M. tuberculosis is transmitted from person to person by respiratory aerosols produced by coughing. The source of the organism is a cavity in the lung that has eroded into a bronchus. The portal of entry is the respiratory tract, and the initial site of infection is the lung. In tissue, it resides chiefly within reticuloendothelial cells (e.g., macrophages). Macrophages kill most, but not all, of the infecting organisms. The ones that survive can continue to infect other adjacent cells or can disseminate to other organs.
Humans are the natural reservoir of M. tuberculosis. Although some animals, such as cattle, can be infected, they are not the main reservoir for human infection. Most transmission occurs by aerosols generated by the coughing of “smear positive” people (i.e., those whose sputum contains detectable bacilli in the acid-fast stain). However, about 20% of people are infected by aerosols produced by the coughing of “smear negative” people.
In the United States, tuberculosis is almost exclusively a human disease. In developing countries, Mycobacterium bovis also causes tuberculosis in humans. M. bovis is found in cow’s milk, which, unless pasteurized, can cause gastrointestinal tuberculosis in humans.
The disease tuberculosis occurs in only a small number of infected individuals. In the United States, most cases of tuberculosis are associated with reactivation in elderly, malnourished men. The risk of infection and disease is highest among socio economically disadvantaged people, who have poor housing and poor nutrition. These factors, rather than genetic ones, probably account for the high rate of infection among Native Americans, African Americans, and Native Alaskans.
In the United States, there are approximately 15 million people with latent tuberculosis and 10,000 cases of active disease. Most cases of active disease in the United States are caused by reactivation of latent infection. The risk factors for infection and reactivation (progression) to disease are listed in Table 1.

Table1. Risk Factors for Infection and Reactivation