxem the least. However, it is to be noted that no comparator vaccine was used in Indian trial of Quinvaxem [36] and the reactogenicity profile of the former was found comparable or even superior to the CRM197-based comparator (Easyfive) vaccine (34). Similarly, in the case of Easyfive-TT, the test vaccine fared equally well to the comparator vaccine (Tritanrix+Hiberix) as far as reactogenicity profile is concerned [38,39]. Further, they did not provide information regarding the number of subjects having fever >38ºC. There is no study where all these products are compared ‘head-to-head’ with each other at the same time. On the other hand when one product was compared with another, they fared comparably well against each other. Hence, the committee concludes that all the available pentavalent products are comparable as far as immunogenicity and reactogenicity profile are concerned.

There is no efficacy, effectiveness or post-marketing surveillance (PMS) study from India available in public domain for any of these pentavalent products. There is a large PMS adverse event surveillance study of around 3000 children from Guatemala for Quinvaxem [41].

WHO pre-qualification and world-wide usage: All the products except Comvac-5 are now WHO prequalified [42]. While the Quinvaxem (since 2006), Pentavac (since 2010), and ComBEfive (since 2012) have never been delisted since attaining pre-qualification, the Easyfive-TT (2011-12) and Shan5 (2010-2013) had to be delisted after attaining this status for variety of reasons. Quinvaxem is the most widely used pentavalent vaccine with >400 million doses used globally [43].

The wP vaccines are standardized by protection in the ‘mouse cerebral test’, not by specific antigen content. The committee acknowledges the fact that the process for standardization of quality and efficacy of pertussis vaccines is challenging. Since randomized controlled studies of protective efficacy are no more permitted now owing to ethical and logistic reasons, the post-marketing surveillance and population-based ‘vaccine effectiveness studies’ assume great significance. WHO has made it mandatory to conduct periodic post-marketing surveillance of any newly launched wP based product to monitor its safety since limited safety data are obtained in pre-licensure studies [32].

WHO pre-qualification guidelines for a new wP vaccine, or a new formulation, require proof of concept in a relevant animal model in terms of both potency and safety. The NRAs are guided to ensure potency and safety of a new wP vaccine in preclinical evaluation through ‘intracerebral mouse protection test’ and ‘mouse weight gain test’ before granting clinical testing of a new wP vaccine containing product [32]. Regarding clinical evaluation, determination of antibody response to individual, specific antigens (at least one assay used should determine antibodies against pertussis toxin) is recommended rather than the measurement of antibodies against whole cell or whole cell extracts. The WHO uses very stringent protocol for awarding pre-qualification status to a wP vaccine product [44]. They issue guidelines to NRAs to ensure their application while licensing a wP- based combination in a country. Hence, achieving WHO pre-qualification assumes a very high significance as far as potency, efficacy and safety of any wP based product is concerned. The ACVIP also acknowledges that achieving WHO pre-qualification, which is a dynamic ongoing process with periodic assessment, is a must for all these products to achieve the committee’s approval.

Cost: All the currently available liquid pentavalent combinations cost around INR 600, except Quinvaxem which is around 2.5 times more expensive (Table II). The committee thinks the price of the product cannot be justified considering all the attributes and performance.

Conclusions: The ACVIP concludes that all the available liquid pentavalent combinations satisfy the licensing criteria set by the Indian NRA and fulfills the requirement of WHO prequalification, except Comvac-5. There is nothing to choose between these products as far as their composition, efficacy and reactogenicity profiles are concerned. However, the lack of published studies on immunogenicity and safety of Comvac-5 and Easyfive-TT, and non-attainment of WHO pre-qualification by the former are indeed source of concern to the committee. Although, Quinvaxem has got highest experience as far as worldwide usage is concerned, the committee believes the product is definitely overpriced. There is an urgent need of conducting large scale PMS studies on the safety and effectiveness of these products in India. The committee urges the CDSCO, MoHFW, GoI to issue notices to the manufacturers to conduct, generate and submit data through PMS studies on the safety and effectiveness of their products.

Funding: None; Competing interests: None stated.

IAP Advisory Committee on Vaccines & Immunization Practices, 2013-14: Office-bearers: CP Bansal (Chairperson), Rohit Agarwal (Co-chairperson), Vijay Yewale (Co-chairperson), Vipin M Vashishtha (Convener), Pravin J Mehta (lAP Coordinator), Members: Shashi Vani, Anuradha Bose, Ajay Kalra, AK Patwari, Surjit Singh; Consultants: Naveen Thacker, NK Arora, Rajesh Kumar, HPS Sachdev, VG Ramchandran, Ajay Gambhir; Rapporteur: Panna Choudhury.

Special invitees: Maharaj Kishan Bhan (Ex-secretary, DBT, GoI, New Delhi), Monjori Mitra, (Institute of Child Health, Kolkata), Sangeeta Yadav (Maulana Azad Medical College, New Delhi), Jyoti Joshi Jain (Immunization Technical Support Unit, MoH& FW, Public Health Foundation of India)

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