Is fear of airborne smallpox behind the federal government’s desire for more health care immunizations?

It’s not going to be a couple of infected martyrs coming into JFK airport’

Adding a compelling new twist to the increasingly complex debate over smallpox immunization, a top bioweapons scientist says the former Soviet Union may have developed a method to spread a vaccine-resistant strain of the deadly virus through the air over large areas, Bioterrorism Watch has learned.

Raising the specter of airborne smallpox dashes most current contingency plans for controlling an outbreak, which typically assume the virus would spread by conventional person-to-person transmission. The public health response discussed thus far — immunized response teams, designated smallpox hospitals, and vaccinating a "ring" around first cases — would prove exceedingly difficult under such a scenario.

"I had long hoped that it couldn’t be done, but now it is clear that it can," says Alan P. Zelicoff, MD, senior scientist in the Center for National Security and Arms Control at Sandia National Laboratories, a national security and weapons laboratory in Albuquerque, NM. "We’re talking about [aerosolized] distances of many kilometers, not a few hundred meters. If you look at Kaplan’s model [Kaplan-Meier curve: time to event = onset of illness] or any of the other models that are out there, what this essentially says is that initial volume of [smallpox] index cases — that is, the first bulge if you will — is not going to be measured in the tens or twenties; it’s going to measured in the thousands or tens of thousands."

While it may be tempting to dismiss such statements as yet another worst-case bioterrorism scenario, Zelicoff is a high-profile scientist in a company connected to the government through the U.S. Depart-ment of Energy. A part of the original Manhattan atomic bomb project, Sandia National describes Zelicoff on its web site as "a physician and physicist, a member of the U.S. delegation to the Biological Weapons Convention, and a vocal authority on bioweapons nonproliferation and early detection of infectious disease outbreaks."

Though Zelicoff’s analysis of a formerly secret Soviet report has elements of speculation, he makes a provocative argument that a 1971 smallpox outbreak in the city of Aralsk can be traced to airborne smallpox experiments on the island of Vozrozhdeniye in the Aral Sea.1 The outbreak was never officially reported to the outside world by the Soviet government. Though ascribing it to natural causes in its internal medical report, the former Soviet Union suppressed reports of the outbreak to protect the secrecy of its bioweapons research program on the island, he notes.

Zelicoff recently reviewed the official Soviet report and interviewed some of the outbreak survivors, including the index case. Now 54 years old, she was a fisheries biologist on a ship that sailed near the island of Vozrozhdeniye in July 1971 to conduct research on the declining marine environment in the Aral Sea. Though she had been immunized against smallpox and the ship was some 15 km from the island, the biologist developed smallpox and subsequently spread it to nine others on her return to the mainland.

"The index case believes that [the island] is where she got it," Zelicoff tells Bioterrorism Watch. "I think it is credible that she believes that because, first, she is a biologist. Secondly, she made it clear that everybody who lived in the area knew there were funny things going on on the island. I don’t even think that the [U.S.] stalwarts who didn’t want to believe that this [airborne smallpox] could happen, believe that [the Soviet outbreak] was anything other than bioweapons tests."

Three of the 10 people who developed smallpox died. All the fatal infections were in people who had not been immunized, but the remaining seven were infected despite a history of smallpox vaccination. Though no vaccine is 100% effective, that finding suggests the smallpox strain may have been at least partially vaccine-resistant, he says.

"I don’t have enough data to give you a 99% confidence level, [but] I do have enough to give you a 90% confidence level that this organism may be vaccine-resistant. That does not mean completely vaccine resistant, but it means that the reproductive ratio,’ which is so important to understanding the dynamics of a smallpox outbreak, is probably higher than it otherwise would be," Zelicoff explains.

A Russian scientist gave a copy of the official Soviet report on the outbreak to the Center for Nonproliferation Studies at the Monterey (CA) Institute of International Studies. Zelicoff was then asked to do an analysis of the report, says Jonathan B. Tucker, PhD, director of the institute’s Chemical and Biological Weapons Nonproliferation Program in Washington, DC. "Because he is an expert on biological warfare and epidemiology, we commissioned him to do an analysis of the Soviet report," he says. "He came up with some interesting findings, but we do not necessarily endorse everything he says. The main implication from the analysis, if true, is that smallpox was weaponized by the Soviet Union in such a form that it could survive in the air over an extended distance of at least nine miles downwind. That indicates that smallpox, at least in the formulation that the Soviet’s developed, would pose a long-range aerosol threat."

Though many factors are at play, the threat may reflect in part the government’s reported interest in immunizing many more people than recently recommended by an advisory committee to the Cen-ters for Disease Control and Prevention (CDC). The CDC’s Advisory Committee for Immunization Practices (ACIP) recently recommended immunizing some first responders, health care workers, and other key personnel against smallpox for state-based response teams.

Though the number to be immunized was not firmly established, somewhere in the range of 15,000 people was the recurrent figure in the discussions, says William Schaffner, MD, a liaison member of the ACIP panel and chairman of the department of preventive medicine at Vanderbilt University in Nashville, TN. That number dramatically — and somewhat inexplicably — increased to 500,000 people in press reports as the recommendation was forwarded along to top public health and bioterrorism officials in Washington, DC.2

"It was impressive to some of us who were at the [ACIP] meeting that the first-order anticipated number was about 15,000, and then all of a sudden, estimates of about a half-million began to appear in the newspapers," Schaffner says. "That sounds much larger than anything the ACIP anticipated."

ACIP was not given any specific risk assessments about smallpox threats, he says, adding that it was even noted in discussions that this was the only time in the committee’s history it made a recommendation to vaccinate people when the risk of disease was unknown.

"They were basically groping in the dark," Tucker says. "In the absence of compelling evidence for the proliferation of the virus and an immediate threat of bioterrorism with smallpox, I think they reasonably took a conservative position, given the very significant risks associated with vaccinia vaccine."

That said, Tucker doubts the government has any firm evidence of any imminent threat of smallpox attack, airborne or otherwise. "I think if the administration had compelling intelligence that the virus was in the hands of terrorists it would have conveyed that information to ACIP, " he says. "That suggests to me that they do not have very solid information and this is just a hypothetical threat at the moment. Given that it is a hypothetical threat, I think we should err on the side of caution with respect to [pre-attack] vaccination."

Regardless, top government bioterrorism officials want to prepare for an attack on a much larger scale than was apparently envisioned by ACIP, Zelicoff argues. "The more people you can vaccinate ahead of time, the less likely that the ring vaccination strategy will fail. The office of Homeland Security is trying mightily, and for good reason, to maximize the number of people who are being vaccinated the first time around. I have to talked to [Homeland Security Chief Tom Ridge’s] advisors, and they are very concerned that if there is going to be a smallpox attack, it’s not going to be a couple of infected martyrs coming into JFK airport."

If Zelicoff is right about a threat of aerosolized smallpox, the next big question is whether terrorist groups or a nation such as Iraq — openly targeted in U.S. invasion plans — could possess the smallpox technology developed by the Soviet Union’s bioweapons program.

"I think that the administration is probably more concerned with Iraq than al-Qa’ida at this point," says Tucker, a former United Nations biological weapons inspector in Iraq. "If the Bush administration is planning to invade Iraq, it might be concerned that if the Iraqis do have smallpox virus — and there is some circumstantial evidence for that — that Saddam might conceivably no longer be deterred if we were intent on overthrowing him. Under those conditions, he might resort to his weapons of mass destruction. I think that this is the scenario that has Bush administration people concerned and perhaps [wanting] more rather than fewer vaccinated. But we need to weigh that risk against the very significant risks of the vaccine."

The author of Scourge: The Once and Future Threat of Smallpox (Atlantic Monthly Press; 2001), Tucker argues against large-scale vaccination absent a clearer terrorist threat. "My personal opinion is that it would be premature to vaccinate that many people (500,000) because of the very significant risks associated with the vaccine itself," he says. "I think we should be conservative at this point unless we have much better evidence that the virus is in the hands of terrorists."

Indeed, rather than a reflection of secret intelligence, the reports of government interest in immunizing many more people than ACIP recommended may have more to do with the realization that the CDC plan of ring containment and designated smallpox hospitals is just not a very good one, says William Bicknell, MD, PhD, professor of international health at Boston University. Bicknell argues that the ring containment strategy will not contain an attack, and attempts to direct patients to designated smallpox hospitals will dissolve into chaos. "I believe they are moving in the direction of immunizing a very substantial number of first responders," he says. "There is growing recognition that designating a smallpox hospital per state is absurd. I think they have figured that one out."

Bicknell recommends immunizing at least 100,000 first responders and health care personnel, and then doing later increments as adverse reactions are assessed and need is warranted. Though risk groups would have to be screened out, Bicknell — who has been immunized twice for smallpox — feels the number of immunized could be steadily increased because the adverse reactions will not be as bad as some have predicted. "I think the vaccine complications have been, not so much overstated, as misrepresented," he says. "There are three types of complications: the really severe, which are encephalisitis, vaccinia necroses, and death. These things are bad, but they are really rare. Then you have scary and unpleasant generalized vaccinia, but nobody [immune-competent] dies from that."

On the contrary, Schaffner warns that that those who haven’t seen a smallpox vaccination "take" in a while — which would include the majority of health professionals — will be surprised at how dramatically the vaccinee is affected. Schaffner favors holding to the ACIP recommendation of about 15,000 people. "This is no tetanus shot," says Schaffner, who had been observing medical staff volunteers at Vanderbilt being immunized. They are participating in a study of some of the old smallpox vaccine donated this year to the government by Aventis Pasteur in Swiftwater, PA. "It is impressive how much local reactivity there is and even systemic illness in these vaccinations," he says. "These are primary takes in people who have never been vaccinated before. I have seen arms quite swollen, swollen lymph nodes, satellite lesions in other parts of their body, people who have awakened in the morning with fever and chills, and people who have had to take time off work."

Given that level of debilitation in a highly motivated, educated group — whose take sites are carefully re-bandaged twice daily by study personnel — the impact of mass vaccinations may be considerable, Schaffner warns. Indeed, it is well documented that the live virus vaccina (cowpox) vaccine used to protect against variola (smallpox) can spread from inoculation site to the contacts of the vaccinee. Meticulous care and bandaging of the take site will be necessary for several days to prevent transmission.

"That is not a realistic expectation if you vaccinate 500,000 people," Schaffner says. "We will get transmission to people who didn’t want to be vaccinated, who didn’t volunteer to be vaccinated, are not in the target group for vaccination and — because of underlying illness — shouldn’t be vaccinated. That will happen, and the more people you vaccinate the more likely it is that this sort of transmission will occur."

References

1. Zelicoff AP. "An Epidemiological Analysis of the 1971 Smallpox Outbreak in Aralsk, Kazakhstan." In The 1971 Smallpox Epidemic in Aralsk, Kazakhstan, and the Soviet Biological Warfare Program Tucker JB, Zilinskas RA, eds. The Center for Nonproliferation Studies (CNS) of the Monterey (CA) Institute of International Studies. Occasional Papers: #9 2002.

2. Broad WJ. U.S. to vaccinate 500,000 workers against smallpox. The New York Times, July 7, 2002.