Link with bowel disease fuels controversy over vaccine

British Medical Journal, March 7, 1998 by Hilary Bower

Doctors at the Royal Free Hospital in London believe they have uncovered a new bowel disease in children that may be linked to autism and triggered by the measles, mumps, and rubella vaccine (MMR). The claim follows controversial work from the same team suggesting a causal link between measles vaccination and inflammatory bowel disease.

The report stems from the investigation of 12 children aged between 3 and 10 years who were consecutively referred to the department of paediatric gastroenterology at the Royal Free Hospital (Lancet 1998;351:637-41). After a period of apparently normal development, the children had lost acquired skills, including language, and had developed gastrointestinal symptoms such as diarrhoea, abdominal pain, and bloating.

All 12 were found to have lumpy swellings of the lymph nodes and patchy recurring inflammation in the intestine. in nine of the children autism had also been diagnosed, and in eight children the parents or the GP associated the start of the behavioural symptoms with MMR vaccination. In two cases an association was made with measles infection and with otitis media.

In another unpublished series, 46 out of 48 children showed similar bowel and behavioural symptoms, and over 700 more children have been referred for assessment to the clinic. The study is the first of five new papers to be published on the new syndrome, which the team have named ileal lymphoid nodular hyperplasia.

The lead researcher, Dr Andrew Wakefield, reader in experimental gastroenterology, said that virological evidence of the measles link would be presented later this month. The team believes that the new syndrome may be causing faulty absorption of opioids released during digestion, allowing them to reach the brain and disrupt its function at a crucial stage of development. it also notes that all the children had markers of vitamin B-12 deficiency -- vitamin B-12 is essential to the development of myelin in the central nervous system.

Several recent studies have failed to replicate the team's link between the measles virus and inflammatory bowel disease, and government and other experts have consistently maintained that there is not sufficient evidence to change vaccination policy. The deputy chief medical officer, Jeremy Metters, said: "Our advice to parents is to continue to vaccinate your children, because there is no evidence that the MMR vaccine carries the risk suggested. And the risk of not using this vaccine far outweighs any possible side effects."

The study's publication has raised fears of another drop in vaccination rates. Media coverage of leaked results from the paper last autumn saw a national fall of 1%, and in a fifth of districts the rates fell by 2% or more (14 February, p 561). Professor Norman Begg of the Public Health Laboratory Service Communicable Diseases Surveillance Centre blamed biased media coverage, which faded to report negative findings exonerating vaccination. He added: "The weight of scientific evidence has subsequently shown that ... there is no causal link between MMR vaccine and Crohn's disease."

But Dr Wakefield insists that to say there is no evidence is "simply wrong." He says: "There is evidence both from our team and from others around the world. The question is whether the evidence is stronger for or against. This is not a capricious attempt to undermine vaccine policy. This is the gulf between clinical medicine and public health medicine. We are obliged to take these patients' stories, test a hypothesis, and report on the data we find. We cannot walk away from what we find. We have 700 children waiting for assessment -- this may represent a huge clinical need that is not being met."

All 13 researchers involved insist that measles vaccination should continue until further research is done. However, Dr Wakefield has called for the components of the MMR vaccine to be given separately to reduce the viral load. "For the vast majority of children, the MMR vaccine is fine, but I believe that there are sufficient anxieties for a case to be made to administer the three vaccinations separately."

The Royal Free Hospital's researchers believe that autistic symptoms may be reversible through treatment of bowel symptoms and have treated several children, some of whom have started talking again for the first time in years. A double blind control trial with sulphasalazine is about to begin. The evidence from the new study and those preceding it will be examined later this month in an independent inquiry organised by the Medical Research Council.