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MMR and autism: the debate continues

2004; Elsevier BV; Volume: 363; Issue: 9408 Linguagem: Inglês

10.1016/s0140-6736(04)15549-9

1474-547X

David Thrower,

Viral gastroenteritis research and epidemiology

Simon Murch has previously made an important contribution towards treating children with regressive autism and bowel problems, and so it is vital to respond to his letter (Nov 1, p 1498)1Murch S Separating inflammation from speculation in autism.Lancet. 2003; 362: 1498Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar with hard fact rather than emotion. The evidence to support his claim that there is no link between the measles, mumps, and rubella (MMR) vaccine and regressive autism comes from a large number of studies, too numerous to comprehensively reference here. But all of these studies have only been epidemiological. Perhaps the most interesting was the study by Kaye and colleagues,2Kaye JA del Mar Melero-Montes M Jick H Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis..BMJ. 2001; 322: 460-463Crossref PubMed Scopus (310) Google Scholar which showed that autism in the UK had increased seven-fold between 1988 (the year MMR was introduced in the UK) and 1999. That study explained the increase away as possibly being “due to increased awareness of the condition among parents and general practitioners, changing diagnostic criteria or environmental factors”, although the authors offered no evidence to support this speculation. There is thus prima facie evidence of an underlying real increase in autism in the UK since 1988. Careful review of the numerous epidemiological studies (how many of MMR's defenders have personally taken the time to read them all carefully and test the methods and conclusions of each to destruction?) exposes each one as flawed, with unsupported assertions, questionable hypotheses, and overstated outcomes. For example, studies based on the UK General Practice Research Database are utterly reliant on the relevance of that database to an affected child's detailed bowel condition and developmental history. This is clearly a heroic assumption on an industrial scale. Few such children have undergone ileocolonoscopy or had tissue samples analysed. And none of the epidemiological studies distinguished between regressive autism and other autism—a crucial failure. Another epidemiological study3UK Committee on Safety of Medicines Report of the Working Party on MMR Vaccine. Committee on Safety of Medicines, London1999Google Scholar —the only one to look at records of actual damaged children—published in support of MMR's safety, was that by the UK Committee on Safety of Medicines. This study, based on records of several hundred UK children obtained from lawyers, was so weak that it was forced to admit that “it was impossible to prove or refute the suggested associations between MMR vaccine and autism or inflammatory bowel disease because of the nature of the information [made available to the study]”. No children were clinically examined, and no parents interviewed. There also have been no clinical studies of damaged children with regressive autism that firmly refute Andrew Wakefield's hypothesis of an association between MMR and regressive autism. Are these epidemiological studies Murch's sole evidence of MMR's safety? We now turn to studies that offer some background support to the ground-floor level of Wakefield's hypothesis (again, note that he has never claimed that MMR causes all autism, only a subset of cases). Several studies have been published, or papers presented, that indeed strongly suggest that Wakefield's hypothesis of a link between gut pathology and regressive autism is correct. Among these is a paper by Timothy Buie.4Buie T Initial autism research findings at Harvard, Massachusetts.http://www.autismnwaf.com/harvardproject2.htmGoogle Scholar Buie found evidence of chronic inflammation of the intestinal tract among autistic children he examined, with ileal lymphoid nodular hyperplasia (ILNH) in 15 of 89 children. Buie concluded that the children “are ill, in distress and pain, and not just mentally, neurologically dysfunctional”. His findings thus support at least some link between a disorder of the gastrointestinal tract and some cases of autism. No contrary published evidence to refute Buie's work has been offered or presented to date. A paper by Arthur Krigsman5Krigsman A. Testimony by Dr Arthur Krigsman MD before the Committee on Government Reform. Presented to US Congressional Committee on Government Reform's hearing, The Status of Research into Vaccine Safety and Autism. Washington DC: Congressional Committee on Government Reform, 2002.Google Scholar noted his finding that a large proportion of his autistic patients had chronic unexplained gastrointestinal symptoms. In his assessment of 40 children, 90% had lymphoid nodular hyperplasia of the terminal ileum. Most of the cohort had a clear history of developmental regression, with a precipitous or gradual decline at age 12–18 months after earlier normal development. Again, no evidence to refute Krigsman has since been offered. These findings, together with those of Wakefield and his co-authors—including Murch—strongly suggest a link between ILNH and regressive autism. The numerous defenders of MMR's safety might at least wish to acknowledge—or provide clinical evidence to contradict—this vital first stage in the unfolding story of regressive autism's cause. The most up-to-date figures available from the US Individuals with Disabilities Education Act (State-sourced) database confirm that children and young people aged 6–21 years with autism, in full-time education, have increased from 12 222 in 1992–93 to 118 602 in 2002–03, a deeply-troubling increase. It emphasises the huge and rapidly-rising cost to the community of autism, in all its forms, and the importance of making real progress in tracing its causes. Child health is not just about measles, or vaccine take-up rates. In the UK, a dozen suspected measles cases is a media headline. A thousand cases of autism go unnoticed, unrecorded, and unreported, yet their lifelong physical and economic effect is vastly greater. It is vital that the medical community now recognises the importance of the pioneering work of Wakefield, Buie, Krigsman, and other co-workers, accepts that there is a prima facie connection between ILNH and regressive autism, and conducts the most urgent research as to its potential causal pathways. It is an extreme understatement to emphasise that there is much at stake. I am the parent of an autistic child. MMR and autism: the debate continuesAuthor's reply Full-Text PDF