Tuberculosis

Tuberculosis (TB) is caused by Mycobacterium tuberculosis, an acid-fast bacillus (AFB) not classified as gram-positive or gram-negative due to its lipid-rich cell wall containing mycolic acids, which makes it hydrophobic and highly resistant to desiccation. M. tuberculosis is a slow-growing organism (generation time 15 to 20 hours) and a facultative intracellular pathogen that survives within macrophages.

Transmission occurs through inhalation of infectious droplet nuclei generated by coughing, talking, or sneezing by active cases. Droplet nuclei can remain airborne for prolonged periods; crowding and poor ventilation increase transmission risk. Host risk factors for progression from infection to active disease include age extremes, HIV, malnutrition, diabetes, smoking, and immunosuppressive therapy (particularly TNF-alpha inhibitors or corticosteroids).

After inhalation, bacilli are phagocytosed by alveolar macrophages, but M. tuberculosis virulence factors prevent phagolysosome acidification and fusion, enabling intracellular survival. The immune response, particularly CD4 T-cell-derived IFN-gamma, activates macrophages to kill intracellular bacilli. TNF-alpha and IFN-gamma are both required for granuloma formation. Granulomas are organised aggregates of activated macrophages and T cells that contain viable bacilli in a hypoxic, nutrient-poor microenvironment. Most primary infections result in latent TB infection (LTBI), in which bacilli are contained but not eliminated. Reactivation (secondary TB) occurs with immunosuppression.

Diagnosis uses the Ziehl-Neelsen (ZN) stain (sensitivity approximately 67%), nucleic acid amplification tests (GeneXpert PCR, which also detects rifampicin resistance), liquid culture (BACTEC MGIT, mean 10 to 14 days, more sensitive than solid culture), and susceptibility testing. Treatment for drug-sensitive TB uses 4 drugs for 2 months (isoniazid, rifampicin, ethambutol, pyrazinamide) followed by 2 drugs for 4 months. Multidrug-resistant TB (MDR-TB, resistant to isoniazid and rifampicin) is treated with regimens including bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for 6 months.