Overview

  • Tuberculosis (TB): Infectious disease caused primarily by Mycobacterium tuberculosis.
  • Transmission: Airborne, via droplets from coughs/sneezes.
  • Affected Organs: Primarily lungs (pulmonary TB), but can affect other organs (extrapulmonary TB).
  • Global Impact: One of the top 10 causes of death worldwide; significant public health challenge.

History of Tuberculosis

Ancient Evidence

  • Prehistoric Signs: Skeletal evidence of TB found in Neolithic remains (~7000 BC).
  • Egyptian Mummies: TB-like lesions observed in mummies (3000–2400 BC).
  • Hippocrates (400 BC): Described “phthisis,” likely TB.

18th–19th Century

  • “White Plague”: TB was rampant in Europe and North America; responsible for up to 25% of deaths.
  • Sanatorium Movement: Patients isolated for rest and fresh air; limited effectiveness.

Discovery of the Pathogen

  • Robert Koch (1882): Identified Mycobacterium tuberculosis as the causative agent using advanced staining techniques.
  • Koch’s Postulates: Established criteria for linking pathogens to diseases; pivotal for TB research.

Early Treatments

  • Collapse Therapy (1930s): Artificial pneumothorax to rest the lung.
  • Surgical Interventions: Resection of infected tissue.

Key Experiments

Koch’s Experiment (1882)

  • Objective: Identify causative agent of TB.
  • Method: Used aniline dyes to stain bacteria in infected tissues.
  • Result: Isolated M. tuberculosis, confirmed its role in TB by infecting animals.

Streptomycin Discovery (1943)

  • Selman Waksman: Isolated streptomycin from soil bacteria.
  • First Effective Antibiotic: Marked the beginning of antibiotic therapy for TB.

BCG Vaccine Development (1921)

  • Calmette & Guérin: Developed Bacillus Calmette–Guérin (BCG) vaccine from attenuated M. bovis.
  • Global Use: Still used today, especially in countries with high TB prevalence.

Modern Molecular Diagnostics

  • PCR-based Assays: Detect M. tuberculosis DNA in patient samples.
  • GeneXpert System: Rapid, automated detection of TB and rifampicin resistance.

Modern Applications

Diagnostics

  • Sputum Smear Microscopy: Traditional method; limited sensitivity.
  • Culture Methods: Gold standard; slow (weeks for results).
  • Molecular Testing: GeneXpert MTB/RIF, Truenat; rapid, sensitive, detects drug resistance.

Treatment

  • First-Line Drugs: Isoniazid, rifampicin, pyrazinamide, ethambutol (6-month regimen).
  • Drug-Resistant TB: Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) require longer, more toxic regimens (e.g., bedaquiline, linezolid).

Vaccination

  • BCG Vaccine: Prevents severe forms of TB in children; variable efficacy in adults.
  • New Vaccine Candidates: M72/AS01E, VPM1002 under clinical trials.

Public Health Initiatives

  • Directly Observed Therapy (DOT): Ensures patient adherence to treatment.
  • Contact Tracing & Screening: Identifies and manages latent TB infections.

Recent Research & News

  • 2022 Lancet Study: “Global burden of drug-resistant tuberculosis in 2020” (Lancet Infect Dis. 2022;22(4):483–494) highlighted rising MDR-TB cases and the need for new diagnostics and treatments.
  • WHO 2023 Report: Emphasized the impact of COVID-19 on TB detection and treatment, with millions of cases missed due to disrupted health services.
  • Novel Therapies: Research into host-directed therapies and shorter regimens (e.g., 4-month rifapentine-moxifloxacin regimen).

Future Directions

Improved Diagnostics

  • Point-of-Care Tests: Affordable, rapid, and accurate diagnostics for low-resource settings.
  • Biomarker Discovery: Use of host immune response markers for early detection.

Drug Development

  • New Antibiotics: Targeting persistent TB bacteria and overcoming resistance.
  • Host-Directed Therapies: Modulating immune response to improve outcomes.

Vaccine Innovation

  • Universal TB Vaccines: Focus on adult protection and prevention of latent TB reactivation.
  • mRNA-Based Vaccines: Inspired by COVID-19 vaccine technology; under investigation.

Digital Health

  • AI-Powered Screening: Automated chest X-ray analysis for TB detection.
  • Mobile Health (mHealth): Apps for patient monitoring and adherence.

Global Strategies

  • End TB Strategy: WHO aims to reduce TB incidence by 80% and deaths by 90% by 2030.
  • Integrated Care: Combining TB, HIV, and diabetes management.

Quiz Section

  1. Which bacterium causes tuberculosis?
  2. What year did Robert Koch identify the TB pathogen?
  3. Name one key advantage of the GeneXpert MTB/RIF test.
  4. What is the main limitation of the BCG vaccine in adults?
  5. Define MDR-TB and XDR-TB.
  6. List two future trends in TB management.
  7. What is the purpose of Directly Observed Therapy (DOT)?
  8. Name a recent TB vaccine candidate in clinical trials.
  9. How did COVID-19 impact TB detection globally?
  10. What is the WHO’s End TB Strategy goal for 2030?

Summary

Tuberculosis remains a major global health threat, with a complex history and evolving challenges. Advances in diagnostics, treatment, and vaccine development have improved outcomes, but drug resistance and variable vaccine efficacy persist as obstacles. Recent research emphasizes the need for shorter regimens, innovative diagnostics, and adult vaccines. Future directions include AI-powered screening, host-directed therapies, and integrated care strategies. Continued investment in research and global health initiatives is essential to achieve the goal of ending TB by 2030.