This is a prospective cohort study of persons tested for latent tuberculosis infection at either high risk for exposure to Mycobacterium tuberculosis or high risk for progression to tuberculosis disease. The study will assess the relative performance and cost of three diagnostic tests for latent tuberculosis infection (tuberculin skin test, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB) and will examine the rates of positive results among the cohort. This study will also determine the risk and rate of progression to active TB disease, overall and by the results of the three tests.

1. Study participants must be at high risk for latent tuberculosis infection or at high risk for progression to tuberculosis disease, including being a:

   • Close contact of a person with pulmonary tuberculosis who is part of a current contact investigation and the index/source case meets the following criteria:

   1. Culture-positive, OR
   2. Culture-negative and smear positive and nucleic acid amplification test-positive.

   Participants may be enrolled before the culture results for the index/source case are available. If the criteria described above are not met once results are available, the participant will be terminated from the study and any collected data will be immediately destroyed.

   A close contact is defined as spending 15 or more hours over a week's period in a shared airspace with a person with active pulmonary tuberculosis while that person was presumed to be infectious.

   • Foreign-born person from a high risk country.
   • Foreign-born person from a medium risk country who moved to the United States within the past 5 years.
   • Person who has spent at least 30 days in total in a high risk country within the last 5 years.
   • Person belonging to a population with a prevalence of latent tuberculosis infection ≥ 25% as demonstrated by local surveys. These populations will vary by site; examples include Mexican immigrants in San Diego, California or homeless drug users in Baltimore, Maryland.
   • HIV-positive person.

2. Study participants (or a parent/guardian, if applicable) must be willing and able to provide informed consent.

4.2 Subject Exclusion Criteria

Subjects meeting any of the exclusion criteria will be excluded from study enrollment.

1. People with known current active tuberculosis.
2. People with a previous anaphylactic reaction to tuberculin.
3. Persons currently being treated for latent tuberculosis infection.
4. Persons anticipating or scheduled to permanently leave the United States (e.g., tourists, visiting scholars, exchange students) in less than 2 years from the time of proposed study enrollment.
5. Foster children.

Individuals at high risk for latent tuberculosis infection or at high risk for progression to tuberculosis from health clinics, hospitals, or health departments at the 10 Tuberculosis Epidemiologic Studies Consortium sites within the United States: California Department of Public Health, Denver Health and Hospital Authority, Duke University, Emory University, Hawaii Department of Health, Maricopa County Department of Public Health, Maryland Department of Public Health, Public Health Seattle-King County, University of Florida Board of Trustees, and University of North Texas Health Science Center