Pathophysiology
Clinical meaning
M. tuberculosis is an acid-fast aerobic bacillus transmitted via airborne droplet nuclei (1-5 micrometres). After inhalation, bacilli are phagocytosed by alveolar macrophages. The organism survives intracellularly by inhibiting phagosome-lysosome fusion. Cell-mediated immunity (CD4+ T cells and activated macrophages) develops over 2-12 weeks, forming granulomas that contain but rarely eliminate the organism (latent TB infection, LTBI). Approximately 5-10% of immunocompetent individuals with LTBI will progress to active TB disease in their lifetime, with half occurring within 2 years of infection. Reactivation risk increases dramatically with HIV (7-10% per year), TNF-alpha inhibitors, organ transplant, and other immunosuppressive states. Active TB presents as pulmonary (85% of cases) or extrapulmonary disease (lymph node, pleural, bone, CNS). The clinician must understand the difference between LTBI (positive TST/IGRA, no symptoms, non-infectious) and active TB (symptoms, potentially infectious, requires multi-drug therapy and public health notification).