Recommended Immunization Schedule
The Advisory Committee on Vaccines and Immunization Practices of the Indian Academy of Pediatrics (IAPACVIP) met on March 25, 2023 in Kolkata, West Bengal, and September 8, 2023 at the National Conference of Pediatric – Infectious Diseases (NCPID), Aurangabad, Maharashtra. ACVIP members who attended the meeting. The aim of the meeting was to discuss and debate the recent developments in the field of vaccinology, to issue the relevant recommendations based on them, and to revise the existing IAP immunization timetable. This document presents the consensus recommendations, arrived at after detailed literature review, debates and discussions, held during the first physical meeting and subsequent meetings held online (dIAP or Zoom platform) and physically.
Process
The process for issuing recommendations included a review of the recent published literature including standard indexed journals, vaccine trials, recommendations of reputed international bodies like Advisory Committee on Immunization Practices (ACVIP), Centre for Disease Control and Prevention (CDC), and World Health Organi-zation (WHO) as well as unpublished data from vaccine manufacturers. Data generated by studies done in India was specifically looked at and available local information was given preference.
1. Td (Tetanus, Diphtheria) Vaccine
Additional Dose of Td at 16-18 y
The National Immunisation Program (NIP) schedule recommends a Tetanus-Diphtheria (Td) booster at 16 years of age and the IAP-ACVIP schedule recommends a final booster of the Tetanus, Diphtheria, Pertussis (Tdap) vaccine at 10 years of age, followed by Td every 10 years [1,2]. Diphtheria surveillance data from Kerala (2016) found that the majority of the diphtheria cases were in the age group 18-45 y (38%; 198/526), followed by the age groups 10-18 y (31%; 161/526), and 5-10 y (18%). In north Maharashtra, the age groups of 5-9 y and 10-14y represented 33.3% (42/126) and 23.8% (30/126) of the total diphtheria cases, respectively. In a serosurvey done in 2,400 school children aged 6-17 y, studying in the various government schools in Hyderabad, only 56% and 64% had protective levels of IgG antibodies against diphtheria and tetanus respectively [5]. These studies suggest a lack of protective antibodies in a significant proportion of older adolescents and adults and a poor uptake of Td beyond 10 y of age.
Studies have demonstrated persistence of diphtheria antibodies in > 95% of adolescents at 5 y and 10 y following a Tdap dose at 10 y of age. Nearly all participants had tetanus antibodies (≥ 0.1 IU/mL) throughout the study, however, the protection against pertussis was variable. Anti-pertussis toxin antibodies declined to pre-vaccination levels approximately 5 y postvaccination; antibodies to filamentous hemagglutinin, pertactin and fimbrae waned at 5 y and 10 y but remained several-fold higher than pre-vaccination levels [6,7]. A Tdap vaccine administered at 10-12 y will provide protection against tetanus and diphtheria for approximately 10 y [8]. These results support the recommendations that one Tdap booster should be administered to all persons and Td boosters every 10 y thereafter between 11-64 y of age. Adolescents rarely visit the doctor unless they have a medical health condition. Estimates of receipt of clinical preventive services among adolescents, is suboptimal in developed countries [9] and very low in low- and middleincome countries. In a study done in rural West Bengal, it was reported that only 29.4% adolescents had utilised adolescent reproductive and sexual health services at least once during adolescence [10]. This may explain the poor uptake of adolescent boosters and the consequent higher incidence of diphtheria and tetanus in older adolescents and adults. A booster of Td at 16-18 y will ensure assured protection against diphtheria and tetanus for the next 10 y.
Replacement of the decennial Td by Tdap is not a costeffective intervention [11], since the protective efficacy of Tdap administered in early adolescence, against pertussis does not last for more than 2-3 y. The reduction in pertussis disease burden attributable to the routine use of a second dose of Tdap, would therefore be limited [12]. However, if there is an increased risk of pertussis in a healthcare setting evident by documented or suspected healthcare-associated transmission of pertussis, revaccination of healthcare personnel with Tdap may be considered
IAP-ACVIP Recommendation
- The IAP-ACVIP recommends a dose of Td vaccine between 16-18 y.
2. Human Papilloma Virus (HPV) Vaccine
All Human Papilloma Virus (HPV) vaccines were originally licensed and marketed using a 3-dose vaccination schedule. A 2-dose schedule was approved, based on demonstration of noninferiority of the immune response in the 9-14 y age group, when compared to young adult women in whom efficacy has been proven. A 2-dose schedule for 9-valent HPV vaccine (9vHPV) for 9-14 y was approved by USA CDC, European Medical Agency, Canada in 2016 and is currently approved in around 80 countries across the globe, including Australia, France, Germany, UK, USA as well as in Asian countries like, Singapore, Malaysia, Taiwan, Thailand and Vietnam.
9vHPV Vaccine Study: 2-dose Schedule Study
An open-label, noninferiority, immunogenicity trial was conducted to compare the seroconversion rates (SCR) and immunogenicity of 2 doses of 9vHPV in girls and boys aged 9-14 y as compared to 3 doses in adolescent girls and young women. Four weeks after the last dose, the SCR to each individual serotype, in the 2-dose cohort, was > 98%. The geometric mean titers (GMT) of HPV antibodies at 1 month after the last dose, for all the 9 HPV subtypes was higher in girls and boys who received 2 doses 6 months apart and in girls and boys who received 2 doses 12 months apart as compared with adolescent girls and young women who received 3 doses over 6 months. Noninferiority criteria for seroconversion rates were met for all 9 HPV types.
At follow up till 36 months, anti-HPV GMTs in girls and boys who received 2 doses were generally similar to or greater than GMTs in young women who had received 3 doses. Seropositive status was maintained across HPV types, in most boys and girls who received 2 doses and young women who received 3 doses till 2 to 2.5 y after the last dose. In a follow-up study of the 9vHPV vaccine, seropositivity rates remained > 90% through month 90 for each of the 9vHPV vaccine types. No cases of vaccine related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population based
on a maximum follow-up of 8.2 y (median 7.6 y) post-dose.
Gender-neutral Vaccination: Need for HPV Vaccination for Males
Infection with the high-risk HPVs, principally serotype 16 and 18, is the cause of almost all cervical cancers in women. However, oropharyngeal cancer (including tonsils and base of tongue), anal and penile cancers are also HPV-associated cancers and impose a significant burden in males as well. It is estimated that HPV is the causal agent in 5% of all human cancers with HPV16 predominating. Apart from cervical cancers, the other HPV-associated cancers are not amenable to screening and are increasing in both males and females and usually detected at a late stage. The aim of any vaccination program is to halt transmission of the pathogens and prevent all associated diseases. Gender neutral vaccination (GNV) will also prevent non-cervical HPV-associated diseases that have serious morbidity in males as well. GNV programs have been found to be cost-effective interventions [17]. GNV will reduce transmission, impart herd immunity, facilitate the eradication of HPV and protect boys from infection. Girls only vaccination programs will not lead to eradication.
