Debate Begins on Smallpox Vaccination

The Advisory Committee on Immunization Practices is expected to make recommendations in June on whether Americans should be vaccinated against smallpox, a disease that no longer exists on the planet.

The United States and the rest of the world have been comfortable for more than two decades in the knowledge that the last case of smallpox occurred in 1977, and the disease was declared completely eradicated in 1980. After eliminating stocks of the virus in laboratories worldwide, the World Health Organization was able to say in 1984 that the only remaining variola virus isolates are stored at just two sites: the Centers for Disease Control and Prevention in Atlanta and the State Research Center of Virology and Biotechnology in Novosibirsk, Russia.

But there are lingering concerns that the virus resides outside those laboratories and could be used as a weapon by terrorists. And the effects of such a terrorist attack would be catastrophic, say public health officials, for two reasons: the virus is highly contagious and spreads readily and rapidly from person to person, and almost no one in the United States is immune to the infection. Smallpox vaccination has not been performed routinely in this country since 1972, so there is now a large population of children and young adults who were never immunized. And even persons born before 1972, who probably received a smallpox vaccination in order to enter school and have the scar to prove it, may no longer be immune, since no one knows exactly how long vaccination-induced immunity lasts.

That means almost everyone in the United States would potentially be at risk if terrorists introduced the smallpox virus, either by sending infected persons to mingle with crowds or by disseminating the virus itself in the air or on commonly used objects. That poses questions for the Committee on Immunization Practices, including:

  • Should we act now to make smallpox vaccine available to everyone in the United States, or, alternatively, to young people between the ages of one year and 29 who were never vaccinated; and should vaccination be compulsory or voluntary?
  • Or should we wait until there is an attack, relying on the fact that immunization within two or three days of exposure seems to prevent or lessen the severity of smallpox?

A number of factors may enter into the committee’s decisions. One is whether there is enough smallpox vaccine to carry through whatever recommendation the committee may come up with. There is currently a limited stockpile of vaccine in this country, most of it produced in 1982 or earlier. In studies published in April in the New England Journal of Medicine, researchers reported that they found those vaccines can be diluted 5- to 10-fold “without substantial loss of efficacy.” “When administered by a bifurcated needle to previously unvaccinated adults, the vaccine produced vesicular skin lesions that correlate with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections.”

… “The current stockpile of 15 million doses of smallpox vaccine may safely be diluted to yield at least 75 million doses.”

— Dr. Anthony Fauci

That means, says Dr. Anthony Fauci of the National Institutes of Allergy and Infectious Diseases, that “The current stockpile of 15 million doses of smallpox vaccine may safely be diluted to yield at least 75 million doses.” In addition, he points out, the ongoing production of second-generation smallpox vaccines will increase our supply to approximately 286 million doses by the end of this year, and the Department of Health and Human Services has said it will test for safety and immunogenicity some 75 million doses of vaccine that recently were discovered to have been stored by a pharmaceutical company since 1972. “Thus, the availability of vaccine will soon become less of a factor in the formulation of a policy,” Fauci said.

Another point the advisory committee may consider is how immunization on a massive scale might be handled, either before or during a terrorist attack. In its successful campaign to eradicate smallpox worldwide 40 years ago, the World Health Organization relied on a technique called “ring vaccination,” which is the approach currently recommended in guidelines developed by the Centers for Disease Control and Prevention. In ring vaccination, patients with suspected or confirmed smallpox are isolated; contacts are traced, vaccinated, and kept under close surveillance; and high-risk persons who may have had direct or indirect contact with the patient are identified and vaccinated.

“Despite the fundamental soundness of this approach and its success in previous naturally occurring outbreaks, there is considerable skepticism about the feasibility of this strategy,” in the event of a terrorist attack, Fauci notes, since multiple exposures and the resulting panic could overwhelm the capacity of CDC and local authorities to carry out the plan. And most importantly, he points out, previous outbreaks that were controlled by ring vaccination were in the context of existing herd immunity, not in an essentially non-immune population.

But the factor that seems most likely to affect public opinion about the need to vaccinate in advance of an attack, says Dr. William Bicknell of the Boston University School of Public Health, is that smallpox vaccination often has adverse reactions in otherwise healthy persons. Commonly, researchers reported, the healthy young volunteers who received either full-strength or dilute vaccine to test its efficacy experienced side effects including the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills, as well as generalized and local rashes.

… “There’s no other vaccine that we currently give that carries with it a risk of death.”

— Alex Kemper

In studies reported to the Pediatric Academic Societies annual meeting in Baltimore, Maryland, May 7, pediatricians Alex Kemper and Matthew Davis of the University of Michigan predicted that a mass campaign to vaccinate Americans against smallpox could result in 200 to 300 deaths and might make several thousand people severely ill with complications such as viral infection spreading from the vaccination site and severe skin rashes. “There’s no other vaccine that we currently give that carries with it a risk of death,” Kemper pointed out. “From a societal viewpoint, we have to decide whether or not we’re willing to take this risk.”

But in making its recommendations, the advisory committee is expected to weigh the very serious nature of smallpox itself against the possibility of adverse reactions to immunization in a limited number of people. Most doctors and nurses now in practice have never seen a case of smallpox, but a doctor who treated 22 smallpox patients while stationed with the military in Japan in 1945 described the experience in a New England Journal of Medicine article. “The disease began with a high fever,” Dr. Murray Dworetzky recalled, “with the temperature exceeding 40 degrees Centigrade and then dropping, although never to normal, before it spiked again. Although some patients had pustular lesions, those who died had confluent subcutaneous hemorrhages that rapidly involved the entire body, with a similar enanthema involving the mucous membrances of the oral cavity, respiratory mucosa, and entire gastrointestinal tract. The pain was intense and morphine relieved it only marginally.” Fourteen of the 22 patients died.

Another New England Journal article notes that the incubation period for the disease is 7 to 17 days, after which severe backache, headache, and fever begin abruptly. Lesions occur first on the face and extremities but then cover the entire body. After severe smallpox, pockmarks or pitted lesions are seen in 65 to 80 percent of survivors, most commonly on the face. Death from smallpox is ascribed to toxemia, associated with immune complexes, and to hypotension.

In any case, the New England Journal of Medicine editorializes, “The debate on preemptive vaccination cannot go on indefinitely. We need to make a decision. If we do proceed with large-scale vaccination, we need to consider what operational plans might be workable, who should be immunized, when they should be immunized, and how to reduce unintended sequelae.”

The complete text of the New England Journal of Medicine’s discussion of smallpox and bioterrorism is available at http://www.nejm.org/toc/nejm/346/17