Adolescent immunisation in India: need of the hour- PART 2- Individual Vaccines and recommendations

Adolescent immunisation in India: need of the hour

Ananya Ray Laskar, Anita S Acharya Department of Community Medicine, Lady Hardinge Medical College, New Delhi. India Corresponding Author: Ananya Ray Laskar A-601, Abhyant Apartments, Vasundhra Enclave, Delhi-110096. India. Email: ananya.ray.laskar@gmail.com  Individual Vaccines and recommendations  Diphtheria, Pertussis and Tetanus (DPT): Diphtheria- The duration of immunity against diphtheria may depend on exposure to diphtheria organisms and thus varies geographically. Data on the persistence of immunity in developing countries like India are scarce. But even where vaccination coverage rates have been high for 5 to 10 years, diphtheria outbreaks have been reported. These are characterised by high case fatality  rates, a large proportion of patients with complications, and occurrence in both younger and older age groups [4]. Epidemics in previously well-controlled settings in Eastern Europe have raised awareness of the need for wider vaccination strategies. Though there is a dearth of studies reporting the actual disease burden of diphtheria in adolescents and adults, several outbreaks have been reported in India [5-9] which points towards waning immunity beyondchildhood. Pertussis- Although the majority of adolescents have received one or more doses of DPT in infancy, there is evidence that protective immunity to pertussis may wane [4]. The duration of immunity following DPT immunisation is not precisely known. Epidemiological investigations with whole-cell pertussis vaccine suggest that the efficacy of the vaccine falls with time after immunisation [10]. An increasing incidence of pertussis cases among adolescents and adults in developed countries may reflect decreasing levels of immunity in these groups. Some serological observations suggest that past infection may not provide protection and that the widely held belief that infection with B. pertussis confers lifelong immunity is probably wrong [11]. Tetanus- National Immunisation Schedule has already targeted adolescents of 10 and 16 years as well as pregnant women to receive tetanus toxoid (TT). As discussed above, TT should be replaced by Td in all states that have had DPT-3 coverage of 70% or more for at least 5 years as per WHO [4]. Recommendations: According to the 2012 guidelines given by the Advisory Committee on Immunisation Practices (ACIP) of CDC, adolescents aged 11 through 18 years who have not received Tdap vaccine should receive a dose, followed by  tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter [12]. However due to the cost factor, it is not feasible to adapt this guideline in the Indian scenario. The latest National Immunisation Schedule of India recommends that DPT vaccine can be given up to 7 years of age, but no specific changes in recommendations are suggested for adolescents [13]. For those who can afford the vaccine, the preferred age for TdaP is 11-12 years. Lower dose of thediphtheria component of the vaccine , (recommended for persons over the age of 7 years) are advised to minimise adverse reactions [14]. Recent field trials conducted in Italy, Sweden, and Germany indicate that 'acellular’ pertussis vaccines cause significantly lower rates of reactions than whole cell pertussis vaccines, and also that acellular vaccines are 70%-90% effective in preventing severe pertussis cases [15]. However considering the cost of acellular pertussis vaccine, only Td vaccine may be feasible for adolescents at 10 and 16 years as nation-wide guideline. School-based programmes for administering booster doses of Td may be the best strategy to cover the gaps in immunity. Measles, Mumps and Rubella (MMR): Measles- Single dose of measles vaccine given at 9 months is effective in protecting 85% of infantsvaccinated. Rationale for second dose is to achieve levels of protection (>92%) where reduction intransmission is achieved; further the second dose addresses the 15% non-responders at first immunisation. Overall, based on these well established scientific facts, changing from one dose to two dose strategy would help catch up those missed but more importantly elevate the level of immunity to break transmission of disease. Even in a developed country like USA where first dose of measles vaccine is given as a part of MMR vaccine at 12-15 months, a second dose of measles vaccine is recommended at 4-6 years, to overcome initial vaccine failures which form a small fraction of vaccines, as well as to boost the falling titres ofprotective antibodies over a period of time [16]. Rubella is a benign disease of childhood but has serious teratogenic effects in the baby in the form ofCongenital Rubella Syndrome. The rate of perinatal transmission is 40-50% overall and 90% during the first trimester of pregnancy. As about 40% women in reproductive age group in India are susceptible to rubella, vaccination against this is desirable in adolescent girls [17]. A community based study by All India Institute of Medical Sciences, India in unmarried adolescent girls reported high seronegativity indicating high susceptibility to rubella infections [18]. It has been seen that inadequate coverage may decrease rubella virus circulation in children sufficiently with the resultant upward shift of the median page at infection; thus leading to higher proportion of girls remaining susceptible up to adulthood leading to a paradoxical increase in the number of rubella infections and of cases of Congenital Rubella Syndrome [17]. Thereforeintroduction of rubella vaccine for adolescent girls is recommended to offset the potential of increase of susceptible women in reproductive age group, if children alone are vaccinated. Mumps does not pose a significant public health problem in children as it is uncommon in children less than 12 months of age and has negligible mortality. Mumps is similar to measles but less transmissible in household setting and has lower crude herd immunity. However some complications are known to occur if the disease occurs after puberty. Orchitis occurs in 37% of the post-pubertal males after mumps while 31% of the affected females have mastitis and pelvic pain due to oophoritis. Also an increase in foetal deaths has been observed in women who develop mumps in the first trimester [19]. Recommendations: A one-time measles “catch-up” campaign targeting children 9 months to 14 years ofage may be carried out at national level to immunise susceptible, accumulated since vaccine introduction [11]. Among the neighbouring countries, Sri Lanka, Bhutan, Maldives and Thailand have already introduced MR/MMR in their national immunisation programme. National Technical Advisory group has proposed the introduction of rubella vaccine as MR/MMR in the Universal Immunisation Programme in states which have the ability to achieve and sustain routine immunisation coverage of >80% [13]. This would also provide asecond opportunity for measles vaccination. Specific choice of MR/MMR should be made on the basis of incremental cost between the two [20]. Thus all adolescents in the country should be immunised regardless of their measles vaccination status. Hepatitis B vaccine: It can be used effectively through routine infant immunisation, but is effective at any age though less after the age of 40 years. If given prior to exposure, it can prevent infection in almost all individuals,  and will reduce dramatically rates of liver cancer later in life [21,22]. Most persons infected with hepatitis B virus (HBV) acquire their infection as young adults or adolescents. Any reduction in HBV- related liver disease resulting from universal vaccination of infants cannot be expected until vaccinated children reach adolescence and adulthood [23]. In 2002, Government of India had launched Hepatitis-B immunisation as part of routine immunisation in 33 districts and 15 metropolitan cities with Global Alliance for Vaccine and Immunisation (GAVI) support [24] and recently it is proposed to be expanded to the whole country [13]. However given that the majority of today’s adolescents will not have received this vaccine in infancy, a short-term programme of immunisation for adolescents may also be indicated as a catch-up strategy [23]. Recommendations: A schedule of 0, 1-2, and 4-6 months is recommended. Flexibility in scheduling is an important factor for achieving high rates of vaccination in adolescents. When the vaccination schedule is interrupted, the vaccine series does not require re-initiation [23]. Studies of "off-schedule" vaccinations indicate that if the series is interrupted after the first dose, the second dose should be administered as soon as possible, and the second and third doses should be separated by an interval of at least 2 months. If only the third dose is delayed, it should be administered as soon as possible. Intervals of up to 1 year between administration of the first and third doses induce excellent antibody responses, and studies are in progress to evaluate longer intervals [23]. As per IAP recommendations there are certain special conditions that warrant special mention to administer the vaccine to high risk adolescents [14]. These are health workers, travellers to endemic countries, intravenous drug users, males having sex with men, an intimate contact with HBs antigen positive patients, patients regularly receiving blood or haemodialysis.  Japanese Encephalitis (JE): It is the leading viral cause of Acute Encephalitis Syndrome (AES) in India. 70% of those who develop illness either die or survive with a long-term neurological disability. Government of India made the decision to control JE by introducing a mass vaccination programme in 104 endemic districts in 11 states of India in a phased manner for 5 years from 2006-2011 by using the live attenuated SA 14-14-2 JE vaccine manufactured in Chengdu Institute of Biological Products, China [25]. Since the disease primarily affects children underthe age of fifteen years, a one-time JE massimmunisation campaign targeting all the children in the 1-15 years age group in the high-risk districts was also started. Some districts of Manipur, Nagaland, Arunachal Pradesh and Uttarakhand showing evidence of ongoing JE transmission were also included in 2010 [25]. A recently conducted hospital-based study among AES patients in Assam reported 259 (47.1%) serologically confirmed cases as JE, of which 66.4% were adult and 33.6% were paediatric. This age shift may be due to the invasion of the disease into new demography or some change in the virus strain over time [26]. The Assam Government has initiated a pilot project to expand JE vaccination in adults in the worst-hit districts of Assam from October 2011. Recommendations for use of JE vaccines: Currently the vaccine has been integrated into the Universal Immunisation for children 16-24 months in all the endemic states in India [25]. In view of the age-shift in the incidence of the disease, JE vaccination should be recommended across all agegroups including adolescents in endemic areas, as part of national immunisation. Haemophilus influenza vaccine: The H. influenzae pitman type b (Hib) organism, which can cause severe bacterial meningitis and pneumonia, is estimated to kill more than 370,000 children worldwide each year. Nearly 20% of these deaths occur in India. Preliminary data from six surveillance centres indicates case fatality rate of Hib meningitis is 25%, 76% cases occur in infants and 40-50% of isolates are resistant to first-line antibiotics. Clinical trials of Hib conjugate vaccines have demonstrated that this vaccine can prevent 20-25% radiologically confirmed pneumonia with consolidation [27]. However there is dearth of studies to estimate the burden of disease in adolescents. A study conducted in the Department of Child Health, CMC Vellore [28] reported that even at relatively low coverage through private sector distribution, Hib vaccine has significant community impact on Hib disease. The annual mean number of Hib cases was 10.7 before Hib vaccine introduction, falling to 3.8 cases following its Recommendations: The risk of disease in adolescents is extremely low and thus routineimmunisation is not indicated for healthy individuals above 5 years as per IAP guidelines [14]. However, in some special conditions like chronic respiratory diseases- asthma, immunocompromisedadolescents like splenectomised or post-bone marrow transplant patients a single dose 0.5 ml byintramuscular route may be administered annually [29]. Chicken Pox: It is another common disease and is mild with low mortality if occurs in childhood. Primary varicella has a mortality rate of 2-3 per 100,000 cases with lowest case fatality rates among children aged 1-4 years and 5-9 years. Most children are infected by age of 15 years with fewer than 5% adults remaining susceptible. Disease is often severe if it occurs after adolescence or in adults. Natural infection provides lifelong immunity [30]. Recommendations: Varicella vaccine is not recommended for children in routine immunisation schedule. At ages 11–12 years, providers should assess the adolescent’s need for varicella virus vaccine, and administer the vaccine to those who are eligible and do not have a reliable history of chickenpox. When administered to children <13 years of age, a single dose of vaccine induces protective antibodies in >95% of recipients. For susceptible persons 13 years and above, two doses separated by 4–8 weeks are recommended. But thevaccine is costly as it costs about Rs.1200 per dose. Therefore, in case of financial constraints parents may be given the option to get their child immunised if they can afford it [29]. Moreover varicella vaccine should not be given to adolescents who are known  to be pregnant or to adolescents who are planning pregnancy within 1 month of vaccination. However the vaccine must be recommended to household contacts of immuno-compromised children or health care workers in ‘Infectious disease hospitals’. Meningococcal Vaccines: Invasive meningococcal disease is most common in children with rates of more than 25/1,00,000 population in the first four months of life. Almost 50% cases occur in children less than 2 years of age. Meningococcal vaccine is a polysaccharide vaccine effective against meningococcemia as well as N. meningitidis meningitis which have a high mortality rate. However, being a polysaccharide vaccine it is poorly immunogenic in children less than two years of age, though its protein conjugate variant has been shown to be efficacious [31]. Recommendations: Currently a quadrivalent vaccine is available (against A, C, Y and W135 strains). As one dose of vaccine provides protection for 3-5 years and repeated doses result in hyporesponse, meningococcal vaccine is recommended for prevention among the close contacts and for control of epidemics and not as a part of routine immunisation [32]. Human Papilloma Virus (HPV) Vaccines Cervical cancer is the most common cancer in women in India. HPV infections are very common among sexually transmitted infections and the lifetime risk of acquired HPV infection is 70–80% in many developing countries [33]. With the advent of two new vaccines, one quadrivalent vaccine “Gardasil” ® (against HPV-6, -11, -16, and -18) developed by Merck and one bivalent “Cervarix” ® (against HPV-16, and -18) by GSK , may hold newer promises for prevention and control of the disease. However, a word of caution that vaccination alone does not prevent all cervical cancers. Nearly 30% of cancers are not prevented by the currently available vaccines [34]. Therefore, age-appropriate screening programmes for cervical cancer should go hand in hand. Also, thecost of this vaccine is a major factor along with other issues such as public awareness and acceptability of the vaccine. Many conservative elements of the society have expressed their concern that it might encourage promiscuity among unmarried. Also there is a question of whether to offer it to boys. Hence, various regulatory and policy changes along with awareness among parents may need to be undertaken to address these issues. Recommendations: The primary target population should be young adolescent girls as vaccination is most efficacious in girls who have not become sexually active. So, the programmes should determine the primary target age group based on data on the age of sexual initiation and the feasibility of reaching young adolescent girls through schools, health-care facilities or community-based methods [35]. The vaccinemanufacturers recommend three doses of the vaccine to be administered to females aged 10-26 years. CDC recommends either HPV4 or HPV2 for females and HPV4 for males aged 11 or 12 years in a 3-dose series. The vaccine series can be started beginning at age 9 years. The second dose to be administered 1 to 2 months after the first dose and the third dose 6 months after the first dose [12]. But each dose cost about Rs. 3000/- and hence is not recommended as part of routine immunisation in adolescents [33]. However, it can be made optional for those who can afford them. In addition, screening at regular intervals after initiation of sexual activity cannot be over-emphasised along with creating public awareness regarding cervical cancer and HPV vaccine. So, currently, only a few vaccines fulfill the criteria for widespread use in adolescents. A summary of theIAP and the recommendations for the National Immunisation for adolescents have been presented in table 1. Table 1- Recommendations for adolescent immunisation SOURCE- http://www.ijms.in/articles/3/1/adolescent-immunisation-in-india.html