Tuberculosis: Etiology, Diagnosis, and Management

Latent TB Infection (LTBI) vs. Active TB Disease

It is clinically vital to distinguish between these two states:

Risk Factors for Progression

The risk of LTBI progressing to active disease is significantly influenced by the patient's immune status:

• HIV infection: Increases lifetime risk to approximately 10% per year.
• Immunosuppressants: Use of TNF-$\alpha$ antagonists (e.g., infliximab, etanercept, adalimumab), long-term high-dose corticosteroids, or organ transplants.
• Other factors: Diabetes mellitus, extreme age (elderly or children), alcohol abuse, and crowded living conditions.

Diagnostic Testing

Detecting LTBI

1. Tuberculin Skin Test (TST/Mantoux): Involves an intradermal injection of purified protein derivative (PPD). The test measures delayed-type hypersensitivity via induration (not redness) after 48–72 hours.
   • Interpretation: Results are based on risk factors. For example, $\ge 5\text{ mm}$ is positive for HIV+ or immunosuppressed individuals, while $\ge 15\text{ mm}$ is required for low-risk individuals.
   • False Results: False negatives can occur due to recent infection, improper administration, or cutaneous anergy (weakened immunity). False positives may occur in those previously vaccinated with the BCG vaccine.
2. Interferon-$\gamma$-release assay (IGRA): A blood test (e.g., QuantiFERON-TB Gold Plus) that measures interferon-$\gamma$ release.
   • Advantages: Requires a single visit and is not affected by the BCG vaccine.

Detecting Active TB

• AFB Microscopy (Smear): Provides rapid results (within 1 day) by looking for acid-fast bacilli in sputum. However, it may yield false negatives if the bacterial load is below $5,000\text{--}10,000$ bacilli/mL.
• Culture: The "gold standard" for species identification and drug susceptibility testing. Due to the slow growth of M. tuberculosis, results can take approximately 14 days.
• Nucleic Acid Amplification (NAA): Used to rapidly detect M. tuberculosis and identify rifampin resistance.
• Radiography: A chest X-ray (CXR) is used to look for signs of disease. While calcified granulomas suggest prior infection, cavitary lesions are indicative of advanced active disease.

Drug Resistance Patterns

As resistance develops, treatment becomes more complex, requiring specialized regimens:

• MDR-TB (Multidrug-resistant): Resistant to at least isoniazid and rifampin.
• Pre-XDR-TB (Pre-extensively drug-resistant): Resistant to isoniazid, rifampin, and either a fluoroquinolone or an aminoglycoside.
• XDR-TB (Extensively drug-resistant): Resistant to isoniazid, rifampin, a fluoroquinolone, and an aminoglycoside (or bedaquiline/linezolid).

Clinical Presentation and Management

Pulmonary TB Presentation

The most common presentation is pulmonary TB, characterized by:

• Persistent cough ($\ge 3$ weeks)
• Hemoptysis (coughing up blood)
• Pleuritic chest pain and dyspnea
• Systemic symptoms: Fever, weight loss, and night sweats

Nonpharmacotherapy and Isolation

Patients with suspected or confirmed pulmonary TB must be placed in respiratory isolation under airborne precautions. This requires:

• A negative pressure room.
• Healthcare workers using N95 respirators or Powered Air Purifying Respirators (PAPR).

Isolation can typically be lifted once TB is ruled out, after three consecutive negative morning sputum smears, or after 2 weeks of effective treatment accompanied by clinical improvement.

[!TIP] Exam Tip: The "E" Rule To remember the side effect associated with Ethambutol, remember that both start with "E": Ethambutol can cause Eye issues (decreased visual acuity and red-green color discrimination).