Tuberculosis (TB) - K. Park PS

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### Introduction to Tuberculosis (TB) - **Causative Agent:** *Mycobacterium tuberculosis* complex (M. tuberculosis, M. bovis, M. africanum, etc.) - **Transmission:** Airborne droplets from infected individuals (coughing, sneezing, speaking). - **Disease Types:** - **Latent TB Infection (LTBI):** Bacteria present but inactive; no symptoms, non-infectious. - **Active TB Disease:** Bacteria multiplying, causing symptoms, infectious. - **Global Burden:** A major public health problem, especially in developing countries. ### Risk Factors for TB - **Immunosuppression:** HIV/AIDS, organ transplant recipients, chemotherapy, steroid use. - **Malnutrition:** Weakens immune system. - **Close Contact:** Living with or prolonged exposure to an active TB patient. - **Overcrowding & Poor Ventilation:** Facilitates airborne transmission. - **Substance Abuse:** Alcoholism, IV drug use. - **Pre-existing Medical Conditions:** Diabetes, chronic renal failure, silicosis. - **Age:** Very young children and elderly are more susceptible. ### Pathogenesis - **Primary Infection:** Inhalation of bacilli, phagocytosis by alveolar macrophages, formation of Ghon focus (granuloma). - **Latent Infection:** Bacilli contained within granulomas; host immune system controls spread. - **Reactivation/Secondary TB:** Breakdown of host immunity, bacilli multiply, granulomas break down, leading to active disease. - **Extrapulmonary TB:** Spread of bacilli to other organs (lymph nodes, pleura, bones, meninges, kidneys). ### Clinical Features of Active TB - **Pulmonary TB (most common):** - Chronic cough (often productive, sometimes with hemoptysis) - Fever (especially low-grade in the evening) - Night sweats - Weight loss (anorexia) - Fatigue/Malaise - Chest pain - **Extrapulmonary TB:** Symptoms vary based on affected organ (e.g., lymphadenopathy, bone pain, neurological symptoms). ### Diagnosis - **Sputum Smear Microscopy (AFB):** Acid-fast bacilli (AFB) detection; rapid, inexpensive, but low sensitivity. - **Sputum Culture:** Gold standard; more sensitive than smear, allows drug susceptibility testing, but takes 2-8 weeks. - **Chest X-ray (CXR):** Infiltrates, cavities, hilar lymphadenopathy. - **Tuberculin Skin Test (TST) / Mantoux Test:** Detects LTBI; measures induration. - **Interferon-Gamma Release Assays (IGRAs):** Detects LTBI; QuantiFERON-TB Gold, T-SPOT.TB. - **Molecular Tests (e.g., GeneXpert MTB/RIF):** Rapid detection of M. tuberculosis and rifampicin resistance. ### Treatment Regimens - **Goal:** Cure the patient, prevent transmission, prevent drug resistance. - **Standard Short-Course Chemotherapy (DOTS strategy):** - **Intensive Phase (2 months):** Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E) - HRZE - **Continuation Phase (4 months):** Isoniazid (H), Rifampicin (R) - HR - **Latent TB Infection (LTBI) Treatment:** - Isoniazid for 6-9 months (daily or twice weekly) - Rifampicin for 4 months (daily) - Isoniazid + Rifapentine weekly for 3 months (for specific populations) - **Drug-Resistant TB (DR-TB):** - **MDR-TB:** Resistant to at least HR. Requires second-line drugs (injectables, fluoroquinolones, etc.) for longer durations (18-24 months). - **XDR-TB:** Resistant to HR, any fluoroquinolone, and at least one of the three second-line injectable drugs (amikacin, kanamycin, capreomycin). More complex and longer treatment. - **Directly Observed Treatment, Short-course (DOTS):** WHO-recommended strategy to ensure adherence and prevent drug resistance. ### Prevention & Control - **Early Diagnosis & Treatment:** Interrupts transmission chain. - **BCG Vaccination:** Prevents severe forms of TB (meningitis, disseminated TB) in children. Variable efficacy against pulmonary TB in adults. - **Contact Tracing:** Identify and screen contacts of active TB patients. - **Infection Control Measures:** - **Administrative Controls:** Rapid diagnosis, isolation of infectious patients. - **Environmental Controls:** Adequate ventilation, UV germicidal irradiation. - **Personal Protective Equipment:** N95 respirators for healthcare workers. - **Improve Socioeconomic Conditions:** Reduce poverty, malnutrition, overcrowding. - **HIV/TB Co-infection Management:** Integrated approach, antiretroviral therapy (ART) for HIV patients. - **Preventive Therapy:** For LTBI in high-risk groups (e.g., HIV-positive, children contacts). ### National TB Control Programmes (NTPs) - **Objectives:** - Achieve high cure rates for active TB. - Reduce incidence and prevalence of TB. - Reduce TB-related mortality. - Prevent development of drug resistance. - **Key Components (as per DOTS strategy):** 1. Sustained political commitment and funding. 2. Case detection by quality-assured bacteriology (sputum smear). 3. Standardized treatment regimen with directly observed treatment (DOT). 4. Effective drug supply and management system. 5. Monitoring and evaluation system for program performance.