3.4 Interferon-gamma release assays

IGRAs are in vitro blood tests that measure interferon-gamma released by circulating lymphocytes in whole blood during overnight incubation with exposure to M. tuberculosisspecific antigens (ELISA based) or the number of T-lymphocytes producing interferon-gamma (ELISPOT based). In 2011, WHO issued recommendations on the use of IGRAs for the diagnosis of TB infection, including the blood-based QIAGEN QuantiFERON-Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and Oxford Immunotec T-SPOT.TB (T-Spot) assays. The QFT-G and QFT-GIT were discontinued by the manufacturer. More recently, QIAGEN released an updated test, QuantiFERON-TB Gold Plus (QFT-Plus), which superseded the QFT-G and QFTGIT; also alternative blood-based IGRAs from other manufacturers have been marketed. To evaluate these technologies and determine whether one or more of them could be included under the existing WHO recommendations for IGRA testing, WHO convened a Technical Advisory Group on TB Diagnostics and Laboratory Strengthening. The group met virtually on 27–29 October 2021 and a subsequent WHO policy statement on the use of alternative IGRAs was issued subsequently (Web Annex).

The two new ELISA-based IGRA assays recommended by WHO for TB infection diagnosis are QFT-Plus and WANTAI TB-IGRA, while T-SPOT®.TB continues to be only ELISPOT-based IGRA that is recommended (8). In contrast with TST, all currently WHO-recommended IGRAs require a well-equipped laboratory and trained laboratory technicians for testing. Because the commercially available currently recommended IGRAs are based on the lymphocyte response to M. tuberculosis-specific antigens (ESAT-6 and CFP-10), results are not affected by prior BCG vaccination, making these tests more specific than TST. The genes that produce these antigens are present in the following nontuberculosis mycobacteria: M. kansasii, M. szulgai and M. marinum. Challenges with phlebotomy in young children mean that these tests have limited applicability, with skin tests being the alternative. Details for each IGRA test are provided in Annex 2.

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