More than 20 years have passed since the last case of smallpox was confirmed and 18 years since the International Commission for the Certification of Smallpox Eradication of the World Health Organization (WHO) concluded that the global eradication of smallpox had been achieved.1,2 Now, new dilemmas confront the world. Could recent outbreaks of human monkeypox in the Democratic Republic of the Congo (known as Zaire from 1971 to 1997)3,4,5 represent the return of another form of smallpox?6 Could variola (smallpox) virus be used as a weapon of biologic terrorism? And what are the implications of the decision of the WHO to advise the destruction of all isolates of the smallpox virus in June 1999?7
Monkeypox in Humans
Recent reports of large outbreaks of possible cases of monkeypox in the Democratic Republic of the Congo have raised questions as to whether monkeypox could sustain itself as an infection transmitted from human to human, in the same way as smallpox.3,4,5 Smallpox vaccine protects against monkeypox, but no one is being immunized against smallpox anymore. Might monkeypox soon take over the ecologic niche left vacant by smallpox?6 The available data do not support this possibility.
The first case of human monkeypox was identified in 1970, and through 1979, 55 cases of monkeypox were confirmed by the WHO in forested areas of western and central Africa, of which 44 cases (80 percent) occurred in the Democratic Republic of the Congo.8,9,10 The clinical picture of monkeypox (Figure 1) resembles that of smallpox in Central Africa.
....Proponents of destruction argue that the genomes of reference strains have been cloned and sequenced,35,36,37 through cooperative efforts of American and Russian scientists.38,39,40,41,42 Moreover, monkeypox virus has proved a valuable surrogate for variola: its genomic DNA has more than 90 percent homology with that of variola virus. Monkeypox illness in humans and in macaques closely resembles smallpox in humans, and the disease can be prevented in animals by vaccination. In contrast, there is no satisfactory animal model of smallpox. Work with variola virus must be performed in a biosafety-level 4 laboratory, whereas studies with monkeypox require less stringent precautions. The views of developing countries where smallpox was formerly endemic must also be weighed, since they contributed the most money and human resources to the eradication of smallpox. These countries have advocated the destruction of variola-virus stocks.7
During 1995, scientists from the Department of Defense and the Department of Health and Human Services undertook to determine what, if any, studies involving the use of intact variola virus would be critical to public health and national security. It was decided that if a model of monkeypox infection in macaques proved unsatisfactory, studies would be warranted to find a technique to grow variola virus in a genetically or chemically altered mammalian host. The macaque monkeypox model indicated that studies of pathogenesis, the protective efficacy of vaccines, and the therapeutic potential of antiviral compounds could be conducted successfully (Jahrling P, U.S. Army Medical Research Institute for Infectious Diseases: personal communication).
....Conclusions Reports suggesting that monkeypox might replace smallpox as a serious epidemic threat are unsubstantiated, but the threat posed by the possible use of smallpox as a terrorist weapon is genuine. Because of the gravity of this threat, all known stocks of variola virus should be destroyed as soon as possible. The deliberate deployment of this virus must be discouraged by whatever means possible.
Poxvirus Dilemmas — Monkeypox, Smallpox, and Biologic Terrorism