Bioterrorism Watch: Should clinicians get smallpox vaccinations?

Questions arise, stockpile expansion fast-tracked

The recent decision to accelerate production of a new smallpox vaccine is raising the complex question of whether health care workers — frontline soldiers in the war against bioterrorism — should be immunized against the disease.

As opposed to the current anthrax attacks, a biological release of smallpox would result in incoming patients with an infectious disease. Even health care workers directly exposed to anthrax could be treated with ciprofloxacin and several other antibiotics, so the anthrax vaccine is not a likely candidate for health care.

On the other hand, legitimate questions have been raised about whether health care workers will stay on the job during a smallpox outbreak unless they and their families are rapidly vaccinated. The only known stocks of smallpox virus are held by the United States and Russia, but many bioterrorism experts have warned for years that another nation or group might have secret stocks.

"I think if smallpox [vaccine] became available, we should definitely immunize all the health care workers," says Martin Evans, MD, hospital epidemiologist at the University of Kentucky Chandler Medical Center in Lexington. "A lot of people think [health care workers] ought to be high on the list because they are part of the response team if there was an outbreak in the community. Not to sound self-serving, but I think we ought to immunize the medical community."

But the question currently is somewhat moot because the Centers for Disease Control and Prevention (CDC) is not wavering from its established policy of mobilizing the available vaccine only if smallpox is released. "I’m sure CDC wants to conserve its current stocks for dealing with an outbreak so it could immunize contacts," Evans says. "If [the agency has] already used [its stock] by immunizing all the health care workers in the country, then it won’t be able to respond."

15 million doses stockpiled

Currently, there are some 15 million doses of the old smallpox vaccine available, according to Secretary of Health and Human Services Tommy Thompson, who recently announced plans to accelerate production of a new smallpox vaccine. Forty million new doses of vaccine are expected to be available by mid-to-late 2002, moving the project up considerably from its original completion date of 2004 or 2005.

The manufacturer of the new vaccine is Acambis Inc. (formerly OraVax) — based in Cambridge, UK, and Cambridge and Canton, MA. The new vaccine will be a purified derivative of the same strain of cowpox virus (vaccinia) that was used in the United States previously, because the old vaccine’s efficacy was clearly demonstrated by direct exposures to those infected. While the method of immunization through scarification will be essentially the same, the new vaccine will be produced in a mammalian cell culture that contains no animal protein.

Acambis stated on its web site that it would have no other comment on the project other than to confirm it has "accelerated" its production plans. But when the project was first announced in 2000, company officials said they had the ability to scale up production well beyond the requested 40 million doses. They were even scouting for other global markets. That means the capability to produce smallpox vaccine in abundance is on the horizon, and the question of immunizing health care workers will invariably arise. Bioterrorism Watch was unable to get a CDC response on the question as this issue went to press, but CDC director Jeffrey Koplan, MD, MPH, outlined the agency’s position in an Oct. 2, 2001 Health Alert posted on a CDC web site.

"Smallpox vaccination is not recommended and, as you know, the vaccine is not available to health providers or the public," Koplan said. "In the absence of a confirmed case of smallpox anywhere in the world, there is no need to be vaccinated against smallpox. There also can be severe side effects to the smallpox vaccine, which is another reason we do not recommend vaccination. In the event of an outbreak, the CDC has clear guidelines to swiftly provide vaccine to people exposed to this disease. The vaccine is securely stored for use in the case of an outbreak."

One factor in favor of the CDC’s position to rapidly deploy the vaccine — rather than do widespread vaccinations — is that immunization should still be effective several days after a smallpox exposure. In the smallpox global eradication campaign, epidemiologists found they could give vaccine two to three days after an exposure and still protect against the disease. Even at four and five days out, immunization might prevent death. Still, though the new vaccine will be improved in many ways, the hazards and risk factors of introducing cowpox into the human body are expected to be roughly the same as those documented with the old vaccine.

"We are looking at probably about one death per million primary vaccinations," says D.A. Henderson, MD, director of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore. "We are looking at one in 300,000 developing post-vaccinal encephalitis — an inflammation of the brain, which occasionally is fatal and sometimes can leave people permanently impaired."

Based on those estimates, if the new stockpile of 40 million doses is eventually rolled out, approximately 40 of those immunized will die, and another 133 will develop encephalitis. In addition to those severe outcomes, the arm lesion created during inoculation can be very large and painful, serving as a reservoir to self-inoculate the eyes or even infect immune-compromised patients.

The downside is real, but as more vaccine becomes available immunization will certainly be discussed at hospitals in previously targeted areas such as New York City and Washington, DC. If they are not immunized in advance, health care workers are going to want vaccine very quickly if they are expected to take care of smallpox patients, says Allan J. Morrison Jr., MD, MSc, FACP, health care epidemiologist for the Inova Health System in Washington, DC. "Forget about smallpox patients. We’re talking about taking care of any patients."