Primary Infection

Primary infection usually results from inhaling droplet nuclei that contain M. tubercu-losis.2,6,17 The progression to clinical disease depends on three factors: (a) the number of M. tuberculosis organisms inhaled (infecting dose), (b) the virulence of these organisms, and (c) the host's cell-mediated immune response.2,4,6,12,18,19 If pulmonary macrophages inhibit or kill the bacilli, the infection is aborted.18 If not, M. tuberculosis eventually spreads throughout the body through the bloodstream.2,6,18 M. tuberculosis most commonly infects the posterior apical region of the lungs, where conditions are most favorable for its survival.

T lymphocytes become activated over the course of 3 to 4 weeks, producing interferon^ (IFN-y) and other cytokines. These stimulate microbicidal macrophages to surround the tuberculous foci and form granulomas to prevent further extension.18 At this point, the infection is largely under control, and bacillary replication falls off dramatically. Any remaining mycobacteria are believed to reside primarily within granulomas or within macrophages that have avoided detection and lysis. Over 1

to 3 months, tissue hypersensitivity occurs, resulting in a positive tuberculin skin

test. ■ ■ Progressive primary disease occurs in roughly 5% of patients, espe cially children, the elderly, and immunocompromised patients.20,21 This presents as a progressive pneumonia and frequently spreads, leading to meningitis and other severe forms of TB, even before their skin tests become positive.20

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