Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

^*Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, and ^‡Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD 21205

Edited by Stephen E. Fienberg, Carnegie Mellon University, Pittsburgh, PA, and approved June 17, 2003 (received for review April 4, 2003)

Abstract

A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity would likely occur before antibiotic prophylaxis could even be initiated. At very low doses, 60 days of antibiotic prophylaxis is adequate. Exposure doses can be estimated from the cumulative attack rate up to the point antibiotic prophylaxis begins. The model explains that whereas ≤60 days of antibiotics were enough to protect persons in the 2001 U.S. outbreak, because doses were very low, at moderate or high doses considerably longer durations would be necessary to adequately protect exposed populations.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: rbrook{at}jhsph.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviation: TD(P), toxic dose level, the dose that causes toxicity or disease in P percent of the population.