Reports gathered by the U.S. armed forces over nearly five decades provide new evidence that the modest risk of serious side effects or death from smallpox vaccine drops dramatically in people who have been vaccinated before.
From 1942 to 1990, when smallpox inoculations ceased for military personnel, the armed forces did not record a single fatality from the vaccine, records reviewed by The Washington Post show. The overall incidence of adverse reactions was so low that the military program continued years after experts counseled that there was no longer a reason to vaccinate, since smallpox had been eradicated worldwide.
Information on the military's experience in published materials and internal military documents from the 1960s through the 1980s comprises the only known body of evidence describing the effects of the U.S. vaccine in a large population over a long period of time.
The armed forces vaccine was made from the same strain of vaccinia virus, a cousin of the smallpox virus, that the government plans to use in the coming months to immunize as many as 11 million police officers, firefighters and medical workers who may be called upon to deal with a biological warfare attack.
But Lt. Col. John Grabenstein, deputy director of the Military Vaccine Agency, cautioned that the armed forces' successful experience with the vaccine cannot be used to predict the likely consequences of vaccinating the civilian population, since military personnel are a selected group of mostly young, healthy adults.
The lessons to be learned "are one of the unknowables," Grabenstein said. "There were millions -- tens of millions -- of vaccinations given, mostly to young, physically fit adults. Although we may know the health of the people in the service, we don't know the health of people not in the service."
Similar concerns prompted the U.S. Centers for Disease Control and Prevention to "play down" their own 1960s data, which showed sharply lower rates of adverse reactions among previously vaccinated people. "There's no question the rates are lower," said Larry J. Anderson, special adviser for smallpox in CDC's Office of Terrorism Preparedness and Response. "But is it tenfold lower or fivefold? We just don't know."
Also, he said, residual immunity produced by the vaccine declines over time -- so someone vaccinated 30 years ago is likely to have more chance of an adverse reaction than someone vaccinated more recently.
Despite the shortage of good scientific data, physicians have long recognized that the best protection against an adverse reaction may simply be to have been vaccinated before.
"Just anecdotally, we're seeing reactions much gentler than those in first-time vaccinees," said pediatrician Margaret Rennels, who is supervising part of a national clinical trial on revaccination at the University of Maryland. Rennels said the trial had vaccinated 52 people between the ages of 30 and 70 over the past month, and there were "no high fevers, nobody missing work" but "just a few sore arms."
Official estimates of the risks of the smallpox vaccine are based on the 1960s CDC studies showing that one or two people die and 15 to 52 suffer serious illness for every million persons vaccinated. The most common serious effects include encephalitis -- brain inflammation -- and several potentially deadly rashes and skin conditions.
But in those who have been previously vaccinated, the rates plunged to one death in every 4 million vaccinees. There were none from encephalitis, regarded as the most dangerous side effect because it cannot be predicted.
"Vaccinia is a superb vaccine against itself," said Michael Lane, emeritus professor of medicine at Emory University and author of two of the CDC studies. "If you've been vaccinated even 30 years ago, there's lots less risk."
The armed forces did not systematically collect data or conduct studies on its experience with the vaccine, but starting in the 1960s, a Commission on Immunization in the Armed Forces Epidemiological Board reviewed the vaccine policy annually.
The commission at times included world-renowned smallpox experts and was briefed by others such as D.A. Henderson, who was supervising the World Health Organization campaign that eradicated smallpox worldwide and now serves as an adviser to Health and Human Services Secretary Tommy G. Thompson.
Summaries and transcripts of the commission meetings show that on several occasions, members mentioned that the U.S. Armed Forces had not had a fatality as a result of a vaccine reaction since an encephalitis case in India in 1942.
Although the United States ceased routine vaccination of civilians in 1972 and the last case of smallpox in the world was reported in 1977, the commission recommended that year that the armed forces continue vaccination indefinitely.
"The cost to the Armed Forces for the vaccination program is insignificant as far as complications are concerned," noted Chairman Abram S. Benenson that year. At the same meeting, the Army reported it had had no cases of encephalitis from 1971 through 1975, and had 64 adverse reactions. The seriousness of the reactions was not described.
The military vaccinations continued -- for recruits only -- until 1990, largely because of the perceived threat of biological warfare, the documents show. But that year the panel decided, for a number of reasons, "that threat was no longer enough," Grabenstein said.
The Soviet bloc was falling apart, and the first crop of unvaccinated 18-year-olds was coming of age. Also, Grabenstein noted, supplies of vaccinia immune globulin used to treat some of the vaccine's adverse reactions were running low, and the armed forces decided not to pay for a special production run.