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Infectious Diseases
Respiratory

Pulmonary Tuberculosis

High EvidenceUpdated: 2026-01-01

On This Page

Red Flags

  • MDR/XDR-TB
  • HIV co-infection
  • Miliary TB
  • TB meningitis
  • Respiratory failure
  • Haemoptysis
Overview

Pulmonary Tuberculosis

1. Clinical Overview

Summary

Pulmonary tuberculosis (TB) is a chronic granulomatous infection caused by Mycobacterium tuberculosis. It remains a major global health burden, causing approximately 1.5 million deaths annually. Classic presentation includes chronic cough (greater than 2 weeks), weight loss, night sweats, and haemoptysis. Diagnosis requires a combination of clinical suspicion, chest radiography (upper lobe infiltrates, cavitation), sputum smear microscopy, culture, and molecular testing (Xpert MTB/RIF). Standard treatment is the RIPE regimen: Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol for 2 months, followed by Rifampicin and Isoniazid for 4 months. Drug-resistant TB requires specialised management. All cases must be notified to public health authorities.

Key Facts

  • Definition: Infection of the lungs with Mycobacterium tuberculosis
  • Incidence: 10 million new cases per year globally; 5,000-6,000 cases/year in UK
  • Demographics: Higher in immigrants from high-incidence countries, HIV+, homeless, prison
  • Pathognomonic: Cough greater than 2 weeks + upper lobe cavitation + positive AFB/culture
  • Gold Standard Investigation: Sputum culture + molecular testing (Xpert MTB/RIF)
  • First-line Treatment: RIPE regimen (2 months) then RI (4 months)
  • Prognosis: Excellent with treatment; MDR-TB more challenging

Clinical Pearls

Xpert Pearl: GeneXpert MTB/RIF detects TB DNA and rifampicin resistance within 2 hours. First-line molecular test.

Contact Tracing Pearl: All household and close contacts must be screened. This is a public health imperative.

Pyridoxine Pearl: Give pyridoxine (vitamin B6) 10-25mg daily with isoniazid to prevent peripheral neuropathy, especially in malnourished, diabetic, or HIV+ patients.

Rifampicin Pearl: Rifampicin turns body fluids orange-red (urine, tears, sweat). Warn patients about contact lens staining.

HIV Pearl: Always test for HIV in TB. TB is the leading cause of death in people living with HIV globally.

Why This Matters Clinically

TB is a re-emerging disease even in low-incidence countries. Delayed diagnosis leads to ongoing transmission. A high index of suspicion, especially in at-risk populations, and prompt appropriate testing saves lives and prevents spread.

2. Epidemiology

Global Burden

MetricValue
New cases/year10 million
Deaths/year1.5 million
MDR-TB cases500,000/year
Countries with highest burdenIndia, Indonesia, China, Philippines, Pakistan

UK Epidemiology

  • Approximately 5,000-6,000 cases/year
  • Higher rates in London, urban areas
  • 70%+ in non-UK born individuals
  • High-risk groups: immigrants, HIV+, homeless, prison, close contacts

Risk Factors for TB

CategoryRisk Factors
ExposureClose contact with active TB, endemic area residence/travel
ImmunosuppressionHIV (greatest risk), TNF-α inhibitors, steroids, transplant, malignancy
Medical conditionsDiabetes, CKD, silicosis, malnutrition
SocialHomeless, prison, substance abuse
AgeElderly (reactivation), young children

Latent TB vs Active TB

FeatureLatent TBActive TB
SymptomsNoneCough, fever, weight loss
InfectiousNoYes
CXRNormalAbnormal
TST/IGRAPositiveUsually positive
TreatmentPreventive therapyFull treatment regimen
3. Pathophysiology

Mechanism Overview

Step 1: Initial Infection (Primary TB)

  • Inhalation of M. tuberculosis-containing droplet nuclei (1-5μm)
  • Bacilli reach terminal alveoli
  • Engulfed by alveolar macrophages
  • Initial innate immune response

Step 2: Granuloma Formation

  • Adaptive immune response develops (2-8 weeks)
  • CD4+ T cells and macrophages form granulomas
  • Central caseous necrosis surrounded by epithelioid cells, giant cells, lymphocytes
  • Most infections contained here (latent TB)

Step 3: Primary Complex

  • Ghon focus: primary pulmonary lesion (usually lower/middle lobes)
  • Ghon complex: Ghon focus + hilar lymphadenopathy
  • In most immunocompetent hosts, infection is contained

Step 4: Latent TB

  • Viable bacilli persist in granulomas
  • Lifetime risk of reactivation: 5-10%
  • Higher with immunosuppression

Step 5: Reactivation (Post-Primary TB)

  • Occurs when immune control fails
  • Typically affects upper lobes (high oxygen tension)
  • Cavitary disease common
  • Highly infectious

Step 6: Dissemination

  • Miliary TB: haematogenous spread
  • Extrapulmonary TB: lymph nodes, pleura, CNS, bone, genitourinary
  • More common in immunocompromised

Virulence Factors

  • Cord factor (trehalose dimycolate)
  • Lipoarabinomannan
  • Mycolic acids (waxy cell wall)
  • ESX secretion systems
4. Clinical Presentation

Symptoms

SymptomFrequencyDuration
Chronic cough90%+Greater than 2-3 weeks
Sputum production70%May be purulent
Haemoptysis20-30%From cavitation
Fever60-80%Often low-grade, evening rise
Night sweats50-70%Drenching
Weight loss60-80%Often significant
Fatigue/malaise70%+Non-specific
Chest pain20-30%Pleuritic
Dyspnoea20-30%Variable

Physical Signs

Atypical Presentations

GroupPresentation
ElderlyNon-specific, minimal cough, confusion
HIV+Atypical CXR, extrapulmonary, smear-negative
ChildrenPrimary complex, miliary, lymphadenopathy
ImmigrantsMay present with complications

Red Flags

[!CAUTION]

  • Haemoptysis (risk of massive haemoptysis from Rasmussen aneurysm)
  • Respiratory failure
  • Miliary pattern on CXR (disseminated disease)
  • TB meningitis (headache, confusion, neck stiffness)
  • MDR-TB contact or prior treatment
May be minimal
Common presentation.
Crackles over affected area
Common presentation.
Bronchial breathing (consolidation)
Common presentation.
Signs of pleural effusion
Common presentation.
Cachexia
Common presentation.
Finger clubbing (chronic disease)
Common presentation.
5. Clinical Examination

General

  • Weight: cachexia, BMI
  • Temperature: low-grade fever
  • Nutritional status

Respiratory

  • Inspection: reduced chest expansion
  • Percussion: dull (effusion, consolidation)
  • Auscultation: crackles, bronchial breathing
  • Signs of cavitation: amphoric breathing (rare)

Systemic Examination

  • Lymphadenopathy (especially cervical in extrapulmonary)
  • Finger clubbing
  • Signs of HIV infection
  • Signs of extrapulmonary TB
6. Investigations

Sputum Testing

TestSensitivityTime to ResultNotes
AFB smear50-60%HoursZiehl-Neelsen or auramine stain
Xpert MTB/RIF85-95%2 hoursAlso detects rifampicin resistance
Culture (MGIT)80-85%1-3 weeksGold standard; allows DST
Culture (LJ)80-85%4-8 weeksSolid media

Collect 3 sputum samples (spot, early morning, spot) OR induced sputum if unable to expectorate.

Chest X-Ray

Classic findings:

  • Upper lobe infiltrates (apical, posterior segments)
  • Cavitation
  • Fibrosis
  • Hilar/mediastinal lymphadenopathy
  • Pleural effusion

Atypical (especially HIV):

  • Lower lobe disease
  • Miliary pattern
  • Minimal changes
  • Lymphadenopathy without parenchymal disease

Additional Investigations

TestPurpose
HIV testMANDATORY in all TB patients
FBCAnaemia of chronic disease
LFTsBaseline before treatment
U&EBaseline
HbA1cScreen for diabetes
Vitamin DOften deficient
Hepatitis B/CBaseline before hepatotoxic drugs

Tuberculin Skin Test (TST) and IGRA

  • TST (Mantoux): Intradermal PPD, read at 48-72 hours
  • IGRA (QuantiFERON, T-SPOT): Blood test measuring IFN-γ release
  • Use: Screening for latent TB, contact tracing
  • Limitation: Cannot distinguish latent from active TB

Drug Susceptibility Testing

  • Essential for all positive cultures
  • Molecular (Xpert, LPA) for rapid rifampicin/isoniazid resistance
  • Phenotypic DST for comprehensive resistance profile
7. Management

Management Algorithm

         SUSPECTED PULMONARY TB
                  ↓
┌──────────────────────────────────────────────┐
│        INITIAL ASSESSMENT                    │
│  - Respiratory isolation                     │
│  - 3 sputum samples (AFB, Xpert, culture)    │
│  - CXR                                       │
│  - HIV test (MANDATORY)                      │
│  - Baseline bloods (FBC, LFT, U&E)           │
└──────────────────────────────────────────────┘
                  ↓
         Smear/Xpert positive?
        ↓ Yes              ↓ No
┌───────────────┐    ┌─────────────────────────────┐
│ Start         │    │ High clinical suspicion?    │
│ treatment     │    │ Consider empirical Rx       │
│ immediately   │    │ or await culture            │
└───────────────┘    └─────────────────────────────┘
                  ↓
┌──────────────────────────────────────────────┐
│      STANDARD TREATMENT (RIPE)               │
│  INTENSIVE PHASE (2 months):                 │
│  - Rifampicin 10mg/kg (max 600mg)            │
│  - Isoniazid 5mg/kg (max 300mg)              │
│  - Pyrazinamide 25mg/kg (max 2g)             │
│  - Ethambutol 15mg/kg                        │
│  + Pyridoxine 10-25mg                        │
│                                              │
│  CONTINUATION PHASE (4 months):              │
│  - Rifampicin                                │
│  - Isoniazid                                 │
│  + Pyridoxine                                │
└──────────────────────────────────────────────┘
                  ↓
┌──────────────────────────────────────────────┐
│          MONITORING                          │
│  - Clinical response                         │
│  - Sputum smear/culture at 2 months          │
│  - LFTs monthly (more if hepatotoxicity)     │
│  - Visual acuity (ethambutol)                │
│  - Contact tracing and notification          │
└──────────────────────────────────────────────┘

RIPE Regimen

DrugDoseDurationSide Effects
Rifampicin10mg/kg (max 600mg)6 monthsOrange secretions, hepatitis, drug interactions
Isoniazid5mg/kg (max 300mg)6 monthsHepatitis, peripheral neuropathy, rash
Pyrazinamide25mg/kg (max 2g)2 monthsHepatitis, hyperuricaemia, arthralgia
Ethambutol15mg/kg2 monthsOptic neuritis (check visual acuity)

Pyridoxine

  • Give with isoniazid to prevent neuropathy
  • Especially important in: HIV, diabetes, alcohol, malnutrition, pregnancy

Directly Observed Therapy (DOT)

  • Recommended by WHO
  • Improves adherence
  • Reduces resistance development
  • Mandatory for MDR-TB

Drug-Resistant TB

TypeDefinitionTreatment Duration
Rifampicin-resistantResistance to rifampicin18+ months
MDR-TBResistance to rifampicin AND isoniazid18-24 months
XDR-TBMDR + resistance to fluoroquinolone + injectableProlonged, often poor outcomes

MDR-TB requires specialist management with second-line agents.

Infection Control

  • Airborne precautions (negative pressure room, N95 masks)
  • Patient to wear surgical mask
  • Continue until smear-negative on treatment (usually 2 weeks)
  • Contact tracing essential

Public Health

  • Statutory notification to public health
  • Contact tracing of household and close contacts
  • Screening with symptom inquiry, CXR, TST/IGRA
8. Complications
ComplicationMechanismManagement
Massive haemoptysisRasmussen aneurysm erosionEmergency: bronchial artery embolisation
Respiratory failureExtensive disease, ARDSICU, ventilation
Pleural effusionImmune response, direct extensionDrainage if symptomatic
EmpyemaSecondary infectionDrainage, prolonged antibiotics
PneumothoraxCavitation, ruptureChest drain
BronchiectasisPost-TB scarringSupportive care
AspergillomaFungal colonisation of cavitySurgery if symptomatic
Drug-induced hepatitisRifampicin, isoniazid, pyrazinamideMonitor LFTs, modify regimen
9. Prognosis and Outcomes

Treatment Response

  • Clinical improvement: 2-4 weeks
  • Sputum conversion: 85% by 2 months
  • Cure rate with drug-sensitive TB: greater than 95%

Poor Prognostic Factors

  • HIV co-infection
  • Drug resistance
  • Extensive disease
  • Delayed diagnosis
  • Poor adherence
  • Malnutrition

Follow-Up

  • End-of-treatment assessment
  • Chest X-ray completion
  • Consider long-term respiratory follow-up if residual damage
10. Evidence and Guidelines

Key Guidelines

  1. NICE Guideline NG33. Tuberculosis — 2016 (updated)

  2. WHO Consolidated Guidelines on TB — 2022

  3. ATS/CDC/IDSA Clinical Practice Guidelines for TB — 2016

  4. BHIVA Guidelines for TB/HIV Co-infection — 2019

Key Evidence

Xpert MTB/RIF

  • Sensitivity 85-95%, specificity 98%
  • Detects rifampicin resistance
  • Revolutionised rapid diagnosis
  • PMID: 20825313

Short-Course Chemotherapy

  • 6-month regimen established in 1980s
  • Hong Kong trials demonstrated efficacy
  • Forms basis of current treatment
11. Patient Explanation

What is tuberculosis?

TB is a bacterial infection that mainly affects your lungs. It spreads through the air when someone with TB coughs or sneezes.

Is it curable?

Yes! TB is curable with a course of antibiotics taken for 6 months. It's very important to complete the full course even when you feel better.

How do I take the treatment?

You'll take several tablets every day for 6 months. The exact combination changes after 2 months. Taking your medication regularly is crucial - missing doses can lead to drug resistance.

Side effects to report

  • Nausea, vomiting, or loss of appetite
  • Yellow skin or eyes (jaundice)
  • Tingling in hands or feet
  • Visual problems (blurred vision, colour changes)

Am I infectious?

Initially yes, but after 2 weeks of treatment, you're usually no longer infectious. We'll test your sputum to confirm.

What about my contacts?

Close contacts (family, housemates) will need to be screened. This protects them and prevents spread.

12. References

  1. NICE Guideline NG33. Tuberculosis. 2016.

  2. WHO. Consolidated Guidelines on Tuberculosis. Module 4: Treatment. 2022.

  3. Nahid P et al. Official ATS/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible TB. Clin Infect Dis. 2016;63(7):e147-e195. PMID: 27516382

  4. Boehme CC et al. Rapid Molecular Detection of Tuberculosis and Rifampin Resistance (Xpert MTB/RIF). N Engl J Med. 2010;363(11):1005-1015. PMID: 20825313

  5. Houben RM, Dodd PJ. The Global Burden of Latent Tuberculosis Infection. PLoS One. 2016;11(9):e0162330. PMID: 27760251

  6. WHO. Global Tuberculosis Report 2023. Geneva: WHO; 2023.

  7. Lawn SD, Zumla AI. Tuberculosis. Lancet. 2011;378(9785):57-72. PMID: 21420161

  8. Theron G et al. Xpert MTB/RIF Ultra for detection of TB. Lancet Infect Dis. 2018;18(8):870-878. PMID: 29860174

13. Examination Focus

Viva Points

"Pulmonary TB presents with cough greater than 2 weeks, weight loss, night sweats. Diagnose with sputum AFB, Xpert MTB/RIF (rapid, detects rifampicin resistance), culture. CXR shows upper lobe infiltrates/cavitation. RIPE for 2 months then RI for 4 months. Give pyridoxine with isoniazid. Always test for HIV. Notify public health. Contact trace."

Key Examination Points

  • Constitutional signs (cachexia, fever)
  • Respiratory examination (crackles, bronchial breathing)
  • Lymphadenopathy
  • Signs of HIV infection

Common Mistakes

  • ❌ Not testing for HIV in all TB patients
  • ❌ Forgetting pyridoxine with isoniazid
  • ❌ Not monitoring LFTs during treatment
  • ❌ Failing to notify public health
  • ❌ Stopping treatment early when feeling better

Differentials

  • Lung cancer
  • Community-acquired pneumonia
  • Non-TB mycobacteria
  • Fungal infection
  • Sarcoidosis

Last Reviewed: 2026-01-01 | MedVellum Editorial Team

Last updated: 2026-01-01

At a Glance

EvidenceHigh
Last Updated2026-01-01

Red Flags

  • MDR/XDR-TB
  • HIV co-infection
  • Miliary TB
  • TB meningitis
  • Respiratory failure
  • Haemoptysis

Clinical Pearls

  • **Xpert Pearl**: GeneXpert MTB/RIF detects TB DNA and rifampicin resistance within 2 hours. First-line molecular test.
  • **Contact Tracing Pearl**: All household and close contacts must be screened. This is a public health imperative.
  • **Pyridoxine Pearl**: Give pyridoxine (vitamin B6) 10-25mg daily with isoniazid to prevent peripheral neuropathy, especially in malnourished, diabetic, or HIV+ patients.
  • **Rifampicin Pearl**: Rifampicin turns body fluids orange-red (urine, tears, sweat). Warn patients about contact lens staining.
  • **HIV Pearl**: Always test for HIV in TB. TB is the leading cause of death in people living with HIV globally.

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines