Key Facts

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. It remains a significant public health problem globally and in the UK, particularly among immigrant communities, the homeless, and immunosuppressed individuals.

Epidemiology

• Global: ~10 million new cases and ~1.5 million deaths per year (leading infectious disease killer)
• UK: ~5,000 cases per year; incidence declining since 2011
• ~60-70% of UK cases are in non-UK born individuals
• London accounts for ~40% of UK cases
• Risk groups: migrants from high-prevalence countries, homeless, IV drug users, HIV-positive, immunosuppressed, prisoners

Aetiology

• Mycobacterium tuberculosis: obligate aerobe, acid-fast bacillus, slow-growing (doubling time ~24 hours)
• Transmitted by airborne droplet nuclei (coughing, sneezing)
• Inhaled bacilli reach alveoli → primary infection
• Granuloma formation (caseating granulomas) contains but may not eliminate infection
• Latent TB: 5-10% lifetime risk of reactivation; higher if immunosuppressed

Pathophysiology

• Primary TB: initial infection, usually lower/middle lobes; Ghon focus (primary lesion) + hilar lymphadenopathy = Ghon complex
• Latent TB: contained by cell-mediated immunity within granulomas; no symptoms; positive IGRA/tuberculin skin test
• Post-primary (reactivation) TB: typically upper lobe cavitating disease; occurs with waning immunity
• Miliary TB: haematogenous dissemination; multiple organ involvement; millet seed pattern on CXR
• Extrapulmonary TB (~40% of UK cases): lymph nodes, pleura, bone/spine (Pott disease), CNS (TB meningitis), genitourinary, peritoneal

Pulmonary TB

• Chronic cough >3 weeks (most common symptom)
• Haemoptysis
• Weight loss, anorexia
• Night sweats
• Low-grade fever
• Malaise, fatigue

Extrapulmonary TB

• Lymph node TB (most common extrapulmonary): painless cervical lymphadenopathy ("cold abscess")
• Pleural TB: unilateral pleural effusion, pleuritic pain
• Bone/joint: Pott disease (spinal TB), chronic joint swelling
• TB meningitis: headache, neck stiffness, cranial nerve palsies, altered consciousness
• Miliary TB: fever, weight loss, hepatosplenomegaly, pancytopenia, millet seed CXR pattern
• Genitourinary: sterile pyuria, frequency, haematuria

Red Flags

• TB meningitis (medical emergency)
• Miliary TB (systemic, multi-organ)
• Massive haemoptysis (Rasmussen aneurysm)
• Spinal TB with neurological deficit
• TB in HIV-positive (atypical presentations)

Bedside

• Sputum samples: 3 early morning sputum for AFB smear and culture
• Pulse oximetry: baseline

Bloods

• FBC: anaemia of chronic disease; pancytopenia in miliary TB
• CRP/ESR: elevated
• U&Es, LFTs: baseline before treatment (hepatotoxic drugs)
• HIV test: all TB patients must be offered HIV testing (NICE)
• HbA1c: diabetes increases TB risk
• Hepatitis B and C serology: if abnormal LFTs

Imaging

• CXR: upper lobe consolidation/cavitation (reactivation), miliary pattern, hilar lymphadenopathy, pleural effusion
• CT chest: better delineation of cavitation, lymphadenopathy, miliary disease
• CT/MRI spine: if spinal TB suspected
• MRI brain: TB meningitis (basal meningeal enhancement, hydrocephalus, tuberculomas)

Special Tests

• Sputum AFB smear (Ziehl-Neelsen or auramine stain): positive in ~50-80% of cavitatory pulmonary TB
• TB culture (Lowenstein-Jensen or BACTEC): gold standard; takes 2-8 weeks; drug sensitivity testing
• GeneXpert MTB/RIF: rapid PCR (results in 2 hours); detects MTB and rifampicin resistance
• IGRA (interferon-gamma release assay): QuantiFERON-TB Gold or T-SPOT.TB; detects latent TB (does not distinguish latent from active)
• Mantoux/tuberculin skin test: intradermal injection of PPD; induration ≥6mm at 48-72 hours positive (less specific than IGRA due to BCG cross-reactivity)
• Bronchoscopy with BAL: if sputum smear-negative but high clinical suspicion
• Tissue biopsy: lymph node, pleural, bone — caseating granulomas on histology; send for culture

Non-pharmacological

• Notification: statutory notification to Public Health England (all cases)
• Contact tracing: screen close contacts (household, workplace) with IGRA and CXR
• Isolation: respiratory isolation until 2 weeks of effective treatment (smear-positive patients)
• DOT (directly observed therapy): for homeless, drug users, prisoners, previous non-adherence
• Nutrition: high-calorie, high-protein diet

Pharmacological

NICE NG33 — Standard treatment for drug-sensitive pulmonary TB:

Intensive phase (2 months):

• Rifampicin 600mg OD (or 450mg if <50kg)
• Isoniazid 300mg OD (+ pyridoxine 10mg OD to prevent peripheral neuropathy)
• Pyrazinamide 2g OD (or 1.5g if <50kg)
• Ethambutol 15mg/kg OD

Continuation phase (4 months):

• Rifampicin + isoniazid (+ pyridoxine)

Total duration: 6 months (9-12 months for CNS TB, bone/joint TB)

Side effects to monitor:

• Rifampicin: orange discolouration of secretions, hepatotoxicity, enzyme inducer (reduces efficacy of OCP, warfarin)
• Isoniazid: peripheral neuropathy (give pyridoxine), hepatotoxicity, SLE-like syndrome
• Pyrazinamide: hepatotoxicity (most hepatotoxic), hyperuricaemia, arthralgia
• Ethambutol: optic neuritis (visual acuity and colour vision testing before and during)

MDR-TB (resistant to rifampicin + isoniazid):

• Specialist management; 18-24 months of second-line agents (fluoroquinolones, aminoglycosides, bedaquiline, linezolid)

Latent TB treatment:

• 3 months isoniazid + rifampicin, OR 6 months isoniazid alone

Surgical/Interventional

• Rarely needed: lobectomy for destroyed lung/aspergilloma in old TB cavity
• Drainage of psoas/spinal abscess
• VP shunt for TB hydrocephalus

Referral Criteria

• All TB cases managed by TB specialist team
• MDR-TB: refer to national MDR-TB service
• Complex extrapulmonary TB: specialist input
• HIV co-infection: joint HIV-TB management
• Contact tracing: public health team

• Drug-sensitive pulmonary TB: cure rate >95% with completed treatment
• MDR-TB: cure rate ~50-80% (improving with newer agents — bedaquiline, pretomanid)
• TB meningitis: mortality ~20-30%; survivors may have neurological sequelae
• Miliary TB: mortality ~15-20% with treatment
• Non-adherence to treatment leads to relapse (~10-20%) and drug resistance
• HIV co-infection increases TB mortality 2-4 fold
• Global: TB responsible for ~1.5 million deaths per year

Anti-TB Drug Side Effects

TB Treatment Duration Summary

Mnemonic: RIPE