Interferon-Gamma Release Assays for Detecting Mycobacterium Tuberculosis Infection

Advantages of IGRAs Over TST

The Centers for Disease Control and Prevention recommends the QuantiFERON-TB Gold (QFT-G) test as an alternative to tuberculin skin testing (TST) for detecting Mycobacterium tuberculosis infection, due to its higher specificity, single patient visit requirement, and lack of interference from prior BCG vaccination 1, 2
IGRAs such as QFT-G measure the release of interferon-gamma in blood samples after stimulation with M. tuberculosis-specific antigens, providing results within 24 hours without requiring a follow-up visit 1
QFT-G eliminates reader bias and errors associated with TST placement and reading, and does not trigger an anamnestic response (boosting) 1

The QuantiFERON-TB Gold In-Tube (QFT-GIT) is an FDA-approved blood test that uses peptides representing ESAT-6, CFP-10, and TB7-7 as TB-specific antigens 3
T-SPOT.TB is another commercially available IGRA that enumerates cells releasing IFN-γ after stimulation with similar antigens, available in Europe and mentioned in US guidelines 4, 5

Immunocompromised patients, such as those with chronic inflammatory diseases on immunosuppressive therapy, may benefit from IGRAs due to their higher sensitivity and specificity compared to TST 5
Dialysis patients often have high rates of anergy with TST, making IGRAs a more reliable option for TB screening 4
Patients who may have difficulty returning for TST reading after 48-72 hours can benefit from the convenience of IGRAs, which provide results within 24 hours 1

Blood specimens for IGRAs must be processed within 12 hours after collection, and laboratory experience with the assay may be limited in some settings 6
Test reproducibility is lower when measured IFN-γ levels are near the cut-off point, and substantial amounts of IFN-γ in the nil sample can invalidate results 1, 6
IGRAs may be more expensive than TST, which can be a consideration in resource-limited settings 5

QFT-G requires phlebotomy and proper handling of blood specimens, but results can be available in less than 24 hours after testing 1, 2
IGRAs show moderate concordance with TST, with kappa values ranging from 0.33 to 0.60 in various studies 1

For international travelers returning from TB-endemic areas, either TST or IGRA can be used for screening, according to guidelines from relevant health organizations 7