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Modernizing stockpiles of medical countermeasures against smallpox: Benefits, risks, and knowledge gaps

Martin B. Oleksiewicz, DVM, PhD, Nina R. Steenhard, DVM, PhD, John-Erik Stig Hansen, MD, DMSc


Objective: New smallpox medical countermeasures are entering the marketplace, offering the opportunity to modernize existing stockpiles. However, new smallpox countermeasures are developed under the animal rule, meaning that human efficacy data are lacking, and human safety data may be limited. Also, stockpile modernization would require prioritization of increasingly limited public funds. Approaches to address these issues are needed.

Methods: Smallpox vaccine data were gathered by literature search. The financial value of vaccination in the face of an outbreak was evaluated using a threat-based cost/benefit analysis model, involving i) estimation of the efficacy of new smallpox vaccines based on available clinical data on virus-neutralizing seroconversion in vaccinees, ii) estimation of the likelihood for a smallpox outbreak in Denmark, and iii) estimation of the expected life-saving effects of postevent vaccination.

Results: The authors estimated that i) the likelihood of a smallpox outbreak in Denmark is very low (one event in 200,000 years), ii) the expected efficacy of currently available and new vaccines is 95 and 75 percent, respectively, iii) the expected frequency of serious side effects from vaccination is between 100 and 10,000 fold lower for new than for existing vaccines, depending on modes of action.

Conclusions: Despite the very low likelihood for a smallpox outbreak, the potentially large consequences combined with the protective effect of vaccination make maintenance of the smallpox vaccine stockpile justified and valuable. For vaccination in the face of a smallpox outbreak, a high efficacy rather than a lowered rate of adverse effects would maximize the number of lives saved.


health security, medical countermeasures, smallpox, bioterrorism, risk/benefit assessment

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