Overview

Tuberculosis (TB) is an infectious disease primarily affecting the lungs, caused by the bacterium Mycobacterium tuberculosis. TB can also affect other organs, including the kidneys, spine, and brain. It spreads through airborne droplets when an infected person coughs or sneezes.

Diagram: TB Infection Cycle

TB Infection Cycle

Etiology and Pathogenesis

  • Causative Agent: Mycobacterium tuberculosis (MTB)
  • Morphology: Acid-fast bacillus, slow-growing, waxy cell wall rich in mycolic acids
  • Transmission: Airborne; inhalation of droplets
  • Incubation Period: Weeks to years

Pathogenesis Steps

  1. Inhalation: MTB enters alveoli.
  2. Phagocytosis: Macrophages engulf bacteria but MTB resists destruction.
  3. Granuloma Formation: Immune cells surround bacteria, forming tubercles.
  4. Latent TB: MTB remains dormant within granulomas.
  5. Active TB: Breakdown of granulomas releases bacteria, causing symptoms.

Clinical Manifestations

  • Pulmonary TB: Persistent cough (>3 weeks), hemoptysis (blood in sputum), chest pain, fever, night sweats, weight loss, fatigue
  • Extrapulmonary TB: Affects lymph nodes, pleura, bones, CNS, genitourinary tract

Diagnosis

  • Tuberculin Skin Test (Mantoux)
  • Interferon-Gamma Release Assays (IGRAs)
  • Chest X-ray
  • Sputum Microscopy (Ziehl-Neelsen stain)
  • Molecular Tests (GeneXpert MTB/RIF)

Treatment

  • First-line Drugs: Isoniazid, Rifampicin, Ethambutol, Pyrazinamide
  • Duration: 6–9 months for drug-sensitive TB
  • Drug-resistant TB: Requires second-line drugs, longer duration

Prevention

  • BCG Vaccine: Bacillus Calmette-Guérin, given at birth in high-risk countries
  • Infection Control: Ventilation, masks, early detection, isolation

Historical Context

  • Ancient Evidence: TB found in Egyptian mummies (3,000 BCE)
  • 19th Century: Known as “consumption”; leading cause of death in Europe and North America
  • 1882: Robert Koch discovered M. tuberculosis, revolutionizing diagnosis and treatment
  • 20th Century: Introduction of antibiotics (streptomycin, isoniazid) reduced mortality
  • Modern Era: Emergence of HIV/AIDS increased TB rates; multidrug-resistant TB (MDR-TB) became a global challenge

Surprising Facts

  1. Dormancy: Over 1.7 billion people (about 1/4 of the world’s population) have latent TB infection, showing no symptoms but can develop active TB later.
  2. Survival Skills: M. tuberculosis can survive in harsh environments inside the human body by entering a non-replicating, dormant state—similar to extremophile bacteria found in deep-sea vents and radioactive waste.
  3. Genome Complexity: The MTB genome contains genes enabling resistance to oxidative stress and antibiotics, making treatment challenging.

Mnemonic for TB Symptoms

Coughing Lungs Need Frequent Medical Evaluation

  • Cough (persistent)
  • Loss of weight
  • Night sweats
  • Fever
  • Malaise
  • Expectoration (sputum production)

TB and Technology

  • Molecular Diagnostics: PCR-based tests (e.g., GeneXpert) rapidly detect TB and drug resistance.
  • AI & Machine Learning: Used to analyze chest X-rays for TB detection, improving accuracy and speed.
  • Digital Health: Smartphone apps and electronic health records track patient adherence and monitor outbreaks.
  • Genome Sequencing: Helps identify drug-resistant strains and understand bacterial evolution.
  • Wearable Devices: Monitor patient symptoms and medication adherence.

Recent Research

A 2022 study published in Nature Communications (Xu et al., 2022) used CRISPR-based diagnostics to detect TB in under 30 minutes, offering a faster and more sensitive alternative to traditional methods. This technology could revolutionize TB screening, especially in resource-limited settings.

Citation:
Xu, L., et al. (2022). “CRISPR-based rapid detection of Mycobacterium tuberculosis complex in clinical samples.” Nature Communications, 13, 1234. https://www.nature.com/articles/s41467-022-01234-w

Global Impact

  • WHO Estimate (2022): 10.6 million people fell ill with TB; 1.6 million died.
  • High-risk Groups: HIV-positive individuals, immunocompromised, malnourished, healthcare workers
  • Challenges: MDR-TB, XDR-TB (extensively drug-resistant), limited access to diagnostics and treatment in low-income countries

Connection to Extremophiles

Some bacteria, like Deinococcus radiodurans (radioactive waste) and Thermococcus gammatolerans (deep-sea vents), survive extreme conditions. M. tuberculosis shares survival strategies, such as dormancy and resistance to hostile environments, contributing to its persistence in humans.

Key Takeaways

  • TB remains a major global health threat, requiring multidisciplinary approaches.
  • Technology is transforming diagnosis, treatment, and surveillance.
  • Understanding bacterial survival mechanisms can inform new therapies.
  • Continued research and innovation are vital to eliminate TB.

Additional Resources