Mtb-Specific Interferon-Gamma ELISpot Assays Have Greater Sensitivity for Detecting Mtb Infection Compared to Tuberculin Skin Test in a Cohort of Experimentally M. tuberculosis-Infected Macaques.

Tuberculosis outbreaks in nonhuman primate (NHP) colonies can result in disastrous financial, scientific, animal welfare, and public health outcomes. Tuberculin skin testing (TST) has been the standard diagnostic method for identifying Mycobacterium tuberculosis (Mtb) infection in NHPs but has limited sensitivity and specificity. In humans, Mtb-specific interferon-γ release assays (IGRAs) have become the preferred diagnostic method, overcoming significant limitations of the TST. We compared the diagnostic qualities of the TST and IGRA in a cohort of 673 rhesus and cynomolgus macaques with experimental Mtb infection. Serial TST and IGRA data were curated retrospectively for animals before and after Mtb infection and temporally matched to assess sensitivity, specificity, and agreement between the 2 tests. The overall sensitivity of the IGRA was 0.84 compared with 0.49 sensitivity of the TST test in detecting Mtb infection. Specificity of the IGRA and the TST was 0.83 and 1.0, respectively, with an overall agreement rate of 72% between the 2 tests. Sensitivity peaked at 3-5 weeks postinfection for TST and 5-7 weeks for IGRA. Data from a second cohort of animals (n = 227) that were not experimentally infected with Mtb, but for whom testing was done for screening and investigational purposes, demonstrated an agreement rate of 96%. To our knowledge, this is the largest reported comparison of TST and IGRA testing in NHPs. Although IGRAs are more labor intensive than TSTs, our data suggest that IGRAs have better diagnostic accuracy in detecting Mtb infection. Our data also suggest that the threshold for a positive TST could be lowered to improve sensitivity.