Autism Biomedical Information Network

Evidence shows genetics, not MMR vaccine, determines autism

by Charles G. Prober, M.D., FAAP

Before measles vaccine was licensed in the United States in 1963, some 400,000 cases of measles were reported on average each year. Yet because virtually all children contracted measles, the actual number of cases probably approached that of the entire birth cohort (3.5 million to 4 million cases per year).

By the early 1980s, however, the annual incidence of reported measles cases had been reduced by more than 99 percent, to less than 1,500 cases.

Unfortunately, later in that same decade, the vaccination rate decreased and an outbreak of measles occurred between 1989-1991, when more than 55,000 cases and greater than 120 measles-related deaths were reported in the United States.

This increase was attributable to two major types of outbreaks: those among unvaccinated preschool-age children and those among vaccinated school-age children; this latter group was susceptible because approximately 5 percent of those receiving a single dose of measles-containing vaccine do not mount a protective immune response.

As a result of this resurgence, a two-dose strategy for measles vaccination was recommended in 1989. The first dose of vaccine was to be given as measles, mumps and rubella vaccine (MMR) at age 15 months, and the second dose also as MMR at entrance to middle school or junior high school. As of 1997, the Academy, the American Academy of Family Physicians and the Centers for Disease Control and Prevention (CDC) recommended that the second dose be administered at school entry. By 2001, the national goal is that all school-age children will have received two doses of measles-containing vaccine.

Q. How effective is the current strategy of measles vaccination?

A. The current two-dose strategy has been very effective. Both epidemiologic and laboratory evidence suggest the transmission of indigenous measles was interrupted in the United States for the first time during 1993. During 1997, the latest year for which data are available, there was a provisional total of only 135 confirmed measles cases. This is the lowest number of cases ever.

Even though indigenous measles transmission has been virtually eliminated, measles cases caused by importation of the virus from other countries continue to occur. A total of 57 of the 135 (42 percent) measles cases reported in 1997 were documented as international importations, primarily from Europe and Asia.

Q. Why should we still vaccinate against measles when cases are so uncommon?

A. Although the number of measles cases in the United States is at an all-time low, there continues to be substantial measles activity throughout the Americas and the remainder of the world.

Between January 1997 and February 1998, some 88,485 suspected measles cases were reported from the Americas, with Brazil and Canada having the greatest number of cases. The highest rates of measles infections outside the Americas are observed in Africa, Western Europe and Southeast Asia.

Because of the continued activity of measles throughout the world, including countries in our own back yard (Canada), U.S. children may contract infection from travelers from these endemic countries. This is true, even considering the presently high vaccination rate in the United States; large measles outbreaks have been observed repeatedly, even in countries that have achieved high levels of measles vaccination coverage and have recorded several years of low incidence of disease.

A reduction in measles immunization rates would substantially increase the potential size of any outbreak, contributing to increased disease-associated morbidity and mortality rates.

Although measles usually is a self-limited infection among normal children in developed countries, complications including otitis media, bronchopneumonia, laryngotracheobronchitis (croup) and diarrhea are not uncommon, especially in young children. Less common, but more serious complications, include acute encephalitis and subacute sclerosing panencephalitis.

Death from measles infection, usually attributed to respiratory and neurologic complications, occurred in one to two of every 1,000 cases reported in the United States in the pre-vaccine era. In developing countries, measles remains one of the leading causes of child mortality, responsible for approximately 10 percent of all deaths among children younger than 5 years.

Case fatality rates are higher among immunocompromised children, including those with underlying malignancy and HIV infection. Measles vaccination of asymptomatic children with HIV infection is safe, whereas natural infection when they have AIDS may be devastating.

Q. What are the known complications of measles vaccination?

A. Measles vaccine is very safe; most persons have no reactions.

About 5 percent to 15 percent of vaccinees may develop a fever five to 12 days after MMR vaccination. The fever usually lasts one to two days and usually is not associated with other symptoms.

About 5 percent of MMR recipients may develop a transient rash one to two weeks after immunization.

Central nervous system disturbances, such as encephalitis, have been reported with a frequency of less than one per 1 million doses administered, a frequency many times lower than the incidence of serious central nervous system disorders that follow natural infection. Because the incidence of encephalitis or encephalopathy after measles vaccination is lower than the observed incidence of encephalitis of unknown etiology, most of the reported cases may be temporally, rather than causally, associated.

Measles vaccine also is safe when administered to children infected with HIV if they are asymptomatic or not severely immunocompromised. Measles vaccine is recommended for these children because of this safety profile and because of reports of severe and often fatal measles infection in children with AIDS.

Q. Is there a link between measles vaccination and autism?

A. Autism is a chronic developmental disorder sometimes noted in infancy as impaired attachment, but more often first identified in toddlers from age 18 months to 30 months. Because MMR vaccine is administered just before the peak age of onset of autism, a temporal relationship between vaccination and onset of autism is expected to be common.

Although the cause of autism is unknown in most instances, the theory favored by many experts is that it is a genetically based disorder that occurs before birth. Evidence that genetics is an important, but not exclusive, cause of autism includes a 3 percent to 8 percent risk of recurrence in families with one affected child.

To date, there is no convincing evidence that any vaccine causes autism.

Stimulated by a hypothesis articulated by a British investigative team, a link between MMR vaccine and autism has been suggested by some parents of children with autism. Based on data from 12 patients, the British physicians speculated that MMR vaccine may have been the possible cause of bowel problems, leading to a decreased absorption of essential vitamins and nutrients and resulting in developmental disorders like autism.

The theory that autism may be caused by poor absorption of nutrients due to bowel inflammation was not supported by the clinical data. Specifically, the behavioral problems appeared before the onset of symptoms of inflammatory bowel disease in at least four of the 12 reported cases. That is, the effect preceded the cause. The authors even acknowledged in their original work that the association was speculative and that they "did not prove an association."

Furthermore, the same authors have published another study in which highly specific laboratory assays in patients with inflammatory bowel disease, the purported mechanism for autism after MMR vaccination, were negative for measles virus.

Other recent investigations do not support a causal association between MMR and autism or inflammatory bowel disease.

A Working Party on MMR Vaccine of the United Kingdom's Committee on Safety of Medicines recently evaluated several hundred reports of autism, inflammatory bowel disease or similar disorders developing after receipt of MMR or MR vaccines. The Working Party conducted a systematic, standardized review of parental and physician information and concluded that the information available "... did not support the suggested causal associations or give cause for concern about the safety of MMR or MR vaccines." Finally, a recently published population-based study from Britain identified all 498 known cases of autism among those born in 1979 or later in certain districts of London and linked the cases to an independent regional vaccination registry. The authors showed that the known number of cases of autism had been increasing since 1979, with no jump after the introduction of MMR vaccine in Britain in 1988.

They also showed that, at age 2 years, the MMR vaccination coverage among the children with autism was almost identical to that in children in the same birth cohorts in the whole region, providing evidence of an overall lack of association with vaccination.

Finally, the authors showed that the first diagnosis of autism or initial signs of behavioral regression were no more likely to occur within time periods following vaccination than during other time periods.

A study of the population of children in two communities in Sweden also found no evidence of an association between MMR vaccination and autism. That study found no difference in the prevalence of autism in children born after the introduction of MMR vaccination in Sweden compared with children born before.

Only 15 cases of autism behavior disorder after immunization were reported to the Vaccine Adverse Events Reporting System (VAERS) between January 1990 and February 1998. Because of the small number of reports over an eight-year period, the cases reported are likely to represent unrelated chance occurrences that happened around the time of vaccination.

Vaccines administered proximal to the onset of autism included diphtheria, tetanus, pertussis (DPT), oral polio vaccine, Haemophilus influenzae type b, hepatitis B and MMR. If measles vaccine, or any other vaccine, causes autism, then it would have to be a very rare occurrence since millions of children have received vaccines without ill health effects.

Q. How are uncommon adverse events possibly associated with vaccination detected?

A. To assure the safety of vaccines, the CDC, the Food and Drug Administration (FDA), the National Institutes of Health (NIH) and other federal agencies routinely monitor and conduct research to examine any new evidence suggesting possible problems with the safety of vaccines.

Currently, the CDC is conducting a study in metropolitan Atlanta to further evaluate any possible association between MMR vaccination and autism. Results are expected sometime in 2000.

Health care providers who administer vaccines are required to report to VAERS certain adverse health events that occur in persons who have received vaccines. Some of these reports are related to vaccines, and other reports are not related but occur from other causes and happen around the time vaccines are given. The CDC and the FDA collect and analyze these reports.

To report a health problem that follows vaccination, call VAERS at (800) 822-7967. The National Immunization Program has established a National Immunization Information Hotline to help answer vaccine questions: (800) 232-2522 (English) and (800) 232-0233 (Spanish).

Dr. Prober is a member of the AAP Committee on Infectious Diseases.

©1999, Reproduced by permission of AAP News
From AAP News, December 1999, p. 24

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