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Questions about Clinical Variola Major | CDC EID

EID Journal Home > Volume 17, Number 4–April 2011

Volume 17, Number 4–April 2011
Policy Review
Remaining Questions about Clinical Variola Major
J. Michael Lane
Author affiliation: Emory University School of Medicine, Atlanta, Georgia, USA (retired)

Suggested citation for this article

After the recent summary of World Health Organization–authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.

After the World Health Organization (WHO) declared smallpox eradicated in 1980, several problems remained concerning the disease and its causative virus, variola major virus. These problems included high rates of adverse events associated with most strains of vaccinia virus; our inadequate understanding of the pathophysiology of smallpox; lack of a good animal model of the disease; difficulty of rapid laboratory diagnosis, including the poor ability of most standard laboratory tests to distinguish between orthopoxviruses; lack of an effective antiviral drug; and rudimentary knowledge about the genetic makeup of the virus.

Although many observers wished to destroy the remaining stocks of variola major virus in 1980, several respected researchers wanted to use the live virus to help answer some of these remaining questions. In 1999, WHO agreed to a research agenda, with oversight by a WHO committee, to continue research with live variola major virus until substantial progress was made on these questions. The WHO oversight committee has now declared that satisfactory (if in some areas imperfect) progress has been made toward developing improved vaccines, better laboratory diagnostics, a reasonable nonhuman primate animal model, effective antiviral drugs, and good understanding of the genetics of orthopoxviruses. Reports of this progress have been published (1–5).

Despite this impressive progress, clinicians have been left with several unanswered questions. However, these questions may never be answered because we hope that there will never be another patient with classical smallpox, and the best nonhuman primate model does not perfectly reproduce clinical smallpox

Questions about Clinical Variola Major | CDC EID

Suggested Citation for this Article
Lane JM. Remaining questions about clinical variola major. Emerg Infect Dis [serial on the Internet]. 2011 Apr [date cited].

DOI: 10.3201/eid1704.101960

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J. Michael Lane, 869 Clifton Road NE, Atlanta, GA 30307, USA
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