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

PLoS Pathogens

Frederick R. Adler¹  Catherine Coghill²  Damon J. A. Toth³  Kenneth Bulmahn³  Adi V. Gundlapalli⁴  Christopher W. Woods⁵  Frank Gallegos⁶  Matthew H. Samore⁷  Thomas E. Walton⁸  Wiley A. Schell⁸ 

[1] Centers for Epidemiology and Animal Health, United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services, Fort Collins, Colorado, United States of America;Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, United States of America;Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America;Department of Mathematics, University of Utah, Salt Lake City, Utah, United States of America;Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America;Division of Infectious Diseases, Department of Medicine, Duke University, Durham, North Carolina, United States of America;Independent Risk Assessment Contractor, Idaho Falls, Idaho, United States of America;VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America

关键词: Bacterial spores;    Anthrax;    Primates;    Antibiotics;    Bacillus anthracis;    Probability distribution;    Antibiotic prophylaxis;    Respiratory infections;   

DOI  :  10.1371/journal.ppat.1003555

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY