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Infection and Immunity, February 2008, p. 726-731, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01366-06
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Dose-Response Model for Listeria monocytogenes-Induced Stillbirths in Nonhuman Primates{triangledown} ,{dagger}

Mary Alice Smith,1,2* Kazue Takeuchi,2,{ddagger} Gary Anderson,1 Glenn O. Ware,3 Harold M. McClure,4 Richard B. Raybourne,5 Nutan Mytle,2,§ and Michael P. Doyle2

Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia 30602,1 Center for Food Safety, College of Agricultural and Environmental Sciences, University of Georgia, Griffin, Georgia 30223,2 Experimental Statistics, College of Agricultural and Environmental Sciences, University of Georgia, Athens, Georgia 30602,3 Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322,4 U.S. Food and Drug Administration, Laurel, Maryland 207085

Received 24 August 2006/ Returned for modification 24 October 2006/ Accepted 16 November 2007

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.

* Corresponding author. Mailing address: University of Georgia, 206 Environmental Health Science Bldg., Athens, GA 30602-2102. Phone: (706) 542-1599. Fax: (706) 542-7472. E-mail: masmith{at}uga.edu

{triangledown} Published ahead of print on 10 December 2007.

{dagger} Dedicated to our friend and colleague Harold M. McClure, 1937-2004.

Editor: J. F. Urban, Jr.

{ddagger} Present address: Procter and Gamble, Cincinnati, OH 45217.

§ Present address: Infectious Disease Research Department, Southern Research Institute, Birmingham, AL 35205.

Infection and Immunity, February 2008, p. 726-731, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01366-06
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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