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Interferon-gamma release assays for diagnosis of latent tuberculosis infection

Dick Menzies, MD, MSc
Section Editor
C Fordham von Reyn, MD
Deputy Editor
Elinor L Baron, MD, DTMH


The development of interferon-gamma release assays (IGRAs) is an important advance in the diagnosis of latent tuberculosis infection (LTBI). IGRAs are in vitro blood tests of cell-mediated immune response; they measure T cell release of interferon (IFN)-gamma following stimulation by antigens unique to Mycobacterium tuberculosis [1].

The goal of testing for LTBI is to identify individuals who are at increased risk for the development of tuberculosis (TB) and therefore who would benefit from treatment of latent TB infection. Only those who would benefit from treatment should be tested, so a decision to test presupposes a decision to treat if the test is positive.

A large number of studies have evaluated IGRAs, and these have been summarized in systematic reviews and guidelines [2-14]. Issues related to the assays and their use will be reviewed here. Other issues related to diagnosis of LTBI are discussed in detail separately. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-infected patients".)


Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI) [15]. They are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis. IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease and should not be used for diagnosis of active TB, which is a microbiological diagnosis. A positive IGRA result may not necessarily indicate active TB, and a negative IGRA result may not rule out active TB [13,16]. (See "Diagnosis of pulmonary tuberculosis in HIV-uninfected adults".)

Because IGRAs are not affected by Bacille Calmette-Guérin (BCG) vaccination status, IGRAs are useful for evaluation of LTBI in BCG-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple (booster) BCG vaccinations are given. In contrast, the specificity of tuberculin skin test (TST) varies depending on timing of BCG and whether repeated (booster) vaccinations are given. A World Atlas of BCG Policies and Practices has been compiled to help clinicians and public health practitioners review variations in BCG policies and their impact on TST and to determine the populations for which IGRAs may be more specific than the TST [17]. Further, although based on limited evidence, IGRAs appear to be unaffected by most infections with environmental nontuberculous mycobacteria (NTM), which can cause false-positive TSTs [18]. In addition, limited data suggest that IGRA results are not affected by intravesical BCG for bladder cancer [19].

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Literature review current through: Oct 2017. | This topic last updated: Jan 25, 2017.
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