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.

C limate change and habitat encroachment by humans have led to overlapping of home ranges of wildlife with human settlements. Subsequently, a vast variety of infectious zoonotic diseases have recently emerged or reemerged, transmitted to humans directly from wildlife or indirectly through domestic animals (1). Tuberculosis (TB), caused by Mycobacterium tuber-culosis bacteria, is an airborne chronic infectious disease with zoonotic potential found among both humans and wildlife (2). TB has been with humanity for thousands of years and has not been eliminated by modern medical efforts, despite identification of the causative agent 140 years ago by Dr. Robert Koch. A 2021 World Health Organization report ranked Thailand as a country with one of the highest burdens of human TB (3).TB has previously been reported among both wild and captive nonhuman primates. Approximately 75% of TB cases in monkeys are caused by M. tuberculosis. Among 500 species of nonhuman primates existing throughout the world, rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques have commonly been used as animal models for TB drug and vaccine research because clinical signs and immune responses after MTB infection are similar to those in humans (4-7).Thailand is located at the center of the rhesus and long-tailed macaque distribution ranges, where the 2 species live close together, and comprises part of their interspecific hybridization zone (8-10). Rhesus macaques are distributed in the north and northeast of Thailand and long-tailed macaques live in central to southern Thailand (11-13); the hybrid zone, where they cohabit, is within 15°-20°N latitude. It has been proposed that, during earth's glacial periods, male rhesus macaques introgressed southwards into longtailed macaque population areas and hybridized with female long-tailed macaques (9,10). Recently, researchers analyzed the level of genetic admixture between rhesus and long-tailed macaque ancestral populations using autosomal single-nucleotide polymorphism markers. Populations of long-tailed macaques from the northern part of their range carry higher levels of genetic admixture of rhesus ancestry than do southern populations (10).

OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

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A Correction to this paper has been published: 10.1007/s10764-021-00222-6