Immunological concepts in tuberculosis diagnostics for non-human primates: a review

Accurate diagnosis of tuberculosis in non-human primates is of critical importance. As with natural human infection with Mycobacterium tuberculosis, infected primates develop a broad spectrum of disease, including subclinical (latent) infection, chronic primary tuberculosis, rapidly progressing fulminant disease, and reactivation tuberculosis. In a primate colony, clinical suspicion is the key to diagnosis. The course of action should be based on careful and thorough clinical assessments in conjunction with screening and microbiologic methods. Diagnostic modalities can be categorized into pathogen identification and immunologic host response techniques. While the classic tuberculin skin test is the standard screening tool, it has limited sensitivity and specificity. Other tools such as interferon gamma releasing assays have similar accuracy results but use different immunologic mechanisms and may be helpful as an additional screening tool. Advantages and disadvantages to these and other assays (e.g., lymphocyte proliferation assay, antibody detection) are also discussed. Surrogates to sputum sample (e.g., gastric aspirate, stool samples, respiratory sample via bronchoscopy) should be obtained for microbiologic identification, as acid-fast smear and culture are critical to pathogen identification for optimal sensitivity and specificity. Interpretation of these immunologic screening tools should be performed cautiously and must be correlated with level of suspicion. While the identification of M. tuberculosis or M. bovis confirms the diagnosis of tuberculosis, negative results do not exclude the diagnosis. Without pathogen detection to confirm diagnosis, thorough gross and microscopic pathological review at necropsy may be required to make a definitive diagnosis. Lastly, the risk and benefits to the primate colony, staff and resources must be carefully weighed when deciding to euthanize monkeys to make the diagnosis of tuberculosis.