Pathogenesis

Humans are the only reservoir for M. tuberculosis. Other than rare cases of ingestion, sexual transmission, or direct cutaneous inoculation, the vast majority of TB transmission occurs by inhalation of infectious respiratory droplet nuclei. Prolonged contact in a relatively contained area is necessary for transmission, and transmission in the outdoors or via fomites is rare.

The risk of infection from close contact with smear-positive sputum varies from 30% to 80% (3,4). The risk is less if the sputum is smear negative and culture positive; nonetheless, one study reported a rate of 17% for this risk (5). HIV coinfected patients can easily transmit the disease, even with negative chest X rays. In patients who are smear positive, infectiousness readily diminishes after initiation of appropriate chemotherapy. In 2005, the Centers for Disease Control and Prevention issued revised criteria for removal of patients from respiratory isolation (2) that were in line with prior stringent criteria from 1990 (6) and 1994 (7,8). According to those criteria, after initiation (2) of anti-TB therapy, three consecutive negative sputum smears (8 to 24 hours apart, with at least one an early-morning specimen) are required for the safe removal of the patient from isolation.

Within 2 to 12 weeks after inoculation of the lungs, the immune response controls the local infection, immunity develops, and the skin test becomes positive. Latency is established [latent TB infection (LTBI)] and the patient is asymptomatic and noninfectious. Local infection and infection to the draining lymphatics can be seen on chest X ray; this is known as the Ranke complex or primary complex (Ghon focus and draining lymphatics and hilar lymph nodes). Hematogenous dissemination is rare during primary infection.

Only 3% to 4% of persons will develop the disease during the first year after the infection. Infants and older persons are at greatest risk. In non-HIV-infected individuals, the risk of reactivation is 5% to 15% overall. In HIV-infected patients, the risk is dramatically higher by 7% to 10% per year.

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