Zoonotic tuberculosis: a complex issue of the Mycobacterium tuberculosis complex

Mycobacterium bovis is considered the proxy for zoonotic tuberculosis by international health organisations. However, in a large screening study of 940 mycobacteria-positive cultures from hospitalised patients, mainly from India and some from Bangladesh and Nepal, Shannon C Duffy and colleagues1Duffy 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 (10) Google Scholar identified seven Mycobacterium orygis isolates but no M bovis. In view of these results, the authors suggest that zoonotic tuberculosis can no longer be referred to as M bovis only. The study used modified PCR tests to detect different Mycobacterium tuberculosis complex (MTBC) subspecies that potentially cause zoonotic tuberculosis, and identified M tuberculosis sensu strictu in most samples (912 [97·0%] isolates). On whole-genome sequencing (WGS) of 25 isolates, M tuberculosis lineage 1 was the most represented lineage among cases of M tuberculosis (nine of 13 M tuberculosis sensu strictu strains), confirming a preferential geographic distribution of this lineage in south Asia.2Saelens JW Viswanathan G Tobin DM Mycobacterial evolution intersects with host tolerance.Front Immunol. 2019; 10: 528Crossref PubMed Scopus (10) Google Scholar 15 (1·6%) isolates were identified as non-tuberculosis mycobacteria. Although the study was of human isolates from a single large referral hospital, a notable finding was the absence of M bovis in a large number of broth cultures from patients with symptomatic tuberculosis. Furthermore, the PCR screen showed two isolates lacking RD12, and identified these as M tuberculosis sensu strictu only after WGS, highlighting the complexity of accurately identifying MTBC members and the relevance of different molecular tools. Many isolates were from the Indian state of Tamil Nadu, where, in a previous molecular screening study from March, 2014, to June, 2015, prevalence of M bovis reached 12·5% in people at high risk of infection (living in the endemic region and in contact with cases of active tuberculosis).3Bapat PR Dodkey RS Shekhawat SD et al.Prevalence of zoonotic tuberculosis and associated risk factors in central Indian populations.J Epidemiol Glob Health. 2017; 7: 277-283Crossref PubMed Scopus (14) Google Scholar As Duffy and colleagues indicate, the analysis should now be extended to other regions in India. Additionally, evaluation of concurrent factors that might explain the absence of M bovis, such as patient occupation and geographical characteristics of places of origin, is warranted. Assessment of risk factors, including the local ecosystem, occupational exposures to cattle, and consumption of unpasteurised milk, is important in the evaluation of zoonotic risk. One question is whether a major diffusion of M orygis might relate to a higher diffusion of its natural hosts in different regions. M orygis has been considered an MTBC subspecies since 2012, and it might have been misidentified as Mycobacterium africanum in prior molecular studies.4van 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 (114) Google Scholar An evolutionary analysis showed that all MTBC members are derived from a single human-restricted common ancestor. In this evolutionary scenario, M orygis is closest in similarity to M africanum; whereas M bovis, as the most recent to emerge, is able to infect a widespread host spectrum in terms of geographical location and different animal species.5Brosch R Gordon SV Marmiesse M et al.A new evolutionary scenario for the Mycobacterium tuberculosis complex.Proc Natl Acad Sci USA. 2002; 99: 3684-3689Crossref PubMed Scopus (1101) Google Scholar A 2020 review on bovine tuberculosis in India described evidence of a major resistance characteristic within autochthon bovine breeds to M bovis, compared with imported breeds such as Jersey and Holstein-Friesians,6Refaya AK Bhargavi G Mathew NC et al.A review on bovine tuberculosis in India.Tuberculosis (Edinb). 2020; 122101923Crossref PubMed Scopus (5) Google Scholar but definitive data are not available. One hypothesis is that M bovis became a pathogen of Bos taurus in Europe and the Americas, whereas M orygis became a pathogen of Bos indicus in south Asia, supported by the fact that all human isolates of M orygis detected to date in different countries are derived from patients from India or other south Asian countries.7Brites D Loiseau C Menardo F et al.A new phylogenetic framework for the animal-adapted Mycobacterium tuberculosis complex.Front Microbiol. 2018; 92820Crossref PubMed Scopus (58) Google Scholar Furthermore, a case of reverse zoonosis has been reported, wherein an M orygis strain from an Indian immigrant was transferred to a dairy cow in New Zealand,8Dawson 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 (31) Google Scholar showing the capacity of this mycobacterium to move through different hosts. However, accurate estimates of M orygis prevalence in humans or cattle across India are lacking and most previous studies on M bovis were mainly involved tuberculin skin tests.6Refaya AK Bhargavi G Mathew NC et al.A review on bovine tuberculosis in India.Tuberculosis (Edinb). 2020; 122101923Crossref PubMed Scopus (5) Google Scholar For accurate risk assessment and a full epidemiological understanding, a One Health approach is fundamental to estimating the prevalence of M orygis in humans and animals across India, and to evaluate herd systems, the presence of indigenous breeds versus imported breeds, and various ecosystems. Epidemiological studies of M bovis in animals in developed countries have shown how animal hosts in natural environments can act as a spillover or reservoir, assuming different epidemiological roles in relation to ecological factors such as sympatry, animal population, and animal density.9Nugent G Maintenance, spillover and spillback transmission of bovine tuberculosis in multi-host wildlife complexes: a New Zealand case study.Vet Microbiol. 2011; 151: 34-42Crossref PubMed Scopus (89) Google Scholar Although further studies are needed, redefining how zoonotic tuberculosis is detected, with consideration of both M bovis and M orygis, is urgent. Detection of M orygis should be included in analyses of human and animal populations, especially in south Asian countries. Furthermore, the reverse-zoonosis case in New Zealand has highlighted a potential need to adopt screening in other countries where south Asian immigrant populations are present. The effect of other MTBC subspecies in zoonotic transmission in addition to M bovis is not a trivial question, but important to consider for the effective control of human and animal tuberculosis. Control strategies and eradication plans for tuberculosis need to be tailored to different ecosystems and epidemiological conditions in many countries, and surveillance extended to an increased range of animal species10Amato B Di Marco Lo Presti V Gerace E et al.Molecular epidemiology of Mycobacterium tuberculosis complex strains isolated from livestock and wild animals in Italy suggests the need for a different eradication strategy for bovine tuberculosis.Transbound Emerg Dis. 2018; 65: e416-e424Crossref PubMed Scopus (17) Google Scholar and possibly other MTBC subspecies. In 2016, use of M bovis as a proxy for zoonotic tuberculosis estimated a global prevalence of 147 000 human cases,6Refaya AK Bhargavi G Mathew NC et al.A review on bovine tuberculosis in India.Tuberculosis (Edinb). 2020; 122101923Crossref PubMed Scopus (5) Google Scholar but as the results of Duffy and colleagues suggest, the actual incidence could be higher and M bovis appears to be an inadequate proxy of zoonotic tuberculosis, particularly in south Asia countries. I declare no competing interests. Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance studyM bovis prevalence in humans is an inadequate proxy of zoonotic tuberculosis. The recovery of M orygis from humans highlights the need to use a broadened definition, including MTBC subspecies such as M orygis, to investigate zoonotic tuberculosis. The identification of M tuberculosis in cattle also reinforces the need for One Health investigations in countries with endemic bovine tuberculosis. Full-Text PDF Open Access