Pulmonary Tuberculosis {TB}

Pulmonary tuberculosis (TB) is a contagious bacterial infection primarily affecting the lungs, caused by Mycobacterium tuberculosis. It spreads through airborne droplets when an infected person coughs, sneezes, or speaks.

Pulmonary TB is the most common form of TB and poses a significant public health challenge, especially in low- and middle-income countries.

Epidemiology

• Global burden: According to the World Health Organization (WHO), TB remains one of the top 10 causes of death worldwide. In 2021, an estimated 10.6 million people fell ill with TB, with about 1.6 million deaths.
• High-risk groups: Includes individuals with HIV, diabetes mellitus, close contacts of TB patients, healthcare workers, and those living in overcrowded or resource-limited settings.
• Drug-resistant TB: Multi-drug resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) present additional treatment challenges.

Pathophysiology

The pathogenesis of TB involves inhalation of M. tuberculosis bacilli, leading to a primary infection in the lungs. The course of the disease can be divided into:

1. Primary TB infection: Initial exposure to M. tuberculosis leads to a localized infection in the lungs. In immunocompetent individuals, the body’s immune response can contain the bacteria, resulting in latent TB infection (LTBI).
2. Latent TB infection (LTBI): The bacilli remain dormant, and the person is asymptomatic and non-infectious. Reactivation may occur if the immune system is compromised.
3. Active TB disease: Occurs when the immune system fails to contain the infection or when latent TB reactivates, causing clinical symptoms. Active pulmonary TB is characterized by progressive lung tissue destruction and cavitation.

Clinical Presentation

1. Symptoms:
   • Cough lasting ≥3 weeks: Often productive, initially dry but may progress to purulent or hemoptysis.
   • Fever: Low-grade, typically more pronounced in the evening.
   • Night sweats: Common in active TB.
   • Weight loss and anorexia: Indicative of chronic illness.
   • Chest pain: Pleuritic pain or discomfort.
2. Signs:
   • Rales or bronchial breath sounds over areas of lung involvement.
   • Lymphadenopathy, especially cervical nodes, in some cases.
   • Digital clubbing: Rarely seen but may occur in chronic cases.

Diagnostic Evaluation

The diagnosis of pulmonary TB involves clinical, radiological, microbiological, and immunological testing:

1. Clinical Evaluation:
   • Detailed history: Assess risk factors such as close contact with a known TB case, history of immunosuppression, or travel to endemic areas.
   • Physical examination: Evaluate for signs of active TB and other possible differential diagnoses.
2. Microbiological Testing:
   • Sputum smear microscopy: Ziehl-Neelsen staining to detect acid-fast bacilli (AFB). It is less sensitive than culture.
   • Sputum culture: Gold standard for TB diagnosis. Cultures on solid (Löwenstein-Jensen) or liquid media (Mycobacteria Growth Indicator Tube) can confirm M. tuberculosis.
   • Nucleic Acid Amplification Tests (NAATs): Rapid molecular tests like GeneXpert MTB/RIF detect M. tuberculosis DNA and rifampicin resistance.
   • Drug susceptibility testing (DST): Essential for detecting drug-resistant TB strains.
3. Radiological Studies:
   • Chest X-ray: Common findings include upper lobe infiltrates, cavitary lesions, and fibrotic changes. Miliary TB appears as numerous small nodules throughout the lungs.
   • CT scan of the chest: Provides more detail, especially in cases with atypical presentations.
4. Immunological Testing:
   • Tuberculin Skin Test (TST) or Mantoux test: Positive result suggests TB exposure, but not active disease.
   • Interferon-Gamma Release Assays (IGRAs): Blood tests (e.g., QuantiFERON-TB Gold) for detecting latent TB. They are not used for active TB diagnosis.

Differential Diagnosis

• Other chronic pulmonary infections: Fungal infections (e.g., histoplasmosis, coccidioidomycosis), non-tuberculous mycobacteria (NTM) infections.
• Lung cancer: Particularly if there is weight loss, hemoptysis, or cavitary lesions.
• Sarcoidosis: May mimic TB on imaging but lacks microbiological confirmation.
• Chronic obstructive pulmonary disease (COPD): In patients with long-standing cough.

Management

The treatment of pulmonary TB involves a multidrug regimen to prevent resistance and ensure the eradication of the bacilli. The standard treatment is divided into two phases:

1. Intensive Phase (2 months):
   • Medications: Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), and Ethambutol (EMB).
   • Dosages:
     • Isoniazid: 5 mg/kg (300 mg daily in adults).
     • Rifampicin: 10 mg/kg (600 mg daily in adults).
     • Pyrazinamide: 15-30 mg/kg (1,500-2,000 mg daily in adults).
     • Ethambutol: 15 mg/kg (800-1,200 mg daily in adults).
   • Monitoring: Evaluate for drug side effects (e.g., hepatotoxicity, optic neuritis from Ethambutol) and patient adherence.
2. Continuation Phase (4 months):
   • Medications: Isoniazid and Rifampicin.
   • Duration: 4 months for drug-sensitive TB; extended to 7 months if the patient had extensive pulmonary disease or did not include Pyrazinamide in the initial phase.
   • Dosages remain the same as in the intensive phase.

Treatment of Drug-Resistant TB

• MDR-TB (resistant to at least INH and RIF): Requires a longer treatment duration (18-24 months) with second-line drugs such as fluoroquinolones (e.g., levofloxacin, moxifloxacin) and injectable agents (e.g., amikacin, capreomycin).
• XDR-TB (resistant to INH, RIF, fluoroquinolones, and at least one injectable agent): Management is complex and requires specialized centers with newer drugs like bedaquiline and linezolid.

Supportive Care and Monitoring

• Nutritional support: Important for recovery, especially in patients with significant weight loss.
• Directly Observed Therapy (DOT): Recommended to improve adherence and treatment outcomes.
• Monitoring for adverse drug reactions: Monthly clinical reviews and liver function tests.

Complications

• Hemoptysis: May occur due to cavitary lesions or bronchial artery erosion.
• Bronchiectasis: Can result from chronic lung damage.
• Chronic pulmonary aspergillosis: A fungal infection that may occur in residual lung cavities.
• Relapse: May occur due to incomplete treatment or drug resistance.

Prevention

• BCG vaccination: Administered at birth in countries with high TB prevalence to reduce severe childhood TB.
• Infection control: Includes isolating contagious patients and ensuring proper ventilation in healthcare settings.
• Contact tracing and treatment of LTBI: Reduces transmission.

Prognosis

• Treatment outcomes: With appropriate therapy, cure rates for drug-sensitive TB exceed 85%.
• Drug-resistant TB: Has a worse prognosis and requires prolonged treatment.