Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores.

Autor: Coleman ME; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Marks HM; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Bartrand TA; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Donahue DW; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Hines SA; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Comer JE; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA., Taft SC; National Homeland Security Research Center, U.S. Environmental Protection Agency, Cincinnati, OH, USA.
Jazyk: angličtina
Zdroj: Risk analysis : an official publication of the Society for Risk Analysis [Risk Anal] 2017 May; Vol. 37 (5), pp. 943-957. Date of Electronic Publication: 2017 Jan 25.
DOI: 10.1111/risa.12688
Abstrakt: Survival models are developed to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple-dose data set to predict the probability of death through specifying functions of dose response and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) is an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed use different underlying dose-response functions and use the assumption that, in a multiple-dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this article. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit data sets. More accurate survival models depend upon future development of dose-response data sets specifically designed to assess potential multiple-dose effects on response and time-to-response. The process used in this article to develop the best-fitting survival model for exposure of rabbits to multiple aerosol doses of B. anthracis spores should have broad applicability to other host-pathogen systems and dosing schedules because the empirical modeling approach is based upon pathogen-specific empirically-derived parameters.
(© 2017 Society for Risk Analysis.)
Databáze: MEDLINE
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