Abstract
BACKGROUND: India has the highest global burden of human tuberculosis (TB) and the largest cattle herd with endemic bovine TB (bTB). However, the extent of cross-species transmission and the zoonotic spillover risk, including drug-resistant Mycobacterium tuberculosis complex (MTBC) strains circulating in cattle, remain uncharacterized. METHODS: To address this major knowledge gap, we investigated tissue samples from 500 apparently healthy cattle at a slaughterhouse in Chennai, India. Whole genome sequencing was performed to characterize the isolates. RESULTS: Sixteen animals (32 per 1000 [95% confidence interval, 16-47]) were MTBC-positive, a rate that is nearly an order of magnitude greater than the reported human TB incidence in the region. Thirteen isolates were identified as Mycobacterium orygis and 3 were M tuberculosis: 1 was a mixed infection of M tuberculosis lineage 1 and M orygis, and the other 2 had pure growth of M tuberculosis lineage 2, in both cases pre-extensively drug-resistant (pre-XDR) with identical resistance patterns and separated by 7 single-nucleotide polymorphisms. The results confirm that bTB in this region is primarily due to M orygis and M tuberculosis, and not Mycobacterium bovis. CONCLUSIONS: The detection of pre-XDR M tuberculosis in cattle highlights a potential public health concern, since controlling human TB alone may be insufficient without addressing bovine TB. Overall, our findings underscore an urgent need for targeted interventions to mitigate zoonotic tuberculosis transmission in regions where bTB is endemic.