The leading edge

Who gets smallpox vaccine?

When this journal began publication in August 2001, smallpox vaccination would have seemed an unlikely subject for public debate. However, it has warranted recent editorials in, for example, the New York Times and Wall Street Journal. The terrorist attacks of last September and subsequent use of anthrax as a weapon of bioterrorism have changed our perception of the importance of this subject.

The Advisory Committee on Immunization Practices (ACIP), a US Centers for Disease Control and Prevention (CDC) advisory body, released their draft supplemental recommendations on the use of smallpox (vaccinia) vaccine on June 20, 2002. The committee's proposals were informed by a series of five CDC-hosted public forums held across the USA. The recommendations must pass through the CDC, who invited comment until July 31, 2002, and the Department of Health and Human Services (HHS) before they can become policy. ACIP proposed vaccination for healthcare workers assigned to investigate smallpox cases and to begin control measures, and for selected workers in hospitals designated to receive the first patients in a smallpox outbreak. 10 000–20 000 people would likely be offered voluntary vaccine under the new recommendations.

The ACIP recommendation that has attracted most press criticism is the advice against vaccinating the general population. “Under current circumstances, with no confirmed smallpox, and the risk of an attack assessed as low, vaccination of the general population is not recommended, as the potential benefits of vaccination do not outweigh the risks of vaccine complications”, said a committee statement.

Three important considerations influenced ACIP's proposals: the level of disease risk and threat, expected severe adverse reactions to vaccination, and vaccine and vaccinia immune globulin (VIG) supply. First, ACIP assessed the risk of deliberate release of smallpox as low because the only known surviving stocks of virus are held securely in the USA and Russia, although the former Soviet Union did develop smallpox as a biological weapon and supplies may still exist. Second, in terms of adverse reactions, smallpox vaccine has been described as “the least safe vaccine ever used in the United States”. When mass vaccination was last given in the USA in 1968, vaccine-related deaths were under one per million, but with many more immuno compromised people around today death rates as high as two to four per million have been predicted, plus several thousand serious adverse events for a mass-vaccination programme. Third, the USA does have supplies of vaccine available, 15 million does of Wyeth Dryvax, which could be used at a one in five dilution, and 85 million doses donated by Aventis Pasteur (see Lancet Infect Dis 2002; 2: 390). However, these vaccines would have to be given under investigational new drug protocols—ie, requiring individual informed consent and strict observation and control by the CDC. As to VIG, the CDC has enough doses available (about 600) to treat the adverse reactions expected from vaccination of 4–6 million people.

Critics of the ACIP recommendation argue that however low the risk of smallpox, it is better to offer vaccination now to everyone rather than try to vaccinate the public in the chaos that will follow the deliberate release of smallpox. Mass voluntary vaccination would cut the number of victims of a smallpox attack, make catch-up vaccination of unimmunised individuals easier, and reduce the attractiveness of smallpox as an agent of bioterrorism.

Events have moved on since the recommendations appeared. On July 8, HHS officials suggested that vaccination may be offered to more than 500 000 healthcare and emergency workers. And on July 25, Donald Henderson, chairman of the Council on Public Health Preparedness at HHS, said, “We will have a policy in days, or 2 weeks at the most”, although nothing had been announced as we went to press.

A compromise probably lies somewhere between the 20 000 vaccinees suggested by ACIP and vaccination for all. Limited availability of VIG is a powerful argument against mass vaccination. However, there are sufficient doses to cover the 500 000 recipients suggested by HHS, and, as William J Bicknell has suggested (NEJM 2002; 246: 1322–25), VIG stocks could be built up from blood donation from emergency workers immunised in the first round of vaccination. Recommendations for expanded immunisation with the current vaccines could then be reassessed in the light of increased stocks of VIG.

By this time next year, the USA should have licensed sufficient stocks of the new Acambis smallpox vaccine to immunise everyone in the country. Because this vaccine is grown in tissue culture, it should be safer than current vaccines. The risk-benefit equation may then tip in favour of mass vaccination.

The Lancet Infectious Diseases