TUBERCULOSIS: PATHOGENESIS, DIAGNOSIS, TREATMENT, DRUG RESISTANCE AND EMERGING THERAPEUTIC TARGETS

Abstract

Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (M. tuberculosis) and remains a major global health challenge. The organism primarily affects the lungs but may disseminate to other organs. Following inhalation, bacilli reach the alveoli, interact with alveolar macrophages and dendritic cells, and may survive intracellularly. Recruitment of immune cells and formation of granulomas can contain the infection as latent TB, whereas failure of immune containment may lead to caseation, cavitation, active pulmonary disease and transmission. According to the WHO Global Tuberculosis Report 2025, an estimated 10.7 million people developed TB and 1.23 million died from TB in 2024. Drug-resistant TB, especially multidrug/rifampicin-resistant TB, complicates treatment and requires rapid susceptibility testing and appropriate combination regimens. Diagnosis increasingly relies on rapid molecular tests in addition to microscopy, culture and clinical/radiological assessment. Treatment of drug-susceptible TB uses combination therapy, while newer medicines such as bedaquiline, delamanid and pretomanid have expanded options for drug-resistant disease. This review summarizes the pathogenesis, clinical manifestations, diagnosis, current treatment principles, drug resistance, tuberculous meningitis, challenges in TB control and emerging drug targets. Continued research is needed to shorten therapy, improve safety and adherence, expand access to rapid diagnostics, and develop novel agents capable of overcoming resistance and bacterial persistence.