Tuberculosis Clinical Guide: Symptoms, Diagnosis & Updated Treatment Regimens

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--- # **Tuberculosis Clinical Guide: Symptoms, Diagnosis & Updated Treatment Regimens** ## **1. Definition** Tuberculosis (TB) is a **chronic granulomatous infection** caused by *Mycobacterium tuberculosis complex* (M. tuberculosis most commonly). Primarily affects lungs (pulmonary TB) but can involve any organ (extrapulmonary TB—EPTB). --- ## **2. Pathophysiology** * Transmission: **Airborne droplet nuclei** inhalation. * Bacilli reach alveoli → phagocytosed by macrophages → survive intracellularly by: * Inhibiting phagolysosome fusion * Modulating host apoptosis * **Primary infection** → Ghon focus + lymph node → Ghon complex. * Cell-mediated immunity develops in 2–10 weeks → forms **caseating granulomas**. * **Latent TB:** bacilli dormant inside granulomas. * **Reactivation TB:** immune failure (HIV, malnutrition, steroids, diabetes, CKD). * **Disease severity** driven by: * Host immunity (CD4 response) * Bacterial load * Virulence factors --- ## **3. Causes & Risk Factors** ### **Host-related** * HIV/AIDS (most powerful risk factor) * Diabetes mellitus * CKD, dialysis * Malnutrition, alcoholism * Smoking * Immunosuppressants (steroids, TNF-α inhibitors) * Silicosis * Young children & elderly ### **Environmental** * Crowding, poor ventilation * Long-term close contact exposure * Healthcare workers --- ## **4. Clinical Features** ### **Pulmonary TB** **Symptoms:** * Chronic cough >2 weeks * Fever, especially evening rise * Night sweats * Weight loss, anorexia * Hemoptysis * Chest pain * Fatigue **Signs:** * Crackles, bronchial breath sounds * Lymphadenopathy * Tachypnea in severe cases ### **Extrapulmonary TB** * **Lymph node TB:** painless, firm, matted nodes; sinus formation * **Pleural TB:** pleuritic chest pain, pleural effusion (lymphocytic) * **TB meningitis:** headache, fever, altered sensorium, neck stiffness * **Bone/Spine (Pott Disease):** back pain, kyphosis, neurological deficits * **Abdominal TB:** pain, ascites, mass, obstruction * **Genitourinary TB:** sterile pyuria, hematuria * **Miliary TB:** fever, hepatosplenomegaly, diffuse nodules on CXR --- ## **5. Investigations & Diagnosis** ### **A. Initial Screening** * **Chest X-ray:** upper lobe infiltrates, cavitations, miliary nodules, hilar lymphadenopathy. * **Symptom screening:** cough >2 weeks. --- ### **B. Bacteriological Confirmation (Preferred WHO/NTEP)** #### **1. Sputum Smear Microscopy** * Ziehl–Neelsen or LED fluorescence. * Detects acid-fast bacilli (AFB). * Rapid; low sensitivity compared to NAAT. #### **2. CBNAAT / GeneXpert (First-line Test)** * Detects MTB DNA + rifampicin resistance. * Results in 2 hrs. * Recommended for **all presumptive TB**, HIV+, children, EPTB samples. #### **3. TrueNat (India NTEP)** * Portable, PCR-based. * Detects MTB + rifampicin resistance. #### **4. Culture** * **Gold standard**, but slow. * Media: LJ medium (4–8 weeks), MGIT (1–2 weeks). * Used for drug sensitivity testing (DST). --- ### **C. Immunological Tests** * **Mantoux (TST)** – >10 mm = positive ( >5 mm in HIV). * **IGRA** (QuantiFERON) – useful for latent TB, not for active TB diagnosis alone. --- ### **D. EPTB-Specific Tests** * CSF analysis (lymphocytic, ↑protein, ↓glucose). * Pleural fluid: ADA >40 U/L supportive. * Biopsy: caseating granulomas. * Imaging: CT/MRI spine, abdomen, CNS. --- ## **6. Differential Diagnoses** * Bacterial pneumonia * Lung cancer * Sarcoidosis * Fungal infections (histoplasmosis) * Chronic bronchitis * Lymphoma (for EPTB nodes) * Viral pneumonia (in early TB) --- ## **7. Management (Updated WHO/NTEP Regimens 2024–2025)** ### **A. Drug-Susceptible Pulmonary TB (DS-TB)** Regimen: **2HRZE + 4HRE** | Phase | Duration | Drugs | | --------------------------- | -------- | ------------- | | **Intensive Phase (IP)** | 2 months | H + R + Z + E | | **Continuation Phase (CP)** | 4 months | H + R + E | **Adult Dosing (Daily):** * **Isoniazid (H):** 5 mg/kg (max 300 mg) * **Rifampicin (R):** 10 mg/kg (max 600 mg) * **Pyrazinamide (Z):** 25 mg/kg * **Ethambutol (E):** 15 mg/kg --- ### **B. Extrapulmonary TB** * Most forms: **same 6-month regimen** * **TB meningitis & spinal TB:** **9–12 months** therapy * Add **corticosteroids** in: * TB meningitis * TB pericarditis * Severe pleural TB --- ### **C. Drug-Resistant TB (DR-TB)** #### **1. MDR-TB / RR-TB (Rifampicin-resistant)** **Shorter all-oral regimen (9–11 months):** * Bedaquiline (BDQ) * Levofloxacin / Moxifloxacin * Clofazimine * Pyrazinamide * Ethambutol * High-dose INH * Ethionamide (optional depending on DST) **Long regimen (18–20 months):** * BDQ for 6 months * Linezolid * Fluoroquinolone * Cycloserine * Clofazimine *Toxicity monitoring is essential.* --- ### **D. Latent TB Infection (LTBI)** * **3HP regimen:** Isoniazid + Rifapentine weekly for 12 doses * **6H or 9H:** isoniazid monotherapy * **3HR:** 3 months INH + RIF --- ## **8. Drug Details (Indication, MOA, Doses, ADRs, Contraindications, Interactions, Monitoring)** ### **1. Isoniazid (H)** * **MOA:** inhibits mycolic acid synthesis. * **ADR:** hepatotoxicity, peripheral neuropathy. * **Prevent neuropathy:** pyridoxine 10–50 mg/day. * **Interactions:** phenytoin toxicity risk. * **Monitoring:** LFTs. ### **2. Rifampicin (R)** * **MOA:** inhibits DNA-dependent RNA polymerase. * **ADR:** orange urine, hepatitis, thrombocytopenia. * **Interactions:** potent CYP450 inducer → ↓OCPs, warfarin. * **Monitoring:** LFTs, CBC. ### **3. Pyrazinamide (Z)** * **MOA:** disrupts membrane energetics at acidic pH. * **ADR:** hepatotoxicity, hyperuricemia → gout. * **Monitoring:** uric acid, LFTs. ### **4. Ethambutol (E)** * **MOA:** inhibits arabinosyl transferase (cell wall). * **ADR:** optic neuritis (red-green color blindness). * **Monitoring:** baseline and monthly visual acuity. ### **5. Bedaquiline** * **MOA:** inhibits ATP synthase of MTB. * **ADR:** QT prolongation, hepatotoxicity. * **Monitoring:** ECG, LFT. ### **6. Linezolid** * **ADR:** peripheral neuropathy, optic neuropathy, myelosuppression. * **Monitoring:** CBC, vision. --- ## **9. Monitoring Treatment & Follow-Up** * **Clinical:** weight gain, symptom improvement. * **Sputum smear/CBNAAT at 2 months** for response. * **LFTs** for hepatotoxic drugs. * **Adherence support:** DOTS or digital adherence technologies. --- ## **10. When to Suspect Failure** * Persistent positive sputum after 4–5 months * Clinical worsening * Weight loss * Consider **DST + NAAT for resistance** --- ## **11. Complications** * Massive hemoptysis * Pneumothorax * Bronchiectasis * Fibro-cavitary disease * TB meningitis sequelae * Spinal deformity * Drug-induced hepatotoxicity * Immune reconstitution inflammatory syndrome (IRIS) in HIV --- ## **12. Patient Counseling Points** * Adherence is crucial → incomplete treatment → drug resistance. * Avoid alcohol (hepatotoxicity risk). * Rifampicin turns urine **orange-red** (normal). * Notify early if jaundice, vision changes, tingling. * Use backup contraception (RIF reduces OCP efficacy). * Family screening for TB. * Ventilation & cough etiquette. ---