The study found that vaccinating 80 percent of a community of 2,000 before the appearance of the first case of smallpox would allow between 12 and 20 cases of illness. A targeted mass vaccination plan implemented after the first case, on the other hand, would permit 26 cases of the disease to slip through the net if roughly 60 percent of the population had leftover immunity to smallpox from inoculations that ended in 1972. Whether that figure reflects reality isn't known, the researchers say.
The modeling showed that immunizing close contacts of those known to be infected with the virus is the most efficient way of containing an outbreak, preventing more cases per dose of vaccine than mass inoculations. This approach becomes increasingly appealing as the level of residual immunity to smallpox in the community rises.
"When there's residual immunity, targeted vaccination is very competitive with mass vaccination," says Ira Longini Jr., a biostatistician at Emory University's Rollins School of Public Health in Atlanta and a co-author of the study. "It can be effective in containing an outbreak."
Mass vaccination would be the only solution against smallpox, as it is against polio, but for the fact that the inoculation -- which is scratched into the skin with a pitchfork-like device -- kills roughly one person in every million who receive it. "It's a dangerous vaccine and it kills people," says Dr. M. Elizabeth Halloran, a Rollins biostatistician and lead author of the study.
The researchers report the results of their simulations in tomorrow's issue of Science.
The computer simulations assumed that anywhere from one to five people would introduce smallpox into the community, and that 57 percent of the population had at least partial protection from prior vaccination. The model considered a variety of scenarios, including how quickly health authorities reacted to the outbreak and when infected people finally stayed home sick.
Targeting 80 percent of those who had been in contact with infected people produced a smallpox death rate of 0.5 per 1,000 people if those over age 30 had prior immunity to the virus, compared with a rate of 0.2 per 1,000 under the same circumstances with a mass vaccine approach covering 80 percent of the population. The death rate climbed to nearly 11 per 1,000 under the targeted system with no residual immunity, versus about one per 1,000 using mass vaccination. If there is no residual immunity and no one was vaccinated after the disease appeared, the rate shot up to 97 per 1,000.
Waiting to vaccinate until 15 or 25 cases of smallpox crop up greatly increased the death rate under all containment strategies.
In addition to the uncertainty about residual protection, a town of 2,000 doesn't simulate the entire country. Using the numbers in the model, expanding the 0.2 and 0.5 per 1,000 death rates to a city of 1,000,000 would leave 300 more lives lost under the targeted vaccination plan -- a far less favorable comparison.
Targeted, or "ring" vaccination, has been the response of choice from the U.S. Centers for Disease Control and Prevention, though experts are split on the issue.
A recent paper in the Proceedings of the National Academy of Sciences, for example, concluded that mass vaccination after a smallpox attack on a major city prevented about 4,100 more deaths than an initial targeted response followed by mass inoculations. The mass vaccination plan also trimmed the lifespan of the outbreak substantially, according to that model.
The Bush administration has yet to declare its intentions regarding smallpox vaccination. Health officials have been considering a policy of immunizing 10 million first responders, or possibly every American, as a precaution against a bioterror attack.
Bill Pierce, a spokesman for the Department of Health and Human Services, says the Bush administration "is getting closer" to making its decision, but he declined to say when it would be announced.
The United States abandoned routine immunization against the virus in 1972, and the World Health Organization declared the infection eradicated in 1980. However, the United States and Russia have preserved samples of the virus, and intelligence experts believe Iraq and North Korea have supplies of it, too.
Health officials are in the process of stockpiling enough doses of smallpox vaccine to immunize the entire country if needed. Scientists don't know how much protection people who were previously vaccinated have retained. A study of 900 people is now underway to determine that.
"To [cause] that kind of really serious complications without knowing that you have a significant risk is unjustified," says Dr. James S. Koopman, a University of Michigan smallpox expert who helped eradicate the disease in India in the 1970s. What Koopman remembers most about his experience in that country were not the people who died of the virus but the children who succumbed to the vaccine.
Moreover, says Koopman, who wrote a commentary accompanying the journal article, even a mass vaccination regime wouldn't completely prevent the spread of smallpox because that strategy relies on people voluntarily coming in to immunization centers. "The people who do not come in are in contact with other people who do not come in and they form pockets of susceptibles that can sustain chains of transmission," he said. "It doesn't make sense to just go willy-nilly trying to vaccinate everyone. We have to focus on individuals who are likely to be infected."
The latest study didn't include the effects of quarantining infected people and their contacts. However, some form of isolation in conjunction with vaccination strategies might be justified, Koopman says.
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