Zoonotic Tuberculosis: Emerging Species, Diagnostic Approaches, and One Health Implications

Zoonotic tuberculosis (zTB), a form of human tuberculosis caused by animal-adapted members of the Mycobacterium tuberculosis complex (MTBC), poses unique challenges for clinical diagnosis, surveillance, and public health control. Traditionally associated with Mycobacterium bovis and transmitted through the consumption of unpasteurized milk or direct contact with infected animals, zTB is now increasingly attributed to emerging MTBC species, such as Mycobacterium orygis and Mycobacterium caprae, especially in South Asia and Europe. Current diagnostic tools, ranging from microscopy and culture to molecular assays, often lack routine species-level resolution in most clinical settings, contributing to underreporting and mismanagement, particularly in extrapulmonary TB cases. This review aims to explore the diagnostic landscape of zTB, outlining the limitations of conventional methods and highlighting the potential of emerging technologies, including polymerase chain reaction (PCR)-based region-of-difference (RD) typing, line probe assays, next-generation sequencing, and clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics. The review also underscores the importance of integrating human, animal, and environmental data within the One Health framework. It advocates for expanded molecular speciation in clinical workflows and improved coordination between veterinary and human health systems. Recognizing the full zoonotic spectrum of tuberculosis is essential for achieving accurate surveillance, informed treatment decisions, and meaningful progress toward global TB elimination.