MODERN PERSPECTIVES ON EXTRAPULMONARY TUBERCULOSIS: PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT

Abstract

Extrapulmonary tuberculosis (EPTB), responsible for 15–20% of global TB cases, is a diagnostically elusive and therapeutically complex manifestation of Mycobacterium tuberculosis (Mtb) infection. Its rising incidence in immunosuppressed populations, coupled with the emergence of drug-resistant strains, underscores the urgent need for a paradigm shift in TB management. This review integrates cutting-edge insights into EPTB’s immunometabolic pathogenesis, site-specific molecular diagnostics, and precision therapeutics. We highlight the role of host-pathogen interactions in driving extrapulmonary dissemination, including Mtb’s exploitation of immune checkpoints and metabolic reprogramming of macrophages. Advanced imaging modalities (e.g., PET-MRI fusion), next-generation sequencing (NGS), and host-directed therapies (HDTs) are critically evaluated. A systematic analysis of 127 studies (2015–2023) reveals persistent gaps in pediatric EPTB management and equitable access to diagnostics. We propose a roadmap for integrating omics technologies and artificial intelligence (AI) into EPTB care, emphasizing the WHO’s "End TB" targets.