MMR vaccine and autism, revisited
Dr. Andrew Wakefield and colleagues first reported a possible association of a syndrome of autistic regression, intestinal complaints, ileal lymphoid-nodular hyperplasia and MMR vaccination (Wakefield AJ et al, Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children, The Lancet 1998(Feb 28);351:637-641). They evaluated 12 children said to have "pervasive developmental disorder," apparent developmental regression, and nonspecific intestinal symptoms. In 6 children with a formal diagnosis of autism, onset of behavioral symptoms by history was linked to recent (within 2 weeks) immunization with MMR vaccine. In 6 other children the diagnosis of autism was apparently not established or the link to a recent MMR vaccination was tenuous. The most consistent finding on ileocolonoscopy was lymphoid nodular hyperplasia of the terminal ileum in 9 of the children. A variety of colonic and rectal mucosal abnormalities was seen in 8 children. Biopsies of the ileum showed reactive lymphoid follicular hyperplasia in 7. Biopsies of the colon showed a diffuse mononuclear cell infiltrate in 6 cases. In their discussion they state: "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described." Since then the putative association between regressive autism and MMR vaccination has taken on a life of its own, including numerous letters to the editor of The Lancet. A Medline search (May 28, 2000) found 43 references including 21 in The Lancet alone.
Fombonne (The Lancet 1998(March 28);351:955) reviewed registries of cases of inflammatory bowel disease and autism and failed to find an association. A Finnish study confirmed the lack of an association (Peltola H et al, The Lancet 1998(May 2);351:1327).
This site previously published an abstract of a paper by Dr. Brent Taylor with data refuting the implied conclusion of Dr. Wakefield that MMR vaccine is causally linked to autistic regression (Lack of a causal relationship between MMR vaccine and autism). Since then a commentary on the Taylor paper has been published in The Journal of Pediatrics, January 2000 (Volume 136, No. 1, pages 125-126), authored by Drs. Frank DeStefano and Robert T. Chen of the Vaccine Safety and Development Branch of the Centers for Disease Control and Prevention.
Dr. Brent Taylor and colleagues, responding to a letter (The Lancet, 2000(Jan 29);355:409-410), point out that 36 autistic children in his study were born before 1987 and later had "catch-up" of MMR vaccination at a somewhat older age than typical for receipt of the vaccine. In 29 instances, there was data as to the age of the child when parents were first concerned and in all cases their concerns preceded MMR vaccination. The authors also responded with data bearing on the question of possible bias because of the somewhat lengthy delay in the diagnosis of autism (which often does not reflect the age of actual onset of symptoms). After re-analyzing their data as to the age of first parental concern (rather than the age of diagnosis), they found no difference in age at first parental concern between children receiving MMR vaccine before 15 or 18 months, those receiving vaccine at 15 or 18 months, and those not receiving vaccine.
Another commentary (anonymous) appeared in the VACCINE BULLETIN, March 2000 issue (No. 133) (NCM Publishers, Inc., 2000 Varick Street, New York, NY 10014), summarizing the controversy and making the following points:
- Since publication of Wakefield's original paper, he and others have reported negative findings for the presence of measles virus in patients with inflammatory bowel disease and autism.
- A 1999 review of cases of autism and inflammatory bowel disease by the Working Party on MMR Vaccine of the UK's Committee on Safety of Medicine did not support a causal connection between MMR vaccine and regression.
- A lack of an association between MMR and autism was also found in Sweden (Autism 1998;2:423-424).
- Between January 1980 and February 1998, only 15 cases of autism were reported to the Vaccine Events Reporting System of the CDC. The vaccines included DPT, oral polio, MMR, HIB, and hepatitis B. These reports are of an anecdotal nature and do not constitute evidence for a proven association between vaccination and autism but "are likely to represent unrelated chance occurrences that happened around the time of vaccination."
The VACCINE BULLETIN quotes Neal Halsey, M.D., director of the Institute for Vaccine Safety at Johns Hopkins University:
"The pathogenesis of most forms of autism is not known. There is good evidence for genetic predisposition for some forms, and there are factors that have been identified, including intrauterine exposure to rubella, head injuries, and encephalitis in very young children. The uncertainty regarding pathogenesis opens the door to speculation about other possible contributing factors. We must use good science to evaluate the possibility of any factor that might contribute to autism, especially vaccines. Some of the publicity about MMR and autism was generated by speculation."
On April 6, 2000, Representative Dan Burton (Republican, Indiana), Chair of the House Government Reform and Oversight Committee, presided over hearings regarding MMR vaccine and autism (see The New York Times, April 7, 2000, page A19, reported by Philip J. Hilts). Rep. Burton has a grandson with autism which, he believes, was caused by MMR vaccine. Drs. Andrew Wakefield and Brent Taylor gave opposing points of view. Dr. Wakefield has coined the term, "autistic enterocolitis", for the syndrome of recent MMR vaccination, apparent autistic regression, and parental reports of abdominal pain and diarrhea. His testimony included preliminary evidence for the presence of measles viral genomic RNA in intestinal biopsy specimens in 24 of 25 autistic children. These data were further amplified by the testimony of Dr. Wakefield's colleague, Dr. John O'Leary. These data have not yet been published in the scientific peer-review literature. Moreover, it is of interest that Dr. O'Leary's data contradict Wakefield's previous study yielding negative results for the presence of measles virus genomic RNA (J Med Virology 1998;55:305-311) in patients with inflammatory bowel disease.
There were other presentations by parents and other professionals. The submitted texts of testimonies can be found at:
Burton committee hearings
The outcome of the two hours of testimony was a letter by the Committee to the Secretary of Health and Human Services, Donna Shalala, asking for an impartial study of a possible link between vaccination and autism. The Centers for Disease Control and Prevention (CDC) has established a new Web page on this issue:
Recent CDC Web page on vaccine safety and autism
The testimony of Dr. Colleen Boyle of the CDC can be found at:
Statement of Dr. Colleen Boyle of the CDC, April 7, 2000
The testimony of Dr. Paul Offit, Chief of Infectious Diseases at the Children's Hospital of Philadelphia, explains why theories of a causative relationship between MMR vaccination and autism are invalid:
Dr. Paul Offit
"Measles, MMR, and autism: the confusion continues," is the title of an editorial commentary in The Lancet, April 22, 2000, Volume 355, p. 1379) which emphasizes that measles is not a benign infection. The editorial cites WHO estimates that there were 30 million cases of measles worldwide in 1998, with 888,000 measles-related deaths. Is is also estimated that about 10 per cent of all deaths in children under age 5 years in developing countries are measles-related. The 1989-1991 measles epidemic (55,000 cases) in the U.S. was associated with 120 deaths. The incidence of subacute sclerosing panencephalitis (SSPE), a fatal complication of measles in children less than 2 years old, has declined dramatically since introduction of measles vaccination. In the wake of Wakefield's original paper (February 1998, see above), a subgroup of the British Medical Research Council recently (April 3, 2000) released a report which concluded that "between March, 1998, and September, 1999, there had been no new evidence to suggest a causal link between MMR and inflammatory bowel disease/autism".
The Lancet editorial further comments on Wakefield's testimony to the Burton Committee cited above, which amounted to a press release, reporting over 150 children with "autistic enterocolitis" and that 24 of 25 children were "positive for measles virus" in intestinal biopsy specimens compared with "one of 15 controls".
The Lancet editorial concludes:
"...parents of such children have not been served well by these latest claims made well beyond the publically available evidence. A congressional hearing, like a press conference, is no place to make controversial scientific assessments. And if scientists question the safety of vaccines without making their evidence fully transparent, harm will be done to many more children than they purport to protect."
It would be an unfortunate consequence of Dr. Wakefield's allegations regarding the safety of MMR vaccine if the rate of immunization declined and another outbreak of measles occurred.
Commentary by Ronald J. Kallen, M.D.