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Smallpox in Theory and Practice: Controversies Abound

Debate continues about the best strategy for vaccination against smallpox.

There have been no cases of smallpox in the U.S. since 1949, but, in the aftermath of the anthrax attacks of 2001, smallpox has become an important theoretical concern. Unlike anthrax bacilli, smallpox virions would make ideal bioweapons: Smallpox is transmissible from person to person, has a high case-fatality rate, and has no validated treatment. In addition, few Americans born after 1972 have been vaccinated against the virus. Carefully safeguarded stocks of smallpox virus exist in the U.S. and Russia, but many fear that illicit stocks survive elsewhere. The current vaccine supply is not sufficient to vaccinate all susceptible U.S. residents.

In a collection of articles, researchers address some of the most pressing clinical and ethical issues that surround smallpox. A comprehensive review of clinical manifestations reminds clinicians of key differences between smallpox and chickenpox: In smallpox, a febrile prodrome precedes rash outbreak, which begins as an oral enanthem and then takes a peripheral distribution on the face and extremities. In chickenpox, fever occurs with rash outbreak, and the rash is concentrated on the torso at first. All smallpox lesions are at the same stage of development, whereas chickenpox lesions evolve in crops at different stages.

Vaccination after smallpox exposure often can prevent or attenuate clinical illness. Encouraging news about the vaccine supply comes from a study of a decades-old vaccine preparation that was administered in various dilutions to healthy, previously unvaccinated, adult volunteers. Equally good success rates were reported in 106 volunteers who received standard, undiluted vaccines, 234 who received 1:5 dilutions of vaccine, and 340 who received 1:10 dilutions. These results imply that current vaccine supplies can be used to vaccinate approximately 10 times as many individuals as had been estimated initially.

However, experts disagree about the best way to use this expanded vaccine supply (which, by the end of the year, should be augmented even further by newly manufactured vaccine). Some, including the CDC, endorse "ring-vaccination," in which vaccine is deployed only after a case of smallpox is identified, and is offered to case contacts and to contacts of contacts. Advocates of this approach cite its proven success in containing smallpox and note that it would minimize vaccine-related morbidity and mortality. Other experts endorse mass voluntary vaccination, in which the complications of quarantine, contact tracing, and crisis-mode decision-making would be avoided. An editorialist anticipates vigorous, continuing public debate about these issues.

— Abigail Zuger, MD

Published in Journal Watch General Medicine May 7, 2002

Citation(s):

Breman JG and Henderson DA. Diagnosis and management of smallpox. N Engl J Med 2002 Apr 25; 346:1300-8.

• Original article (Subscription may be required)
• Medline abstract (Free)

Frey SE et al. Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med 2002 Apr 25; 346:1265-74.

• Original article (Subscription may be required)
• Medline abstract (Free)

Bicknell WJ. The case for voluntary smallpox vaccination. N Engl J Med 2002 Apr 25; 346:1323-5.

• Original article (Subscription may be required)
• Medline abstract (Free)

Fauci AS. Smallpox vaccination policy -- The need for dialogue. N Engl J Med 2002 Apr 25; 346:1319-20.

• Original article (Subscription may be required)
• Medline abstract (Free)