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New Approaches to Tuberculosis Surveillance in Nonhuman Primates

Nicholas W. Lerche, JoAnn L. Yee, Saverio V. Capuano, and Joanne L. Flynn

Nicholas W. Lerche, DVM, MPVM, is Director of the Pathogen Detection Laboratory and Associate Director for Primate Services at the California National Primate Research Center, and a professor in the Department of Medicine and Epidemiology at the School of Veterinary Medicine, University of California, Davis; JoAnn L. Yee, MT(ASCP), CLS, is Technical Supervisor of the Pathogen Detection Laboratory; Saverio V. Capuano, DVM, is the attending veterinarian and Associate Director for the Animal Services Division at the Wisconsin National Primate Research Center, University of Wisconsin, Madison; and Joanne L. Flynn, PhD, is a professor in the Department of Molecular Genetics and Biochemistry at the University of Pittsburgh School of Medicine.

Address correspondence and reprint requests to Dr. Nicholas W. Lerche, California National Primate Research Center, One Shields Avenue, University of California, Davis, CA 95616 or email nwlerche@ucdavis.edu.

Abstract

Despite significant progress in reducing the incidence of tuberculosis in nonhuman primates (NHPs) maintained in captivity, outbreaks continue to occur in established colonies, with potential serious consequences in human exposures, animal losses, disruption of research, and costs related to disease control efforts. The intradermal tuberculin skin test (TST) using mammalian old tuberculin (MOT) has been the mainstay of NHP tuberculosis surveillance and antemortem diagnosis for more than 60 years. But limitations of the TST, particularly its inability to reliably identify animals with latent TB infections, make it unsuitable for use as a single, standalone test for TB surveillance in nonhuman primates in the 21st century. Advances in technology and the availability of Mycobacterium spp. genomic sequence data have facilitated the development and evaluation of new immune-based screening assays as possible adjuncts and alternatives to the TST, including in vitro whole blood assays that measure the release of interferon gamma in response to stimulation with tuberculin or specific mycobacterial antigens, and assays that detect antibodies to highly immunogenic secreted proteins unique to M. tuberculosis, M. bovis, and other species belonging to the M. tuberculosis complex. It is becoming apparent that no single screening test will meet all the requirements for surveillance and diagnosis of tuberculosis in nonhuman primates. Instead, the use of several tests in combination can increase the overall sensitivity and specificity of screening and surveillance programs and likely represents the future of TB testing in nonhuman primates. In this article we describe the characteristics of these newer screening tests and discuss their potential contributions to NHP tuberculosis surveillance programs.

Key Words: diagnosis; nonhuman primates; screening tests; surveillance; tuberculosis





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