Modeling the Incubation Period of Inhalational Anthrax

Ever since the pioneering work of Philip Sartwell, the incubation period distribution for infectious diseases is most often modeled using a lognormal distribution. Theoretical models based on underlying disease mechanisms in the host are less well developed. This article modifies a theoretical model originally developed by Brookmeyer and others for the inhalational anthrax incubation period distribution in humans by using a more accurate distribution to represent the in vivo bacterial growth phase and by extending the model to represent the time from exposure to death, thereby allowing the model to be fit to nonhuman primate time-to-death data. The resulting incubation period distribution and the dose dependence of the median incubation period are in good agreement with human data from the 1979 accidental atmospheric anthrax release in Sverdlovsk, Russia, and limited nonhuman primate data. The median incubation period for the Sverdlovsk victims is 9.05 (95% confidence interval = 8.0 - 10.3) days, shorter than previous estimates, and it is predicted to drop to less than 2.5 days at doses above 10 6 spores. The incubation period distribution is important because the left tail determines the time at which clinical diagnosis or syndromic surveillance systems might first detect an anthrax outbreak based on early symptomatic cases, the entire distribution determines the efficacy of medical intervention — which is determined by the speed of the prophylaxis campaign relative to the incubation period — and the right tail of the distribution influences the recommended duration for antibiotic treatment.