Tuberculosis (TB) — Causes, Symptoms, RIPE Therapy & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, an aerobic, acid-fast bacillus transmitted via airborne droplet nuclei when an infectious person coughs, sneezes, or speaks. TB is the second leading infectious disease killer globally (after COVID-19 during pandemic years, historically first), with 10 million new active cases and 1.5 million deaths annually — WHO End TB Strategy targets 90% reduction by 2030. TB affects people of all ages, predominantly in low- and middle-income countries — South-East Asia (India, Indonesia, Pakistan), Africa, and the Western Pacific account for 87% of cases. Latent TB infection (LTBI) — estimated to affect 2 billion people (25% of the world's population) — represents contained infection with no symptoms or transmission risk; approximately 10% of immunocompetent LTBI individuals develop active TB disease in their lifetime (highest risk in first 2 years after infection). HIV co-infection increases this risk 20-30 fold. Drug-resistant TB — MDR-TB (resistant to rifampicin and isoniazid) and XDR-TB (additionally resistant to fluoroquinolones and aminoglycosides) — represents a growing global threat.

M. tuberculosis is transmitted by droplet nuclei (1-5 microns in diameter) that remain suspended in air for hours in poorly ventilated spaces. Transmission requires prolonged close contact — brief contact rarely transmits TB. Risk factors for infection: close contact with active TB case; crowded or poorly ventilated environments; homelessness; immigration from high-burden countries. Risk factors for progression from LTBI to active TB: HIV infection (25-30x risk — the most significant single risk factor globally; TB is the leading cause of death in people with HIV); immunosuppression (TNF inhibitors 2-10x; anti-CD20 biologics; prolonged systemic steroids; organ transplant immunosuppression); malnutrition and underweight (BMI below 18.5); diabetes mellitus; chronic kidney disease and dialysis; silicosis; active tobacco smoking; alcohol dependence; substance use disorders; overcrowding and incarceration; and prior inadequately treated TB. M. bovis — bovine tuberculosis — causes TB in cattle and occasionally humans via unpasteurised dairy products (rare in high-income countries).

Latent TB infection (LTBI): completely asymptomatic; chest X-ray may be normal or show old granulomata or calcification; not infectious. Active pulmonary TB (most common — 85% of TB cases): subacute to chronic course over weeks to months; productive cough (initially dry, then purulent) lasting 2-3 or more weeks; haemoptysis (blood in sputum — from cavitary disease or bronchial vessel erosion); night sweats (drenching, requiring change of clothing); unintentional weight loss (typically more than 5% over 3 months — the 'wasting' of historic TB); low-grade fever and malaise; fatigue; and pleuritic chest pain. Classical CXR: upper lobe infiltrates, cavitation, and hilar lymphadenopathy. Extrapulmonary TB (15% of cases, higher in HIV): lymphadenitis (most common extra-pulmonary site — cervical lymph node 'cold abscess' — fluctuant, non-tender, matted lymph nodes); TB meningitis (worst outcome — headache, photophobia, meningism, cranial nerve palsy, altered consciousness — high morbidity and mortality); Pott's disease (spinal TB — back pain, vertebral collapse, spinal cord compression); TB pericarditis (haemodynamic compromise); TB peritonitis (ascites, abdominal pain); renal TB (sterile pyuria — white cells in urine with negative standard culture); TB laryngitis (hoarseness); and miliary TB (disseminated haematogenous spread — bilateral fine miliary nodules on CXR, severe systemic illness).

GeneXpert MTB/RIF (NAAT): WHO-recommended first diagnostic test globally — detects M. tuberculosis DNA and rifampicin resistance in 2 hours from sputum or other samples; sensitivity 88%, specificity 99% for pulmonary TB; game-changing for resource-limited settings. AFB sputum smear microscopy: rapid (30-60 minutes), cheap, available everywhere; identifies AFB in 50-60% of pulmonary TB — lower sensitivity in HIV-positive patients; cannot detect drug resistance. Sputum culture: gold standard for sensitivity (detects all viable mycobacteria) and full drug susceptibility testing (DST); liquid culture (MGIT) takes 2-3 weeks; solid Lowenstein-Jensen medium 6-8 weeks. Chest X-ray: upper lobe infiltrates with or without cavitation are classic — but CXR is neither sensitive nor specific; normal CXR does not exclude TB; essential for all suspected cases. Histopathology: caseating granulomata on biopsy of lymph node or tissue — pathognomonic for TB. IGRA (interferon-gamma release assay — QuantiFERON-TB Gold Plus, T-SPOT.TB): detects immune sensitisation to M. tuberculosis antigens in blood — identifies LTBI; positive in active TB; not affected by BCG vaccination (unlike Mantoux); preferred over Mantoux (TST) in most settings. Lumbar puncture for TB meningitis: lymphocytic pleocytosis, elevated protein, very low glucose, AFB smear and culture, GeneXpert Ultra on CSF. HIV testing: all TB patients must be offered HIV testing.

Active drug-sensitive TB: 6-month RIPE regimen. Intensive phase (2 months): Rifampicin (R) + Isoniazid (H) + Pyrazinamide (Z) + Ethambutol (E) daily (RHZE). Continuation phase (4 months): Rifampicin + Isoniazid daily (RH). Directly Observed Therapy (DOT): a TB nurse observes patients swallowing each dose — gold standard to ensure adherence and prevent resistance. Pyridoxine (vitamin B6 25 mg daily): prescribed with isoniazid to prevent peripheral neuropathy (depletion of B6). Fixed-dose combination (FDC) tablets simplify regimens. Monitor: LFTs at baseline and if symptomatic (all three drugs are hepatotoxic — rifampicin, isoniazid, pyrazinamide); uric acid (pyrazinamide causes hyperuricaemia — gout); colour vision and visual acuity (ethambutol — monthly in first 2 months). All TB cases notified to public health for contact tracing. Corticosteroids: dexamethasone or prednisolone added for TB meningitis (reduces mortality by 33% — NEJM 2004 trial) and TB pericarditis. MDR-TB (resistance to R and H): BPaL/BPaLM regimens — bedaquiline (B) + pretomanid (Pa) + linezolid (L) ± moxifloxacin (M) — 6-month regimen (ZeNix, TB-PRACTECAL trials); replaces 18-24 month toxic regimens with amikacin. LTBI treatment: 6H (6 months isoniazid), 3HR (3 months isoniazid + rifampicin), 1HP (1 month daily rifapentine + isoniazid — shortest and equally effective) — recommended for LTBI contacts and HIV-positive LTBI individuals.

Untreated or inadequately treated tuberculosis leads to extensive pulmonary destruction with cavity formation, bronchiectasis, and permanent lung function impairment. Massive haemoptysis (coughing of blood) from erosion of a pulmonary artery by a cavitating lesion — Rasmussen's aneurysm — is a life-threatening complication with mortality exceeding 50% without emergency intervention. Miliary tuberculosis (haematogenous dissemination producing millet seed-sized granulomas throughout the body) and TB meningitis are the most lethal forms — TB meningitis carries mortality of 20-40% and neurological sequelae in 50% of survivors. Pericardial tuberculosis causes constrictive pericarditis with cardiac tamponade and heart failure. Spinal tuberculosis (Pott's disease) — accounting for 50% of musculoskeletal TB — causes vertebral body destruction, spinal cord compression, paraplegia, and gibbus deformity. Renal and adrenal tuberculosis cause renal failure and Addison's disease (adrenocortical insufficiency) respectively. Multi-drug resistant TB (MDR-TB — resistant to isoniazid and rifampicin) requires 18-24 months of second-line agents with significantly lower cure rates (50-60%) and greater toxicity. Extensively drug-resistant TB (XDR-TB) is nearly untreatable with conventional agents. IRIS (immune reconstitution inflammatory syndrome) occurs in HIV-TB co-infected patients initiating ART, causing paradoxical worsening of TB symptoms.

BCG vaccination (Bacillus Calmette-Guerin): the most widely used vaccine globally; given at birth in TB-endemic countries; 70-80% effective against severe childhood TB (miliary TB, TB meningitis); less effective against adult pulmonary TB; does not prevent LTBI. Contact tracing: all close contacts of active pulmonary TB cases screened for LTBI (IGRA) and active TB — those with LTBI offered preventive therapy. Infection control: airborne isolation of infectious cases until sputum smear-negative on 3 consecutive specimens (typically after 2 weeks of effective treatment); negative pressure rooms in hospitals; N95 respirators for healthcare workers; cough etiquette and mask use for patients. LTBI treatment in high-risk individuals (HIV-positive, immunosuppressive therapy, close TB contact) prevents progression to active TB by 60-90%. End TB strategy goals: eliminate TB as a public health threat by 2035 — requires universal access to diagnosis, treatment, and preventive therapy.

Seek emergency medical care immediately for: severe headache with neck stiffness, photophobia, or altered consciousness in anyone with known or suspected TB — TB meningitis is a medical emergency with high mortality if untreated; massive haemoptysis (coughing large amounts of blood) — contact emergency services; haemodynamic collapse, severe breathlessness, or cardiac tamponade (muffled heart sounds, pulsus paradoxus) in known TB — TB pericarditis; spinal cord compression symptoms (leg weakness, loss of bladder/bowel control) in someone with back pain and TB risk. See your GP urgently for: persistent cough more than 3 weeks with fever, night sweats, or weight loss — always seek evaluation; fever and lymphadenopathy in anyone from a high TB-burden country or with HIV; anyone who has had close contact with a confirmed TB case — requires contact tracing and LTBI testing.