Diagnosing Tuberculosis Infection: From the Host to the Pathogen

Tuberculosis (TB) continues to pose a significant global health challenge. An estimated quarter of the world's population has a TB infection (TBI) with an immune response to <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) without clinical, microbiological, or radiological signs of TB disease. Individuals with TBI have a lifelong risk of reactivation, leading to TB disease in 5%-10% of cases during a lifetime. Current diagnostic tools, including interferon-γ release assays and skin tests, are endorsed by the World Health Organization (WHO) for identifying TBI and guiding preventive therapy. This paper outlines existing diagnostic methods for TBI and explores emerging experimental approaches, focused on detecting circulating bacillary components-such as DNA, mycobacterial proteins, peptides, lipoglycans, and lipoprotein antigens. The development of diagnostic tools that target bacillary elements directly-rather than relying solely on antigen-specific immune responses-could help overcome key limitations of current immunodiagnostic assays, thus offering viable alternatives or complementary solutions. However, these new experimental assays are still under research and not yet validated for clinical use.