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Drug Safety
Published in: Drug Safety 12/2004

01-10-2004 | Current Opinion

MMR Vaccination and Autism

What is the Evidence for a Causal Association?

Authors: Dr Kreesten M. Madsen, Mogens Vestergaard

Published in: Drug Safety | Issue 12/2004

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Abstract

It has been suggested that vaccination with the measles-mumps-rubella (MMR) vaccine causes autism. The wide-scale use of the MMR vaccine has been reported to coincide with the apparent increase in the incidence of autism. Case reports have described children who developed signs of both developmental regression and gastrointestinal symptoms shortly after MMR vaccination.
A review of the literature revealed no convincing scientific evidence to support a causal relationship between the use of MMR vaccines and autism. No primate models exist to support the hypothesis. The biological plausibility remains questionable and there is a sound body of epidemiological evidence to refute the hypothesis. The hypothesis has been subjected to critical evaluation in many different ways, using techniques from molecular biology to population-based epidemiology, and with a vast number of independent researchers involved, none of which has been able to corroborate the hypothesis.
Literature
1.
Panum P. Observations made during the epidemic of measles on the Faroe Islands in the year 1846 [in Danish]. Bibl Læger 1847; 1: 270–344
2.
Enders J, Peebles TC. Propagation in tissue cultures of cytopathogenic agents from patients with measles. Proc Soc Exp Biol Med 1954; 86: 277–86PubMed
3.
Katz SL, Enders J. Immunization of children with a live attenuated measles virus. Am J Dis Child 1959; 98: 605–7
4.
Measles eradication: recommendations from a meeting cosponsored by the World Health Organization, the Pan American Health Organization, and CDC. MMWR Recomm Rep 1997; 46 (RR-11): 1–20
5.
Anderson RM, May RM. Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes. J Hyg (Lond) 1985; 94(3): 365–436CrossRef
6.
McLean ME, Walsh PJ, Carter OA. Measles in Canada-1989. Can Commun Dis Rep 1990; 16(42): 213–8
7.
8.
9.
Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoidnodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351(9103): 637–41PubMedCrossRef
10.
Wakefield AJ, Anthony A, Murch SH, et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol 2000; 95(9): 2285–95PubMedCrossRef
11.
California Department of Developmental Services HaHSA. Changes in the population of persons with autism and pervasive developmental disorders in California’s Developmental Services System: 1987 through 1998. A report to the Legislature. California: California Health and Human Services Agency, 2001
12.
13.
MMR vaccine: how effective and how safe? Drug Ther Bull 2003; 41 (4): 25–9
14.
15.
Furlano RI, Anthony A, Day R, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr 2001; 138(3): 366–72PubMedCrossRef
16.
Robbins FC. Measles: clinical features. Pathogenisis, pathology, and complications. Am J Dis Child 1962; 103: 266–73PubMed
17.
Johnson RT, Griffin DE, Hirsch RL, et al. Measles encephalomyelitis: clinical and immunologic studies. N Engl J Med 1984; 310(3): 137–41PubMedCrossRef
18.
Griffin DE, Ward BJ, Jauregui E, et al. Immune activation in measles. N Engl J Med 1989; 320(25): 1667–72PubMedCrossRef
19.
Singh VK, Lin SX, Yang VC. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol 1998; 89(1): 105–8PubMedCrossRef
20.
Sidhu MS, Crowley J, Lowenthal A, et al. Defective measles virus in human subacute sclerosing panencephalitis brain. Virology 1994; 202(2): 631–41PubMedCrossRef
21.
Gibbs FA, Gibbs EL, Carpenter PR, et al. Electroencephalographic abnormality in “uncomplicated” childhood diseases. JAMA 1959; 171: 1050–5CrossRef
22.
Ward B, DeWals P. Association between measles infection and the occurrence of chronic inflammatory bowel disease. Can Commun Dis Rep 1997; 23(1): 1–5PubMed
23.
Kawashima H, Mori T, Kashiwagi Y, et al. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 2000; 45(4): 723–9PubMedCrossRef
24.
Afzal MA, Armitage E, Begley J, et al. Absence of detectable measles virus genome sequence in inflammatory bowel disease tissues and peripheral blood lymphocytes. J Med Virol 1998; 55(3): 243–9PubMedCrossRef
25.
Chadwick N, Bruce IJ, Schepelmann S, et al. Measles virus RNA is not detected in inflammatory bowel disease using hybrid capture and reverse transcription followed by the polymerase chain reaction. J Med Virol 1998; 55(4): 305–11PubMedCrossRef
26.
Haga Y, Funakoshi O, Kuroe K, et al. Absence of measles viral genomic sequence in intestinal tissues from Crohn’s disease by nested polymerase chain reaction. Gut 1996; 38(2): 211–5PubMedCrossRef
27.
Iizuka M, Nakagomi O, Chiba M, et al. Absence of measles virus in Crohn’s disease [letter]. Lancet 1995; 345(8943): 199PubMed
28.
Afzal MA, Armitage E, Ghosh S, et al. Further evidence of the absence of measles virus genome sequence in full thickness intestinal specimens from patients with Crohn’s disease. J Med Virol 2000; 62(3): 377–82PubMedCrossRef
29.
Sugiura A, Yamada A. Aseptic meningitis as a complication of mumps vaccination. Pediatr Infect Dis J 1991; 10(3): 209–13PubMedCrossRef
30.
Dourado I, Cunha S, Teixeira MG, et al. Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs. Am J Epidemiol 2000; 151(5): 524–30PubMedCrossRef
31.
Katz M, Plotkin SA. Parainfectious encephalopathies associated with measles, mumps, chickenpox, and German measles. Philadelphia (PA): Lea & Febiger, 1977
32.
Plotkin SA, Cochran W, Lindquist JM, et al. Congenital rubella syndrome in late infancy. JAMA 1967; 200(6): 435–41PubMedCrossRef
33.
Sheppard S, Smithells RW, Dickson A, et al. Rubella vaccination and pregnancy: preliminary report of a national survey [letter]. BMJ (Clin Res Ed) 1986; 292(6522): 727CrossRef
34.
Weil ML, Itabashi H, Cremer NE, et al. Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. N Engl J Med 1975; 292(19): 994–8PubMedCrossRef
35.
Parkman PD. Combined and simultaneously administered vaccines: a brief history. Ann N Y Acad Sci 1995; 754: 1–9PubMedCrossRef
36.
DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60(4): 504–9PubMedCrossRef
37.
Hornig M, Lipkin WI. Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: epidemiology, hypotheses, and animal models. Ment Retard Dev Disabil Res Rev 2001; 7(3): 200–10PubMedCrossRef
38.
Carbone KM, Rubin SA, Pletnikov M. Borna disease virus (BDV)-induced model of autism: application to vaccine safety test design. Mol Psychiatry 2002; 7Suppl. 2: S36–7PubMedCrossRef
39.
Pletnikov MV, Moran TH, Carbone KM. Borna disease virus infection of the neonatal rat: developmental brain injury model of autism spectrum disorders. Front Biosci 2002; 7: d593–607PubMedCrossRef
40.
Kennedy RC, Shearer MH, Hildebrand W. Nonhuman primate models to evaluate vaccine safety and immunogenicity. Vaccine 1997; 15(8): 903–8PubMedCrossRef
41.
Bachevalier J. Brief report: medial temporal lobe and autism: a putative animal model in primates. J Autism Dev Disord 1996; 26(2): 217–20PubMedCrossRef
42.
Stratton K, Gable A, Shetty P, et al., editors. Immunization safety review: measles-mumps-rubella vaccine and autism. Washington, DC: National Academy Press, 2001
43.
Peltola H, Patja A, Leinikki P, et al. No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. Lancet 1998; 351(9112): 1327–8PubMedCrossRef
44.
45.
Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999; 353(9169): 2026–9PubMedCrossRef
46.
Patja A, Davidkin I, Kurki T, et al. Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up. Pediatr Infect Dis J 2000; 19(12): 1127–34PubMedCrossRef
47.
Farrington CP, Miller E, Taylor B. MMR and autism: further evidence against a causal association. Vaccine 2001; 19(27): 3632–5PubMedCrossRef
48.
Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ 2001; 322(7284): 460–3PubMedCrossRef
49.
Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California. JAMA 2001; 285(9): 1183–5PubMedCrossRef
50.
Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics 2001; 108(4): E58PubMedCrossRef
51.
Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002; 347(19): 1477–82PubMedCrossRef
52.
Makela A, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 2002; 110(5): 957–63PubMedCrossRef
53.
Rosenthal S, Chen R. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 1995; 85(12): 1706–9PubMedCrossRef
54.
Taylor B, Miller E, Farrington P. Autism and measles, mumps, and rubella vaccine: authors’ reply. Lancet 2000; 355(9201): 409–10CrossRef
55.
Farrington CP. Relative incidence estimation from case series for vaccine safety evaluation. Biometrics 1995; 51(1): 228–35PubMedCrossRef
56.
Gillberg C, Steffenburg S, Schaumann H. Is autism more common now than ten years ago? Br J Psychiatry 1991; 158: 403–9PubMedCrossRef
57.
Smeeth L, Hall AJ, Fombonne E, et al. A case-control study of autism and mumps-measles-rubella vaccination using the general practice research database: design and methodology. BMC Public Health 2001; 1(1): 2PubMedCrossRef
58.
Bertrand J, Mars A, Boyle C, et al. Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation. Pediatrics 2001; 108(5): 1155–61PubMedCrossRef
59.
Yeargin-Allsopp M, Rice C, Karapurkar T, et al. Prevalence of autism in a US metropolitan area. JAMA 2003; 289(1): 49–55PubMedCrossRef
60.
Larsson HJ, Eaton WW, Madsen KM, et al. Risk factors for autism: perinatal factors, parental psychiatric history and socioeconomic status. Am J Epidemiol. In press
61.
Bircher J, Benhamou JP, McIntyre N, et al., editors. Oxford textbook of clinical hepatology. 2nd ed. Oxford: Oxford University Press, 1999
62.
Segal MB. The choroid plexuses and the barriers between the blood and the cerebrospinal fluid. Cell Mol Neurobiol 2000; 20(2): 183–96PubMedCrossRef
63.
64.
Madsen KM, Lauritsen MB, Pedersen CB, et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics 2003; 112(3 Pt 1): 604–6PubMedCrossRef
65.
Halsey NA, Hyman SL. Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New Challenges in Childhood Immunizations Conference convened in Oak Brook; 2000 Jun 12-13; Illinois. Pediatrics 2001; 107(5): E84PubMedCrossRef
66.
Medical Research Council. MRC review of autism research: epidemiology and causes. London: British Medical Research Council, 2001
67.
DeStefano F, Chen RT. Autism and measles-mumps-rubella vaccination: controversy laid to rest? CNS Drugs 2001; 15(11): 831–7PubMedCrossRef
68.
Wilson K, Mills E, Ross C, et al. Association of autistic spectrum disorder and the measles, mumps, and rubella vaccine: a systematic review of current epidemiological evidence. Arch Pediatr Adolesc Med 2003; 157(7): 628–34PubMedCrossRef
69.
DeStefano F. MMR vaccine and autism: a review of the evidence for a causal association. Mol Psychiatry 2002; 7Suppl. 2: S51–2PubMedCrossRef
70.
71.
Strategies for reducing global measles mortality. Wkly Epidemiol Rec 2000; 75 (50): 411–6
Metadata
Title
MMR Vaccination and Autism
What is the Evidence for a Causal Association?
Authors
Dr Kreesten M. Madsen
Mogens Vestergaard
Publication date
01-10-2004
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 12/2004
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200427120-00001

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