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TUBERCULOSIS

MICROBIOLOGY

Tuberculosis (TB) is caused by organisms of the Mycobacterium tuberculosis complex, which includes M. tuberculosis, the most common and important agent of human mycobacterial disease, and M. bovis, which (like several other mycobacterial species) is acquired via ingestion of unpasteurized milk. M. tuberculosis is a thin aerobic bacillus that is neutral on Gram’s staining but that, once stained, is acid-fast; i.e., it cannot be decolorized by acid alcohol because of the cell wall’s high content of mycolic acids and other lipids.

EPIDEMIOLOGY

An estimated 10.4 million new cases of TB occurred worldwide in 2016, with ∼1.7 million TB-related deaths—almost entirely in low-income countries. Globally, TB rates are stable or falling.

  • In the United States, TB primarily affects HIV-infected adults, immigrants, the elderly, and disadvantaged/marginalized populations.

  • Isolates of M. tuberculosis that are multidrug-resistant (MDR; resistant to at least isoniazid and rifampin) and extensively drug-resistant (XDR; resistant to isoniazid, rifampin, and fluoroquinolones and to amikacin, kanamycin, or capreomycin) are increasing in frequency; ∼500,000 cases of MDR-TB may have emerged in 2016, of which ∼9.5% were probably XDR.

  • Disease from a pt with pulmonary TB is spread by droplet nuclei that are aerosolized by coughing, sneezing, or speaking.

    • – Droplets <5–10 µm in diameter may be suspended in air for several hours.

    • – Transmission is determined by the intimacy and duration of contact with a pt with TB, the degree of infectiousness of the pt, and the shared environment.

    • – Pts with cavitary or laryngeal disease are most infectious, with as many as 105–107 acid-fast bacilli (AFB)/mL of sputum.

  • Risk factors for development of active disease after M. tuberculosis infection include recent acquisition (i.e., within the preceding 18 months), comorbidity (e.g., HIV disease, diabetes, silicosis, immunosuppression, gastrectomy), malnutrition, tobacco smoking, and presence of fibrotic lesions.

PATHOGENESIS

AFB that reach alveoli are ingested by macrophages. The bacilli impair phagosome maturation, multiply, lyse the macrophages, and spread to regional lymph nodes, from which they may disseminate throughout the body. These initial stages of infection are generally asymptomatic and induce cellular and humoral immunity.

  • About 2–4 weeks after infection, a tissue-damaging response resulting from delayed-type hypersensitivity (the basis for tuberculin skin testing [TST]) destroys nonactivated macrophages that contain multiplying bacilli, and a macrophage-activating response activates cells capable of killing AFB. A granuloma forms at the site of the primary lesion and at sites of dissemination. The lesions can then either heal by fibrosis or undergo further evolution. Despite “healing,” viable bacilli can remain dormant within macrophages or in necrotic material for years.

  • Cell-mediated immunity confers partial protection against TB. Cytokines secreted by alveolar macrophages contribute to disease manifestations, granuloma formation, and mycobacterial killing.

CLINICAL MANIFESTATIONS

TB is classified as pulmonary, extrapulmonary, or both. Extrapulmonary TB may occur in 10–40% of pts, ...

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