1. Overview

Tuberculosis (TB) is a chronic infectious disease primarily affecting the lungs, caused by the bacterium Mycobacterium tuberculosis. It remains a leading cause of morbidity and mortality worldwide, especially in resource-limited settings.

2. Etiology & Pathogenesis

  • Causative Agent: Mycobacterium tuberculosis (MTB), a slow-growing, acid-fast bacillus.
  • Transmission: Airborne droplets from coughs/sneezes of individuals with active pulmonary TB.
  • Infection Process:
    • Inhaled bacilli reach alveoli.
    • Macrophages ingest MTB; bacteria may survive and multiply.
    • Formation of granulomas (tubercles) as immune response.
    • Latent TB: Bacilli remain dormant; no symptoms.
    • Active TB: Bacilli multiply, causing tissue damage.

3. Clinical Manifestations

  • Pulmonary TB: Persistent cough (>3 weeks), hemoptysis, chest pain, fever, night sweats, weight loss.
  • Extrapulmonary TB: Can affect lymph nodes, pleura, bones, CNS (e.g., TB meningitis), genitourinary tract.
  • Latent TB Infection (LTBI): Asymptomatic, non-contagious, risk of reactivation.

4. Diagnosis

  • Tuberculin Skin Test (TST): Measures immune response to MTB antigens.
  • Interferon-Gamma Release Assays (IGRAs): Blood tests for immune response.
  • Chest X-ray: Detects lung abnormalities.
  • Sputum Microscopy: Ziehl-Neelsen stain for acid-fast bacilli.
  • Molecular Methods: PCR-based assays (e.g., GeneXpert MTB/RIF).
  • Culture: Gold standard; slow (weeks for results).

5. Treatment

  • First-line Drugs: Isoniazid, Rifampicin, Ethambutol, Pyrazinamide.
  • Duration: 6 months (2 months intensive phase, 4 months continuation phase).
  • Drug-resistant TB: MDR-TB (multi-drug resistant), XDR-TB (extensively drug-resistant).
  • Directly Observed Therapy (DOT): Ensures adherence.

6. Epidemiology

  • Global Burden: ~10.6 million new cases (2022, WHO).
  • High-risk Populations: HIV-positive individuals, immunocompromised, healthcare workers, prisoners.
  • Geographical Distribution: Highest incidence in South-East Asia, Africa.

7. Emerging Technologies

7.1 Rapid Molecular Diagnostics

  • GeneXpert MTB/RIF Ultra: Detects MTB and rifampicin resistance in <2 hours.
  • CRISPR-based Diagnostics: New platforms (e.g., SHERLOCK) for ultra-sensitive detection.

7.2 Artificial Intelligence (AI)

  • AI-assisted Radiology: Automated interpretation of chest X-rays for TB screening.
  • Predictive Analytics: Machine learning models for outbreak prediction and patient risk stratification.

7.3 Vaccine Development

  • M72/AS01E Vaccine: Phase IIb trial shows 50% efficacy in preventing active TB (Lancet, 2019).
  • Host-Directed Therapies: Modulate immune response to improve outcomes.

7.4 Digital Adherence Technologies

  • Smart Pillboxes: Monitor medication intake.
  • Mobile Apps: Reminders and remote monitoring.

8. Latest Discoveries

  • Host Genetic Susceptibility: Recent GWAS studies identify novel loci associated with TB risk (Nature Genetics, 2023).
  • Non-invasive Biomarkers: Urine LAM tests for rapid diagnosis in HIV-positive patients.
  • Bacteriophage Therapy: Early-stage research on phages targeting MTB.
  • TB and COVID-19 Interaction: Studies show increased severity and mortality in co-infected patients.

Recent Study:

  • “Global Tuberculosis Report 2023” (WHO) highlights a surge in drug-resistant TB cases and the impact of COVID-19 on TB control efforts.
  • Nature Genetics (2023): “Genome-wide association study identifies genetic variants linked to TB susceptibility in diverse populations.” Link

9. Diagrams

TB Pathogenesis

TB Pathogenesis Diagram

TB Granuloma Structure

TB Granuloma

10. Surprising Facts

  1. Ancient Disease: TB DNA has been found in Egyptian mummies, indicating its presence over 4,000 years ago.
  2. Silent Epidemic: Over 1/4 of the world’s population is estimated to have latent TB infection.
  3. Drug Resistance: India and China account for nearly half of the world’s MDR-TB cases.

11. Further Reading

12. Summary Table

Aspect Details
Causative Agent Mycobacterium tuberculosis
Transmission Airborne droplets
Diagnosis TST, IGRA, PCR, Culture, X-ray
Treatment 4-drug regimen, DOT, MDR/XDR-TB management
Emerging Technologies AI, CRISPR, new vaccines, digital adherence tools
Latest Discoveries Host genetics, biomarkers, phage therapy, COVID-19

13. Key Takeaways

  • TB remains a major global health challenge.
  • Rapid diagnostics, AI, and vaccine innovation are transforming TB control.
  • Drug resistance and latent infection are critical hurdles.
  • Ongoing research is reshaping our understanding of host-pathogen interactions.

End of Study Notes