Future shock: Defeated pox targeted with new vaccine as CDC prepares for worst
"Thus, even though the plague had ended,
they continued to live by its standards."
Albert Camus, The Plague
In a grim concession to the way of the world, public health officials and the pharmaceutical industry are rapidly gearing up production of millions of doses of a new vaccine for a disease that has been eradicated across the globe: smallpox.
If nothing else, the commitment of $343 million to create a stockpile of 40 million vaccine doses is a chilling indication of how serious the U.S. government is taking the threat of smallpox as a weapon of bioterrorism. The disfiguring, highly infectious disease that killed untold millions worldwide for ages was eradicated case by case three decades ago in one of the greatest public health achievements of all time.
Now, in a move that sobers all the abstract discussions of bioterrorism over the last few years, the Centers for Disease Control and Prevention has signed a 20-year vaccine production contract with OraVax, a biopharmaceutical company based in Cambridge, MA. The initial 40-million-dose stockpile is expected to be delivered by mid-2004, and the contract calls for maintaining and replenishing that supply.
The vaccine, made from vaccinia (cowpox), will be deployed rapidly should a bioterrorist or rogue nation unleash the dreaded variola major (smallpox) virus. The CDC already has begun preparations for mobilization of its old vaccine supply, roughly 8 million doses, that — though still considered effective — were created under methods that would no longer be acceptable in the pharmaceutical industry. (See Hospital Infection Control, March 2000.) The new vaccine will be distributed to strategic sites that, understandably, have not been identified.
"Part of it will be in rapid-deployment storage areas," says John Beecher, RPh, chief of CDC’s drug service and project officer for the smallpox vaccine. "It will not be stored all in one place, but how it will be broken out is going to be worked out. CDC has not made the recommendation to start mass inoculations again. This is basically [planned for] full release in case of a reintroduction of the variola virus into the general population."
The new vaccine contract calls for both routine production and "surge" capabilities, so that more vaccine could be supplied as needed. "We could scale [the 40 million] up a few times, but if there became a need for national or global immunization, the technology would have to be shared with other companies," says Lance K. Gordon, PhD, executive vice president of OraVax.
In that regard, other nations already are interested in buying vaccine, he notes, emphasizing that the contract gives the company exclusive rights to produce and market a fully licensed product. "Certainly, the secondary markets were a critical component on us bidding on the contract," he says. "We have had some preliminary communication with other governments."
It’s a sad commentary’
Although few question the prudence of the project, that the world has come to this — 30 years after the last known smallpox cases in humans — is somewhat stunning.
"It is a sad commentary to have reached this point," says Ruth Carrico, RN, MA, CIC, director of infection control at the University of Louisville (KY) Hospital and a consultant on bioterrorism issues. "But [as long as] any viral culture is left, we are at risk to have it fall in the wrong hands for the wrong purposes."
The officially acknowledged stocks of live smallpox virus are stored at the CDC in Atlanta and the Russian State Research Center of Virology and Biotechnology in Koltosovo. But many bioterrorism experts suspect smallpox is no longer contained solely at those two locations, particularly since the collapse of the former Soviet Union. Among those experts is D.A. Henderson, MD, a former epidemiologist with the World Health Organization who was among the scientists who set off on a 10-year global odyssey in 1967 to identify the last cases and eradicate the disease. Now director of the Center for Civilian Biodefense Studies at Johns Hopkins University in Baltimore, Henderson says he never dreamed that, years after that historic achievement, the world would be preparing again for possible smallpox exposures.
"No, I certainly didn’t," he says. "I must say the whole reason for doing this comes as a shock. I am really extremely disappointed by what has happened."
Henderson blames the former Soviet Union for secretly weaponizing the virus even as public health officials were tightening a ring around the last cases. Given that — and the increasingly open question about whether the last vials of live virus are confined solely to their historic repositories — producing a new vaccine is a good idea, he notes. "The risk that smallpox is going to be released by a terrorist somewhere is low — it’s not very likely. But if it were released, it could be an absolute catastrophe. So this is kind of a permanent insurance policy."
The new vaccine is needed because the global population is strikingly susceptible to a release of smallpox, with even those immunized as children unlikely to have any lasting immunity. Mass immunization efforts ended in 1972 in the United States and globally in 1980, three years after global eradication of the pathogen was declared.
"Since the last clinical cases, there have been billions born who have not been vaccinated," says Allan J. Morrison Jr., MD, MSc, FACP, health care epidemiologist for Inova Health System in Washington, DC. "We used to have herd immunity. Now we have herd susceptibility."
Aggravating that vulnerability is the fact that few clinicians in the nation’s hospitals have ever seen a case of smallpox, Gordon adds. "If a case showed up, the concern is whether it would be recognized fast enough," he says. "There are very few clinicians today — possibly no clinician in the United States — who have seen or diagnosed a U.S. case of smallpox. The last case of smallpox in the U.S. was in the ’40s. So if somebody were to show up at an emergency room, it might be diagnosed as chicken pox or allergic rash."
Indeed, production of new vaccine has raised the question of whether health care workers should be vaccinated so they can safely treat incoming cases. This is more than an academic question because OraVax, as previously noted, has the capability and interest in producing much more vaccine than that designated for the CDC stockpile. Thus, as the product becomes available, infection control professionals likely will face questions from clinical staff about whether they or their families should be vaccinated.
A complicated question
The problem is that even though the vaccine will be a new and presumably improved version, the hazards and risk factors of introducing cowpox into the body are expected to be roughly the same as those documented with the old vaccine. "What its comes down to is that you have a risk of causing complications," Henderson says. "There is a finite risk there. We are looking at probably about one death per million primary vaccinations. 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 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, warns Michael Bell, MD, an epidemiologist and bioterrorism specialist in the CDC hospital infections program.
"Vaccinia, which is the vaccine strain of cowpox, can actually spread in the population and cause disease in immunocompromised people," he says. "We are keeping a lot more people alive on immunosuppressive therapy, [including those] with transplants and HIV. That population didn’t exist before. What would it mean to have even the cowpox virus floating around in the community? Those are all things we have to consider before we say clearly whether we can immunize health care workers or the population."
As a practical matter, even if the immunization caused has no side effects, a health care worker would have to keep the inoculation lesion covered and not touch it prior to treating patients, he says. "If they inadvertently scratch it and contaminate their fingertips and they happen to be caring for someone who has a transplanted kidney, you could actually hurt people," Bell says. "So it’s bi-directional. There is risk to health care workers and risk to patients from health care workers. It’s never as cut and dried as you would like it to be."
More data will be needed to formulate rational recommendations, Morrison concurs, but he notes that some level of immunization inevitably will be discussed at his hospital, given its location in the nation’s capital. One thing is clear: Health care workers are going to want vaccine very quickly if they are expected to deal with incoming smallpox patients. "Who is going to be here to take care of the patients?" Morrison asks. "Forget about the smallpox patients. We’re talking about taking care of any patients. It’s not going to happen."
Family first
Indeed, in the event of a smallpox incident, hospitals probably would have to immediately promise workers vaccinations for themselves and their families to staff a facility, Carrico emphasizes. "I know as a parent I would be waiting at home for my child to show that first sign of fever and irritability," she says. "My work would not be my highest priority. So you want to save vaccine and be able to bring it into a community and say everybody who is going to help with this disaster is going to get vaccine first for themselves and their families, then I would be in line."
As an alternative, Carrico questions whether it might be wise to immunize a "strike force" of health care workers who could safely come into stricken areas. "If you begin to see significant casualties in a given area, you would have to assume that some portion of those exposed and infected would be health care workers," she says. "So you would have to bring in health care workers from somewhere else, either through a mutual aid agreement or through the military. It would take in the neighborhood of 500 personnel to staff a 1,000-bed facility. I would say immunize that group of people, but I don’t know if we are at that level of organization yet."
The reality is that smallpox spreads so fast, and the population is so vulnerable, that whole cities may have to be vaccinated as soon as a few cases appear, Henderson warns. One of the reasons smallpox could be eradicated, even in Third World countries with poor health systems, was that the disease leaves immune those it does not kill.
"We were [immunizing] in populations where, most of the time, 70% to 80% of the people were protected," he says. "So it did not spread with great speed. Thirty percent of them had died, but those who lived had a solid immunity and never saw a second case of smallpox. That is one big difference. Logistically, [today] this poses enormous problems. I think very quickly you would do large-scale vaccination. Realistically, this is what I think health commissioners are going to face. They will practically just have to say, [for instance,] We are recommending vaccination for the city of Baltimore.’"
Henderson and fellow smallpox clinicians found the vaccine could be given two to three days after an exposure and still protect against the disease. "Even sometimes if you went out four or five days, it could protect against death. The immunity comes quite rapidly. What you would do is vaccinate all of your health care workers straightaway who might be in contact with the patients."
The consensus at this time, however, is not to recommend routine vaccination for any group other than researchers who work with the smallpox virus, Henderson says. "That could change overnight," he says. "If we find one guy walking through Dulles Airport with a thermos full of live virus, we might want to do a lot of vaccinating very quickly."
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