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  Does Measles Immunization Increase The Risk of Developing Ulcerative Colitis and Crohn's Disease?
  

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By: Markus Sommer, M.D.
(Original title: Erhoeht die Masemimphmg das Risiko, an Colitis ulcerosa und Morbus Crohn zu erkranken? Der Merkurstab 1996; 49:77-9. English by A. R. Meuss, FIL, MTA.)

The Lancet recently carried a report on a large, retrospective, epidemiological study concerning the connection between measles immunization and the development of inflammatory bowel disease in Great Britain. The question had arisen because persistent measles viruses are frequently found in the intestinal mucosa of patients with Crohn's disease. It was also noted that the introduction of routine immunization with live measles vaccine in 1968 coincided with a marked increase in Crohn's incidence in the UK.

3,545 individuals, who had been immunized against measles at the age of 10-24 months and included in an immunization study of the Medical Research Committee (MRC), were compared with 11,407 from the National Child Development Study (NCDS), who had not been immunized and 90% of whom had measles up to the age of 11. It was found that the relative risk for immunized individuals to develop Crohn's disease was 3.01 (95% confidence interval 1.45-7.25; p = 0.004). The odds ratio for ulcerative colitis was 2.53 (95% confidence interval 1.15-5.58; p= 0.03). No risk ratio was found for celiac disease.(1) In a population of equal size, therefore, three times as many of those immunized against measles would develop Crohn's disease than those not immunized. Remarkably, this fits in fairly well with incidence evolution. The incidence for 1960 was 0.8, that for 1980-84, 4.2 per 100,000 people per annum.(2)

The authors believe they have demonstrated an increased risk of developing inflammatory bowel disease. I would suggest it to be more probable that measles prevention confers a predisposition to autoimmune diseases in later life, the above-mentioned diseases belonging to these at least in some respects. In my opinion, the fight against the inherited body is delayed in this case but occurs "physiologically" and within a strict time schedule in the case of measles. "If the inner human being is delicate, so that he is always shrinking back, wanting to shape the substances that are taken in more according to himself, and if he fights against the model, the struggle presents in form of measles. This is why the mutual battle comes to expression in the childhood diseases. We shall only be able to gain a proper understanding of what happens later on if we are able to take account of these things."(3)

A connection may, thus, be seen between childhood diseases being increasingly prevented from happening at the right time on one hand and the rising incidence of autoimmune diseases at a later time on the other, catching up, as it were, in a way that is both inadequate and often threatening. It will be interesting to see what other correlations between diseases and immunization are discovered as time goes on.

Admittedly, there is another possible interpretation of the above results. Contact with measles vaccine is in the first two years of life, whereas wild infection tends to come later. A Swedish study has shown a connection between perinatal measles infection and Crohn's disease.(4) It seems reasonable to assume that early immunization with live vaccine may be as unfavorable in its effects as early wild measles infection.

Addendum
The study by Thompson et al. was accompanied with a critical commentary by Patricaria and Beeler(5) and mostly critical Letters to the Editor.(6-11) Most of those who commented are working in the public health sector in various countries, some of them directly responsible for measles immunization campaigns. Unanimously, they warn against forgetting the positive effects of measles immunization over the risks under discussion ("... millions of lives have been spared as a result of vaccination"(5)). Major objections were connected with the methodology, those that can be taken seriously referring to structural differences in the populations. It is, of course, not easy to examine large, homogeneous groups 30 years after immunization. Thompson et al. have given plausible reasons for selecting the subjects for their studies, which we cannot go into here. The most important objections were that the subjects in the MRC study were younger, at an average of 31 years, than the people in the control group, who were 33 on average.

As participants had been asked if they had ever had one of the inflammatory bowel diseases under investigation, this meant a relative increase in incidence in the control group and did not explain the much higher incidence among the immunized. The criticism is, therefore, out of place in this instance. There is also a significant difference in dropout rate during the c. 30 years of follow-up to the two studies. Only 76% of the NCOS study and 41% of the MRC study still responded. Yet, in their reply to the Letters to the Editor, Thompson et al. said that, even assuming all subjects of the immunization study who ceased to take part early to have been healthy, it would still leave an unusually high incidence of inflammatory bowel disease among the immunized.(12) The faults which met with criticism, thus, seem to obscure the effect of immunization rather than give it undue emphasis.

Although one would agree that further studies (ideally case record studies) are needed to confirm the suspected risk, there appears to be more evidence for than against an association between early measles immunization and bowel disease later in life.

References
1 Thompson NP, Montgomery SM, Pounder RE, Wakefield AJ. Is measles vaccination a risk factor for inflammatory bowel disease? Lancet 1995; 345:1071-4.
2 Goebell H. Allgemeine Probleme bei chronisch-entzuendlichen Darmerkrankungen. In Goebell H (Hersg): Gastroenterologie, Teil C/D, in Gerok W, Hartmann, Schuster HP: Innere Medizin der Gegenwart Bd 11. Munich 1992.
3 Steiner R. Course for Young Doctors (GA 316), lecture of 21 April 1924. Revised by G. Kamow. Spring Valley: Mercury Press 1994.
4 Ekbom A, Wakefield AJ, Zack M, Adami HO. The role of perinatal measles infection in the etiology of Crohn's disease: a population-based epidemiological study. Lancet 1994; 344:
508-10.
5 Patricaria PA, Beeler JA. Commentary. Measles and inflammatory bowel disease. Lancet 1995; 345:1062-3. 611 Letters to the Editor in Lancet 1995; 345:1062-3 by:
6 Farrington P, Miller E.
7 Caiman KC.
8 Minor CD
9 MacDonald TT.
10 Miller D, Renton A.
11 Baxter T,Radford J.
12 Thompson NP, Montgomery SM, Pounder RE, Wakefield AJ. Author's reply. Lancet 1995; 345: 1364.





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