Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study
PLoS ONE 3(9): e3140
Mady Hornig [1], Thomas Briese [1], Timothy Buie [2], Margaret L. Bauman [3], Gregory Lauwers [4], Ulrike Siemetzki [1], Kimberly Hummel [5], Paul A. Rota [5], William J. Bellini [5], John J. O'Leary [6], Orla Sheils [6], Errol Alden [7], Larry Pickering [8], W. Ian Lipkin [1]
[1] Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, United States of America, [2] Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts, United States of America, [3] Department of Neurology, Harvard Medical School and Departments of Neurology and Pediatrics and Learning and Developmental Disabilities Evaluation and Rehabilitation Services (LADDERS), Massachusetts General Hospital, Boston, Massachusetts, United States of America, [4] Department of Pathology of Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America, [5] Measles, Mumps, Rubella, and Herpesvirus Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, [6] Department of Histopathology, Trinity College Dublin, Dublin, Ireland, [7] American Academy of Pediatrics, Elk Grove Village, Illinois, United States of America, [8] National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
Background
The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine.
Methodology/Principal Findings
The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression.
Conclusions/Significance
This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD.
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