Key Facts

Tuberculosis remains a significant public health concern in the UK, particularly in London and other urban centres. Most cases arise from reactivation of latent infection, especially in immigrant populations. Multi-drug combination therapy is essential to prevent resistance.

Epidemiology

• UK: ~4,500 new cases/year (declining trend); London ~35% of cases
• 73% of UK TB cases are in non-UK-born individuals
• Global: ~10.6 million new cases/year; ~1.3 million deaths/year (WHO 2022)
• HIV-TB co-infection: ~8% of global TB cases; higher mortality
• MDR-TB: ~1.5% of UK cases; globally ~450,000 cases/year

Aetiology

• Mycobacterium tuberculosis: acid-fast bacillus (Ziehl-Neelsen stain), slow-growing aerobe
• Transmitted via airborne droplet nuclei from pulmonary/laryngeal TB
• Risk factors for TB: HIV, immunosuppression, malnutrition, homelessness, imprisonment, IVDU, healthcare workers, close contacts
• Risk of progression from latent to active: 5–10% lifetime (50% within first 2 years); much higher with HIV (~10% per year)

Pathophysiology

• Inhalation of M. tuberculosis → alveolar macrophage phagocytosis → bacilli survive intracellularly
• Granuloma formation: epithelioid cells, Langhans giant cells, caseating necrosis — walled-off infection (primary complex)
• Latent TB: contained infection; positive IGRA/Mantoux, no symptoms, not infectious
• Active TB: immune failure → caseating necrosis, cavitation, dissemination
• Miliary TB: haematogenous spread → disseminated disease (liver, spleen, bone marrow, meninges)
• Cell-mediated immunity (CD4+ T cells) is critical — hence increased risk with HIV

Pulmonary TB (most common)

• Chronic cough (>3 weeks) — initially dry, then productive
• Haemoptysis
• Night sweats
• Weight loss, anorexia
• Low-grade fever
• Upper lobe consolidation/cavitation on CXR

Extrapulmonary TB

• Lymph node (most common extrapulmonary): painless cervical lymphadenopathy, cold abscess
• Pleural: pleuritic chest pain, effusion (lymphocyte-predominant, low glucose)
• Bone/joint: Pott's disease (spinal TB) — back pain, kyphosis, psoas abscess
• CNS: TB meningitis — headache, cranial nerve palsies, hydrocephalus; TB cerebral abscess
• GI: ileocaecal (mimics Crohn's), peritoneal TB (ascites)
• Genitourinary: sterile pyuria, epididymo-orchitis, tubal infertility
• Miliary TB: disseminated — fever, hepatosplenomegaly, miliary pattern on CXR, pancytopenia

Red Flags

• TB meningitis (high mortality — treat empirically if suspected)
• Miliary/disseminated TB
• Spinal TB with neurological compromise (cord compression)
• MDR-TB suspected (previous treatment, travel to high-MDR areas)
• Immunosuppressed patient with atypical symptoms

Bedside

• CXR: upper lobe consolidation, cavitation, miliary pattern, lymphadenopathy, pleural effusion
• Sputum collection: 3 early-morning specimens for AFB smear and culture
• Observations: weight, temperature

Bloods

• FBC: normocytic anaemia, lymphopenia (or lymphocytosis)
• CRP/ESR: elevated
• LFTs: baseline before treatment (hepatotoxic drugs)
• U&Es: baseline
• HIV test: MUST be offered to all TB patients (NICE NG33)
• Hepatitis B/C: baseline
• Vitamin D: commonly deficient in TB patients

Imaging

• CXR: first-line
• CT chest: if CXR inconclusive or extrapulmonary disease suspected
• MRI spine: spinal TB
• CT/MRI brain: TB meningitis (basal meningeal enhancement, hydrocephalus, tuberculomas)

Special Tests

• Sputum AFB smear (Ziehl-Neelsen): rapid but sensitivity 50–80%
• Sputum culture (Löwenstein-Jensen or liquid BACTEC): gold standard — 2–8 weeks; provides sensitivity testing
• GeneXpert MTB/RIF: PCR-based, result in 2 hours, detects rifampicin resistance
• IGRA (interferon-gamma release assay): for latent TB diagnosis (not affected by BCG)
• Mantoux test: intradermal tuberculin injection, read at 48–72 hours (≥5mm positive in immunocompromised, ≥15mm in BCG-vaccinated)
• Lymph node biopsy: caseating granulomas, AFB, PCR
• CSF: lymphocytic, high protein, low glucose, AFB culture/PCR (TB meningitis)
• Pleural biopsy: caseating granulomas (higher yield than fluid culture alone)

Non-pharmacological

• Notification: statutory notification to local health protection team
• Contact tracing: household and close contacts — symptom screen, CXR, IGRA
• Isolation: negative-pressure room if smear-positive pulmonary TB; minimum 2 weeks of treatment before de-isolation
• Directly observed therapy (DOT): for non-adherent patients, MDR-TB, homeless, substance misuse
• Nutritional support: vitamin D supplementation

Pharmacological

Standard treatment (NICE NG33):

• Intensive phase (2 months): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol (RIPE)
• Continuation phase (4 months): Rifampicin + Isoniazid (RI)
• Total: 6 months for pulmonary TB and most extrapulmonary

Doses (adults):

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

Extended treatment (12 months):

• TB meningitis: 12 months (2 RIPE + 10 RI)
• TB meningitis: add dexamethasone (reduces mortality by ~30%)
• Bone/joint TB: 12 months

MDR-TB:

• Specialist management — second-line agents (fluoroquinolone, amikacin, linezolid, bedaquiline, delamanid)
• Duration: minimum 9–20 months

Monitoring:

• LFTs at baseline, 2 weeks, then monthly (hepatotoxicity)
• Visual acuity: before and monthly during ethambutol (optic neuritis)
• Sputum: repeat at 2 months — if still culture-positive, extend intensive phase and review

Drug interactions:

• Rifampicin: potent CYP3A4 inducer — reduces efficacy of warfarin, OCP, calcineurin inhibitors, antiretrovirals

Surgical/Interventional

• Spinal TB: decompression if cord compression
• Abscess drainage: psoas, cold abscesses
• Pericardial window: TB pericarditis with effusion

Referral Criteria

• All cases: TB specialist/infectious diseases
• MDR-TB: regional MDR-TB centre
• TB meningitis: neurology + infectious diseases
• HIV co-infection: joint HIV-TB MDT
• Paediatric TB: specialist paediatric ID

• Drug-sensitive pulmonary TB: cure rate >95% with completed treatment
• TB meningitis: mortality 15–30% even with treatment; neurological sequelae in 20–50%
• Miliary TB: mortality 15–20% with treatment
• MDR-TB: treatment success 50–70% (lower with XDR-TB)
• HIV-TB co-infection: higher mortality, especially if CD4 <100
• Relapse rate with completed 6-month treatment: <5%
• Non-adherence is the major risk factor for treatment failure and resistance
• UK TB mortality: ~300 deaths/year (~6%)

Standard TB Treatment Regimen

Key Drug Side Effects

Contact Tracing Approach