Measles-Mumps–Rubella Vaccine

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Chapter: Pharmacovigilance: Gastrointestinal ADRs

A study published in 1995 suggested that there may be a link between measles vaccination and the subsequent development of Crohn’s disease and ulcerative colitis.


A study published in 1995 suggested that there may be a link between measles vaccination and the subsequent development of Crohn’s disease and ulcerative colitis (Thompson et al., 1995). The study was reported by the Inflammatory Bowel Disease Study Group at the Royal Free Hospital School of Medicine in London.

The prevalence of Crohn’s disease and ulcerative colitis was determined in three cohorts: (a) a vacci-nated group of 3545 people who had received measles vaccine in 1964 as part of a measles vaccine trial, (a) a control group of 11 407 people born in 1958 who were unlikely to have been vaccinated due to their age and of whom 89% had reported measles by age 11 and (c) a second control group of 2541 partners of individuals in the vaccinated group whose vaccination history was not known.

Disease prevalence data were collected by means of a postal questionnaire. The vaccinated group and their partners were asked whether they had ever been told, by a doctor, that they had Crohn’s disease, ulcerative colitis, coeliac disease or peptic ulcer disease. The unvaccinated group were asked about any condition that required regular medical supervision, the presence of any long-standing illness, disability or infirmity, and details of all out-patient appointments and hospital admissions. Reports of Crohn’s disease and ulcerative colitis were confirmed with the subject’s physicians in the vaccinated and unvaccinated groups only.

Respondents were assumed to have inflammatory bowel disease if they reported it, and the diagnosis was not refuted by their physician. Reports of inflam-matory bowel disease where no confirmation could be made were included.

Crohn’s disease and ulcerative colitis were reported more often among the measles vaccine group than among the control groups. The difference in the preva-lence of inflammatory bowel disease was signifi-cantly higher in the vaccinated group when compared with the unvaccinated group. It was reported that, compared with the birth cohort, there was a relative risk of 3.01 (95% confidence interval: 1.45–6.23) of developing Crohn’s disease in the vaccinated group. The relative risk of developing ulcerative colitis was 2.53 (95% confidence interval: 1.15–5.58). There was no difference in the rates for coeliac disease.

By contrast, a case–control study in the United Kingdom, which included 140 patients with inflam-matory bowel disease (83 with Crohn’s disease), was unable to show an association with measles vaccina-tion (Feeney et al., 1997).

The Inflammatory Bowel Disease Study Group reported another study in 1998 that suggested an association between the combined MMR vaccine and gastrointestinal disease resulting in malabsorp-tion, neurological damage and autism (Wakefield et al., 1998).

Twelve children between the ages of 3 and 10 years were studied. All had been referred to a paedi-atric gastroenterology unit with a history of normal development followed by the loss of acquired skills, together with diarrhoea and abdominal pain. Gastroen-terological, neurological and developmental assess-ments and a review of developmental records were performed.

All 12 children had intestinal abnormalities, includ-ing lymphoid nodular hyperplasia in 10. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in 7 but no granulomas. Behavioural disorders included autism in nine children, disintegrative psychosis in one and possible postviral or postvaccinal encephalitis in two.

The onset of behavioural symptoms was associated, by the parents or the child’s physician, with MMR vaccination in 8 of the 12 children, with measles infection in one child and otitis media in another. The average interval from MMR vaccination to the onset of behavioural symptoms was 6.3 days (range 1– 14). Parents were less sure about the timing of onset of abdominal symptoms because children were not toilet trained at the time or because behavioural features made children unable to communicate symptoms.

Conflicting findings have been reported by long-term follow-up data for children receiving MMR vaccination in Finland (Peltola et al., 1998; Patja et al., 2000). A national surveillance system to detect seri-ous adverse events was established in Finland when their MMR vaccination programme was launched in 1982. A potentially serious adverse event was defined as an event in any temporal association (no time limit was imposed) with MMR vaccination that fulfilled one or more of three characteristics: a potentially life-threatening disorder, the possibility that a chronic disease had been triggered by the vaccination or the patient had been hospitalised for reasons possibly attributable to MMR vaccine. Reports were collected from all hospitals and health centres from 1982 to 1996. During this period, about 3 million vaccine doses had been administered to 1.8 million individu-als.

The health of children who had developed gastroin-testinal symptoms, lasting 24 h or more following vaccination, was reviewed (Peltola et al., 1998). The time between the reported event and the health review ranged from 1 year 4 months to 15 years (mean 9 years 3 months). Thirty-one children had gastrointestinal symptoms, of whom 20 were admitted to hospital. The most common symptom was diarrhoea (55%). The time from MMR vaccination to the onset of symptoms ranged from 20 h to 15 days. Symptoms generally resolved within a week. No evidence of an associa-tion between MMR and inflammatory bowel disease or developmental disorder was found.

All serious adverse event reports collected in the Finnish 14-year surveillance programme were anal-ysed with the finding that serious events causally related to MMR vaccine were rare (Patja et al., 2000). No cases of inflammatory bowel disease were detected.

The proposal continues (Wakefield and Montgomery, 2000) although it is apparent that other studies have failed to confirm associations between either Crohn’s disease or autism and MMR vaccination (Elliman and Bedford, 2001). Independent prospective studies are urgently needed to resolve this important issue as parents in the United Kingdom vote with their feet and abstain from vaccinating their children.

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