Threat from Mycobacterium orygis-associated tuberculosis in south Asia

South Asia is a hotspot of tuberculosis with an estimated annual incidence of 3·7 million cases, accounting for 37% of the global tuberculosis incidence in 2019.1SAARC Tuberculosis and HIV/AIDS Centre, (STAC)Burden of TB in SAARC.https://www.saarctb.org/burden-of-tb-in-saarc/Date: 2022Date accessed: March 10, 2022Google Scholar The southeast Asia region, which includes south Asia, has a high burden from zoonotic tuberculosis, with an estimated 43 000 (31·76%) new cases in 2016; however, as the causative agent of this zoonotic tuberculosis has not been fully defined, the true incidence could be underestimated.2WHOZoonotic Tuberculosis.https://cdn.who.int/media/docs/default-source/hq-tuberculosis/zoonotic-tb-factsheet-2017.pdf?sfvrsn=66fdf3a1_3&download=trueDate: 2017Date accessed: March 10, 2022Google Scholar Reports of tuberculosis caused by Mycobacterium orygis in animals and humans in south Asia, and the discovery of M orygis in south Asian migrants, highlights an overlooked threat from M orygis in south Asia and beyond. M orygis is a genetically distinct animal-adapted subspecies of the Mycobacterium tuberculosis complex that causes tuberculosis in animals and humans.3van Ingen J Rahim Z Mulder A et al.Characterization of Mycobacterium orygis as M. tuberculosis complex subspecies.Emerg Infect Dis. 2012; 18: 653-655Crossref PubMed Scopus (141) Google Scholar It has been isolated from a range of animals in south Asian countries, across livestock farms, zoos, and free-ranging wild animals, suggesting endemicity in the region.3van Ingen J Rahim Z Mulder A et al.Characterization of Mycobacterium orygis as M. tuberculosis complex subspecies.Emerg Infect Dis. 2012; 18: 653-655Crossref PubMed Scopus (141) Google Scholar, 4Rahim Z Thapa J Fukushima Y et al.Tuberculosis caused by Mycobacterium orygis in dairy cattle and captured monkeys in Bangladesh: a new scenario of tuberculosis in South Asia.Transbound Emerg Dis. 2017; 64: 1965-1969Crossref PubMed Scopus (30) Google Scholar, 5Thapa J Paudel S Sadaula A et al.Mycobacterium orygis-associated tuberculosis in free-ranging rhinoceros, Nepal, 2015.Emerg Infect Dis. 2016; 22: 570-572Crossref PubMed Scopus (21) Google Scholar, 6Thapa J Nakajima C Maharjan B Poudel A Suzuki Y Molecular characterization of Mycobacterium orygis isolates from wild animals of Nepal.Jpn J Vet Res. 2015; 63: 151-158PubMed Google Scholar Direct evidence of M orygis transmission between livestock and humans has been reported from an Indian immigrant working in a cattle farm in New Zealand.7Dawson KL Bell A Kawakami RP Coley K Yates G Collins DM Transmission of Mycobacterium orygis (M. tuberculosis complex species) from a tuberculosis patient to a dairy cow in New Zealand.J Clin Microbiol. 2012; 50: 3136-3138Crossref PubMed Scopus (40) Google Scholar M orygis in migrants from India, Nepal, and Pakistan who live in the USA and Norway, indicate that the origin of such M orygis infections is in south Asia.8Marcos LA Spitzer ED Mahapatra R et al.Mycobacterium orygis lymphadenitis in New York, USA.Emerg Infect Dis. 2017; 23: 1749-1751Crossref PubMed Scopus (13) Google Scholar, 9Eldholm V Ronning JO Mengshoel AT Arnesen T Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway.BMC Infect Dis. 2021; 21: 562Crossref PubMed Scopus (4) Google Scholar The US study found that the eight cases of M orygis did not belong to an epidemiological transmission cluster, suggesting that the infections were independently acquired. The only epidemiological risk factor in all cases was that patients emigrated from south Asia.8Marcos LA Spitzer ED Mahapatra R et al.Mycobacterium orygis lymphadenitis in New York, USA.Emerg Infect Dis. 2017; 23: 1749-1751Crossref PubMed Scopus (13) Google Scholar Similarly, in the study from Norway, the authors concluded that all M orygis isolates were uniquely imported to Norway from south Asian migrants at various time points, and no transmission of M orygis occurred in Norway during the patients' residence there.9Eldholm V Ronning JO Mengshoel AT Arnesen T Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway.BMC Infect Dis. 2021; 21: 562Crossref PubMed Scopus (4) Google Scholar In a comprehensive molecular epidemiological survey of 940 mycobacteria-positive cultures from clinical patients, mainly from different states of India and some from Nepal and Bangladesh, seven M orygis isolates but no Mycobacterium bovis isolates were reported, prompting the authors to argue that M bovis should be reconsidered as a sole proxy for zoonotic tuberculosis as per the WHO definition.10Duffy SC Srinivasan S Schilling MA et al.Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance study.Lancet Microbe. 2020; 1: e66-e73Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar These seven cases of M orygis were reported from four different states in northern and southern India, and six of them were associated with extrapulmonary tuberculosis, as in the typical case of zoonotic tuberculosis. These reports of M orygis from across humans, livestock, and wildlife in south Asia suggest that M orygis is endemic and a causative agent of animal and zoonotic tuberculosis in the region. In-depth epidemiological surveillance should be conducted across humans, livestock, and wildlife to understand the unique epidemiological, ecological, and pathogenomic drivers of distribution, risk factors, and transmission dynamics of M orygis in south Asia. South Asia is a biodiversity hotspot and home to many iconic endangered animals such as tigers, rhinoceros, and elephants. M orygis was reported to originate from a free-ranging rhinoceros at the Chitwan National Park in Nepal, a transboundary national park between Nepal and India.5Thapa J Paudel S Sadaula A et al.Mycobacterium orygis-associated tuberculosis in free-ranging rhinoceros, Nepal, 2015.Emerg Infect Dis. 2016; 22: 570-572Crossref PubMed Scopus (21) Google Scholar Furthermore, M orygis was reported in zoo animals in Nepal originally from Chitwan National Park, suggesting unknown maintenance hosts of M orygis in and around the national park.6Thapa J Nakajima C Maharjan B Poudel A Suzuki Y Molecular characterization of Mycobacterium orygis isolates from wild animals of Nepal.Jpn J Vet Res. 2015; 63: 151-158PubMed Google Scholar The case of M orygis in an endangered rhinoceros in Nepal and many unreported cases of tuberculosis in wild animals in zoo and captive facilities of south Asian countries suggest an unexplored threat of tuberculosis, perhaps due to M orygis, to wildlife conservation in the region. The emphasis on diagnosis and control of tuberculosis in south Asia is given to human tuberculosis, particularly multidrug-resistant tuberculosis. Commonly used diagnostic methods, such as those that make use of clinical signs, Ziehl-Neelsen staining, and cultures, cannot identify the particular species of the M tuberculosis complex. Similarly, the popular GeneXpert MTB/RIF test does not differentiate between species of the M tuberculosis complex, so the true burden of zoonotic tuberculosis is unknown because of inaccurate diagnosis. Furthermore, the real burden of animal tuberculosis in the region is unknown as there are no livestock or wildlife tuberculosis control programmes being implemented. In the light of WHO's End TB Strategy to diagnose and cure every tuberculosis case to end the epidemic by 2030, the threat from M orygis in south Asia must be recognised at national and international levels, and the appropriate control programmes implemented. This study was supported by the JSPS KAKENHI grant number 21K14969 from the JSPS to JT. The funder had no role in study design, manuscript preparation, and decision to publish. We declare no competing interests.