An interferon-gamma release assay (IGRA) is a diagnostic tool for indicating a latent tuberculosis infection (LTBI). IGRAs are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis if the latter is present.
Active vs latent tuberculosis IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used as a sole method for diagnosis of active TB, which is a microbiological diagnosis. A positive IGRA result may not necessarily indicate TB infection, but can also be caused by infection with non-tuberculous mycobacteria. A negative IGRA does not rule out active TB disease; a number of studies have shown that up to a quarter of patients with active TB have negative IGRA results.
BCG status 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.
Commercial IGRA test Quantiferon, also known as QFT, is the registered trademark of an interferon gamma release assay (IGRA) for tuberculosis diagnosis manufactured by QIAGEN. The QFT-GIT assay is an ELISA-based, whole-blood test that uses peptides from three TB antigens (ESAT-6, CFP-10, and TB7.7) in an in-tube format. The result is reported as quantification of IFN-gamma in international units (IU) per mL. An individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control).
Mantoux vs IGRA test Since IGRAs are more costly and technically complex to do than the Mantoux test, in their 2011 policy statement, the WHO did not recommend replacing the Mantoux test by IGRAs as a public health intervention in low- and middle-income countries.
Quantiferon-TB (QFT) Quantiferon-TB Gold In-Tube (QFT-GIT), the third generation test, has replaced Quantiferon-TB (QFT) and Quantiferon-Gold, which are no longer marketed. According to the U.S. Centers for Disease Control, in 2001, the Quantiferon-TB test (QFT) was approved by the Food and Drug Administration (FDA) as an aid for detecting latent Mycobacterium tuberculosis infection. This test is an in vitro diagnostic aid that measures a component of cell-mediated immune reactivity to M. tuberculosis. The test is based on the quantification of interferon-gamma (IFN-γ) released from sensitized lymphocytes in whole blood incubated overnight with purified protein derivative (PPD) from M. tuberculosis and control antigens. Tuberculin skin testing (TST) has been used for years as an aid in diagnosing latent tuberculosis infection (LTBI) and includes measurement of the delayed type hypersensitivity response 48–72 hours after intradermal injection of PPD. TST and QFT do not measure the same components of the immunologic response and are not interchangeable. Assessment of the accuracy of these tests is limited by lack of a standard for confirming LTBI. As a diagnostic test, QFT:
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