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U.S. Department of Health and Human Services


Core Curriculum on Tuberculosis, 2000

Chapter 2
Transmission and Pathogenesis


When droplet nuclei are inhaled, most of the larger particles become lodged in the upper respiratory tract, where infection is unlikely to develop. However, smaller droplet nuclei containing the tubercle bacilli may reach the alveoli, where infection begins.

The tubercle bacilli that reach the alveoli are ingested by alveolar macrophages; the majority of these bacilli are destroyed or inhibited. A small number multiply intracellularly and are released when the macrophages die. These bacilli can spread through the lymphatic channels to regional lymph nodes and then through the bloodstream to more distant tissues and organs, including areas in which TB disease is most likely to develop: the apices of the lungs, the kidneys, the brain, and bone. Extracellular bacilli attract macrophages from the bloodstream. The immune response kills most of the bacilli, leading to the formation of a granuloma. At this point the person has TB infection, which can be detected by using the tuberculin skin test. It may take 2-10 weeks for the infected person to develop a positive reaction to the tuberculin skin test. Immune responses soon develop to kill the bacilli. Within 2 to 10 weeks after infection, the immune system is usually able to halt the multiplication of the tubercle bacilli, preventing further spread.

Persons who are infected with M. tuberculosis, but who do not have TB disease cannot spread the infection to other people. TB infection in a person who does not have TB disease is not considered a case of TB and is often referred to as latent TB infection (LTBI).

In some people, TB bacilli overcome the defenses of the immune system and begin to multiply, resulting in the progression from TB infection to TB disease. This process may occur soon after or many years after infection. In the United States, unless they are treated, approximately 5% of persons who have been infected with M. tuberculosis will develop TB disease in the first year or two after infection and another 5% will develop disease sometime later in life. Recent infection (within the past 2 years) with M. tuberculosis is therefore an important risk factor for progression to TB disease. In all, in approximately 10% of persons with normal immune systems who are infected with M. tuberculosis, TB disease will develop at some point.

Some medical conditions increase the risk that TB infection will progress to disease. Some studies suggest that the risk may be approximately 3 times greater (as with diabetes) 6,7 to more than 100 times greater (as with HIV infection)  6, 7, 8 for persons who have these conditions than for those who do not. HIV infection is the strongest known risk factor for development of TB disease in persons with LTBI. Compared with immunocompetent persons who are infected with M. tuberculosis, infected persons who are immunosuppressed are at considerably greater risk of developing TB disease. For example, studies suggest that the risk of developing TB is 7% to 10% each year for persons who are infected with both M. tuberculosis and HIV, 8,9 whereas it is 10% over a lifetime for persons infected only with M. tuberculosis.

Conditions that increase the risk of progression to TB disease include:

  • HIV infection

  • Substance abuse (especially drug injection)

  • Recent infection with M. tuberculosis (within the past 2 years)

  • Chest radiograph findings suggestive of previous TB (in a person who received inadequate or no treatment)

  • Diabetes mellitus

  • Silicosis

  • Prolonged corticosteroid therapy

  • Other immunosuppressive therapy

  • Cancer of the head and neck

  • Hematologic and reticuloendothelial diseases (e.g., leukemia and Hodgkin's disease)

  • End-stage renal disease

  • Intestinal bypass or gastrectomy

  • Chronic malabsorption syndromes

  • Low body weight (10% or more below the ideal)

TB disease most commonly affects the lungs; 73% of TB cases are exclusively pulmonary. 10 Patients with pulmonary TB usually have a cough and an abnormal chest radiograph, and are likely to be infectious.

However, TB is a systemic disease and may also commonly occur in the following ways: as a pleural effusion; in the central nervous, lymphatic, or genitourinary systems; in the bones and joints; or as disseminated disease (miliary TB). More rarely, TB can occur in other body sites; for example, the breast, skin, or peritoneum. Extrapulmonary TB is more common in immunosuppressed persons and in young children; lymphatic TB and miliary disease are particularly common in immunosuppressed persons. Extrapulmonary TB is often accompanied by pulmonary TB.


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination -

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