Tuberculosis (TB)

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Tuberculosis (TB):  

1. Etiology

Causative Agents:

  • Mycobacterium tuberculosis complex:


    • M. tuberculosis – primary human pathogen; transmitted via airborne droplets.

    • M. bovis – zoonotic; transmitted via contaminated milk.

    • M. africanum – common in West and Central Africa.

    • M. microti – rare, primarily affects rodents.

Characteristics of M. tuberculosis:

  • Acid-fast, slow-growing, facultative intracellular bacillus.

  • Cell wall rich in mycolic acids → resistance to desiccation and many antibiotics.

  • Special stains: Ziehl-Neelsen (red bacilli), Auramine-rhodamine (fluorescent detection).

  • Culture media: Löwenstein-Jensen, Middlebrook broth.

  • Virulence factors:

    • Cord factor – inhibits neutrophils, induces TNF-α.

    • Sulfatides – block phagolysosome fusion.

    • Lipoarabinomannan – scavenges ROS, modulates immune response.

    • Catalase-peroxidase – detoxifies reactive oxygen species.

Risk factors for infection:

  • Healthcare work, crowded living conditions, immunocompromised states (HIV, diabetes, malnutrition).

  • Recent travel or migration from high TB-burden countries.

2. Pathophysiology

Primary Infection:

  • Inhalation of aerosolized bacilli → alveolar macrophage uptake.

  • M. tuberculosis survives intracellularly by blocking phagosome maturation and lysosome fusion.

  • Th1 immune response activated → IFN-γ released → macrophage activation.

  • Granuloma formation limits bacterial spread.


    • Ghon focus: primary lung granuloma.

    • Ghon complex: Ghon focus + lymph nodes + lymphatic connection.

  • Outcome depends on immune competence:

    • Strong immunity: latent TB (LTBI), granulomas calcify → Ranke complex.

    • Immunocompromised: progressive primary TB or miliary TB.

Secondary (Reactivation) TB:

  • Occurs when immune surveillance weakens (HIV, corticosteroids, TNF-α inhibitors).

  • Predilection for upper lobes due to higher oxygen tension.

  • Cavitation and fibrosis are common.

Extrapulmonary Spread:

  • Hematogenous or lymphatic dissemination → organs: lymph nodes, meninges, bones (Pott disease), adrenal glands, pericardium, kidneys, skin.


3. Clinical Features

Latent TB (LTBI):

  • Asymptomatic, non-contagious.

  • Lifetime risk of reactivation: 5–10%.

Pulmonary TB:

  • Systemic: low-grade fever, night sweats, weight loss, malaise.

  • Respiratory: chronic cough (purulent ± hemoptysis), pleuritic chest pain, dyspnea.

  • Examination: consolidation, cavitation, rhonchi, diminished breath sounds.

  • Advanced disease: clubbing, wasting.

Extrapulmonary TB:

  • Lymphadenitis: cervical, axillary, inguinal nodes.

  • CNS: tuberculous meningitis → headache, neck stiffness, cranial nerve deficits.

  • Skeletal: Pott disease (spinal TB) → kyphosis, vertebral collapse.

  • Pericardial TB → effusion, constriction.

  • Adrenal TB → Addison’s disease.

  • Cutaneous TB: lupus vulgaris, scrofuloderma, tuberculous chancre.

HIV-TB Coinfection:

  • Often atypical presentation.

  • Low bacillary load → negative smear.

  • Imaging may be subtle; disseminated TB more frequent.


4. Diagnosis

Microbiological Tests:

  • Sputum: ≥3 samples, including early morning.

  • Smears: Ziehl-Neelsen (low sensitivity, rapid), Auramine-rhodamine.

  • Culture: gold standard; slow (2–6 weeks); allows drug susceptibility testing.

  • NAAT/PCR: rapid, highly sensitive, detects drug resistance.

  • Extrapulmonary: fluid or tissue samples, AFB smear, culture, PCR.

Imaging:

  • Primary TB: consolidation, hilar lymphadenopathy, Ghon complex.


  • Reactivation TB: upper lobe cavitation, fibrocaseous lesions, tree-in-bud pattern.

  • Miliary TB: diffuse tiny nodules (“millet seed” pattern).

Latent TB Screening:

  • PPD TST: intradermal injection, measure induration at 48–72h.

  • IGRA: measures IFN-γ response to TB antigens (preferred if BCG-vaccinated).

  • Chest X-ray needed to exclude active TB before starting LTBI treatment.

5. Differential Diagnosis

  • Pulmonary: pneumonia, lung cancer, lung abscess, sarcoidosis, fungal infections, granulomatosis with polyangiitis.

  • Extrapulmonary: lymphoma, syphilis, leprosy, systemic autoimmune disorders.

6. Treatment

Active TB (RIPE regimen):

  • Intensive phase (2 months): Rifampin + Isoniazid + Pyrazinamide + Ethambutol.

  • Continuation phase (4 months): Rifampin + Isoniazid.

    Orange urine secondary to rifampicin therapy

     

  • Supportive: Pyridoxine with isoniazid to prevent neuropathy.

  • Directly Observed Therapy (DOT): ensures adherence.

Drug-Resistant TB:

  • MDR-TB: resistant to Rifampin + Isoniazid.

  • XDR-TB: MDR + fluoroquinolone + second-line injectable.

  • Requires second-line agents: moxifloxacin, bedaquiline, linezolid, clofazimine, amikacin.

Latent TB (LTBI):

  • Preferred regimens:

    • 3 months: weekly INH + rifapentine (3HP)

    • 4 months: daily rifampin (4R)

    • 3 months: daily INH + rifampin (3HR)

  • Alternative: 6–9 months INH.

  • Goal: prevent reactivation.

Extrapulmonary TB: therapy individualized, often 6–12 months depending on site.

Monitoring:

  • Monthly follow-up.

  • Symptom review, liver function, vision (ethambutol), sputum smears.

  • Early detection of adverse drug reactions.

7. Complications

  • Pulmonary: cavitation, bronchiectasis, hemoptysis, secondary infection (aspergilloma).

  • CNS: hydrocephalus, cranial nerve palsies.

  • Skeletal: deformities, neurological deficits.

  • Cardiac: constrictive pericarditis.

  • Adrenal: Addison’s disease.

  • Disseminated TB in immunocompromised: multiorgan involvement.

8. Epidemiology

Global:

  • One of the top infectious causes of death worldwide.

  • Estimated 25% of population has LTBI.

  • Highest incidence: India, Indonesia, China, Philippines, Bangladesh, Nigeria, Pakistan, South Africa.

  • Rising incidence of MDR/XDR-TB.

USA:

  • Incidence 2.8/100,000 (2018).

  • Two-thirds of new cases in foreign-born individuals.

  • LTBI prevalence ~5%.

9. Prevention

  • Early detection and treatment of LTBI.

  • Vaccination: BCG (limited protection; mainly prevents severe childhood TB).

  • Infection control: airborne precautions, contact tracing, mask use.

  • Adherence to full course of therapy to prevent drug resistance.

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