Measles-containing vaccines, IBD and autism

April 2001

Vaccines are given to almost every child in America and each child receives multiple vaccines. It is likely that some children will experience a significant event, by chance, either before or after an immunization visit.

I remember seeing a child whom I diagnosed as having infantile spasms a few days before the scheduled visit for his first diphtheria-tetanus-pertussis immunization. Had this occurred a few weeks later, his parents would have thought there was an association between immunization and infantile spasms.

Because we mandate immunization of children, some parents feel a loss of empowerment over the management of their most precious possession — their child — and, thus, become concerned about any allegation about the safety of vaccines. Vaccines have been suspected of a variety of ill effects for many years and no doubt there will be additional allegations in the future. Suspicion is not all bad, as they result in our being alert to possible dangers. The safety of vaccines has been an increasing concern and substantial resources have been allocated to assuring safety. Witness the relationship between intussusception and rotavirus vaccine (RotaShield, Wyeth Lederle) as an example of the success of the system and the justification for being vigilant.

MMR and autism

The current concern over the association between measles-containing vaccines (MCV) and inflammatory bowel disease (IBD) and autism is fueled largely by the report of Wakefield, et al. which appeared in The Lancet (1998;351:637) entitled “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.” They reported on 12 children, some of whom had loss of milestones, and some developed gastrointestinal symptoms. In 8 children, the parents related symptoms to administration of measles-mumps-rubella vaccine (MMR).

One child who received monovalent measles vaccine, and later received MMR, had some developmental slowing after both doses, which the mother did not relate to immunization. Studies of specimens of bowel have been said to have tested positive for evidence of measles virus. This led to a series of testimonials of other cases, some to a congressional committee whose chairman’s grandchild has autism. I have been reminded recently that the plural of anecdote is not proof.

When first presented with an association of bowel disease with measles, mumps or rubella, the initial question has been plausibility.

Unfortunately, we do not know the etiology of IBD, and thus, one can propose whatever ones wishes. Dr. Wakefield, a gastroenterologist, has had an interest in measles and IBD for some time. In the original article in The Lancet moreover, he indicates that Asperger “recorded the link between coeliac disease and behavioral psychosis.” Thus, he appears to view these cases through the eyes of a gastroenterologist. Although it is useful to have people think “outside of the box,” it is important to determine whether they are “over the top.” Unfortunately, virologists have been unable to confirm his virologic findings, and epidemiologists have problems with his methodology in this area.

Wakefield and his colleagues have found that specimens of bowel have tested positive for evidence of measles virus in patients with Crohn’s disease. In addition, the specimens obtained from some of the patients in the original report were said to have been positive.

Unfortunately, this discussion has proceeded in the absence of these data having been published so that it is difficult to examine them. A number of investigators have failed to find measles antigens in bowel specimens of patients with IBD. One investigator found that the monoclonal antibody used in the Wakefield studies cross-reacted with a measles-related protein, which may accumulate in areas of inflammation, eg, the bowel in IBD. The product found by reverse-transcriptase polymerase chain reaction was the same size as a human gene (Lancet. 2000;356:160). Thus the specificity of the Wakefield findings are questionable.

The Wakefield group was undoubtedly influenced by an earlier English study reporting an increased risk of IBD following MCV (Lancet. 1995;345:1071). The methodology of this study has been seriously questioned. There have been numerous studies that have failed to find an epidemiologic association between the use of MCV and IBD. Most recently, a study in HMOs representing about 2% of all children younger than 7 failed to find an association (Arch Ped Adol Med. 2001;155:355). The authors cited one unexpected finding namely that immunization with MMR after 18 months apparently had a protective effect against IBD. One must be careful in interpreting associations. One is reminded of the story of the child who arrived in front of his burning house and wanted to know why the firemen had set his house aflame.

Is there an association?

The association of autism with MCV also has undergone scrutiny. In a recent study from California, the putative increase in autism appears to be out of sync with the increased use of MMR (JAMA. 2001;285:1183). The presumed increase in autism also has been questioned (Pediatrics. 2001;107:411). The increase in population and the changing definition of autism are believed to account for at least some of the increase. A number of studies now reject the association of autism with MCV.

There will continue to be concerns about the safety of vaccines, concerns that we share with parents. The systems to detect problems have become more sophisticated, and these systems are costly but necessary. We must be aware that allegations need to be answered and the cost may be measured in more than money. The MMR scare left some children in the United Kingdom unimmunized against measles, and this is not a trivial disease.

We must remember that not vaccinating children has consequences. The recent mercury scare in this country resulted in curtailment of hepatitis B immunization of newborns and this, too, may have its cost (MMWR. 2001;50:94).

We must not shirk questions of safety, and it is important that we be armed with the information needed to respond to parental concerns. The data needed to respond will continue to be accumulated, not only during vaccine trials, but during the equally important post-marketing trials. It is important, moreover, to carefully analyze data. In the case of rotavirus vaccine, where the vaccine clearly was culpable, one must determine whether a proven adverse effect outweighs the risk of immunization. What often is lost in these discussions is consideration of the alternatives. Could we, for instance, stop MMR if it was shown that it was responsible for rare cases of IBD or autism? So far, we do not have to make this decision, as the preponderance of evidence is that it is not.