MMR vaccine from gsk.What IAP Recommends? Are there real ADV.over MMR Vaccin available?

It is unfortunate that MMR is still not a part of EPI in India. The argument that we do not have enough data on the incidence of Rubella and Congenital Rubella syndrome or of Mumps is no excuse for not including it as a routine vaccine. That way we have poor data of many such medical problems. Mumps is a common cause of obvious or overt orchitis or oopheritis leading to sterility later in the life. It can also lead to rare but fatal complications like pancreatitis and encephalitis. Congenital rubella syndrome is a devastating condition once it occurs, both for the child and the parents, and is must be prevented. Measles is already a part of universal immunization included in the EPI since 1981 in India. This makes the use of MMR an ideal choice for use at the age of 12-15 months, as is the practice in most of the western countries.

The question is whether one dose of MMR is enough? In west, where MMR is used now universally for more than a decade, 2 problems have occurred. One is the shift to the right of the age of exposure and subsequent clinical disease at an older age in those who are not vaccinated and the second is the small but significant increase in the cases of break through measles in the vaccinees at a later (older) age due to waning of the immunity. This is obvious, as the natural boosting does not occur due to very low occurrence of natural disease in the community due to mass vaccination. This means that there is a need to boost the immunity by giving one more dose of MMR later, either at 5 years i.e. school entry or at 12-15 years i.e. at school exit. This will also provide the opportunity to catch up with those who have missed their first dose of MMR. In US and most of the western world, 2 doses of MMR are given routinely, one at 12-15 months and the second at 5-15 years. The second dose can be given even earlier; any time 6-8 weeks after the first dose till 5 years of age (1). In India it is too early to say but one dose will suffice till we use MMR as universal vaccine for sufficient length of time, after which we may need 2 doses.

The next question is the adverse effects attributed to MMR vaccine and the social uproar created by such allegations. MMR was linked with various adverse reactions like autism, inflammatory bowel disease, SIDS, GB syndrome etc. None of them have been proved to be causally associated with MMR including autism.

A flutter was created when Wakefield et al reported in 1998 Lancet a report of 12 children who had pervasive developmental disorder, non-specific colitis and ileal lymphoid nodular hyperplasia probably linking them to MMR vaccination (2). 10/12 patients had autism and the remaining 2 had neuroregression. 10/12 patients had association with MMR vaccine with the mean interval between exposure to MMR and the first CNS symptoms being 6.3 days. 8/12 patients had gross changes on colonoscopy, 10/12 had nodular lymphoid hyperplasia, 7/12 had histological changes of lymphoid follicular hyperplasia. There were similar reports form the same group and others linking measles vaccine with such GI and CNS side effects. This report gained a lot of media attention and the parents in UK lost their confidence in the safety of MMR vaccine. However the same group who did not find measles virus by PCR from the biopsy material disproved this later. Peltola et al studied cases of CNS and GI side effects after MMR from Finland over 14 years (3). More than 3 million doses of MMR were given in that period. They failed to identify any relation between MMR and autism of inflammatory bowel disease. Similarly Taylor et al from UK did a systemic study of cases of autism from 1979 and its relation with MMR, which was introduced for mass vaccination in 1988 (4). They failed to demonstrate any increase of autism cases after the mass MMR vaccination program was introduced in 1988. The age of onset autism did not differ in those who received MR before the age 18 months vs. those who did not receive MMR at all. Similarly there was no clustering of cases within the months following MMR vaccination. They postulated that autism is usually reported with a peak at 18 months and the MMR is given at around 15-18 moths leading to erroneous belief that it is caused by MMR.

Lastly, the controversy of the strain of Mumps antigen and the chances of aseptic meningitis. 3 cases of Aseptic meningitis were reported following use of Urabe MMR from Canada in 1987. The Urabe MMR was recalled from Canada in 1988. Urabe MMR was introduced in UK in 1987-88 and 1 case was reported in the pre-licensure study. The risk estimated varied from 1 in 10,000 to 1 in 100,000. Meanwhile similar cases were reported from Japan too. In 1991 active surveillance program started in UK (5). The risk of aseptic meningitis was estimated to be 1 in 143,000. This led to withdrawal of Urabe MMR in September 1992 and it was replaced by the JL strain MMR. The active surveillance continued and the risk was estimated to be 1 in 143,00 with Urabe and 1 in 227,000 with JL strain (p: 0.0096). This proves that the Jerryl Lynn strain is much safer. However the JL strain containing MMR vaccine is 3-4 times more costly than Urabe strain MMR. In west the Urabe strain is not used at all and most of the countries use JL strain. It is interesting to note that the Urabe strain MMR continue to be marketed in developing countries by the same companies that have withdrawn it from the western world! This is entirely because of the cost factor. Even with the existing cost of Rs 50 per dose, MMR is not included in the EPI; it will be more difficult if the cost goes up 3-4 times. Very soon the JL strain containing MMR will be introduced in the Indian market. It may be worthwhile offering the same to those who can afford the extra cost, as it is definitely safer than the Urabe strain MMR. Incidentally aseptic meningitis is rarely reported following Urabe strain MMR from developing countries. This may be another reason for continued use of this vaccine in India.