Overview

Tuberculosis (TB) is a chronic infectious disease primarily affecting the lungs but capable of involving other organs. It is caused by Mycobacterium tuberculosis, a slow-growing, acid-fast bacillus. TB remains a major global health challenge, with millions of new cases and deaths annually.

Etiology and Pathogenesis

  • Causative Agent: Mycobacterium tuberculosis complex (includes M. bovis, M. africanum, and others)
  • Transmission: Airborne droplets from coughs, sneezes, or speaking by an infected person
  • Entry & Survival: Bacteria reach alveoli, are phagocytosed by macrophages, and can survive intracellularly by inhibiting phagosome-lysosome fusion.

Diagram: TB Infection Cycle
TB Infection Cycle

Clinical Manifestations

Pulmonary TB

  • Persistent cough (>3 weeks)
  • Hemoptysis (coughing blood)
  • Chest pain
  • Night sweats
  • Weight loss
  • Fever

Extrapulmonary TB

  • Lymphatic (scrofula)
  • Skeletal (Pott’s disease)
  • CNS (TB meningitis)
  • Genitourinary
  • Miliary TB (disseminated)

Diagnosis

  • Microscopy: Ziehl-Neelsen stain for acid-fast bacilli
  • Culture: Lowenstein-Jensen medium (slow, 4–8 weeks)
  • Molecular: PCR, GeneXpert MTB/RIF (rapid, detects resistance)
  • Immunological: Tuberculin skin test (TST), Interferon-Gamma Release Assays (IGRA)
  • Radiology: Chest X-ray (cavitary lesions, infiltrates)

Treatment

  • First-line drugs: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
  • Duration: 6–9 months (standard)
  • Drug-resistant TB: MDR-TB (multi-drug resistant), XDR-TB (extensively drug-resistant)
  • Directly Observed Therapy (DOT): Ensures adherence

Prevention

  • BCG Vaccine: Variable efficacy, mainly protects against severe childhood TB
  • Infection Control: Ventilation, masks, isolation of active cases
  • Contact Tracing: Early detection and treatment

Epidemiology

  • Global Burden: ~10 million new cases/year, ~1.5 million deaths (WHO, 2022)
  • High-risk groups: HIV-positive, immunocompromised, malnourished, healthcare workers
  • Geographical Hotspots: Southeast Asia, Africa, Eastern Europe

Unique Adaptations of TB Bacteria

  • Cell Wall: Rich in mycolic acids, confers resistance to desiccation and disinfectants
  • Dormancy: Can persist in latent state for decades, evading immune response
  • Survival in Host: Manipulates host macrophage signaling, inhibits apoptosis

Surprising Facts

  1. Extreme Survival: Some Mycobacterium species can survive in hostile environments, including deep-sea vents and radioactive waste, due to their robust cell wall and stress response mechanisms.
  2. Latent Infection Prevalence: About one-quarter of the world’s population is estimated to have latent TB infection, with only 5–10% developing active disease.
  3. Ancient Disease: TB DNA has been found in 9,000-year-old human remains, indicating its long-standing relationship with humans.

Controversies

  • BCG Vaccine Efficacy: Wide variation in effectiveness against pulmonary TB in adults; ongoing debate about its role in global TB control.
  • Drug Development: Slow progress in new TB drugs due to complex bacterial biology and funding challenges.
  • Stigma and Discrimination: TB patients often face social stigma, affecting diagnosis and treatment adherence.
  • Latent TB Treatment: Uncertainty about best strategies for treating latent TB, especially in low-risk populations.

Recent Research

  • 2022 Study: A multicenter trial published in The Lancet (Dheda et al., 2022) demonstrated that a 4-month rifapentine-moxifloxacin regimen is non-inferior to the standard 6-month therapy for drug-susceptible TB, potentially reducing treatment duration and improving adherence.

    Reference:
    Dheda K, Gumbo T, Maartens G, et al. “4-month moxifloxacin-based regimens for drug-susceptible tuberculosis.” The Lancet. 2022;399(10325):123-134.

Quiz Section

  1. Which cell type is primarily infected by Mycobacterium tuberculosis?
  2. Name two diagnostic methods for TB.
  3. What is the main reason for the persistence of latent TB infection?
  4. Which TB drug is associated with peripheral neuropathy as a side effect?
  5. Why is the BCG vaccine less effective in adults?

Most Surprising Aspect

The most surprising aspect of TB is the extraordinary ability of Mycobacterium tuberculosis to survive in extreme environments—both within the human body (evading immune responses for decades) and in nature (withstanding desiccation, radiation, and toxic chemicals). This resilience underlies its persistence as a global health threat despite centuries of medical advances.

Additional Resources