Confronting Smallpox

The defeat of the deadly smallpox virus still stands as one of modern science's most stunning achievements. The wretched disease engulfs the body in pustules that itch and ooze and often blind or disfigure victims who survive. Smallpox killed a half-billion people between 1880 and 1980, the year the World Health Organization declared the disease "eradicated." The victory was fueled by a vaccine that uses a milder but still-dangerous relative of the smallpox virus to provoke an immune response. The vaccine hasn't been used widely since the early 1980s, but the specter of bioterrorism has resurrected it. Last Friday, President George W. Bush ordered vaccinations for U.S. military personnel serving in high-risk areas. He also announced plans to offer the shot to health-care and emergency workers--and eventually to the public. "It is prudent to prepare for the possibility that terrorists... would use disease as a weapon," Bush said.

But does vaccination pose a greater risk than the threat of terrorism? That's a question health officials will no doubt be grappling with in the coming months as they debate exactly who else should be protected and how best to deploy the vaccine. Throughout the 1980s and 1990s, the variola virus, which causes smallpox, remained very much alive in Soviet military laboratories, and their stockpile has never been fully accounted for. Many fear that samples could fall into the hands of terrorists--if they haven't already. Iraq may also possess clandestine samples. But the vaccine itself poses real hazards. According to the U.S. Centers for Disease Control and Prevention, 15 of every million people receiving the vaccine for the first time could suffer life-threatening reactions--conditions such as encephalitis (brain inflammation), generalized vaccinia (a systemic infection from the vaccinia virus) and eczema vaccinatum (a widespread skin eruption).

President Bush acknowledged the dilemma when he unveiled his plan. He stopped short of ordering vaccinations for the general public, citing the vaccine's "inherent health risks." By 2004, however, Bush plans to make the vaccine available to almost anyone who wants it. Routine vaccination could prove far more dangerous today than it was before the vaccine went out of use two decades ago. In an age of AIDS, chemotherapy and organ transplants, millions more people now live with compromised immune systems. Those people are all at high risk of complications from the vaccine.

Two leading U.S. experts highlight the debate. Back in 1969, Drs. Donald Millar and Michael Lane wrote a seminal paper on smallpox vaccinations, declaring that they were no longer necessary in the United States. Smallpox itself had not been seen in the country since 1948, yet thousands of children were suffering adverse reactions to the vaccine, and roughly one in a million was dying of complications. "The benefits of routine... vaccination no longer outweigh its risks," they wrote in The New England Journal of Medicine. Today the two no longer agree. Millar favors voluntary peacetime vaccination as a strategy for restoring some of America's lost immunity. His approach could actually minimize the damage done by the vaccine. During peacetime, health workers would have the luxury of screening people before inoculating them--and caring for those who suffered complications. If even half the population were vaccinated in advance, everyone would be safer because fewer people would be capable of contracting smallpox and spreading it. "We've just spent millions on airport security," says Dr. Bill Bicknell of Boston University's School of Public Health. "We could spend less on smallpox and just take it off the table."

But should we go to such lengths to eliminate a threat that might never materialize? Lane continues to believe a post attack strategy is the only one needed. Under plans laid out in the U.S. government's new "Smallpox Vaccination Clinic Guide," states and cities must establish clinics that can open quickly during an emergency to screen, counsel and vaccinate anyone who walks through the door. Most experts believe that's a feasible goal. Smallpox doesn't spread easily from person to person during its seven- to 17-day incubation period, and even infected people can often avoid serious illness by getting vaccinated before they develop symptoms. Inoculating the nation that quickly would pose big challenges, says Yale health analyst Edward Kaplan, "but it's not impossible."

Can anything be done to make smallpox vaccines less risky? The U.S. government is now stocking up on vaccinia-immune globulin, a medicine that can ease adverse reactions to the vaccine. At the same time, it is funding research aimed at developing entirely new smallpox vaccines. The most promising of these third-generation products--based on a weakened vaccinia strain known as MVA (Modified Vaccinia Ankara)--is already being used as a delivery vehicle in gene-therapy and AIDS-vaccine experiments. Even extremely ill patients tolerate it well. After confirming MVA's safety, says Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases, researchers will begin testing its efficacy against smallpox. At the very least, he says, it may provide a good booster for people vaccinated decades earlier. When scientists devise a vaccine that is as safe as MVA and as effective as the vaccines that eradicated smallpox in the 1970s, perhaps we'll all take the shot and stop worrying about smallpox emergencies. Short of that, it seems that no plan can keep people completely immune from tough choices that could cost lives.

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