Detection of tuberculosis in cynomolgus macaques (Macaca fascicularis) using a supplementary Monkey Interferon Gamma Releasing Assay (mIGRA).

Cynomolgus monkeys (Macaca fascicularis; MF) are commonly used as nonhuman primate models for pharmaceutical product testing. In their habitat range, monkeys have close contact with humans, allowing the possibility of bidirectional transmission of tuberculosis (TB) between the two species. Although the intradermal tuberculin skin test (TST) is used for TB detection in MF, it has limitations. Herein, we established the mIGRA, combining human QuantiFERON-TB Gold-Plus and monkey IFN-γ ELISApro systems, and used it to investigate 39 captive MF who were cage-mates or lived in cages located near a monkey who died from the naturally TB infection. During a 12-month period of study, 14 (36%), 10 (26%), and 8 (21%) monkeys showed TB-positive results using the mIGRA, the TST, and TB culture, respectively. Among the 14 mIGRA-positive monkeys, 8 (57.1%) were TST-positive and 7 (50%) were culture-positive, indicating early TB detection in the latent and active TB stages with the mIGRA. Interestingly, 3 (37.5%) of the TST-negative monkeys were culture-positive. Our study showed that the mIGRA offers many advantages, including high sensitivity and high throughput, and it requires only one on-site visit to the animals. The assay may be used as a supplementary tool for TB screening in MF.

Indo-Oceanic Mycobacterium tuberculosis strains from Thailand associated with higher mortality.

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province.OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality.DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models.RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death.CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.