10.05 Tuberculosis (TB)

Tuberculosis (TB) Overview & Causative Agents

Definition:

• Tuberculosis (TB) is an infectious disease primarily affecting the lungs but can disseminate to other parts of the body.

Causative Agents:

• Mycobacterium tuberculosis
• Mycobacterium bovis

Primary Site of Infection:

• Lungs: Most common site.
• Extrapulmonary Sites: Lymph nodes, bones, kidneys, and gastrointestinal tract.

Dormant Infection:

• Latent TB: Bacteria remain inactive for years without symptoms.
• Reactivation Triggers: Weak immune system due to factors like malnutrition, HIV/AIDS, diabetes, alcoholism.

Transmission of TB

1. Airborne Transmission (M. tuberculosis):

• Mechanism: Inhalation of airborne droplets expelled when an infected person coughs or sneezes.
• High-Risk Environments: Overcrowded housing, homelessness, settings with poor ventilation (e.g., prisons, shelters).

2. Foodborne Transmission (M. bovis):

• Mechanism: Consumption of undercooked meat or unpasteurized milk from infected cattle.
• Current Status: Rare in developed countries due to stringent pasteurization and animal testing protocols.

Risk Factors for TB Activation

• Immunocompromised States: HIV/AIDS, malnutrition, diabetes, alcoholism.
• Environmental Factors: Overcrowding, poor ventilation.
• Other Health Conditions: Chronic kidney disease, certain cancers, immunosuppressive therapies.

Note: TB is a leading cause of death among individuals with HIV/AIDS.

Clinical Features of TB

Diagnosis of TB

1. Sputum Sample Microscopy:
   • Acid-fast bacilli (AFB) staining (e.g., Ziehl-Neelsen stain).
2. Molecular Testing:
   • PCR-based tests for M. tuberculosis DNA.
3. Chest X-Ray:
   • Identifies lung abnormalities typical of TB.
4. Culture Methods:
   • Long-Term Culture: Up to 12 weeks for definitive diagnosis if other tests are inconclusive.

Treatment of TB

1. Drug Treatment:

• First-Line Drugs:
  • Isoniazid (INH)
  • Rifampicin (RIF)
  • Pyrazinamide (PZA)
  • Ethambutol (EMB)
• Combination Therapy:
  • Typically involves multiple drugs to prevent resistance.
• Duration:
  • 6–9 months due to the slow-growing nature of M. tuberculosis.
• DOTS (Directly Observed Treatment, Short Course):
  • Ensures adherence by having healthcare workers or designated individuals supervise medication intake.

2. Drug-Resistant TB:

• Multiple-Drug-Resistant TB (MDR-TB):
  • Resistant to at least isoniazid and rifampicin.
  • Requires longer treatment (up to 2 years) with second-line drugs.
• Extensively Drug-Resistant TB (XDR-TB):
  • Resistant to first-line drugs and at least one second-line drug.
  • Treatment is more complex, costly, and prolonged (over two years).
• 2017 Estimates:
  • 558,000 cases of rifampicin-resistant TB globally.
  • 82% of these are MDR-TB.
  • 8.5% are XDR-TB.

3. New Drugs:

• Bedaquiline:
  • Effective against MDR-TB.
  • Expensive and requires careful monitoring for side effects.

Prevention of TB

1. Vaccination:

• BCG Vaccine:
  • Derived from M. bovis.
  • Efficacy: 70–80% effective in preventing severe forms of TB in children.
  • Usage: Recommended in high-incidence countries; not routinely administered in low-incidence regions.

2. Cattle and Milk Safety:

• Cattle Testing:
  • Infected animals are identified and culled to prevent transmission.
• Milk Pasteurization:
  • Kills M. bovis bacteria, reducing the risk of foodborne TB.

3. Public Health Measures:

• Contact Tracing:
  • Identifies and screens individuals exposed to TB-infected persons.
• Improved Living Conditions:
  • Reduces overcrowding and enhances ventilation in housing, decreasing transmission risk.

Global TB Trends

1. Decline in Developed Countries:

• Achieved through the use of antibiotics, improved living conditions, and better nutrition before the introduction of the BCG vaccine in the 1950s.

2. Resurgence in Developing Regions and Urban Centers:

• Contributing Factors:
  • Emergence of drug-resistant TB strains.
  • HIV/AIDS pandemic compromising immune systems.
  • Poor housing and homelessness.
• High Prevalence Areas:
  • Regions with large migrant populations from high-incidence countries (e.g., certain parts of London).

Additional Key Points:

Pathogenesis of TB:

• Inhalation: M. tuberculosis enters the lungs and infects alveolar macrophages.
• Immune Response: Formation of granulomas to contain the bacteria.
• Latency: Bacteria can remain dormant within granulomas.
• Reactivation: Occurs when the immune system is compromised.

Immune Evasion:

• M. tuberculosis can survive within macrophages by inhibiting phagosome-lysosome fusion.
• The thick, waxy cell wall (mycolic acid) resists destruction and limits immune detection.

Public Health Strategies:

• Screening Programs: Regular screening in high-risk populations.
• Education: Raising awareness about TB transmission and prevention.
• Vaccination Policies: Implementing BCG vaccination in endemic regions.

Emerging Challenges:

• HIV Co-infection: Complicates TB control efforts.
• Globalization: Facilitates the spread of drug-resistant TB strains.
• Healthcare Access: Limited in low-resource settings, hindering effective TB management.

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