The ACIP and smallpox vaccine

July 2002

On this web site is an article describing the recent Advisory Committee on Immunization Practices (ACIP) recommendation against widespread use of smallpox vaccine in the U.S. population at this time. This was widely reported in the public media as well. In a nutshell, the ACIP recommended that smallpox vaccine be used on a limited basis only in selected smallpox response and smallpox health care teams in each state. Furthermore, since the vaccine used would likely be the diluted Dryvax (Wyeth) product, it would need to be used as an Investigational New Drug (IND), requiring individual informed consent and strict observation and control under the aegis of the FDA and CDC. The recommendation will not become public policy until accepted by the CDC, HHS and very likely under the present circumstances, the White House as well. Don’t be surprised if this recommendation is overridden somewhere up the chain.

The processes leading up to this recommendation are of interest. Interested health care organizations as well as the public were invited to comment, either by letter or at one of four one-day public forums held in the last two months; these were held in New York City, San Francisco, San Antonio and St. Louis. In addition, a special meeting was arranged at the Institute of Medicine-National Academy of Sciences in Washington on Saturday, June 15, at which additional input and opinions were solicited. Finally, the ACIP made its recommendation in Atlanta, during the week following. There was, theoretically at least, opportunity for both professional and public input in this process, yet the whole effort seems to have fallen well short of the broad public dialogue called for by Tony Fauci in a recent New England Journal of Medicine editorial.

The recommendation itself probably surprised no one. When viewed purely as a public health issue, weighing risks and benefits, it was probably the correct recommendation under the presently “remote” or “low” or “very low” likelihood of a smallpox exposure event. It was solidly supported by a number of professional medical organizations, including the Infectious Diseases Society of America, whose public policy statement can be found on the IDSA Web site. Yet, I find myself curiously uneasy with this recommendation, and I’m not at all convinced that it was the best one for the country at the present time.

My concerns are twofold: (1) Should health care personnel in fact be much more broadly immunized, at least in major urban areas; and (2) should the public have been given the opportunity to voluntarily choose to be vaccinated? These are both complex questions and raise issues of informed consent, IND status, monitoring for adverse effects, liability considerations, screening for immunocompromise and the like. Furthermore, there would need to be focused educational programs for virtually all primary care physicians and infectious disease physicians, most of whom have never encountered complications of smallpox vaccine or even needed to know anything about their diagnosis and management. Yet all of these issues would need to be addressed in any scenario involving use of smallpox vaccine; a strong argument could be made for doing so now in a noncrisis setting, rather than in response to an exposure event.

Would threat place rings around policy?

The heart of my concerns surely lies in my doubts that the “ring vaccination” policy is really the proper one for a wholly unimmunized population in the United States in the event of a bioterrorist smallpox exposure. This policy is one of surveillance, case identification, identification and immunization of contacts, and further case identification and contact identification and immunization in concentric “rings.” In the partially immunized and relatively immobile rural populations of Africa and India, this policy was highly effective in achieving global eradication of smallpox. With this policy, transmission from a single case could typically be contained within two generations of secondary cases.

Would this policy work in the United States? For low-level exposures that resulted in only a handful of cases in a handful of states, it is likely that it would work satisfactorily, and the outbreak could be terminated after two to three generations of secondary cases. In the event of multiple major exposures or of a single massive exposure, such as at a major sports event or at a major international airport, I am skeptical that the “ring vaccination” policy would prove to be equal to the challenge in a dense, highly mobile and wholly susceptible population such as ours.

Dark winter

For an object lesson in what might likely happen under such a circumstance, readers would do well to read about “Dark Winter,” a simulated exercise carried out by investigators at the Johns Hopkins University Center for Civilian Biodefense Strategies. In the simulation, a total of 3,000 people were infected with smallpox during three simultaneous exposures in three separate shopping malls in Philadelphia, Atlanta and Oklahoma City. The simulation ended about two weeks after cases were first recognized, but already there were an estimated 16,000 cases. In essence, the simulation made it clear that there was absolute havoc. The written report is very sobering reading.

Based on these kinds of considerations, I think a strong case could be made for voluntary smallpox immunization, as suggested by Bicknell. Polls suggest that perhaps half or more of the U.S. population would avail themselves of that opportunity. Although seriously incomplete, even a 50% immune population would increase the likelihood that the ring vaccination policy could contain exposure events, should they occur. Furthermore, as is intuitively obvious, the higher the smallpox immunity in the population, the less attractive we are as a smallpox bioterror target.

The ACIP has stated that the smallpox vaccine policy will be re-examined as the need arises. Absent a new and potentially safer vaccine, the only other variable in the equation is the level of perceived threat of an attack. Assuming for the moment that does not change and the recommendation does become public policy, the public will need to be given sufficient information to have some confidence in this decision — confidence that does not seem to exist at present.

For more information:

• Fauci AS. Smallpox vaccination policy – the need for dialogue. New Engl J Med. 2002;349:1319-1320.
• O’Toole T, Mair M, Inglesby TV. Shining light on “Dark Winter.” Clin Infect Dis. 2002;34:972-983.
• Bicknell WJ. The case for voluntary smallpox vaccination. New Engl J Med. 2002;349:1323-1325.