Health strategies to protect a nation against smallpox

When it comes to homeland security, few issues keep lights burning later in Washington than how best to protect Americans if terrorists carry out a smallpox attack on an unsuspecting public.

Health experts note that the virus spreads rapidly, demanding a quick response. Yet smallpox vaccines themselves can trigger sometimes-fatal symptoms.

Thus, public-health officials face difficult trade-offs as they struggle to develop a strategy that will blunt a smallpox attack with the least harm to the people they are trying to protect. "The big question in my mind is how well would targeted vaccinations do in an attack, versus mass vaccinations," says Ira Longini Jr., a biostatistics professor at Emory University in Atlanta.

One answer to that question has emerged. A research team from Emory, led by M. Elizabeth Halloran, unveiled the results of computer simulations suggesting that the most effective strategy involves two steps: vaccinations for "first responders" and perhaps a program of voluntary vaccinations for the general public before an attack; and, after the outbreak, vaccinations for people diagnosed with smallpox and those they come in contact with.

The effort contrasts with results published in August by Yale epidemiologist Edward Kaplan and colleagues. Their effort, which used a different modeling approach, suggested that mass vaccinations after an attack would be most effective.

The Emory team's research, to be published Friday in the journal Science, comes at a time when policymakers are struggling to develop approaches to combating bioterrorism. Concerns have heightened in recent days following revelations that Iraq, North Korea, Russia, and France have stockpiles of the smallpox virus. By international agreement, only labs in the US and Russia were to have retained any of the viruses.

Intelligence and law-enforcement agencies are working to thwart any bioterror attack before it occurs. But, analysts say, the nature of infectious biological agents - easy to conceal and virulent once introduced - makes prevention difficult.

In September, the federal Centers for Disease Control and Prevention in Atlanta issued an interim response plan that relies on a vaccination approach for a localized outbreak. It targets people diagnosed with smallpox and those they've come in close contact with. The center deemed mass vaccinations too risky and likely to overwhelm hospitals.

In addition, President Bush is weighing a plan to inoculate up to 500,000 US troops against smallpox. The first recipients would include medical specialists. Troops assigned to duty in the Middle East also would be among the earliest to be vaccinated.

Vaccination plans are likely to change as research progresses. Indeed, the differences between the Yale and Emory results indicate just how dramatic these changes can be.

The Yale team's inoculate-everyone results stem from a model assuming 10 million people in the population. Infection was treated as moving through the whole population without considering the random nature of one person's contact with others, says Jim Koopman, an epidemiologist at the University of Michigan. The Yale model also assumed no residual immunity within the population.

The Emory team bit off a smaller chunk, limiting its population to 2,000, but modeling the interactions of each resident and family based on the latest US Census information. For example, Dr. Halloran says that "30 percent of households are single-person households." Such characteristics can be central in determining how readily an infection spreads.

Like the Yale group, Halloran's team found that mass vaccinations were the most effective if the population exhibits no immunity from previous vaccinations. As the team plugged increasing levels of "herd immunity" into the model, the effectiveness of mass vaccinations and targeted shots increased. But a reliance on targeted vaccinations and residual immunity prevented more cases per application of vaccine - a vital factor given its history of sometimes fatal effects on patients.

Given the relatively large number of single-person households, during an outbreak "...people should just stay calm and stay home," Halloran says. "The last thing you want is thousands of people running out to get vaccinated" when smallpox is spread through human contact.

Neither study may be the final word on the best strategy. It's been so long since anyone in the US was immunized against smallpox that the level of residual immunity among nearly 289 million people is uncertain. Nor does any model account for ways to deal with people who either can't take the vaccine or refuse for religious or other reasons.

The Emory group "used a very sound method" for modeling, says Edward Richards III, a public-health expert at Louisiana State University. But they assume a 1 in 1 million death rate from the effects of the vaccine itself, he says, noting that this rate is taken from a time when far fewer people exhibited immune-system problems.

In a program of mass inoculation, he says, up to 280,000 people might succumb in some way to the vaccine. In a big attack, that may be an acceptable cost to save millions of lives. Short of that, he says, more thought must be given to ways to quarantine and care for people who aren't vaccinated.