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Updated: Aug 14 2020

Mycobacterium Tuberculosis

  • Snapshot
    • A 33-year-old man presents to his primary care physician for a cough and generalized malaise. His symptoms are associated with 2 episodes of mild hemoptysis and night sweats. He denies any sick contacts or recent travels; however, he states he was released from prison 4 months ago. Physical examination is unremarkable. A chest radiograph is obtained, which demonstrates pulmonary infiltrates and cavitations in the upper lobe.
  • Introduction
    • Classification
      • acid-fast, rod-shaped, obligate aerobic, intracellular bacteria
    • Epidemiology
      • risk factors
        • traveling to endemic areas (e.g., Angola and the Central African Republic)
        • close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals)
        • immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes)
    • Transmission
      • airborne spread of droplet nuclei from patients with infectious tuberculosis (TB)
    • Microbiology
      • acid-fast on Ziehl-Neelsen staining
      • immune system itself causes damage
        • TB contains no endotoxins or exotoxins
      • cord factor
        • inhibits leukocyte migration
        • causes characteristic serpentine growth pattern
        • induces TNF-α release
      • tuberculin
        • triggers cell-mediated immunity → caseation and granulomas
        • triggers delayed hypersensitivity reaction
        • a surface protein
      • sulfatides
        • prevent phagosome-lysosome fusion
    • Pathogenesis
      • the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person
        • alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues
        • more alveolar macrophages are recruited, leading to granuloma formation
          • granulomas are formed to "wall off" TB, where it lies dormant
      • secondary TB occurs when the patient's immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition)
        • macrophages' ability to maintain their barrier decreases, facilitating possible dissemination
        • TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension
  • Presentation
    • TB can lead to pulmonary and extrapulmonary manifestations
      • lymph nodes (tuberculous lymphadenitis)
      • pleura
      • genitourinary
      • skeleton (can lead to Pott disease with spinal involvement)
      • meninges
      • gastrointestinal system
      • pericardium (tuberculous pericarditis)
    • Symptoms
      • typically asymptomatic in primary TB
      • cough
      • hemoptysis
      • fever
      • night sweats
      • malaise
    • Physical exam
      • weight loss
      • lymphadenopathy
      • dullness to percussion or decreased/absent breath sounds if there is a pleural effusion
      • back pain in spinal TB (Pott disease)
  • Imaging
    • Chest radiograph
      • indication
        • initial imaging study in the evaluation of TB
      • findings
        • middle or lower lung infiltrate (suggestive of primary infection)
        • upper lobe infiltrate (suggestive of latent TB reactivation)
          • apices have higher oxygen tension and reduced perfusion/lymph clearance compared to the base
        • cavitary lesions
        • Ghon complex (lobar or perihilar lymph node involvement)
  • Studies
    • Sputum acid-fast testing
      • demonstrates acid-fast bacilli
    • Real-time nucleic acid amplification
      • rapidly confirms TB and is considered the first-line diagnostic study
    • Tuberculin skin test (TST)
      • most widely used to screen for latent TB infection
      • a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced
        • the size of the induration is assessed after 48-72 hours
        • note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results
        • a false negative result can be seen in immunocompromised patients
      • interpretation (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-γ release assay
      • measures interferon levels released by the patient's immune system in response to TB antigens
        • the results are not affected by previous BCG vaccination
  • Differential
    • Lung cancer
      • differentiating factor
        • patients will not have positive TB studies
  • Treatment
    • Medical
      • rifampin, isoniazid, pyrazinamide, and ethambutol therapy
        • indication
          • first-line treatment for active pulmonary TB infection for 4 months
            • after 4 months, treatment involves isoniazid and rifampin
        • comments
          • isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring
            • can also cause hepatitis
          • ethambutol can cause optic neuropathy
          • mutations in RNA polymerase lead to rifampin resistance
      • isoniazid monotherapy
        • indication
          • prophylactic treatment for latent primary TB after active TB has been excluded
  • Complications
    • Pott disease
    • Miliary or disseminated TB
    • Meningitis
    • Pericarditis
    • Lymphadenitis
    • Adrenal insufficiency
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