The objective of this pilot project is to continue the characterization of the tuberculosis model in rhesus monkeys. We previously found that high dose inoculation (six million bacteria) of Mycobacterium tuberculosis H37Rv and Erdman strains produced lethal lung disease within five to ten weeks. Monkeys developed clinical signs of dyspnea, coughing, anorexia, and weight loss 4-6 weeks after inoculation. Skin testing with Old tuberculin became mildly positive after 5 weeks while PPD skin tests remained negative. Animals developed extensive necrotizing granulomatous lesions in the inoculated half of the lung with spread to the contralateral lung and bronchial lymph node in animals with H37Rv, and to the liver and kidney in animals with the Erdman strain. Animals vaccinated with culture filtrate from H37Rv and challenged with two million bacteria developed the same clinical disease as unvaccinated controls. However, low dosage inoculation of a pair of animals with each strain (<300 Erdma n, <30 H37Rv) failed to produce clinical disease within 18 weeks. Lesions in three of four animals were confined to the bronchial lymph node. To confirm this finding, four more animals per strain have been inoculated with low dosages of bacteria. All animals have strongly positive skin tests but remain clinically normal four weeks after inoculation. Characterization of this model by culture, blastogenesis, flow cytometry, and cytokine detection continues. Results contradict old literature and indicate that tuberculosis in rhesus monkeys may present as a chronic disease based on the dose of the inoculum. This suggests that future studies using low dose inoculation will be feasible in SIV-infected monkeys to study tuberculosis as an opportunistic infection. FUNDING Venture Research PUBLICATIONS Scollard DM, Didier PJ, Dietrich MA, Bohm Jr RP. Selective increases in CD45RO(+) CD38(+) T cells in 1? and 2? responses to BCG in rhesus macaques. [Abstract]. Proceedings of the 9th International Immunology Congress, San Francisco, CA, July 23-29, 1995. Scollard DL, Didier PJ, Bohm Jr RP. A method to assess changes in rhesus lymphatic T cells in vivo during local immune responses. [Abstract]. Second Annual Molecular Biology and Biotechnology Conference, Baton Rouge, LA, February 9-10, 1996. Didier PJ, Blanchard JL, Gormus BJ. Pulmonary tuberculosis in normal rhesus monkeys infected with Mycobacterium tuberculosis H37Rv. [Abstract #159]. Amer Soc Trop Med Hygiene, 57(3):156, 1997. Didier PJ, Blanchard JL. Chronic tuberculosis produced by low dosage of M. tuberculosis (Erdman) in rhesus monkeys. [Abstract #734]. Amer Soc Trop Med Hygiene 59(3):361, 1998.
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