How Valid Are Assumptions About Re-emerging Smallpox? A Systematic Review of Parameters Used in Smallpox Mathematical Models

Globally eradicated in 1980, smallpox is listed as a category A bioterrorism agent. If smallpox were to re-emerge, it may be due to an act of bioterrorism or a laboratory accident, and the impact is likely to be severe. Preparedness against smallpox is subject to more uncertainty than other infectious diseases because it is eradicated, there is uncertainty about population immunity, and the current global health workforce has no practical experience or living memory of smallpox. In the event of re-emergence of smallpox, mathematical modeling plays a crucial role in improving the evidence base to inform preparedness, mitigation, and response activities. However, the predictions of mathematical models about outbreak magnitude and impact depend critically on the assumptions and disease parameters used. We aimed to identify modeling studies that would be applicable to re-emerging smallpox and to evaluate consistency and the certainty of the evidence published about the key parameters used.