Smallpox is an acute, contagious, and potentially fatal disease caused by the variola virus, which killed as many as 30% of those exposed to it as recently as 1967. In 1980, the disease was declared eradicated as a result of successful global vaccination programs. Stores of the virus remain, however, and in the aftermath of the events of September 11th and the anthrax scare of October 2001, the government is taking precautions against a bioterrorist attack using smallpox as a weapon.

From December 2002 through May 2003, the U.S. Department of Defense (DoD) implemented a program of smallpox vaccinations for approximately 500,000 of its personnel. This was done despite concerns about its safety, which, compared to other vaccines, has been associated with higher rates of complications, including severe skin infections, permanent neurological damage, and even death.

Were it not for the lingering threat from terrorists, the risks of the vaccine would clearly outweigh its benefits, particularly in the absence of a confirmed smallpox case. A new study published in the June 25, 2003 issue of the Journal of the American Medical Association (JAMA), demonstrates that smallpox vaccinations can apparently be conducted safely and effectively on a large-scale—which, at the very least, should help to allay fears about the vaccine.

About the Study

Between December 13, 2002 and May 28, 2003 researchers from the Military Vaccine Agency and the Pentagon observed the experience of 450,293 U.S. service members and DoD civilian workers who were administered smallpox vaccinations by well-trained health care workers throughout the world, beginning with four pilot sites in the U.S. The median age of vaccinees was 26. Most (70.5%) were primary vaccinees (they received the vaccine for the first time).

Reports of number of vaccinations, rates of vaccination exemptions, symptoms, and adverse events (defined by expert consultants) were gathered via symptom surveys sent to headquarters of the DoD on multiple continents and ships at sea. An independent safety-monitoring panel reviewed weekly updates.

The Findings

The researchers found nearly all (95.5%) of primary vaccinees at the four pilot sites were successfully vaccinated with a single vaccine (they had a major or primary-type reaction on their skin within 3-4 days, and neutralizing antibodies appeared in their blood within 10 days of vaccination). Among 975 people who had been vaccinated previously, 934 (95.8%) were successfully revaccinated with a single vaccination. As it happens, a second study about the smallpox vaccine, also published in this issue of JAMA , suggests that previously vaccinated persons can be successfully revaccinated with diluted smallpox vaccine.

Around the world, two vaccine recipients who suffered acute allergic events were successfully treated. Not one transmission of vaccinia (the live virus) from a health care worker to a patient was identified. And, conversely, no vaccinee later treated as a patient transmitted vaccinia to a health care worker.

All vaccine recipients who experienced expected temporary symptoms (notably, itching, muscle ache, and “feeling lousy”) returned to duty promptly. The moderate or serious adverse events that occurred were at rates below historical levels—and none were fatal (the DoD rate per million vaccinees for encephalitis , acute myopericarditis, and eczema vaccinatum were 2.2, 82, and 0, respectively; historically, the rates per million are 2.6-8.7, 100, and 2-35, respectively).

Before opening this vaccination program to large groups of civilians, however, it is important to consider the study’s limitations. For one, it is possible that some cases of temporary symptoms or adverse events were not reported, although this is less likely given the military’s global communications and surveillance capabilities. Also, the descriptive design of this study (and lack of a control group), precluded researchers from determining precisely how effective their program was. Lastly, because 87% of vaccinees were men and 73% were white, the study findings may not be universally applicable.

How Does This Affect You?

The question of how significant is the threat of a bioterrorist attack with weaponized smallpox remains to be answered. The government has decided that pre-attack vaccination is the best way to protect our troops against smallpox. A similar program for civilian health care workers has not been widely accepted, mostly out of fear of vaccine complications. This study suggests that wide-scale smallpox vaccinations programs may not be as dangerous as first thought. Nevertheless, historically-speaking the vaccine has killed from one to three out of every million who received it; an unacceptably high rate if you consider vaccinating every American.

Although this study provides support for expanding vaccinations to the civilian population, it does not end the debate. Given the current state of the world, perhaps we’ll one day see the resurrection of a vaccine that was triumphantly declared unnecessary only a short time ago.

Note that certain people should not receive the smallpox vaccine under any circumstance since they are at greater risk for serious adverse events. For more information about who should not get the smallpox vaccine, visit the Centers for Disease Control and Prevention (CDC) website at