MMR: where are we now?

T he combined measles, mumps and rubella (MMR) vaccine was introduced to the UK in 1988 and uptake of the vaccine rose rapidly to a high of 92%. In 1992, brands containing the Urabe strain of the mumps vaccine virus were withdrawn after it was noted to be associated with an increased risk of aseptic meningitis. This did not appear to have a deleterious effect on uptake. In 1995, a paper was published suggesting a link between measles vaccines and the development of bowel disorders in adulthood. This was associated with a small decline in the uptake of MMR vaccine. In 1998, the same group of researchers published observations of 12 children with pervasive developmental disorders and bowel disease and suggested that the latter may have led to the former. In eight children, the history of the onset of symptoms coincided with receipt of MMR vaccine. Although the researchers stated in the paper that ‘‘we did not prove an association between measles, mumps, and rubella vaccine and the syndrome described’’, and an accompanying commentary was heavily critical of any suggestion of such a link, the story attracted much attention in the media. This was largely fuelled by a paragraph in the press release accompanying a press conference: ‘‘The majority opinion among the researchers involved in this study supports the continuation of MMR vaccination. Dr Wakefield feels that vaccination against the measles, mumps, and rubella infections should undoubtedly continue but until this issue is resolved by further research there is a case for separating the three vaccines into separate measles, mumps, and rubella components and giving them individually spaced by at least 1 year’’. Subsequently, public confidence in the vaccine was dented and uptake of the vaccine in England fell to 79%, with some parents seeking the single antigen components. In this article we consider the evidence in relation to the proposed link, the effect the scare has had on the control of measles, mumps and rubella, and the current situation. EPIDEMIOLOGICAL STUDIES While there are known adverse reactions following receipt of the vaccine, as with any live vaccine, these are predictable in that they are also complications of the diseases, for example febrile convulsions and idiopathic thrombocytopenic purpura. On the other hand, features of autism do not follow postnatal measles, mumps or rubella, unless accompanied by severe encephalitis. For this reason, prior to its release, no studies had been carried out specifically looking for autism after administration of the vaccine and no significant concerns had been raised in this respect after 16 years of use in the USA. However, once the question was posed, it had to be addressed. Because the vaccine was already used in most children in the countries where it was available, it would have been unethical to conduct randomised controlled trials with administration of the vaccine being delayed or withheld entirely. Thus, the studies that have been carried out have been observational, although in many cases they included controls. Numerous studies have been conducted in different countries. It is not within the remit of this article to review these in full and we will thus only consider some of the key papers using sound methods. A few months after the Lancet article appeared, Gilberg and Heijbel reported no rise in referrals of children with autism to their clinic in Sweden following the introduction of MMR. Studies conducted in London by Taylor and colleagues have shown no link between MMR and autism, either in general or, specifically, with disintegrative autism. 9 Using record linkage in Denmark, Madsen and colleagues compared the incidence of autism in children who had had MMR vaccine with those who had not and found no significant difference. While all of these studies have some limitations, it is most unlikely that between them they would have failed to detect a significant link between MMR and autism and even in a review which adopted the most restrictive inclusion criteria for the studies reviewed, the authors concluded ‘‘no credible evidence of an involvement of MMR with either autism or Crohn’s disease was found’’.