CDC weighs vaccinating now or waiting until first smallpox attack

Would you take smallpox vaccine? A pox on both your choices

If smallpox vaccine were made available by the government, would you bare your arm for that tattoo of skin pricks with the little pitchfork needle, hoping that the live cowpox virus entering your bloodstream would do you more good than harm?

That’s what it may come down to: individual choice. Because whatever the Centers for Disease Control and Prevention (CDC) recommends about the controversial smallpox vaccine, it certainly will be voluntary (at least for nonmilitary personnel). The CDC recently called together a working group of clinicians and experts in Atlanta to solicit advice and opinion about possibly immunizing people with vaccinia (cowpox) against variola (smallpox), one of the more dreaded potential weapons of bioterrorism. The group will forward its analysis of a set of options — without making a consensus recommendation — to the CDC’s Advisory Committee on Immunization Practices. That committee and the CDC will hold a series of meetings in the coming months and decide whether to resurrect voluntary smallpox immunization programs in the United States.

The disfiguring infectious disease that killed millions worldwide for ages was eradicated case by case decades ago in one of the greatest public health achievements of all time. The last smallpox immunization programs in the United States were disbanded in 1972. The last known stores of smallpox virus in the world are officially in Russia and the United States, but the increasingly broad consensus is that the dreaded pox could be in the hands of rogue nations and/or terrorist groups. It is known that smallpox was developed as a weapon in the sweeping bioweapons program in the former Soviet Union. With a new vaccine under production and dilution studies showing that existing vaccine supplies can be greatly expanded, mass immunizations are a possibility again.

In that regard, some of the consultants at the meeting called for action, urging the CDC to recommend voluntary immunizations for health care workers and the public. Others cautioned about a host of potential side effects and the fact that there are some 300,000 people in the United States who do not know they are HIV-positive. Vaccinating them and other immune-compromised people could lead to one of the worst complications of cowpox: fatal, progressive vaccinia. In addition, a Food and Drug Administration (FDA) official at the meeting warned the CDC that wide- spread use of the live virus vaccine could imperil the blood supply because those immunized must wait one year before donating blood.

"Currently in the country, there are about 13 million blood donations donated by 9 million blood donors," said Allan Williams, PhD, director of the FDA division of blood application. "The current industry standard for a blood donor vaccinated with live virus is a one-year deferral. That’s very conservative, but [it is] really unknown what duration of viremia may be associated with vaccinia immunization. If large scale vaccination were considered, a fairly large number of blood donors would be deferred and this could potentially create shortage problems in what is really a very fragile blood supply."

The margin is so thin that cutting the blood supply by 10% could result in serious morbidity and mortality in blood-product recipients, Williams said. Before large-scale immunizations are undertaken, he said it might be necessary to first recruit and vaccinate a large group of repeat, dedicated blood donors.

David Liebershach, one of the CDC advisors and the state director for the Alaska division of emergency services, made it clear he would not be lining up for voluntary immunization for any reason. "I don’t want smallpox vaccination," he told the work group. "I have a 12-year-old child and a 5-year-old child, and I don’t want them vaccinated pre-attack. That’s speaking from one person from a state where the [likelihood of attack] is probably pretty low. And if it does occur, it is cold and dry up there and your population is about one [person] per square mile density, so the face-to-face contact would be minimized quite a bit."

Again, individual choice is the key. Having been immunized as a child and later in life after joining the Peace Corps, William Bicknell, MD, PhD, professor of international health at Boston University, made one of the more compelling arguments for voluntary mass immunization.1 "The primary argument is that it should be up to the people to decide, with appropriate guidelines," he told Bioterrorism Watch. "Don’t immunize [pre-attack] little babies and people with organ transplants and AIDS. But otherwise, let’s say, Here’s what we know about the vaccine; here is what we know about the risk: Make your choice.’"

While risk groups should be screened out, there are also some 157 million people in the United States who were immunized as children, he notes. Whether they have any immunity left is an open question, but they are much less likely than first-time vaccinees to have any adverse reaction to the vaccine, Bicknell argues. "If you look at the people who already have been vaccinated, the complications are much lower of all types and there are virtually no deaths in that group," he said. "Then if you eliminate [immunizing] people under 5, that cuts about half the deaths and half the complications. Suddenly, you have almost no complications. It’s much less dangerous than driving to work in the morning."

The CDC’s current draft smallpox plan hinges on "ring" vaccination, which requires rapid mobilization of vaccine to immunize the first reported smallpox cases and their contacts. The ring approach was used to successfully eradicate smallpox from the world, but the demographics of the disease are strikingly different today because most people in the world are susceptible. The ring concept was effective when many people already were immune due to vaccination or past infection. "There were growing levels of immunity in the population," Bicknell said. "They were working in remote areas with small numbers. Ring vaccination is great for that, but not if you have a malicious exposure," he explained.

While there have been various scenarios about how such an attack would occur, some have dismissed the likelihood of self-inoculated terrorists moving about the country to infect the populace. That is because smallpox is not infective in its incubation period and presumably terrorists with onset of fever and pustules would be noticeably ill and incapable of much widespread movement.

However, Bicknell warns that there is a "pre-eruptive period" as the incubation phase wanes when the self-inoculated terrorist could be infective without obviously having smallpox. Even as disease progresses, he adds, "If you are motivated, you can feel pretty terrible and move around." Moreover, a mass smallpox immunization in Yugoslavia in the 1970s began with an atypical index case that had no rash, he reminds.2

Indeed, given the possibility of a well-organized release of smallpox over a broad area, the CDC immediately should begin immunizing first responders and medical personnel, advised Steven Christianson, DO, MM, medical director of the Visiting Nurse Service of New York City. "If an attack is credible, it will possibly come in multiple areas and multiple sites within those areas," he said. "It will be designed to overwhelm the public heath system and the medical system. Our perspective is that voluntary vaccination of first responders and medical people should be encouraged even while the vaccine is still unlicensed."

However, Christianson recommended against routine mass immunizations of the public due to adverse effects and deaths. One recent study estimated that vaccinating people ages 1 to 65 years would result in 4,600 serious adverse events and 285 deaths.3

But if there is an attack and mass public immunization has not been done, will emergency departments (EDs) be overwhelmed? They are practically overwhelmed right now, pointed out Thomas Terndrup, MD, who represented the American College of Emergency Physicians at the meeting. "If you expect the emergency departments in America to supply [surge] capacity you are seriously mistaken," he said. "Our emergency departments are already operating to capacity. On Sept. 10th, the day before the World Trade Center bombings, there was an article outlining this in Time magazine. We continue to see significant increases in patient visits to the emergency departments. The CDC estimates that in 2002, something like 108 million visits will be made to emergency departments."

Though Terndrup left it to the CDC to decide who to immunize, he underscored the chaotic impact a smallpox release would have on emergency workers and departments. "Think about an outbreak of smallpox and what would happen to emergency services and those emergency responders out there picking people up off the street," he said. "This is the only source of federally mandated care. Any patient for any reason that shows up at a hospital in America that has an operating ED [must be treated] by federal law." There are some 9 million first responders when you add ED clinicians, paramedics, police, and firefighters, he said. "Should first responders be immunized?" Terndrup said. "I don’t have any answers."

Whatever policy is adopted, the CDC better have answers for the AIDS community, cautioned John Bartlett, MD, HIV expert, and clinician at Johns Hopkins University School of Medicine in Baltimore. "The AIDS community is a very cohesive group," he said. "It’s loud and well-organized. Whatever is decided, [you] need to work with that group and get buy-in. If the decision here is that we ought to give people the vaccine, and there is not buy-in from the AIDS care community, it is not going to happen."

There are about 900,000 people living with HIV infection in the United States, and about one-third of them do not know they are infected, he said. HIV patients are contraindicated for live vaccines, and that should probably remain the rule for smallpox as well, he said. Bartlett cited a case in the literature of an HIV-positive patient who died of progressive vaccinia after being immunized for smallpox.4 But trying to screen out people who are HIV-infected as part of a smallpox immunization program could open up a legal quagmire of testing and confidentiality issues.

Complicating the issue further is the possibility that the HIV-infected person may be a health care worker or one of the other groups recommended for immunization. While the vaccine poses a possible danger to the HIV-infected, how would they fare in a smallpox attack?

"What might happen if somebody with HIV gets smallpox?" Bartlett said. "I don’t think any of us know. It might be universally lethal." Co-infection with tuberculosis for example, speeds the progression of HIV, he said. In a worst-case scenario, where vaccinating the HIV infected was considered necessary, there would still be a question of whether they could mount an immune response, he added. "A number of vaccines have been tested on individuals with HIV infection, and they show that the cleave point for response and non-response . . . risk and no risk is a CD4 count in adults of about 200," Bartlett said. "Below 200, there will probably not be an immune response."

Comparable populations exist of other immune compromised groups, including organ transplants and those under chemotherapy treatment for cancer, meaning vaccinia immune globulin must be available in sufficient quantities.

If the choice is to immunize, a massive education effort will be necessary to influence physician attitudes and explain the reasoning of the program, said Glen Nowak, PhD, CDC, associate direction for health communications in the CDC national immunization program. A series of public focus groups and interviews with physicians revealed current attitudes on the smallpox situation, he said. "We found that many — again the younger ones more than the older physicians — thought that ring vaccination was a counter-intuitive strategy," Nowak said. "[Their thinking was] if we do vaccinate we should try to vaccinate as many people as possible rather than as few people."

It was also evident that the anthrax experience has engendered skepticism regarding containment strategies. "Many of these physicians said that during the anthrax experience recommendations were changing on a frequent basis," Nowak said. "What was true on Monday may not have been true on Wednesday. So they wanted to know how could we know that the current medical and public health assumptions regarding ring vaccination are valid today?"

Likewise, the ring vaccination approach is not something you want to explain one on one to patients besieging an ED in the wake of a smallpox attack. "There was still was some confusion [among the public] about what ring vaccination was," he said. "It is a difficult concept to explain to the public. They tend to view vaccination in terms of broad or mass vaccination. The public also raised some questions about whether such a policy — because it was selective in nature — would limit access among minority groups or groups with [low socioeconomic status] if there was an outbreak. They saw ring vaccination as a selective vaccination strategy."

In additional findings of the project, physicians expressed concern about their personal liability if they were asked to give the smallpox vaccine. They also felt they did not know enough to discuss the risk and benefits of vaccination with their patients, he added. If there is a recommendation to immunize physicians, they are going to want a lot more information on the rationale behind such a move, he said.

"From the physicians and the public, basically, the message was if there was an outbreak, they would prefer broad, rapid access to smallpox vaccine," Nowak said. "Most of [the physicians] wanted to know why should they be vaccinated [pre-attack]? You couldn’t just put them in a group and say get vaccinated. They wanted to know why."

Indeed, risk — some specific probabilities that smallpox will be used as a weapon — was the great unknown that held sway over every scenario at the meetings. Some are sufficiently convinced that the risk is real if only because the CDC has already immunized some of its own staff and is now considering reintroducing a potentially dangerous vaccine for a disease that has been vanquished in the wild.

"One of my colleagues thinks I am a complete nut case on this," Bicknell told Bioterrorism Watch. "He says, It will never happen.’ His assessment of the risk of attack is different than mine. His is infinitesimal; mine is low, but real. Therein lies the difference."

References

1. Bicknell WJ. The case for voluntary smallpox vaccination. Sounding Board N Engl J Med 2002; 356:1,323-1,324.

2. Fenner F, Henderson DA, Arita I, et al. Smallpox and Its Eradication. Geneva: World Health Organization; 1988.

3. Kemper, AR, Davis MM, Freed GL. Expected adverse events in a mass smallpox vaccination campaign. Effective Clinical Practice March/April 2002; 5:98-99.

4. Redfield R. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987; 316:673.