IOM panel to focus on safety of vaccines

The task is to explore concerns like the alleged link between the MMR vaccine and autism to maintain public confidence in immunization policies.

By Stephanie Stapleton, amednews staff. March 26, 2001.

Washington -- Many parents of children with autism tell a similar story. Sometimes hours, sometimes days after receiving the measles-mumps-rubella vaccine, the child experienced violent symptoms -- a startling illness, a serious rash, a high fever. Then the previously developmentally typical child began regressing.

This association has caught the attention of many parent-advocates, as well as some clinicians and researchers. To them, it offers a possible explanation for the sudden onset of this mysterious developmental disorder. However, the hard science backing it up has yet to emerge. Moreover, many public health experts worry that the concern will accelerate an erosion of confidence regarding immunization and lead to a society vulnerable to diseases that have now been battled into submission.

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In an effort to inform the debate, the Institute of Medicine held the first in a series of meetings of its Immunization Safety Review panel March 8. The panel is charged with exploring the existing body of science related to this possible causal link and focusing on the gaps of information that must be filled before concrete findings and recommendations can be offered.

"I hope as clinicians and researchers that we don't get put into a position that by requesting investigation we are saying that the parent is wrong," said Kathryn Carbone, MD, chief of the laboratory of pediatric and respiratory viral diseases at the Food and Drug Administration's Vaccines Research and Review Office. "Clinical associations are very important. But associations can be harmful as well as helpful. They must be studied objectively." Dr. Carbone was a presenter at the March IOM meeting.

The IOM panel, established in response to a request by the Centers for Disease Control and Prevention and the National Institutes of Health, will review hypotheses about existing and emerging immunization safety concerns. This is the third time the IOM has convened such a panel. Ultimately, the panel, which will meet three times a year during a three-year period, will issue specific reports to provide a framework through which immunization safety can be considered.

Incidence of autism, once considered rare, has increased as much as 500% by some counts. Its dramatic rise has led to a stepped-up search for possible causes, both genetic and environmental. And that is where questions about vaccines have found traction. Some advocates look to the MMR vaccine as a starting point. Others cite the burden placed on the immune system by the 22 separate vaccines given between birth and age 2 as triggering a whole array of illnesses.

Speaking at the IOM committee's organizational meeting in January, Louis Cooper, MD, vice president of the American Academy of Pediatrics, acknowledged the concerns. But he urged caution, saying that the "remarkable success of immunization has altered perceptions of the need for and safety of vaccines." He also said that the "almost universal acceptance of childhood immunization is being threatened by allegations of vaccine-induced adverse events," much of which is based on anecdotal evidence.

"Since every child receives multiple vaccines at almost two monthly intervals during the first two years of life, it is inevitable that most illnesses of early childhood occur in some temporal relationship to immunization," he said. "The challenge ... is to sort out causality from coincidence. Coincidence and anecdote play important roles in advancing medical science but are where the investigative process begins -- never the conclusion."

Efforts to get at this question during the March IOM meeting focused on research advanced by Dr. Andrew Wakefield of the Royal Free Hospital in London. He investigated the relationship between the MMR vaccine and inflammatory bowel disease in children with pervasive developmental disorder. Dr. Wakefield examined a sample of 12 children, age 3 to 10. Eleven had chronic or acute nonspecific colitis. Eight had a definitive diagnosis of autism, one was "questionable and possibly disintegrative disorder," with another in the "autistic spectrum disorder." Two had "postvaccinial encephalitis."

Those who support Wakefield's findings are intrigued by the fact that he identified the weakened virus used in the measles vaccine in the intestines of these children, who had shown developmental regression within 14 days of being given the MMR vaccine. He maintains that this viral infection may have allowed certain potential toxins to enter the bloodstream and be transported to the brain. He is expected to publish findings from a larger study soon.

Still, questions remain about his hypothesis. According to an IOM background report, his study is the only one to date to link autism, the vaccine and gastrointestinal involvement. Meanwhile, other epidemiologic studies reviewed by the IOM provided little concrete information about the relationship between MMR vaccine and autism. Also, analysis of the number and characteristics of children diagnosed with autism and related disorders remains limited. Trends in the diagnosis and possible changes in prevalence complicate attempts to relate increases in the number of cases to introduction of MMR vaccine. In addition, because the onset of autism is typically insidious, it is difficult to find a precise connection between vaccination and onset.

Meanwhile, a separate study in the March 7 JAMA offered evidence against the MMR-autism link.

Loring Dales, MD, of the Immunization Branch of the California Dept. of Health Services, and colleagues concluded that no correlation was observed between the trend of early childhood MMR immunization rates in California and the increase in children with autism enrolled in the state's regional service center system.

The study charted a marked, sustained increase in autism case numbers from 44 cases per 100,000 live births in 1980 to 208 per 100,000 in 1994. Changes in early childhood MMR immunization coverage were much smaller and of shorter duration.