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There has been considerable public interest in the potential role of measles/MMR vaccines in relation to their alleged association with Crohn's disease and juvenile autism. Part of this interest stems from the original findings of studies published by the Royal Free IBD study group predicting a possible association between measles or measles-based vaccines with Crohn's disease and ulcerative colitis.1,2 Since the inception of the measles–Crohn's hypothesis in 1993, there have been a series of studies published in the areas of IBD epidemiology, case control studies, serology and molecular diagnosis with relation to measles virus being a possible etiological agent.3,4,5,6,7,8,9,10 Although there is a lack of agreement between the findings of the Royal Free IBD group and those published by others, the bulk of the published data do not support any causal association between measles, measles/MMR vaccination and IBD. The first report that predicted an association between measles vaccination and IBD was that of Thompson et al,2 which examined a cohort of vaccinated children enrolled in the study co-ordinated by the Medical Research Council to examine the efficacy of the live measles virus vaccine. The vaccinated cohort of the MRC study was compared with the unvaccinated cohort of the National Child Development Study comprising of children born in Great Britain during one week in 1958. It was predicted that compared to the control group the vaccinated cohort had a 3-fold increased risk of Crohn's disease and a 2.5-fold increased risk of ulcerative colitis. It is understood that unparalleled study cohorts were examined and compared in that study.
Over the past few years we have conducted several experimental studies using a measles virus-specific RT-PCR based system to test the hypothesis originally proposed by the Royal Free IBD study group. The group had originally reported the presence of measles virus particles in the gut tissues of Crohn's disease and ulcerative colitis patients by a variety of methods including Transmission Electron Microscopy (TEM), immuno-gold staining and in situ hybridisation.1 Our results and those published by other groups based on the examination of IBD clinical samples by the RT-PCR method failed to substantiate the findings of the Royal Free group.4,5,6,8 However, it has been argued by the Royal Free group that failure to detect measles virus genome sequence in IBD tissue is due to poorer diagnostic sensitivities of RT-PCR methods that were applied in different laboratories.7 This argument is scientifically unfounded on the grounds that published data (Table 1) of RT-PCR results show that methods established and applied in different laboratories were sufficiently sensitive to detect the presence of measles virus genome sequences if they were genuinely present. At this stage, however, the sensitivity limits of assays established in different laboratories can not be directly correlated with each other, as they have been defined either in terms of genome copy numbers or tissue culture infectious dose, eg plaque forming units (p.f.u). In order to resolve the controversy of the diagnostic sensitivities of RT-PCR based assays, or methods similar to them, it is vital that a few preparations of measles virus nucleic acid and virus particles should be evaluated simultaneously under identical experimental conditions in different laboratories. In order to do that, the NIBSC has taken up an initiative to arrange and co-ordinate an international collaborative study in which measles virus-specific samples will be supplied to various independent laboratories, including the laboratory of Professor J O'Leary, Dublin, Ireland, for in-house method(s) evaluation. The Dublin group has established the procedures of TaqMan RT-PCR and in-cell RT-PCR for the detection of measles virus sequences in clinical samples. These procedures have not been applied in any laboratory for the detection of measles virus genome sequences in clinical tissues of IBD and autism cases, therefore, their advantages, in term of assay sensitivity and contamination controls, over the conventional methods remain to be assessed.
Table 1 Summary results of RT-PCR based and other molecular investigations
