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Measles, Mumps, and Autism?
Nov 10, 2008
A controversial study published in 1998 by Wakefield et al. described a link between the relatively new MMR vaccine and autism in the United Kingdom. His findings caused a stir among concerned parents everywhere and, as a result, England suffered a decrease in MMR vaccination rates and loss of confidence in the vaccine (Offit, 2003). Since this time, numerous studies have been done to rebuild the reputation of the vaccine and assure the public of its safety. Wakefield et al. (1998) claim that the autistic symptoms of his patients can be linked to the MMR vaccine based on the correlation between the disorder and the date of vaccination. Uhlmann et al. (2002) support Wakefield’s findings but are not convincing because they fail to establish a direct causal link between the vaccine and the disease. In response to Wakefield and his supporters, numerous epidemiological studies have questioned the causal link, and these studies refute the Wakefield study on the grounds of sample size.
What is the MMR vaccine?
The acronym MMR stands for measles, mumps, and rubella. A publication from CDC (Center for Disease Control and Prevention) states that these three viruses are dangerous diseases that can spread from person to person through the air. Measles can lead to cold-like symptoms with a rash and fever and can cause pneumonia, seizures, brain damage, and death. Mumps is a similar virus characterized by a fever, headache, and swollen glands; mumps can cause deafness, meningitis, and occasionally death. Rubella, the third virus in the vaccine, can cause rash, fever, and arthritis, and can harm a developing fetus. The vaccine contains live viruses, but the side effects are minimal and can include pain at the injection site, as well as fever, rash, and swollen glands. MMR is administered in two doses at the ages of 12-15 months and again at 4-6 years (http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-mmr.pdf). According to a worksheet published by the Immunization Action Coalition, approximately 95% of children become immune to the viruses after the first dose, and the second dose to immunize the remaining 5%. Due to good immunization coverage, measles,
mumps, and rubella are rare in the United States, but the occasional outbreak does occur. For example, in 2006, over 5500 confirmed or probable cases of the mumps were reported to the CDC, and the majority of these cases occurred on college campuses in 45 states (http://www.immunize.org/catg.d/p4211.pdf).
What is autism?
According to the Autism Society of America, autism is a developmental disability that presents itself in the toddler years, and it can vary in its severity and symptoms. The CDC estimates that 1 in 150 children are affected by autism, which includes 1 in 94 boys. In addition, about 1.5 million Americans have the disability. Studies have shown that early detection and intervention can lessen the effects of the disability as the child grows (http://www.autism-society.org/site/PageServer?pagename=about_home). Regressive autism is a type of autism that causes children to lose their ability to speak and function correctly. It is this type of autism that has been linked to the MMR vaccine (http://www.mmrthefacts.nhs.uk/library/regressive.php).
When the Wakefield study was released in February of 1998, the popular media soon began warning the public against the dangers of the MMR vaccine. According to an article published by BBC News on February 27, 1998, reported that “a common childhood vaccine may be linked with autism and cause an intestinal disorder” (http://news.bbc.co.uk/2/hi/uk_news/60510.stm). The article recommends that children be vaccinated against each virus (measles, mumps, and rubella) separately because “the combination of the three virus strains may overload the body's immune system and cause the bowel disorder to develop” (http://news.bbc.co.uk/2/hi/uk_news/60510.stm). The story was presented to the public through popular news forums, and though they intended to warn the public of a potential threat, the media caused an unnecessary amount of parental concern. As a result of the media warnings, some data suggests vaccination rates fell from 90% to 84.6% because of the Wakefield article; in addition, three deaths occurred in Northern Ireland as a result of a measles outbreak linked to the decline in immunizations (http://www.idinchildren.com/200404/frameset.asp?article=mmr.asp).
Relevant scientific literature
As mentioned above, the Wakefield et al. (1998) paper started the MMR controversy and much of the following research has worked to disprove the hypothesis that the vaccine can cause autism in children. I will examine the Wakefield et al. paper, one additional paper that explores a possible link between the vaccine and the disease, and three other papers that provide evidence against any correlation.
Wakefield, Murch, Anthony, Linnell, Casson, Malik, Berelowitz, Dhillon, Thomson, Harvey, Valentine, Davies, Walker-Smith (1998)
Wakefield and his associates set out to study the relationship between chronic enterocolitis (inflammation of the gastrointestinal tract) and regressive autism in the study titled “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.” The investigators collected data on 12 children who were referred to them with gastrointestinal symptoms and an apparent loss of communication and normal functioning. The children went through various behavioral and laboratory tests including biopsy sampling, MRI (magnetic resonance imaging), EEG (electroencephalography), lumbar punctures, and biochemical profiles. The investigators found an association between the onset of the regressive autism symptoms and the time when the children received the MMR vaccine. The researchers proposed a new disease path caused by the MMR vaccine that includes gastrointestinal and regressive development symptoms (Wakefield et al., 1998).
Uhlmann, Martin, Sheils, Pilkington, Silva, Killalea, Murch, Walker-Smith, Thomson, Wakefield, O’Leary (2002)
The Uhlmann group looks at the presence of the measles virus in the intestines of children with inflammatory bowel disease (IBD) and a developmental disorder in the paper titled “Potential viral pathogenic mechanism for new variant inflammatory bowel disease.” The investigators collected samples in various ways from the terminal ileum of 91 children affected with ileal lymphonodular hyperplasia and 70 controls not affected by the disease. The samples were then analyzed for the presence of the measles virus. The study found that 75 of the 91 affected children had evidence of the measles virus, compared with 5 of the 70 controls. This study suggests there is a positive correlation between children with developmental disorders with accompanying gastrointestinal symptoms and the measles virus (Uhlmann et al., 2002).
Fombonne and Chakrabarti (2001)
The study “No evidence for a new variant of measles-mumps-rubella-induced autism” examines the claim that the MMR vaccine is linked to a new form of autism that is a combination of developmental and gastrointestinal symptoms (referred to as “autistic enterocolitis”). The paper attempts to disprove that this new form of autism exists based on 6 criteria. The study used three different sources of data: epidemiological data that includes 96 children immunized with MMR and diagnosed with a pervasive developmental disorder, and two previous clinical samples that included data pre- and post-MMR vaccine for autistic children. In addition, gastrointestinal data was collected from the epidemiological sample. The study found that the prevalence of a developmental disorder was 0.6/10,000, which suggests that children that received the MMR vaccine do not have a higher frequency of disease than children who did not receive the vaccine. Also, there was no difference in the mean age when parents first started to note developmental problems between children who received the vaccine and children that did not. This means that the MMR vaccine is not causing children to develop autism earlier in life. This study concludes that “autistic enterocolitis” does not seem to exist, and there was no link found between the MMR vaccine and autism (Fombonne and Chakrabarti, 2001).
Peltola, Patja, Leinikki, Valle, Davidkin, Paunio (1998)
The study from Peltola et al. titled “No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study” examined the supposed link between the MMR vaccine and autism or inflammatory bowel disease. The study examined medical records in Finland to determine any link. The investigators looked at over three million doses of the vaccine given from 1982-1996, and traced any children that showed gastrointestinal symptoms that lasted 24 hours or more. 31 children fit these criteria and, of these children, the majority experienced diarrhea and vomiting. No children were found with developmental disorders. The study concludes that the MMR vaccine does not cause inflammatory bowel disease or developmental disorders (Peltola et al., 1998).
Madsen, Hviid, Vestergaard, Schendel, Wohlfahrt, Thorsen, Olsen, Melbye (2002)
The study “A population-based study of measles, mumps, and rubella vaccination and autism” from Madsen et al. looks at the relationship between the MMR vaccination and autism disorders. The investigators obtained the medical records for all children born in Denmark between January 1991 and December 1998 from the Danish Civil Registration System, among other sources. A total of 537,303 children were investigated, and 440,655 received the MMR vaccine. Of these, the authors found 316 children with autism and 422 with a related autism-spectrum disorder. The researchers found there was no link between the MMR vaccine in any way (age at vaccination, date of vaccination or time elapsed) and autistic disorders (Madsen et al., 2002).
The Wakefield paper, which started the controversy in the UK that quickly spread to the rest of the world, has subsequently been retracted by 10 of the 12 authors. The retraction states “no causal link was established between MMR vaccine and autism as the data were insufficient” (Murch et al., 2004). Furthermore, the paper was flawed in several ways. Dr. Offit point out in his paper “Vaccines and Autism” that since autism is usually diagnosed in the same point in time when the first MMR vaccine is given, it is not out of the ordinary that children with autism have received the vaccine. The only way to determine if the vaccine causes autism is to study autism in children who have received the vaccine as well as children who have not received the vaccine (http://www.immunize.org/catg.d/p2065.pdf).
The claims made in the Wakefield et al. (1998) paper have not held up against the scientific community. The Wakefield paper is weakened by its small sample size (12) and by the fact that the correlation between the vaccine and disorder does not suggest causation. Similarly, the Uhlmann study suffers from a relatively small sample size (91) and shows a correlation but not a direct causal link. The Fombonne, Peltola, and Madsen papers are more convincing because of their significantly larger sample size and the nature of the epididemiological studies. It follows that the media coverage of the MMR scare was incorrect since the study they were reporting from (Wakefield et al.) was inherently flawed. Though the media’s intentions were to simply inform the public of a threat to their health, the attention produced unnecessary concern that resulted in a decline in vaccination rates. The research put forth since the paper was published in 1998 has sufficiently established that the MMR vaccine is not linked to autism, and it is safe to vaccinate children against the three viruses. In addition, the CDC has deemed the vaccine safe and formally recommends that the vaccine be administered to all children. I agree with this recommendation, since the benefits of the vaccine seem to far outweigh the potential side effects or risks of other disease.
Fombonne, E., & Chakrabarti, S. (2001). No evidence for a new variant of measles-mumps rubella-induced autism. Pediatrics, 108(4).
Madsen, K. M., Hviid, A., Vestergaard, M., Schendel, D., Wohlfahrt, J., Thorsen, P., Olsen, J., & Melbye, M. (2002). A population-based study of measles, mumps, and rubella vaccination and autism. New England J Med, 347(19), 1477-1482.
Murch, S. H., Anthony, A., Casson, D.H., Malik, M., Berelowitz, M., Dhillon, A. P., Thomson, M. A., Valentine, A., Davies, S. E., & Walker-Smith, J A. (2004). Retraction of an interpretation. The Lancet, 363(9411), 750.
Peltola, H., Patja, A., Leinikki, P., Valle, M., Davidkin, I., & Paunio, M. (1998). No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. The Lancet, 351, 1327-1328.
Uhlmann, V., Martin, C. M., Sheils, O., Pilkington, L., Silva, I., Killalea, A., Murch, S. B., Walker Smith, J., Thomson, M., Wakefield, A. J., & O’Leary, J. J. (2002). Potential viral pathogenic mechanism for new variant inflammatory bowel disease. J Clin Pathol: Mol Pathol, 55, 84-90.
Wakefield, A. J., Murch, S. H., Anthony, A., Linnell, J., Casson, D. M., Malik, M., Berelowitz, M., Dhillon, A. P., Thomson, M. A., Harvey, P., Valentine, A., Davies, S. E., & Walker-Smith, J. A. (1998). Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet, 351, 637-641.
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