Tuberculosis (TB) continues to be a worldwide problem in the human population despite the use of vaccines and the development of several drug therapies. It has also been a disease of major concern in animal populations, especially in captive nonhuman primates in zoos and research facilities. With very few exceptions, TB research utilizing nonhuman primates has not been conducted since the mid-70s. Tulane Regional Primate Research Center (TRPRC) has initiated several TB studies using macaques. In studying the pathogenesis of TB using modern immunologic and molecular biologic techniques, our goals are to establish the rhesus monkey as a model of human TB, and to provide a mechanism to develop and test vaccines and therapeutic agents in an animal more closely related to humans than the small animal models currently used. We will also have an excellent source of material to develop and test new, reliable means of diagnosing TB in nonhuman primates.
We have completed preliminary studies using rhesus and cynomolgus monkeys. Studies were performed to develop techniques for inoculating monkeys with TB, to determine an infectious dose that would cause disease but not rapid death, and to test the efficacy of BCG and subunit vaccines. Tests using different doses and strains of TB provided us with ample material to study the immune response and demonstrated the unreliability of the existing skin test reagents for diagnosis of disease in experimentally infected monkeys. Some of the high dose animals became anergic very rapidly, and two of the low dose monkeys died before showing a positive skin test.
An ongoing study will be the focus of this presentation and will include results of several types of diagnostic measures and some immunologic parameters. We are testing two skin test reagents (old tuberculin and 250-unit PPD) and a commercially available colorimetric test kit. In addition, clinical parameters such as body wt, chest films, clinical pathology data, and bronchoalveolar lavage (BAL) will be correlated with laboratory results of BAL fluid cultures, blood cultures, and BAL cell populations.
A brief presentation of the techniques and safety considerations of performing TB research will be included.