Tuberculosis (TB) screening tests are not used as general population screens but are used to screen people who are at high risk for TB exposure, such as:

• People with diseases or conditions that weaken the immune system, such as HIV or AIDS, which makes them more vulnerable to a TB infection
• Those who are in confined living conditions such as homeless shelters, migrant farm camps, nursing homes, schools, and correctional facilities
• Healthcare workers and others whose occupations bring them in close contact with those who may have active TB
• Those who have been in close contact with someone who has an active case of TB
• People who have signs and symptoms consistent with active tuberculosis
• Those who come from or have lived for a period of time in a foreign country where TB may be more common
• Those who inject illegal drugs

TB screening tests are also used sometimes as part of a routine examination prior to starting school or a new job. Since mothers can pass TB to their unborn children, pregnant women are sometimes screened.

Either a tuberculin skin test (TST) or an interferon gamma release assay (IGRA) may be performed to screen for TB:

• The tuberculin skin test involves two steps: the injection of a small amount of purified protein derivative (PPD) solution under the first layer of skin of the forearm and an evaluation of the injection site conducted by a health practitioner at 48 and/or 72 hours to see if a local skin reaction has occurred.
• The IGRA test measures the release of a substance called gamma interferon by white blood cells in a sample of blood when the cells are exposed to specific TB antigens. The IGRA test is not performed by all laboratories. The test requires viable white blood cells, so the IGRA blood sample must be received and tested by a laboratory within a designated window of time.

Recommendations from the Centers for Disease Control and Prevention (CDC) list preferences for an IGRA test for people who are less likely to comply with returning to have their TST evaluated or when the person being tested has received the BCG (Bacille Calmette-Guérin) vaccine that might interfere with the interpretation of a TST. BCG is not used as a vaccine in the United States, but it is often routinely administered in countries with a higher incidence of TB and it is used in the U.S. as a treatment for some cancers.

The CDC lists a preference for the TST for testing children younger than 5 years of age and says that both tests might be useful when someone with a negative initial TST or IGRA test has an increased risk for TB infection and/or clinical suspicion of active tuberculosis exists. Sometimes the TST is given in a two-step process. If there is a risk that the first TST is a false-negative reaction, a second skin test is given so that the TST may stimulate the immune system, causing a positive or boosted reaction in the second test. This is typically performed for healthcare workers at the start of their employment.

TB screening tests may be ordered:

• On a yearly basis for those who are part of a high-risk group, either because they have a disease that weakens their immune system or because they work or live around others in high-risk groups
• Prior to a person joining an at-risk population, such as going to college or becoming a teacher or healthcare worker
• When someone has been in close contact with someone who has an active case of TB; this would be done a few weeks after a suspected exposure as it usually takes about 6 weeks after contact and initial infection before a positive result would be detected.
• When an individual has lived for an extended time in a country where TB is more common
• When a person has signs and symptoms of TB, such as a chronic cough that produces phlegm or sputum, sometimes with bloody streaks, fever, chills, night sweats, and unexplained weight loss

A TB skin test should not be done when a person has had a previous positive reaction. Once positive, a TST reaction will usually remain positive and the skin reaction to subsequent tuberculin skin tests may become increasingly severe.

A health practitioner will interpret a tuberculin skin test result by looking at the injection site on the person's forearm at 48 or 72 hours (in most cases). A positive result will form a red and swollen circle at the site of the injection. The size (diameter) of the swollen raised circle determines whether exposure to TB has occurred. The size that is considered positive varies with the health status and age of the individual. Even when infected, children, the elderly, and people who are severely immune compromised (such as those with AIDS) may have smaller, delayed, or even negative reactions to the TST.

A positive TST or IGRA test result means that the person is likely to have been exposed to TB. It may be due to a latent or active TB infection. If a health practitioner suspects that someone has active tuberculosis, other tests, such as chest X-rays and AFB laboratory testing, are used to confirm the diagnosis.

A negative result for either test means that it is likely that the person tested does not have a TB infection. However, it does not entirely rule out tuberculosis. It may mean that the person's immune system has not responded to the antigen in the test or that it is too early to detect exposure. It takes about 6 weeks after infection before a person demonstrates a positive reaction to TB screening tests. If suspicion of TB remains high and a health practitioner wants to confirm a negative or indeterminate result, he or she may repeat the same test or do either the TST or IGRA as an alternate follow-up test.

Occasionally, a person infected with or exposed to other Mycobacterium species, for example Mycobacterium kansasii, will give a false-positive TST or IGRA result for TB. Positive results must be followed up by other tests such as chest X-rays to look for signs of active TB disease. If active TB disease is suspected, AFB testing including smears and cultures and sensitivity testing, may be used to confirm the diagnosis and determine the drug susceptibility for the M. tuberculosis infecting the person.

Positive TST results are commonly seen in those who have received a BCG (Bacille Calmette-Guérin) vaccination. IGRA results are not affected by BCG.

A negative TST may cause mild itching or discomfort at the injection site. A person may not respond to a TB skin test (even with TB exposure) if the person has had a recent viral infection, a "live" vaccine (such as measles, mumps, chickenpox, influenza), or has overwhelming tuberculosis, another bacterial infection, or is taking immune suppressive drugs such as corticosteroids.

A person should generally wait 4-6 weeks to do a TB skin test after having had a vaccination with a live-virus vaccine.