Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

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.

Isolation and Characterization of Superdormant Spores of Bacillus Species

“…However, this simple strategy has been largely nullified because germination of spore populations is heterogeneous, with some spores, often called superdormant spores, germinating extremely slowly and potentially coming back to life long after treatments are applied to inactivate germinated spores (8,9,16). The concern over superdormant spores in populations also affects decisions such as how long individuals exposed to B. anthracis spores should continue to take antibiotics, since spores could remain dormant in an individual for long periods and then germinate and cause disease (3,11).…”

A review of back-calculation techniques and their potential to inform mitigation strategies with application to non-transmissible acute infectious diseases

“…The incubation period is defined as the time from pathogen exposure to the onset of symptoms [16,20]. Owing to factors such as host susceptibility, size of inoculum, strain virulence and chance, infected persons can experience different incubation periods.…”

“…n can subsequently be estimated indirectly by using equation (3.7) with the known E and the estimate of d. This latter process can be illustrated with a fictitious example (devised for this review) in which E ¼ 1300 people who are situated inside the same building on 30 March are exposed to an aerosolized release of the causative agent of anthrax. Each person is assumed to inhale d ¼ 1000 spores, and their probability of infection is derived from a withinhost model where the inhaled spores can either germinate in the lungs of the host (resulting in infection) or be cleared by the host's defence mechanisms [16,52]. In the form of equation (3.7) with g ¼ fl, ug, this 'competing risks' model is given…”

“…Even if there are concurrent cases occurring within the same country then initial epidemiological investigation possibly combined with cluster detection techniques [57] might indicate the occurrence of multiple outbreaks. Indeed, some of the temporal models described in §3 were separately applied to the three main clusters of inhalational anthrax in the 2001 US attacks [14][15][16]. When cases are considered to be linked together as a consequence of epidemiological investigation, then data relevant to their spatial locations during the time prior to their disease rsif.royalsocietypublishing.org J. R. Soc.…”

Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity

“…9,10 Prior modeling and simulation studies have indicated that rapid response to an anthrax attack significantly reduces morbidity and mortality, with estimated effects of various strategies dependent on model parameters and timing of the response. [11][12][13][14][15] For example, Wein et al estimated that 1 kilogram of anthrax spores released upwind of 11.5 million persons would result in 123,400 deaths if the public health response began on Day 2 after an attack, but the number of deaths would more than double if the response was delayed until Day 5. 11 Other studies evaluated the comparative cost-effectiveness of various response strategies and found important advantages in responding rapidly and combining postattack vaccination with antibiotic prophylaxis for anthrax exposed victims.…”