Tuberculosis Study Guide

📖 Core Concepts Tuberculosis (TB) – infectious disease caused mainly by Mycobacterium tuberculosis (acid‑fast, lipid‑rich, waxy cell wall). Latent vs. Active TB – Latent: no symptoms, not contagious. Active: symptomatic, contagious, 10 % of latent infections progress. Granuloma – organized immune structure (macrophages, epithelioid cells, giant cells, lymphocytes, fibroblasts) with central caseous necrosis; site of bacterial dormancy. Transmission – airborne aerosol droplets (0.5–5 µm) expelled when a person with active pulmonary TB coughs, sneezes, speaks, sings, or spits. Drug‑resistance categories – MDR‑TB (resistant to isoniazid + rifampicin); XDR‑TB (MDR + resistance to fluoroquinolones + ≥ 3 second‑line drugs); totally drug‑resistant TB (resistant to all available drugs). BCG vaccine – only licensed TB vaccine; ≈ 20 % protection against infection, ≈ 60 % protection against progression to active disease in children; wanes after 10 years. 📌 Must Remember Global burden (2022): 10.6 M new cases, 1.3 M deaths – 2nd leading infectious cause of death after COVID‑19. Progression risk: 10 % of latent infections become active; HIV increases reactivation risk to 10 %/yr. Key risk factors: HIV, corticosteroids/immunosuppressants, diabetes (≈ 3‑fold), silicosis (≈ 30‑fold), smoking (≈ 2‑fold), alcoholism, malnutrition, crowding. Standard 6‑month regimen (new pulmonary TB): 2 mo HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) → 4 mo HR. Latent TB treatment options: Isoniazid ± rifampicin/rifapentine; duration 3–9 months. Contagious period: ≈ 2 weeks after starting effective therapy for non‑resistant disease. Diagnostic hallmarks: Persistent cough/fever/night sweats >2 weeks, chest X‑ray + sputum AFB smear, culture (2–6 weeks), NAAT (rapid DNA detection). Latent testing: Tuberculin skin test (TST) → induration read 48‑72 h; IGRA (interferon‑γ release assay) not affected by BCG. 🔄 Key Processes Inhalation → Alveolar macrophage uptake Bacteria survive phagosome (waxy wall resists ROS & acid). Primary lesion formation – Ghon focus (upper‑lobe lower segment or lower‑lobe upper segment). Hematogenous spread – Simon focus in lung apex; possible seeding to lymph nodes, kidney, brain, bone. Granuloma assembly – macrophages → epithelioid → multinucleated giant cells; T‑cell recruitment → caseous necrosis. Latent state – bacilli dormant within granuloma; host immunity contains infection. Reactivation – immune compromise → bacterial replication → active pulmonary/extrapulmonary disease. Miliary dissemination – bloodstream spread → numerous tiny tubercles (high mortality). 🔍 Key Comparisons Pulmonary vs. Extrapulmonary TB Pulmonary: chronic cough, sputum (± blood), chest pain; most contagious. Extrapulmonary: pleurisy, meningitis, miliary disease; less contagious, often presents with organ‑specific symptoms. Latent TB vs. Active TB Latent: asymptomatic, non‑contagious, positive TST/IGRA, no radiographic lesions. Active: symptomatic, contagious, positive sputum AFB, radiographic abnormalities. Primary vs. Secondary (reactivation) TB Primary: Ghon focus, often in children, may calcify. Reactivation: upper‑lobe cavitary disease, common in adults with immune compromise. First‑line vs. Second‑line drugs First‑line: INH, RIF, PZA, EMB – high efficacy, short course. Second‑line (e.g., bedaquiline, linezolid): used for MDR/XDR, longer duration, higher toxicity. ⚠️ Common Misunderstandings “Latent TB isn’t dangerous.” – Reactivation can occur, especially with HIV, diabetes, immunosuppression. “BCG prevents pulmonary TB in adults.” – BCG mainly protects children against severe forms; adult efficacy is limited. “A negative sputum smear rules out TB.” – Smear sensitivity is modest; NAAT or culture may still be positive. “All TB patients need isolation for the whole treatment.” – Most become non‑contagious after 2 weeks of effective therapy. 🧠 Mental Models / Intuition “The granuloma is a prison.” – Think of it as a fortified cell where bacteria hide; weakening the walls (immunosuppression) lets them escape. “Airborne droplets = tiny time‑bombs.” – The 0.5–5 µm size lets droplets stay suspended, travel >1 m, and infect deep alveoli. “Treatment = combination lock.” – Multiple drugs act on different bacterial targets; dropping one is like removing a pin – resistance re‑emerges. 🚩 Exceptions & Edge Cases BCG‑induced false‑positive TST – Prior BCG vaccination can enlarge induration; IGRA preferred in such individuals. Non‑resistant TB still contagious after 2 weeks? – Rare if adherence is poor or drug malabsorption occurs. Miliary TB in immunocompetent hosts – Possible after massive inoculum or unchecked primary disease. 📍 When to Use Which Diagnostic test selection Suspected active pulmonary TB → sputum AFB smear + NAAT + chest X‑ray. High‑risk latent screening (HIV, recent contacts) → IGRA (no BCG interference). Treatment regimen choice Drug‑sensitive new pulmonary TB → standard 6‑month HRZE/HR. Isoniazid‑resistant region → add ethambutol to continuation phase. Latent infection → 3‑month weekly isoniazid + rifapentine (if available) or 9‑month isoniazid monotherapy. MDR‑TB → at least 4 effective drugs for 18–24 months; include bedaquiline/linezolid as needed. 👀 Patterns to Recognize Upper‑lobe cavitary lesions on CXR → classic reactivation pulmonary TB. Night sweats + weight loss + chronic cough >2 weeks → high pre‑test probability of active TB. Positive AFB smear + HIV status → anticipate rapid progression, need early ART integration. Silicosis + TB → markedly increased risk; screen aggressively. 🗂️ Exam Traps “BCG is 100 % protective.” – Over‑states efficacy; only partial, waning protection. “All smear‑negative patients are not infectious.” – Smear‑negative but culture‑positive patients can still transmit, especially if cavitary disease is present. “MDR‑TB is defined only by isoniazid resistance.” – True definition requires resistance to both isoniazid and rifampicin. “Latent TB treatment always lasts 6 months.” – Duration varies (3–9 months) depending on regimen. --- Use this guide for a quick, high‑yield review before your exam. Focus on the bolded facts, memorize the standard regimens, and spot the classic clinical patterns.