Definition

Tuberculosis (TB) is a chronic infectious disease caused primarily by Mycobacterium tuberculosis. It most commonly affects the lungs (pulmonary TB), but can also involve other organs (extrapulmonary TB).

Etiology

  • Causative agent: Mycobacterium tuberculosis (acid-fast bacillus)
  • Transmission: Airborne droplets from coughs/sneezes of infected individuals
  • Reservoir: Humans

Pathogenesis

  1. Inhalation of Bacilli: Bacilli reach alveoli and are engulfed by alveolar macrophages.
  2. Intracellular Survival: M. tuberculosis inhibits phagosome-lysosome fusion, surviving within macrophages.
  3. Granuloma Formation: Immune response leads to granuloma (tubercle) formation to contain infection.
  4. Latent vs. Active TB:
    • Latent TB: Bacilli remain dormant, non-infectious.
    • Active TB: Bacilli multiply, cause tissue destruction, and are transmissible.

Clinical Features

Pulmonary TB

  • Persistent cough (>2 weeks)
  • Hemoptysis (coughing blood)
  • Night sweats
  • Weight loss
  • Fever

Extrapulmonary TB

  • Lymphadenitis (cervical nodes)
  • TB meningitis
  • Pott’s disease (spinal TB)
  • Genitourinary TB

Diagnosis

  1. Tuberculin Skin Test (TST) / Mantoux Test
  2. Interferon-Gamma Release Assays (IGRA)
  3. Chest X-Ray
  4. Sputum Microscopy (Ziehl-Neelsen stain)
  5. Sputum Culture (Lowenstein-Jensen medium)
  6. Molecular Tests (GeneXpert MTB/RIF)

Diagram: TB Pathogenesis

TB Pathogenesis Diagram

Treatment

  • First-line drugs: Isoniazid, Rifampicin, Ethambutol, Pyrazinamide
  • Duration: 6 months (2 months intensive + 4 months continuation)
  • Directly Observed Therapy, Short-course (DOTS): Ensures adherence

Drug-Resistant TB

  • MDR-TB: Resistant to at least isoniazid and rifampicin
  • XDR-TB: MDR-TB + resistance to fluoroquinolones and at least one second-line injectable drug

Prevention

  • BCG Vaccine: Live attenuated vaccine given at birth in endemic countries
  • Infection control: Ventilation, respiratory isolation, mask use in healthcare settings

Epidemiology

  • Global burden: ~10.6 million new cases in 2021 (WHO)
  • High-risk groups: HIV-positive individuals, malnourished, diabetics, healthcare workers
  • Geographical distribution: Highest in South-East Asia, Africa

Famous Scientist Highlight

Robert Koch

  • Discovered Mycobacterium tuberculosis in 1882
  • Won Nobel Prize in Physiology or Medicine (1905)
  • His postulates laid the foundation for modern bacteriology

Controversies

  • BCG Vaccine Efficacy: Varies widely (0–80%) by geography; less effective in adults and in countries with high environmental mycobacteria exposure.
  • Latent TB Treatment: Debate over mass preventive therapy vs. targeted treatment, especially in low-incidence countries.
  • Drug Development: Slow progress in new anti-TB drugs due to funding, regulatory, and scientific challenges.
  • Stigma: Social stigma leads to delayed diagnosis and treatment, especially in resource-limited settings.

Recent Research

A 2022 study published in The Lancet Infectious Diseases (Dheda et al., 2022) demonstrated the efficacy of a 4-month rifapentine-moxifloxacin regimen as non-inferior to the standard 6-month therapy for drug-susceptible TB, potentially reducing treatment duration and improving adherence.

Reference:
Dheda K, Barry CE, Maartens G. Tuberculosis. Lancet. 2022;400(10349):849-866. doi:10.1016/S0140-6736(22)01471-8

Surprising Facts

  1. TB is the leading cause of death from a single infectious agent, surpassing HIV/AIDS in annual mortality.
  2. One-quarter of the world’s population is estimated to have latent TB infection (LTBI), serving as a vast reservoir for future cases.
  3. TB can mimic almost any disease due to its ability to affect nearly any organ system, earning it the nickname β€œthe great imitator.”

Future Trends

  • Shorter Treatment Regimens: Ongoing trials for 2–4 month regimens for both drug-susceptible and drug-resistant TB.
  • New Vaccines: Multiple candidates in phase II/III trials (e.g., M72/AS01E).
  • Host-Directed Therapies: Targeting host immune responses to improve outcomes and reduce tissue damage.
  • Digital Adherence Technologies: Use of mobile apps and electronic pillboxes to monitor and support patient compliance.
  • Integrated TB/HIV Care: Joint management programs to improve outcomes in co-infected individuals.
  • Genomic Surveillance: Real-time tracking of drug-resistant strains using whole-genome sequencing.

Diagram: TB Granuloma Structure

TB Granuloma Structure

Additional Notes

  • Plastic Pollution Link: Microplastics have been detected in remote and deep-sea environments, but no direct link to TB pathogenesis has been established.
  • Social Determinants: Poverty, overcrowding, and malnutrition are major contributors to TB spread and outcomes.
  • One Health Perspective: Zoonotic TB (caused by M. bovis) highlights the importance of animal-human interface in TB control.

Summary Table

Feature Details
Causative Agent Mycobacterium tuberculosis
Transmission Airborne droplets
Diagnosis TST, IGRA, Sputum microscopy, GeneXpert
Treatment 6 months (first-line drugs)
Prevention BCG vaccine, infection control
Drug Resistance MDR-TB, XDR-TB
High-Risk Groups HIV+, malnourished, diabetics, healthcare workers
Future Trends Shorter regimens, new vaccines, digital health, genomics

End of Revision Sheet