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Latent Tuberculosis Testing Guidelines

There are two reasons to screen for tuberculosis:

  1. To detect active disease and cure it to stop transmission
  2. To find latent disease and treat it to prevent progression to active disease

In the United States, the greater focus is to find individuals with latent infection. Interferon-gamma release assays (IGRA) have become the preferred method for detecting latent disease. IGRA are in vitro T-cell–based assays that measure interferon gamma release by sensitized T cells in response to highly specific M. tuberculosis antigens.

Four conditions need to be met to justify primary use of an IGRA:

  1. A person age five or older who is likely to be infected with 
  2. A low or intermediate risk of disease progression
  3. A decision that testing for latent infection is warranted
  4. A person who has received BCG vaccination or is unlikely to return to have his or her tuberculin skin test read.

IGRAs are much better in detecting latent tuberculosis than TST in persons who have received BCG (bacillus Calmette-Guérin) vaccination because a positive TST is not meaningful. Most countries outside the U.S. administer BCG vaccination routinely. Persons who are not likely to return to have a TST read include undocumented immigrants, homeless persons, prisoners released before their TST is read. If even one of these conditions is not met, the tuberculin skin test, or TST, could be used. TST is much less expensive than IGRA. At this time, TST is also preferred in children under age five.

Testing is warranted in those who have had a known exposure to a person infected with M. tuberculosis, those entering the U.S. from an area with a high prevalence of TB, HIV-infected patients, and those who are immunocompromised from other conditions, such as chronic renal failure or intravenous drug use. Prisoners could also qualify for testing. There is an active program to test some who go through the formal process to immigrate to the U.S., including refugees. In this program IGRA is used because most come from countries where BCG vaccination is administered.

Many health care institutions require staff to be screened for latent M. tuberculosis infection, even though many employees are in a low-risk group. Typically the tuberculin skin test is performed annually in this population. Studies have shown that in this very low-risk population in the U.S., serial testing could lead to false-positive results. Conversion to a positive test occurs most commonly with IGRA.

The incidence of active tuberculosis in the U.S. is low. Diagnosing active tuberculosis is entirely different from diagnosing latent infection. Diagnosis requires a culture for M. tuberculosis and in some cases a nucleic acid amplification test. IGRA or TST can be performed, but they do not make the diagnosis. If a patient has a positive TST or IGRA, the clinician has to rule out active disease. It is crucial to rule out active disease before initiation of treatment because the most popular choice for latent infection is a one-drug regimen, which is not recommended for active tuberculosis. The new guideline recommends that nucleic acid amplification tests (NAATs) be used to more rapidly identify M. tuberculosis in respiratory specimens. Commercially available NAATs include the Hologic Amplified Mycobacteria Tuberculosis Direct test and the Cepheid Xpert MTB/RIF test. The Cepheid test detects the presence of M. tuberculosis and rifampin resistance mutations in two hours.


Lewinsohn DM, et al. Clin Infect Dis. 2017;64[2]:e1–e33

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