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Mycobacterium tuberculosis Disease

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  • Tuberculosis: Disease
    • Risk factors
      • Immunocompromised patients
      • Imprisonment
      • Immigrants (TB-endemic regions)
      • Healthcare workers
    • General Symptoms
      • weight loss
      • night sweats, fever
      • cough, hemoptysis
        • Obvious due to pulmonary infection
    • Primary tuberculosis
      • Inhaled droplets with bacteria phagocytosed by alveolar macrophages
        • TB replicates in alveolar macrophages
      • Granulomatous focal lesion (Ghon focus) in lower lung
        • Since inhaled droplets mainly end up in lower lung lobes
        • Ghon complex describes a focus + lymph node
          • Seen as focal lesion and hilar adenopathy on CXR
      • Primary TB may be eliminated, but bacteria often survives in large caseating granulomas
    • Latent tuberculosis
      • Containment of bacteria in granulomas with healing and calcification
        • asymptomatic, unremarkable CXR (hence “latent”)
      • Positive tuberculin/PPD skin test due to past exposure
      • Treat with INH
    • Secondary (reactivated) tuberculosis
      • Seen in immunocompromised individuals
        • e.g. Advanced age, HIV/AIDS, steroid use, biologic drugs
        • Failure of granulomas to contain bacterial spread
      • Granulomatous cavitary lesions in upper lung
        • Bacteria are predisposed to apex likely due to increased oxygen tension
        • Liquefactive and caseating necrosis causes cavitation
      • May disseminate (spread) into blood
        • Miliary tuberculosis
          • Widespread dissemination and seeding results in little focuses resembling millet seeds (hence, “miliary”)
        • Potts disease (vertebrae)
          • TB osteomyelitis caused by vertebral involvement
        • TB meningitis
        • Any organ may be involved
          • Pericarditis, mediastinitis, skin lesions, and hepatic lesions also seen
  • Diagnosis/Laboratory Tests for TB
    • Real-time nucleic acid amplification (PCR)
      • Rapid, first-line diagnostic study
    • PPD (tuberculin) test for M. Tuberculosis (high yield)
      • PPD stands for purified protein derivative
      • Test for prior exposure + cell-mediated immunity (type 4 HSR)
        • False negative result seen in immunocompromised patients
        • False positive in BCG (Bacille Calmette-Guerin) vaccination
      •  Interpretation of positive results 
        • ≥ 15 mm in patients with no risk factors
        • ≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison)
        • ≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients)
        • Positive tests require a chest radiograph
    • Interferon-gamma release assay (IGRA)
      • Measure amount of IFN-gamma released by T-cells when exposed to TB antigens
      • Test prior exposure and cell-mediated immunity
        • Preferred over PPD b/c BCG-vaccinated people are negative
  • Treatment 
    • RIPE is 1st line treatment for active pulmonary TB:
      • Rifampin
      • Isoniazid
        • Administered alone for latent TB
      • Pyrazinamide
      • Ethambutol