Human Dose–Response Data for Francisella tularensis and a Dose‐ and Time‐Dependent Mathematical Model of Early‐Phase Fever Associated with Tularemia After Inhalation Exposure
Abstract
Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early‐phase febrile illness following administration of well‐characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de‐identified case reports is also presented. A unified, logically consistent model of early‐phase febrile illness is described as a lognormal dose–response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near‐maximum body temperature. Inhaled dose‐dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual‐by‐individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early‐phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 25, 2018
- Source ID
- 10.1111/risa.12995
Entities
People
- Alec Thurman
- Brandolyn Thran
- David Crary
- Gene Mcclellan
- Margaret Coleman
Organizations
- Applied Research Associates (United States)
- United States Army Center for Health Promotion and Preventive Medicine