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February 14, 2009

No Evidence Supports Previously Held Link Between Vaccines and Autism




Laurie Barclay, MD

February 9, 2009 — There is no cause for parental concern that childhood immunization might cause autism, according to the results of a new review that shows no link between vaccines and autism. The review is published in the February 15 issue of Clinical Infectious Diseases.
"Vaccines don't cause autism — 20 studies now show no link between vaccines and autism," senior author Paul A. Offit, MD, chief of infectious diseases, The Children's Hospital of Philadelphia in Pennsylvania, told Medscape Infectious Diseases. "I think that many people are reassured by these studies, although there are still a group of parents who hold that vaccines cause autism, much as some people hold a religious belief. To those people, it really doesn't matter how many studies you do, it's not going to change their minds."
More education is needed to prevent further disease resurgence among children whose parents have refused vaccination based on this unfounded fear, he added.
Three Theoretical Links
Three specific hypotheses have been offered to suggest a theoretical link between vaccines and autism. The review describes how each of these theories originated and summarizes the pertinent epidemiological data, which refute the 3 hypotheses.
"The first theory concerned the Measles-Mumps-Rubella (MMR) vaccine; the second, that it wasn't the MMR vaccine specifically but a mercury-containing preservative, thimerosal; and the third, that the simultaneous administration of many vaccines is just too much for a young child's immune system," Bryan H. King, MD, co-chair, American Academy of Child and Adolescent Psychiatry Autism and Intellectual Disabilities Committee, told Medscape Infectious Diseases when asked for independent comment.
The first hypothesis is that the combination MMR vaccine damages the gastrointestinal lining, thereby permitting the entrance of encephalopathic proteins and causing autism. After publication of a 1998 study in The Lancet suggesting an association between MMR vaccine and autism, 13 subsequent studies performed in 5 different countries showed no such link. The reviewers concluded that no data supported any causal connection between the MMR vaccine and autism, and that any apparent association was coincidental, because the MMR vaccine is typically administered at the age when symptoms of autism first emerge.
"While rates of immunization have been constant or declined, the incidence of autism has increased, and the rate of autism in vaccinated and unvaccinated children is the same," said Dr. King, who is professor and vice chair of Psychiatry and Behavioral Sciences and director of Child and Adolescent Psychiatry at University of Washington and Seattle Children's Hospital. "Neither the timing of onset, nor the severity of autism, differ whether or when a child gets immunized,"
The second hypothesis is that thimerosal, an ethyl mercury–containing preservative used for more than 50 years in some vaccines, causes central nervous system toxicity. However, the review describes 7 studies from 5 countries demonstrating that autism rates were not affected by the presence or absence of thimerosal in vaccines.
These 20 epidemiologic studies showing that neither thimerosal nor MMR vaccine causes autism were conducted by many different investigators, using a variety of epidemiologic and statistical methods.
"Even very rare associations, if they existed, would have been detectable given the large size of studied populations," Dr. King said. "Studies on the causes of autism should focus on more promising leads."
The third hypothesis is that giving multiple vaccines simultaneously overwhelms or weakens the immune system. In rebuttal, the review authors point out that the immune system in childhood routinely processes far more antigenic material than the relatively small amount contained in vaccines, and that it is biologically implausible that vaccines overwhelm a child's immune system, even if the system is still immature.
"The challenge to the immune system from modern vaccines — even in multiple combinations — is actually significantly less than was given routinely to children back in 1980 (long before the autism epidemic)," Dr. King said.
Finally, the review authors note that autism is not triggered by an immune response, and they suggest that future research on the biological basis of autism should prove or refute alternative, more plausible hypotheses.
While the risks of vaccination concerning autism are theoretical and shown not to be valid, the risks of not being vaccinated are real and sometimes fatal.
"We've already seen the outcomes of choosing not to comply — over the last 10 years or so, we've had outbreaks of pertussis among a relatively unvaccinated population of children," Dr. Offit said. "We had a measles outbreak in this country that was bigger than anything we've had in a decade. Now we have a cluster of cases of Haemophilus Influenzae meningitis where 3 parents chose not to have their child vaccinated; all 3 children got meningitis, and all 3 of them died."
Dr. Offit noted, "The question becomes, ultimately, when do we reach the tipping point? When do we say that exempting from vaccines is creating a problem not only for those children whose parents choose not to vaccinate but for those children in the community?"
Education of the lay public, as well as the healthcare community, is needed if unfounded fears of vaccination are to be dispelled.
The "Right to Catch and Transmit Potentially Fatal Infection"
"Public health officials and the academic community are really trying to communicate this science to the public, but it's a real challenge," Dr. Offit said. "Is it your right to catch and transmit a potentially fatal infection? Right now, the answer to that question is yes, but we'll see how long it takes before the answer to that question is no."
He added that it would be unethical to do a prospective study in which some children were not vaccinated, given the known harms of failure to vaccinate, and that retrospective studies would have methodological issues because the groups would differ in characteristics other than their vaccination status.
"Focusing our precious research time and talent on questions that have been asked and answered not only contributes to ongoing confusion — for example, about whether or not to be immunized — but also will delay us from finding real answers to this critical problem," Dr. King concluded. "Parents and clinicians should have candid discussions about the risks and benefits of vaccination including the avoidance of potentially catastrophic diseases. It will be hard not to mention autism in this context, as it may give the impression that doctors are trying to hide something, and parents should feel empowered to ask these and any other questions of their clinicians, but on the other hand, constantly linking autism and vaccines in the same sentence may continue to suggest that a relationship exists when there is no evidence to support it."
Dr. Offit is a coinventor and patent coholder of the rotavirus vaccine Rotateq (Merck) and has served on a scientific advisory board to Merck. Dr. King has disclosed no relevant financial relationships.
Clin Infect Dis. 2009;48:456–461.

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