CDC gearing up rapid vaccine response plans for smallpox bioterror

First-case contacts, front-line staff targeted

Addressing the most feared pathogen in the potential arsenal of the bioterrorist, the Centers for Disease Control and Prevention is preparing a smallpox virus emergency response plan that calls for rapidly dispensing precious vaccine to first responders, health care workers, and first-case contacts in stricken communities, Hospital Infection Control has learned. An ancient scourge that has been eradicated in the wild, smallpox would be a formidable bioweapon because of waning immunity in the world population and limited stockpiles of vaccine.

The CDC response plan, which will be detailed in an upcoming report from the agency’s office of bioterrorism preparedness and response, is to quickly mobilize and administer the available vaccine should the virus be released in the United States. "The way the bioterrorism program is looking at this is that there would be groups of people, including first responders who are going to take care of patients or evaluate them, who would need to be immunized," says Michael Bell, MD, an epidemiologist and bioterrorism specialist in the CDC hospital infections program. "If a documented case was found within a certain community, then people likely to have shared contact in that community would also be vaccinated. By the same token, if a patient is [discovered] with smallpox in a hospital, then the hospital would also be receiving vaccine. Part of it is contact. Whether you are a health care worker or not, potential contact would be a reason [to be immunized]. Then the people who have to care for the patients would also need to be protected."

Highly infectious, with a 30% mortality rate and dramatically disfiguring pustules and scars, smallpox resonates beyond any other pathogen when discussions turn to potential bioterrorist weapons. (See related story, p. 31.) "If you consider all of the agents of bioterrorism, the reason that smallpox is particularly concerning is that the possibility of person-to-person transmission is great," Bell says. "It is a very efficiently transmitted virus. It is transmitted respiratorily, and [there is] the possibility of one person being infected but then wandering about early in their disease and exposing a lot of other people. The incubation period is [as much as] 18 days, so people can actually move quite a ways away before they manifest symptoms. The possibility of satellite spread is very great."

Thus, as opposed to possible bioweapons such as anthrax or botulism, smallpox could create a widening circle of secondary cases that would make initial containment via quarantine and immunization critical. "Whoever inhales [anthrax] might become sick, but people taking care of that person are not likely to become sick," Bell says. "The same thing with botulism toxin. The only other real exception would be pulmonary plague — pneumonic plague. But it is less frightening to many people because of the visual manifestations of smallpox. When you are covered in purulent pox, it is fairly dramatic."

Regardless of the agent, infection control professionals could play important roles in education, surveillance, and response throughout a heath care system that is largely unprepared for bioterrorism, says Tara O’Toole, MD, MPH, senior research fellow at the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore. (See related story, p. 33.) "[ICPs] clearly have an important role to play, particularly if the weapon were a contagious disease," she tells Hospital Infection Control. "I would hope that [these issues] would put a spotlight on infection control and hospitals generally. I think there are a number of ways good preparations for bioterrorism attack would dovetail with other priorities of infection control [i.e., surveillance for emerging infections]."

Many have lost immunity

Currently, the United States has a limited stockpile of some six to seven million doses of smallpox (variola) vaccine, made from the traditional method of using cowpox (vaccinia). The supply is widely regarded as inadequate, but because mass immunization efforts ended with global eradication of the pathogen in 1980, it may take several years to gear up production and increase supplies.

Moreover, because the vaccine’s efficacy has been generally estimated at some 10 years, immunity has long since waned for most of those vaccinated as children. With millions more never even vaccinated, the United States could be strikingly vulnerable should a terrorist group or rogue nation obtain and release the virus. The biodefense center at Johns Hopkins warns that an "aerosol release of smallpox virus would disseminate readily, given its considerable stability [in] aerosol form and epidemiological evidence suggesting the infectious dose is very small. Even as few as 50-100 cases would likely generate widespread concern or panic and a need to invoke large-scale, perhaps national emergency control measures."1

The only confirmed stocks of smallpox virus remaining in the world are reportedly in storage at the CDC and at the Russian State Research Center of Virology and Biotechnology in Koltosovo. However, the Center for Civilian Biodefense Studies warns that the former Soviet Union embarked on an ambitious bioweapons campaign with smallpox, and the pathogen may now be in the hands of other countries. "Because of the fact that many laboratories in Russia, including the one in Koltosovo, are now fiscally constrained and decreasing in size, there are growing concerns that the existing bioweapons expertise and equipment might move or perhaps have already moved to other countries," according to a World Health Organization (WHO) report posted on the center’s Web site.2

"A number of people think Russia has worked with smallpox in terms of weaponizing it, and a lot of people fear that North Korea worked with smallpox as a weapon," says O’Toole, who recently testified before Congress on bioterrorism. "There were rumors that [North Korea] vaccinated troops, for example, some years ago." In addition to inadequate supply of vaccine, existing antiviral drugs are not thought to be an option for post-infection treatment, she adds. "They tested the available antivirals, and those don’t do much," O’Toole tells HIC. "Those who survive it are scarred for life, and many of them are blind. It is a dreadful disease. It would be a tragedy to have it abroad on the planet again."

Indeed, the WHO Variola Research Committee is expected to formally recommend in May 2000 that the stocks of virus in the United States and Russia be destroyed no later than the year 2002. While some have argued that the virus may have research value, the threat of it falling into the wrong hands appears to be taking precedence. With military questions complicating the issue, it is important to remember that destroying the known viruses would not hinder vaccine research, O’Toole emphasizes. "One of the things that is not well-understood about the WHO decision is that destruction of smallpox really has no impact whatsoever on our ability to prepare new vaccines, which are not made from the smallpox virus [cowpox]," she stresses. "They are made from vaccinia virus, which a lot of people in the [political] policy realm don’t understand. It will have no impact on our ability to develop new antiviral therapies."

Whistling in the graveyard

In that regard, the CDC is reportedly placing a high priority on increasing current stockpiles of available smallpox vaccine after a top-level, closed-door meeting last August intended to cut the red tape between the various arms of government, drug regulators, and public health officials.3 As part of that effort, the Department of Defense Joint Vaccine Acquisition Plan has prioritized development of a new cell culture vaccinia vaccine, which would increase production capabilities and replace the traditional method of scarifying and infecting the flanks and bellies of calves.4

"Hopefully, we may be in a position in the next two years of ramping up a new vaccine in unlimited supplies," says Allan J. Morrison Jr., MD, MSc, FACP, health care epidemiologist for Inova Health System in Washington, DC, and a frequent speaker on bioterrorism issues at infection control conferences. "That’s sort of whistling through the graveyard until we get through, come out the other side, and have all we want to vaccinate everybody or have stockpiles available. But we’re not there."

Questions have been raised about using the existing vaccine to immunize some health care workers in advance of any outbreak, but determining the recipients is the problem. "I don’t think you can say that one area is less likely to be [targeted] than another," Bell says. "The predictability of these things is low. So if you really wanted to [immunize health care workers], you wouldn’t be able to pick and chose. Because of that limitation, the federal approach right now is to stockpile [vaccine] for emergency use. In the interim, if you don’t have people with documented immunity — and by that I think the guidelines that we are releasing will say known vaccine receipt within three years rather than 10 — then we would recommend using full protective measures, including masks and gowns and so forth." (See infection control measures, p. 31.)

Morrison agrees it would be a mistake to squander any of the current vaccine by immunizing health care workers in advance, even in potentially high-risk target areas like Washington, DC. For one thing, the U.S. supplies may be needed to help avert a global pandemic should terrorists or governments unleash smallpox in some other part of the world, notes Morrison, a former member of the U.S. Army Special Forces. It is estimated that some 50 to 100 million vaccine doses may be available worldwide, but there are questions about whether governments would release their limited supplies should an event occur elsewhere.

"I think [the U.S.] would have to give it up," Morrison says. "So there is a broader [reason for] holding back with the vaccine: so that you would have a resource elsewhere. If everybody in the Washington metropolitan area who is a key player in health care is vaccinated, but the epidemic is launched in Thailand, the world goes down. There’s no way to stop it. Whereas, if you have the doses — if you keep your powder dry — then you might get a shot at creating a ring around a zone, cordoning it off, quarantining it, and then vaccinating those around it."

Should an exposure occur in the United States, the CDC and military will have to dispense the available vaccine quickly if they expect health care workers to stay on the job in the face of smallpox, he says. "If they can’t mobilize [quickly], it may be beyond the boundaries that you can control," Morrison says. Though Bell could not say how quickly the vaccine could be delivered to a targeted area, some CDC data suggest smallpox immunization within three days of exposure may confer immunity. "We can infer some things from Department of Defense experience and from the old smallpox eradication experience at the CDC, but there were never any controlled trials, obviously," Bell says. "There was observation that seemed to say that postexposure vaccination might mitigate the number of lesions, but that is clearly soft data."

The rapidity of response may well depend on clearly established lines of communication in the affected area, he notes, adding that this issue is emphasized in a bioterrorism template prepared last year by the CDC and the Association for Professionals in Infection Control and Epidemi ology.5 "The more efficiently and quickly the facility is able to contact the right places and report the cases, the quicker the response will be," Bells says. "Having that done in advance and having a hot-list of phone numbers is something that we recommend very specifically so that we can improve the turnaround time. Now, what the actual timing and logistics would be once the FBI is notified and the stockpiles are mobilized — obviously, if it is at a big urban center that is served well with transportation facilities, that might make a difference. I really can’t predict what the exact timing would be. But [rapid response] is the reason for repeatedly stressing the communications preparations."

Prepare workers by educating them

By the same token, educating health care workers about smallpox and other potential bioterrorism agents could provide reassurance in the face of an actual event, Bell adds. "Health care worker response on a personal level is something that we can help with by doing teaching ahead of time," he says. "Health care workers in our country have demonstrated in numerous different scenarios that there is a certain selflessness and professionalism that we pride ourselves on. If they are given information ahead of time that if such a thing were to happen, this is how it is transmitted, this it how we try to protect you from it, and this is the relative risk, then each person can say this is something I can or can’t deal with."

References

1. Center for Civilian Biodefense Studies. John Hopkins University. http://www.hopkins-biodefense.org/pages/ response/agent.html.

2. Henderson DA. Risk of deliberate release of smallpox virus: Its impact on virus destruction. Working paper — World Health Organization ad hoc Committee on Orthopoxvirus Infections. 1999. http://www.hopkins-biodefense.org/pages/news/risk.html.

3. Preston R. Updating the smallpox vaccine. The New Yorker, Jan. 17, 2000:27.

4. Russell PK. Vaccines in civilian defense against bioterrorism. Emerg Infect Dis 1999; 5:531.

5. Association for Professionals in Infection Control and Epidemiology Bioterrorism Task Force and Centers for Disease Control and Prevention Hospital Infections Program Bioterrorism Working Group. Bioterrorism readiness plan: A template for healthcare facilities. 1999. http://www.cdc. gov/ncidod/hip/Bio/bio.htm.