Tuberculosis (Fierer)

Mode of transmission: aerosolized droplets from infected people. Transmission in a previously uninfected person leads to primary foci of TB in the lung (Ghon focus granuloma, or Ghon complex if accompanied by perihilar lymph node calcified granulomas) and other organs to which it has spread hematogenously; in 5% of cases, reactivation in first two years, and an addition 5% lifetime risk. Reactivation risk is higher in the young, the elderly, and the immunocompromised. In AIDS patients, reactivation risk is 10% per year!

TB is known as consumption due to weight loss; as in cancer, cachexia is caused by chronic hypersecretion of tumor necrosis factor.

Isoniazid led to drastic decline of TB incidence in the U.S., 1950s-present.

Mycobacterium tuberculosis is a slow growing, acid-fast, obligate aerobe (that nevertheless can survive anaerobically, if not grow, inside granulomas). Virulence factors include mycosides, cord factor (inhibit neutrophil chemotaxis, damages mitochondria and triggers TNF release), Wax D (actually an adjuvant to our immune response), and sulfatides (inhibit phagosome-lysosome fusion).

IFN-gamma, secreted by TH1 CD4 cells, is required for macrophages to kill intracellular TB. If you put patient on TNF inhibitors, you predispose to miliary TB. IL-12 is also important to prevent disseminated TB infection.

Diagnosis of TB: sputum stain (not sensitive and not specific), culture (slow, 4-6 weeks), nucleic acid methods (not sensitive but very specific), skin test (anergy can give false negative, BCG can give false positive); IFN-gamma test (gold standard).

Positive PPD: treat with INH (inhibits mycolic acid synthesis), 9 months; Rifampin, 4months. Other drugs: ethambutol (inhibits arabinogalactan synthesis); pyrazinamide.