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Dose-Response Model for Listeria monocytogenes-Induced Stillbirths in Nonhuman Primates

Smith, Mary Alice, Takeuchi, Kazue, Anderson, Gary, Ware, Glenn O., McClure, Harold M., Raybourne, Richard B., Mytle, Nutan, Doyle, Michael P.
Infection and immunity 2008 v.76 no.2 pp. 726-731
Listeria monocytogenes, Macaca mulatta, dose response, etiology, humans, issues and policy, mice, models, oral exposure, pregnant women, risk assessment
A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10⁷ CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10² to 10¹⁰ CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10⁷ CFU, comparable to an estimated 10⁶ CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10¹³ CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths.