Tuberculosis (TB) — Causes, Pulmonary Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis — a slow-growing, aerobic, acid-fast bacillus — transmitted via airborne droplet nuclei generated when an infectious person coughs, sneezes, speaks, or sings. Pulmonary TB (PTB) is the most common form, accounting for 85% of all TB cases globally. TB kills approximately 1.5 million people annually — making it the second leading infectious disease killer globally (historically first, before COVID-19) and the leading cause of death from a single infectious agent among people aged 15-49 in high-burden countries. The WHO End TB Strategy aims for a 90% reduction in TB deaths by 2030. An estimated 2 billion people have latent TB infection (LTBI) — contained, asymptomatic infection without disease or transmission risk. Drug-resistant TB — MDR-TB (resistant to rifampicin and isoniazid) and XDR-TB (additionally resistant to fluoroquinolones) — is a growing global threat with significantly harder treatment.

M. tuberculosis is transmitted by droplet nuclei (1-5 microns) — small enough to remain suspended in air for hours in poorly ventilated spaces. An infectious person (smear-positive pulmonary TB) can infect 10-15 contacts per year. Brief casual contact rarely transmits TB — prolonged close exposure (household contacts, shared sleeping spaces, crowded environments) is typically required. Primary TB: first infection in an immunologically naive host — the immune system usually contains the infection (forming granulomata), establishing LTBI. Reactivation TB: breakdown of immunological containment, typically triggered by: HIV (25-30x increased risk — the most significant risk factor); TNF-alpha inhibitors (2-10x risk — biologics for RA, IBD, psoriasis — NICE recommends LTBI screening before starting); prolonged systemic corticosteroids; organ transplant immunosuppression; malnutrition (BMI below 18.5); diabetes mellitus; chronic kidney disease (CKD); silicosis; tobacco smoking; alcohol dependence; overcrowding and incarceration. Bovine TB (M. bovis): rare in high-income countries — from unpasteurised dairy products. Key geographic risk: South-East Asia (India, Indonesia, Pakistan — 44% of global burden), Africa, and Western Pacific.

Latent TB infection (LTBI): completely asymptomatic; chest X-ray may be normal or show old calcified granulomata; not infectious to others. Subacute onset of pulmonary TB distinguishes it from acute pneumonia (rapid onset, high fever, productive cough from day 1). Pulmonary TB develops over weeks to months: chronic productive cough (initially dry, then mucopurulent) lasting 3 or more weeks — the key symptom; haemoptysis (blood-stained sputum or frank blood coughing) — from cavitary disease or bronchial vessel erosion; classic constitutional symptoms: night sweats (drenching, requiring change of clothing or bedding), unintentional weight loss (typically 5-10 kg or more — the 'consumption' of historical medicine), and low-grade fever with malaise and fatigue; pleuritic chest pain (if pleural involvement); shortness of breath (extensive disease, pneumothorax, or pleural effusion). Classic chest X-ray findings: upper zone and posterior segment infiltrates (apical shadowing); cavitation (air-filled cavities within consolidation — highly infectious, smear-positive); calcification (old healed TB); lymphadenopathy; hilar or paratracheal lymph nodes; pleural effusion (may be the primary presentation — TB pleuritis). Normal CXR does not exclude TB — particularly in HIV or immunocompromised patients.

Sputum collection: ideally 3 sputum specimens (induced sputum with hypertonic saline if unable to expectorate) — early morning specimens preferred (highest mycobacterial load). Chest X-ray: essential first investigation for suspected pulmonary TB — upper zone infiltrates, cavitation, and lymphadenopathy are classical. GeneXpert MTB/RIF (NAAT — nucleic acid amplification test): WHO-recommended first-line diagnostic test globally; detects M. tuberculosis DNA and rifampicin resistance in 2 hours; sensitivity 88%, specificity 99% for smear-positive PTB; lower sensitivity (68%) for smear-negative PTB. AFB sputum smear microscopy: rapid (30-60 minutes), inexpensive, widely available; sensitivity 50-60% for PTB; does not detect drug resistance; lower sensitivity in HIV-positive patients. Sputum culture on liquid (MGIT — 2-3 weeks) or solid Lowenstein-Jensen medium (6-8 weeks): gold standard for sensitivity and comprehensive drug susceptibility testing (DST). CT thorax: better defines extent of disease (cavities, miliary nodules, lymphadenopathy, pleural disease) when CXR is ambiguous. Fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy: for smear-negative PTB, suspicious CXR, or immunocompromised patients. IGRA (interferon-gamma release assay — QuantiFERON-TB Gold Plus, T-SPOT.TB): blood test detecting M. tuberculosis-specific immune response — identifies LTBI and is positive in active TB; not affected by BCG vaccination (unlike Mantoux TST); preferred for LTBI screening. HIV testing: all TB patients must be offered HIV testing. Notification: TB is a notifiable disease in the UK — all confirmed cases must be notified to the local Health Protection Team within 3 working days.

Standard 6-month RIPE regimen for drug-sensitive pulmonary TB: intensive phase (2 months): Rifampicin (R) + Isoniazid (H) + Pyrazinamide (Z) + Ethambutol (E) daily — RHZE; continuation phase (4 months): Rifampicin + Isoniazid daily (RH). Fixed-dose combination (FDC) tablets simplify regimens. Directly Observed Therapy (DOT): TB nurse observes patients swallowing each dose — gold standard for adherence, preventing resistance, and ensuring cure; video-observed therapy (VOT) is an alternative. Pyridoxine (vitamin B6 25 mg daily) prescribed with isoniazid to prevent peripheral neuropathy. Drug monitoring: LFTs at baseline and if symptomatic (rifampicin, isoniazid, and pyrazinamide are all hepatotoxic — drug-induced liver injury occurs in 5-10%; stop treatment if transaminases above 3x ULN with symptoms); visual acuity and colour vision monthly (ethambutol causes optic neuropathy — reversible if drug stopped promptly). Cavitary disease: culture at 2 months — if still positive, may need extended continuation phase (7 months total). Corticosteroids: dexamethasone or prednisolone added for TB meningitis (NEJM 2004 trial — 33% mortality reduction) and pericarditis. MDR-TB (resistance to rifampicin and isoniazid): BPaL regimen — bedaquiline + pretomanid + linezolid (± moxifloxacin — BPaLM) for 6 months (ZeNix and TB-PRACTECAL trials); achieves 90% success rate — revolutionised MDR-TB treatment. LTBI preventive therapy: 3HR (3 months isoniazid + rifampicin), 6H (6 months isoniazid), or 1HP (1 month rifapentine + isoniazid daily) — recommended for close contacts with positive IGRA and high-risk individuals. Cure rate for drug-sensitive PTB: above 95% with complete adherence.

Untreated or inadequately treated tuberculosis causes serious local and systemic complications. Pulmonary complications: haemoptysis — erosion of pulmonary vessels by cavitary disease causes blood-streaked sputum or massive haemorrhage requiring emergency bronchial artery embolisation; spontaneous pneumothorax — rupture of cavitary lesions into the pleural space; bronchiectasis — permanent bronchial dilatation from repeated infection and fibrosis; fibrothorax — restrictive lung disease from pleural scarring; and post-TB lung disease with significantly reduced FEV1. Systemic spread (haematogenous dissemination): miliary TB — widespread haematogenous seeding causing bilateral miliary (millet seed-sized) pulmonary nodules, fever, and multi-organ failure; TB meningitis — the most life-threatening form, causing permanent cognitive impairment, cranial nerve palsies, hydrocephalus, and 20-30% mortality despite treatment; Pott's disease (spinal TB) — vertebral body destruction causing spinal cord compression and paraplegia. Drug-related complications: RIPE regimen hepatotoxicity causes drug-induced liver injury in 5-10% of patients; isoniazid causes peripheral neuropathy without pyridoxine supplementation; ethambutol causes reversible optic neuropathy. Treatment non-adherence leads to acquired drug resistance — generating MDR-TB with dramatically worse outcomes.

BCG vaccination (Bacillus Calmette-Guerin): given at birth in TB-endemic countries; offered in the UK to babies with parents from high-incidence countries and healthcare workers without evidence of prior immunity; 70-80% effective against severe childhood TB (miliary TB, TB meningitis); less effective against adult pulmonary TB; does not prevent LTBI. Airborne infection control: isolation of infectious pulmonary TB cases (smear-positive) in negative pressure single rooms in hospital; N95 respirator masks for healthcare workers; patient cough etiquette and surgical mask; discharge when smear-negative on 3 specimens (typically 2 weeks of effective treatment). Contact tracing: all close contacts of index smear-positive cases screened — IGRA testing and symptom review; LTBI treatment offered to contacts with positive IGRA. LTBI treatment in high-risk groups: all close contacts (household and prolonged workplace exposure) with LTBI; all HIV-positive individuals with LTBI; immunosuppressed patients (TNF inhibitors, transplant) with LTBI — reduces TB risk by 60-90%. Latent TB: pre-biologic treatment screening (IGRA and CXR) before starting TNF-alpha inhibitors, JAK inhibitors, and other high-risk immunosuppressants.

Call emergency services (999/911) or attend Emergency Department immediately for: massive haemoptysis (coughing large volumes of blood) — life-threatening complication of cavitary TB requiring urgent bronchoscopy and embolisation; severe breathlessness or respiratory collapse — spontaneous pneumothorax (cavitary TB can rupture into pleural space) or extensive bilateral disease with hypoxia; sudden severe headache with neck stiffness, photophobia, or altered consciousness in anyone with TB — TB meningitis emergency requiring urgent LP and IV dexamethasone. Attend GP or call 111 urgently for: persistent cough more than 3 weeks with any of: fever, night sweats, or weight loss — always requires evaluation for TB; haemoptysis of any amount unexplained by recent URTI; unexplained weight loss with fatigue and fever; any household contact of a confirmed TB case — requires urgent contact tracing and LTBI testing. Once on treatment: attend urgent review for any yellowing of skin or eyes, right upper quadrant pain, or dark urine — possible drug-induced liver injury requiring immediate LFTs and treatment review.