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Tuberculosis

Clinical Subject Page

Tuberculosis (TB)

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, most commonly affecting the lungs but capable of involving almost any organ.

Also called

Tuberculous infection

ICD-10

A15.9

Specialty

Pulmonology

Onset

Chronic

Reviewed

July 2026

On This Page

Overview

Tuberculosis spreads through the air when a person with infectious pulmonary or laryngeal Tuberculosis releases bacteria.

After infection, Tuberculosis may exist as:

  • Latent Tuberculosis infection (LTBI) → Infection without active disease
  • Active Tuberculosis disease → Bacterial multiplication causing symptoms and tissue damage

The lungs are the most commonly affected site.

Etiology & Risk Factors

Cause

Tuberculosis is caused mainly by:

  • Mycobacterium tuberculosis

Transmission

Spread occurs through airborne particles released by a person with infectious pulmonary or laryngeal Tuberculosis.

Risk Factors for Exposure

  • Close contact with a person with active Tuberculosis
  • Living or working in crowded settings
  • Residence in areas with a high Tuberculosis burden
  • Healthcare exposure
  • Poor ventilation

Risk Factors for Active Disease

  • HIV infection
  • Immunosuppressive therapy
  • Malnutrition
  • Diabetes mellitus
  • Chronic kidney disease
  • Silicosis
  • Smoking
  • Young age
  • Older age

Important Note

Latent Tuberculosis infection is not contagious; active pulmonary or laryngeal Tuberculosis may be infectious.

Pathophysiology

Inhalation of Mycobacterium tuberculosis
⬇
Bacteria reach the alveoli
⬇
Macrophage uptake
⬇
Intracellular bacterial survival and multiplication
⬇
Cell-mediated immune response
⬇
Granuloma formation
⬇

Two Possible Outcomes

Immune control
→ Latent Tuberculosis infection

OR

Failure of immune control
→ Active Tuberculosis disease
→ Caseous necrosis + Tissue destruction

Key Concept

Tuberculosis may remain latent for years and later reactivate when immune control weakens.

Clinical Presentation

  • Pulmonary Symptoms

    • Persistent cough
    • Sputum production
    • Hemoptysis
    • Chest pain
    • Dyspnea in advanced disease

    Constitutional Symptoms

    • Fever
    • Night sweats
    • Weight loss
    • Fatigue
    • Loss of appetite

    Extrapulmonary Tuberculosis

    May affect:

    • Lymph nodes
    • Pleura
    • Bones and joints
    • Central nervous system
    • Genitourinary system
    • Abdomen
    • Pericardium

History Taking

  • Ask about:

    • Persistent cough?
    • How long has it lasted?
    • Sputum production?
    • Hemoptysis?
    • Fever?
    • Night sweats?
    • Weight loss?
    • Loss of appetite?
    • Close contact with a person with Tuberculosis?
    • Previous Tuberculosis infection or disease?
    • Previous Tuberculosis treatment?
    • Travel or residence in a high-burden area?

Physical Examination

Look for:

  • Weight loss
  • Fever
  • Cachexia
  • Pallor
  • Lymphadenopathy
  • Respiratory distress

Chest Examination

May show:

  • Crackles
  • Bronchial breathing
  • Reduced breath sounds
  • Signs of pleural effusion

Important Note

Physical examination may be normal, especially in early pulmonary Tuberculosis.

Extrapulmonary Examination

Look for:

  • Enlarged lymph nodes
  • Spinal tenderness or deformity
  • Neurological abnormalities
  • Abdominal swelling
  • Signs of pericardial disease

Investigations of Tuberculosis

  • Chest Imaging

    Chest X-ray

    May show:

    • Upper-lobe infiltrates
    • Cavitation
    • Nodules
    • Fibrosis
    • Hilar or mediastinal lymphadenopathy
    • Pleural effusion

    CT Chest

    Provides better assessment of:

    • Cavities
    • Nodules
    • Lymphadenopathy
    • Extent of disease

    Microbiological Testing — Essential for Active Tuberculosis

    Sputum Tests

    • Nucleic acid amplification test (NAAT)
    • Acid-fast bacillus (AFB) smear
    • Mycobacterial culture

    Key Point

    Mycobacterial culture confirms the organism and allows drug-susceptibility testing.

    Tests for Tuberculosis Infection

    • Tuberculin skin test (TST)
    • Interferon-gamma release assay (IGRA)

    Important Note

    TST and IGRA detect Tuberculosis infection but cannot alone distinguish latent Tuberculosis from active Tuberculosis disease.

    Additional Tests

    • HIV testing
    • CBC
    • Liver function tests
    • Renal function tests
    • Testing of extrapulmonary specimens when indicated

Diagnosis

TB Diagnosis · Steps 1–2 — History & Examination

1
Clinical history
Symptoms & risks
2
Physical exam
Signs
3
Imaging
CXR & CT
4
TST / IGRA
Immunological
5
Microbiology
Smear, culture, Xpert
6
Extra-pulmonary
Biopsy & fluids
Step 1 — Clinical History
Classic symptoms
Cough >3 weeks
Haemoptysis
Drenching night sweats
Low-grade afternoon fever
Weight loss >10%
Fatigue & malaise
Risk factors
High-burden country (MENA, South Asia, Sub-Saharan Africa)
Close contact with TB case
HIV — increases risk 20–30×
Immunosuppression (steroids, anti-TNF, diabetes)
Malnutrition, alcohol, overcrowding
Latent vs Active TB
Latent (LTBI) — positive test, no symptoms, not infectious, normal CXR
Active TB — symptoms present, infectious, positive smear/culture
Always exclude active TB before treating LTBI
Step 2 — Physical Examination
Pulmonary
Often normal early — extensive disease with minimal signs is classic TB
Dullness + reduced breath sounds — pleural effusion
Post-tussive crackles over upper lobes
Bronchial breathing over cavitation
Extra-pulmonary clues
Cervical lymphadenopathy (scrofula) — matted, may form collar-stud abscess
Meningism — neck stiffness, altered GCS → TB meningitis (emergency)
Choroidal tubercles on fundoscopy — pathognomonic of miliary TB
Vertebral gibbus (kyphosis) — Pott's disease

TB Diagnosis · Steps 3–4 — Imaging & Immunological Tests

1
Clinical history
Symptoms & risks
2
Physical exam
Signs
3
Imaging
CXR & CT
4
TST / IGRA
Immunological
5
Microbiology
Smear, culture, Xpert
6
Extra-pulmonary
Biopsy & fluids
Step 3 — Imaging
CXR patterns
Primary TB: Ghon focus + hilar lymphadenopathy (Ranke complex); pleural effusion
Post-primary (reactivation):
Upper lobe consolidation — apical & posterior segments
Cavitation — thick-walled; hallmark of infectious TB
Fibrosis, volume loss, calcified granulomas
Miliary TB — 1–3 mm nodules throughout both lungs; haematogenous spread
CXR may be normal in HIV+ — always test sputum regardless
CT thorax
More sensitive than CXR — detects early disease, small cavities
Tree-in-bud pattern — centrilobular nodules + branching opacities; endobronchial spread
Necrotic mediastinal LN with rim enhancement — classic on contrast CT
Brain MRI — basilar enhancement, tuberculomas, hydrocephalus (TB meningitis)
Step 4 — Immunological Tests (TST & IGRA)
TestMechanismPositive thresholdAdvantagesLimitations
TST (Mantoux)
Intradermal		 0.1 mL PPD injected. Read induration at 48–72h. ≥5 mm HIV+, close contact
≥10 mm high-risk groups
≥15 mm low-risk		 Cheap, no lab. Useful in low-resource settings. False positive with BCG. 2 visits. Anergy in immunosuppression.
IGRA
QuantiFERON / T-SPOT
Blood test		 Blood incubated with TB antigens (ESAT-6, CFP-10). Measures IFN-γ release. Positive / Negative / Indeterminate Not affected by BCG. Single visit. Preferred in BCG-vaccinated. Expensive. Indeterminate in severe immunosuppression.
Key: Neither TST nor IGRA can distinguish active from latent TB — always integrate with clinical picture + imaging + microbiology.

TB Diagnosis · Steps 5–6 — Microbiology & Extra-pulmonary Workup

1
Clinical history
Symptoms & risks
2
Physical exam
Signs
3
Imaging
CXR & CT
4
TST / IGRA
Immunological
5
Microbiology
Smear, culture, Xpert
6
Extra-pulmonary
Biopsy & fluids
Step 5 — Microbiological Confirmation
AFB Smear
3 sputum samples on 3 consecutive mornings
Ziehl-Neelsen (ZN) stain — identifies acid-fast bacilli
Sensitivity ~60%; lower in HIV+
Smear+ = highly infectious — isolate immediately
Cannot distinguish MTB from NTM — culture needed
Xpert MTB/RIF (GeneXpert)
WHO first-line test — result in 2 hours
Detects MTB DNA + rifampicin resistance simultaneously
Sensitivity ~90% (smear+); ~70% (smear−)
Works on sputum, BAL, CSF, lymph node, urine
Culture — Gold Standard
Liquid (MGIT) — result 1–3 weeks
Solid (Löwenstein-Jensen) — 4–8 weeks
Drug sensitivity testing (DST) — mandatory before treatment
Required even if Xpert positive
Step 6 — Extra-pulmonary TB Workup
TB Meningitis
LP: Lymphocytic pleocytosis, low glucose, high protein
CSF Xpert — sensitivity ~60%; test of choice
Brain MRI — basilar enhancement, tuberculomas, hydrocephalus
Pleural TB
Pleural ADA >40 IU/L — ~90% sensitive for TB pleuritis
Pleural biopsy — highest yield (~80%)
Fluid: exudate, lymphocyte-predominant, low glucose
Lymph node & other
FNAC / core biopsy — granulomas + AFB + Xpert + culture
Bone marrow biopsy — miliary TB
Urine AFB × 3 — renal TB (early morning urine)
ADA (Adenosine Deaminase) — elevated in all TB-related effusions. Rapid and cheap. ADA >40 IU/L in pleural fluid = high specificity for TB pleuritis.
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Related Topics

Management of Tuberculosis

TB Treatment · Standard First-line Regimen (DS-TB) — WHO 2022

Standard First-line Regimen — Drug-sensitive TB (DS-TB)
Drug (abbreviation) Daily dose (adult) Phase Duration Principal side effects Monitoring
Isoniazid H
5 mg/kg/day
(max 300 mg)
 300 mg OD
Fasting or with food		 Intensive
Continuation		 6 months Peripheral neuropathy Hepatotoxicity Drug-induced lupus Mood changes Rash
Neuropathy prevented by pyridoxine (B6) 10–25 mg/day — give routinely to HIV+, malnourished, diabetics, alcohol users, pregnancy
LFTs at baseline & if symptomatic
Symptoms of neuropathy
Rifampicin R
10 mg/kg/day
(max 600 mg)
 600 mg OD
30 min before food		 Intensive
Continuation		 6 months Hepatotoxicity Orange discolouration Flu-like syndrome Drug interactions Thrombocytopenia
Potent CYP450 inducer — reduces efficacy of OCP, warfarin, antiretrovirals, phenytoin, methadone. Warn patients: urine/sweat/tears turn orange — stains contact lenses permanently.
LFTs at baseline
Drug interaction review
FBC if prolonged
Pyrazinamide Z
25 mg/kg/day
(max 2g)
 1.5–2 g OD
With food		 Intensive only 2 months Hepatotoxicity Hyperuricaemia / gout Arthralgia Rash, nausea Photosensitivity
Asymptom­atic hyperuricaemia common — treat only if symptomatic gout. Avoid in severe hepatic disease and gout.
LFTs at baseline & monthly
Uric acid if symptomatic
Joint symptoms
Ethambutol E
15–20 mg/kg/day
(max 1.6 g)
 800–1200 mg OD
With or without food		 Intensive only 2 months Optic neuritis Colour vision loss (red-green) Peripheral neuropathy Rash
Optic neuritis is dose-dependent and usually reversible if caught early — warn patients to report blurred vision or colour change immediately. Avoid in pre-existing optic nerve disease. Dose-reduce in renal impairment.
Visual acuity at baseline
Red-green colour test
Monthly symptoms check
eGFR (dose-adjust if low)
Standard regimen summary: 2HRZE / 4HR — Intensive phase (2 months): Isoniazid + Rifampicin + Pyrazinamide + Ethambutol. Continuation phase (4 months): Isoniazid + Rifampicin. Total duration = 6 months.
Extended to 9 months (2HRZE / 7HR) for: CNS TB (meningitis), bone/joint TB, extensive pulmonary disease, HIV-positive patients with CD4 <100.
All four drugs are given together in fixed-dose combination (FDC) tablets where available — improves adherence and reduces risk of inadvertent monotherapy.

TB Treatment · MDR-TB Regimen BPaLM / BPaL — WHO 2022

MDR-TB Regimen — WHO BPaLM / BPaL (2022)
Drug (abbreviation) Daily dose (adult) Phase Duration Principal side effects Monitoring
Bedaquiline B
400 mg OD × 2 weeks
then 200 mg 3×/week
 With food
(increases absorption)		 All phases 6 months QTc prolongation Hepatotoxicity Nausea, arthralgia Headache
Avoid with other QT-prolonging drugs. Do NOT combine with fluoroquinolones without ECG monitoring. Diarylquinoline class — novel mechanism (inhibits ATP synthase).
ECG at baseline, 2, 12, 24 weeks
LFTs monthly
Serum K, Mg, Ca
Pretomanid Pa
200 mg OD
 With food All phases 6 months Peripheral neuropathy Hepatotoxicity QTc prolongation Anaemia, rash
Nitroimidazooxazine class — requires reductive activation by bacillary F420 enzyme. Only used within BPaL/BPaLM regimen.
LFTs monthly
Neuropathy symptoms
ECG monitoring
FBC
Linezolid L
600 mg OD
(reduce to 300 mg if toxicity)
 OD — may reduce dose for tolerability All phases 6 months Myelosuppression Peripheral neuropathy Optic neuropathy Serotonin syndrome Nausea, diarrhoea
Most toxic drug in regimen. Dose reduction to 300 mg OD often required. Avoid SSRIs, MAOIs (serotonin syndrome). Monitor FBC weekly initially.
FBC weekly × 4, then monthly
Visual acuity monthly
Neuropathy assessment
Drug interactions review
Moxifloxacin M
400 mg OD
 OD — added in BPaLM if susceptible BPaLM only 6 months QTc prolongation Tendinopathy / tendon rupture Arthralgia, myalgia GI upset, dizziness Photosensitivity
Added only if moxifloxacin-susceptible strain confirmed. Additive QTc risk with bedaquiline — mandatory ECG monitoring. Avoid in fluoroquinolone-resistant MDR-TB.
ECG at baseline & monthly
Tendon pain symptoms
Serum electrolytes
MDR-TB definition: Resistance to at least Isoniazid + Rifampicin simultaneously.
BPaLM regimen (preferred, 2022): Bedaquiline + Pretomanid + Linezolid + Moxifloxacin × 6 months — if moxifloxacin-susceptible.
BPaL regimen: Bedaquiline + Pretomanid + Linezolid × 6–9 months — if fluoroquinolone-resistant (XDR-TB).
Confirm DST before starting. Treat under DOTS (directly observed therapy) supervision. Notify TB authorities. All MDR-TB managed by specialist TB unit.

TB Treatment · Latent TB Infection (LTBI) Preventive Therapy — WHO 2022

Latent TB Infection (LTBI) — Preventive Therapy
Regimen Dosing Schedule Duration Principal side effects Monitoring
Isoniazid alone 6H
5 mg/kg/day (max 300 mg)
 300 mg OD Daily 6 months Hepatotoxicity Peripheral neuropathy Rash, GI upset
Give pyridoxine 10–25 mg/day with all INH-containing LTBI regimens. Hepatotoxicity risk increases with age and alcohol use.
LFTs at baseline
Monthly symptom review
Adherence assessment
Isoniazid alone 9H
5 mg/kg/day (max 300 mg)
 300 mg OD Daily 9 months Hepatotoxicity Peripheral neuropathy Rash, GI upset
Preferred by CDC guidelines. More protective than 6H (~90% efficacy). Higher hepatotoxicity risk with longer duration. Preferred for HIV-positive patients when rifampicin interactions are a concern.
LFTs at baseline & if symptomatic
Monthly review
Rifampicin alone 4R
10 mg/kg/day (max 600 mg)
 600 mg OD Daily 4 months Hepatotoxicity Drug interactions (CYP inducer) Orange discolouration Flu-like reactions
BTS-preferred regimen for LTBI. Fewer side effects and better completion rates than 6H. Lower hepatotoxicity. Check drug interactions (OCP, antiretrovirals, warfarin).
LFTs at baseline
Drug interaction review
Monthly adherence review
Rifampicin + Isoniazid 3HR
Rifampicin 600 mg + Isoniazid 300 mg OD
 Both OD together
30 min before food		 Daily 3 months Hepatotoxicity (additive) Peripheral neuropathy Drug interactions GI upset, rash
Widely used WHO-endorsed short regimen. Good adherence due to shorter duration. Give pyridoxine. Monitor LFTs baseline + monthly.
LFTs baseline & monthly
Drug interactions
Pyridoxine prescribed
Rifapentine + Isoniazid 3HP
Rifapentine weight-based + INH 900 mg
 Once weekly — DOT or self-administered Weekly 3 months
(12 doses)		 Hepatotoxicity Flu-like reactions (systemic) Drug interactions Rash, hypersensitivity
Highest completion rates of all LTBI regimens. Preferred by CDC 2020. Once-weekly dosing ideal for DOT. Not recommended in HIV+ on antiretrovirals (major drug interactions). Avoid in pregnancy and age <2 years.
LFTs at baseline
Systemic reaction symptoms
Drug interactions (HIV ARVs)
LTBI treatment principle: Always exclude active TB before starting — symptom screen + CXR mandatory. Positive TST or IGRA + no symptoms + normal/old changes on CXR = LTBI.
Priority groups for LTBI treatment: HIV-positive, close contacts of smear-positive TB, immunosuppressed (anti-TNF, transplant, steroids), new migrants from high-burden countries, those with fibrotic CXR changes (old healed TB).
Pyridoxine 10–25 mg/day with all isoniazid-containing regimens to prevent peripheral neuropathy.

Complications of Tuberculosis

  • Massive hemoptysis
  • Permanent lung damage
  • Bronchiectasis
  • Respiratory failure
  • Pleural disease
  • Disseminated or miliary Tuberculosis
  • Tuberculosis meningitis
  • Spinal Tuberculosis
  • Pericardial Tuberculosis
  • Drug-resistant Tuberculosis
  • Death

Prognosis of Tuberculosis

  • Drug-susceptible Tuberculosis is usually curable with appropriate treatment.
  • Prognosis depends on:
    • Early diagnosis
    • Drug susceptibility
    • Treatment adherence
    • Disease extent
    • Immune status
    • Presence of complications
  • Delayed diagnosis increases transmission and complications.
  • Drug-resistant Tuberculosis is more difficult to treat and generally requires longer, more complex therapy.
  • Early diagnosis and completion of treatment greatly improve outcomes.

Key Points / Clinical Pearls of Tuberculosis

  • Tuberculosis is caused mainly by Mycobacterium tuberculosis.
  • Pulmonary Tuberculosis is the most common form.
  • Latent Tuberculosis infection is not contagious.
  • Active pulmonary or laryngeal Tuberculosis may be infectious.
  • Persistent cough, weight loss, fever, and night sweats are classic features.
  • NAAT, AFB smear, and culture are important tests for active pulmonary Tuberculosis.
  • TST and IGRA cannot alone distinguish latent from active Tuberculosis.
  • Always exclude active disease before treating latent Tuberculosis infection.