In the aftermath of September 11, Yale public health specialist Edward H. Kaplan, Ph.D., started thinking about how to fight bioterrorism. The result was a study on smallpox vaccination that made national headlines, in no small part because it criticized federal government terror reaction plans as being too little, too late.

Using a mathematical model, Kaplan found mass vaccination of the population in the area of an outbreak to be far more effective than “ring vaccination,” the limited immunization strategy the government first recommended as the initial response to a smallpox attack. He published his study in the Proceedings of the National Academy of Sciences in July, shortly after the Bush Administration announced its policy.

Working with MIT colleagues David L. Craft, M.S., and Lawrence M. Wein, Ph.D., Kaplan used their model to analyze how different vaccination strategies contain the spread of a smallpox attack that infects 1,000 people in a large city. Their study took key features of guidelines from the Centers for Disease Control and Prevention (CDC) and applied them to a disease transmission model. The least effective method was ring vaccination, which isolates the infected and vaccinates people found to be in close contact with them. Ring vaccination would allow 367,000 cases of smallpox and 110,000 deaths and would take 350 days to end the outbreak.

By contrast, a mass vaccination begun as soon as authorities learned of the attack would result in 1,830 cases and 560 deaths and end the outbreak in 115 days. (It takes two weeks for smallpox to incubate and for symptoms to appear.) The analysis found that switching from ring to mass vaccination on the 33rd day of a crisis would still allow 15,570 cases and 4,680 deaths.

Before smallpox was eradicated in 1980, ring vaccination was the accepted strategy, because cases were isolated and most people had been immunized. Throughout the history of the disease, the government has been reluctant to undertake mass vaccination, since the vaccine uses a live virus that can cause severe side effects and even death. Still, Kaplan said the fatality risk of mass vaccination—about one person in 1 million—is minuscule compared to the possible death toll of a terror attack.

As Yale Medicine went to press in October, the CDC director, Julie L. Gerberding, M.D., M.P.H., and other top bioterrorism officials announced a change in strategy away from ring vaccination, recommending instead that voluntary immunization begin immediately for 1 million military personnel, followed by 10.5 million health care workers and emergency responders. The vaccine would then be offered to the public, most likely in early 2004. As President Bush considered the proposal, physician organizations including the American Medical Association and the American Academy of Pediatrics (AAP) urged caution and a continued policy of ring vaccination.

“The [recommendation] is flexible and could change if there is an actual outbreak of smallpox, or if a safer vaccine becomes available,” said Robert S. Baltimore, M.D., professor of pediatrics and epidemiology at Yale and lead author of the AAP’s policy statement.

Kaplan has found himself in political territory before. His landmark work on the New Haven needle exchange program led some to label him an activist for AIDS patients and drug addicts. But Kaplan rejects any notion that his research has a political dimension. “Many if not most would consider the needle exchange results to come from the political left and the smallpox results to come from the political right,” he said. “The truth is, in both cases, the results came from reasoned analysis.”