Inflammatory Bowel Disease and Vaccines

1. What is Inflammatory Bowel Disease?

Inflammatory Bowel Disease, also known as IBD, is a general medical term used to refer to chronic inflammatory diseases of the intestine.

Two common inflammatory bowel diseases are ulcerative colitis and Crohn's disease. These chronic illnesses can inflame the gastrointestinal tract causing bloody diarrhea, abdominal pain, and weight loss. Ulcerative colitis can affect the entire large intestine or the rectum. Crohn's disease mainly affects short segments of both the small and large intestine. Although IBD can begin at any age, it's usual onset is from age 15 to 30 years. IBD is a rare disease with 3-20 new cases recognized per 100,000 persons per year.

2. What causes inflammatory bowel disease?

The cause(s) of inflammatory bowel disease is not known.

There are several unproven theories as to the cause(s) of IBD: A) IBD is known to occur in the same family suggesting a possible inherited cause. B) A possible environmental cause is suggested because Crohn's disease most often occurs in people who smoke , residents of Northern European countries and in urban areas. C) Another theory is that significant emotional events in a persons life may trigger the disease. D) Other researchers speculate that the disease may be caused by an infection or virus. E) Still others believe that the body's immune system is reacting to unidentified or unknown antigens (a protein marker on the surface of cells that identifies the cell). This antigen would cause the immune system to respond inappropriately resulting in chronic inflammation.

It is not known if measles, mumps or rubella virus infection can cause IBD. The virus that causes measles disease infects the respiratory system and then spreads to lymphatic tissue (an important part of our immune system). During the acute infection, lymph cells in the gastrointestinal (GI) tract are infected but whether this causes chronic inflammation is highly questionable. One theory speculates that measles virus may persist in the intestine in certain individuals and later trigger a chronic inflammatory infection, however this has not been proven. Because MMR vaccine contains a very weak live measles virus it has been suggested that measles vaccine could cause an inflammatory process in the intestine. This theory has not been proven and is speculative. Two types of data - epidemiological and pathological-link measles infection and IBD. However, because conflicting results have been obtained for both types of data by different investigators, this link can not be established.

3. Does the measles virus vaccine cause IBD?

There is no scientific proof that measles vaccine virus can cause IBD.

In fact, because almost everyone is vaccinated when they are young, most people with IBD will have received a vaccine. In order to prove that measles vaccine caused IBD it would be necessary to prove that the measles virus is definitely present in GI lesions, that it is active, and that it can cause an inflammatory response. Additionally, it would have to be shown that this reaction was caused by the measles virus or by the attenuated (weakened) measles vaccine virus.

4. What about studies that have suggested an association between measles virus vaccine and IBD?

Isolated studies that have suggested an association are weak and have several flaws.

The possibility of an association between measles virus and chronic inflammatory bowel disease was recently discussed in a British medical journal, The Lancet. Researchers believe they discovered a new childhood illness that caused bowel disease and psychiatric problems including behavioral disorders and autism. MMR vaccine was suggested as a possible cause. The theory is that MMR vaccine could lead to intestinal inflammation resulting in decreased absorption of the intestinal tract to essential vitamins and nutrients which in turn could lead to developmental disorders. An editorial expressing concerns about the study was also published in the same issue. That all patients had bowel disease is not surprising since all were referred to a department of gastroenterology. Some of the concerns expressed were that in this small study (12 patients) there is no report of detection of vaccine viruses in GI or brain tissue for any of the patients. Multiple laboratories using more sensitive and specific laboratory tests, have failed to detect any findings to suggest this. In addition the GI pathology should have existed prior to the behavioral symptoms to support there theory. The researchers reported the onset of GI symptoms was unknown in 5 patients and noted after the onset of behavioral symptoms in another 5 patients.

A few Swedish studies have also suggested a high risk of Crohn's Disease in those exposed to measles in utero. However, the Swedish studies involved very small numbers of cases, 2 cases in the first study and 4 in the second study (2 of which were cases in the first study).

Another study suggested in a retrospective cohort study that MMR vaccine might be a risk factor for Crohn's disease. However, the selection and recall biases and the differences in data collection in this study were so substantial as to cast doubt on the validity of the findings.

Another study has reported finding measles virus proteins and RNA in the intestinal tissue of cases of Crohn's disease using in situ hybridization and immunologic staining .

5. Is there scientific evidence (both epidemiologic and laboratory) to show there is no association between measles vaccine and inflammatory bowel disease?

There is strong scientific evidence (both epidemiologic and laboratory) to show there is no association between measles vaccine and inflammatory bowel disease.

In June 2000, the results of a population-based epidemiologic study conducted by the CDC, concluded that there was no evidence that vaccination with MMR or other measles-containing vaccines, or the the age of vaccination early in life, was associated with an increased risk for the the development of IBD. Using a case-control design, the study compared patients diagnosed with IBD and those without IBD, and looked at the vaccination history of MMR vaccine and the  timing of vaccinations. No association was found to link the MMR vaccine and IBD. This study was the result of a collaborative project between the CDC and four large HMO's, part of the Vaccine Safety Datalink Project.

Four other epidemiologic studies have failed to confirm the possible association between measles virus and inflammatory bowel disease. Nielsen et al. examined all possible cases of measles in pregnant women admitted to a Copenhagen hospital from 1915-1966. None of the offspring of the 25 identified women had developed Crohn's disease. In 1995, Hermon-Taylor compared the incidence of Crohn's disease in England and Wales with measles infection, including information after the introduction of measles vaccine. No association was found. In their case-control studies, Jones et al and Feeney et al found no association between IBD and measles infection or measles vaccine, respectively.

In another study, researchers used the same laboratory methodology as Wakefield et al., and could not identify any measles virus in patients with IBD, although they did find the presence of other viral and bacterial agents (Liu). Several other research groups using more sensitive and specific tests (polymerase chain reaction, PCR) have not found any evidence of measles virus RNA in the gastrointestinal tissues of patients with Crohn's Disease or ulcerative colitis.

6. What does the CDC recommend for measles, mumps rubella (MMR) vaccine?

The CDC continues to recommend two doses of MMR vaccine for all persons; for children, the first dose is recommended at 12-15 months of age and the second dose is recommended at 4-6 years of age.

Although the risk of Inflammatory Bowel Disease (IBD) is higher for those who have relatives with IBD, there are no data to suggest that measles vaccine will increase or decrease this risk. Measles vaccine is recommended for children with a family history of IBD unless there is another specific reason not to vaccinate. (for example, in persons who very ill and are not able to fight infections)

Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, November 2000

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