Those conclusions, from an analysis performed by researchers at the University of Michigan Health System, were presented May 7 at the meeting of the Pediatric Academic Societies.

The federal government currently prefers a post-attack strategy called �ring vaccination," in which individuals identified with smallpox would be quarantined and their close contacts would receive smallpox vaccine after exposure to reduce the spread of illness.

The study examined the cost-effectiveness of different pre-attack vaccination strategies in conjunction with ring vaccination, compared to ring vaccination alone. It found that campaigns to immunize 50 percent to 75 percent of Americans aged 1 to 30 years, if completed before a smallpox terrorist attack, could save hundreds of lives compared to the potential deaths from an attack managed with only with ring vaccination.

The researchers, led by U-M pediatrician and internist Matthew Davis, M.D., M.A.P.P., hope their results may help guide public officials at a time when terrorist attacks and anthrax cases have renewed fears of a smallpox attack and led the U.S. government to increase its stockpile of smallpox vaccine.

Routine inoculation of US children was stopped in 1972 when the risk of vaccine side effects was judged to outweigh the benefit. National infectious disease experts assume that individuals immunized prior to 1972 have no remaining immunity against smallpox. This is a major concern, because smallpox is lethal in about 30 percent of those it infects.

However, the smallpox vaccine � composed of live vaccinia (cowpox) virus � also carries risks. Prior experiences with smallpox vaccine indicate that one in a million vaccinees is expected to die from severe complications of immunization, while many more will develop less severe side effects. Children under 1 year are not vaccinated for fear of high complication rates.

After last fall's terrorist attacks, the federal government ordered over one hundred million doses of the smallpox vaccine � enough by the end of 2002 to vaccinate all Americans aged 1 to 29 years old. The recent discovery of tens of millions of stockpiled smallpox vaccine doses by a manufacturer, and their donation to the federal government, has made the prospect of mass vaccination even more feasible.

"Given the larger anticipated supply of smallpox vaccine, we set out to evaluate the potential effects of different mass vaccination campaigns targeting those born after the end of routine vaccination in 1972, to compare them with the currently favored ring vaccination strategy," says Davis. "We developed a computer model to assess the effects of campaigns that reached either 50 percent of people aged 1 to 29 years old, or 75 percent of them, and based our calculations on risks, probabilities and costs from the best available data."

In all, the researchers estimate that vaccinating half of all people aged 1 to 29 years (57.5 million people) prior to a smallpox attack would cost about $286 million, including the costs of the mass immunization program itself as well as the costs of time lost from work and hospitalizations for complications related to vaccination. A campaign to vaccinate 75 percent of young people would cost about $430 million. In contrast, ring vaccination efforts after an attack that initially infected 100 people would cost about $3 million.

But 2,160 people would die with ring vaccination alone during the year after an attack, as opposed to 358 people in the 50-percent vaccination scenario or 244 people in the 75-percent pre-attack vaccination scenario. Neither mass vaccination approach in the model would reach all young people, because the researchers estimate that approximately 25 percent are expected to have medical conditions that put themselves at high risk for complications of vaccination, or to have household contact with someone at high risk.

"The initial cost and logistics of mass vaccination campaigns may seem daunting, but when you consider the possible loss of life from a smallpox attack in an unvaccinated community like the U.S., mass vaccination appears cost-effective," says Davis. The estimated cost per year of life saved was $6,773 in the 50-percent vaccination strategy, and $9,675 in the 75-percent model.

The researchers caution that a number of the deaths in either hypothetical mass-vaccination scenario would come from reactions to the vaccine itself. In addition, their analyses also show that the estimates of effectiveness of pre-attack mass vaccination efforts depend heavily on how many people would be initially infected, how rapidly the illness would spread from people with smallpox to other susceptible individuals, and how effective ring vaccination efforts would be.

For example, if the initial attack initially infects as few as 10 people, rather than 100, then mass immunization efforts would cause many more deaths than they would save, and ring vaccination alone would be the preferred strategy. On the other hand, if 1,000 individuals were initially infected, then pre-attack mass immunization supplemented with post-attack ring vaccination is much more likely to control the resulting epidemic than ring vaccination alone.

"Another essential issue to consider is the probability of a smallpox attack," says Davis. "If there's never an attack, then conducting a mass vaccination campaign has no protective effect and only adverse effects, unless you believe that mass vaccination would deter terrorists from using smallpox as a weapon. However, it appears that the probability of a smallpox attack is significant enough to warrant the government's plans to stockpile enough smallpox vaccine for every American. Our analysis indicates that immunizing 1- to 29-year-olds remains cost-effective at an attack probability as low as 10%."

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