Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

Abstract

Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID50) of 11,000 spores (95% confidence interval 7,200–17,000), ID10 of 1,700 (1,100–2,600), and ID1 of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID50, 11.8 days (9.5–15.0) for ID10, and 12.1 days (9.9–15.3) for ID1. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses.

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

“…This estimate was derived from an exposure scenario of 11,000 inhaled B. anthracis spores, a dose proposed to cause infection in 50% of susceptible nonvaccinated individuals (ID 50 ). Lower estimated exposure doses had associated longer periods of incubation (34). Historically, the estimated exposure levels in high-risk industrial environments were estimated at 21 to 2,100 infectious particles per 8-h day (35,36), significantly lower than those proposed by Toth et al A systematic review and analysis of 82 inhalation anthrax cases by Holty et al indicated that postincubation, the mean time from symptom onset to death was 4.8 days (31).…”

Reaerosolization of Spores from Flooring Surfaces To Assess the Risk of Dissemination and Transmission of Infections

“…The inhalational ID1 (1% infectious dose) of Bacillus anthracis is estimated to be 160 spores (95% confidence interval, 100 to 250 spores) (19). The level of potential exposure for sampling personnel within these parameters, in the absence of respiratory protective equipment (RPE), would clearly pose an unacceptable risk.…”

Modeling Tool for Decision Support during Early Days of an Anthrax Event

“…¶360 spores is a dosage estimated to have occurred during the 1979 Sverdlovsk (USSR) anthrax event ( 13 ). One spore represents the minimum possible infectious dose, and 8,000 is a plausible high dose ( 14 ). #Cannot exceed the value of the Epidemic-Curve model “Population size of the impacted jurisdiction” parameter.…”