{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:09:04Z","timestamp":1784282944236,"version":"3.55.0"},"reference-count":125,"publisher":"PAGEPress Publications","issue":"2","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Monaldi Arch Chest Dis"],"abstract":"<jats:p>Traditionally, tuberculosis (TB) has been viewed as having two distinct manifestations, known as TB infection (TBI) and TB disease. The spectrum, however, has recently been expanded to include the elimination of TBI with the help of innate and\/or adaptive immunity, TBI, incipient and subclinical TB disease, and TB disease. Epidemiologically speaking, identifying individuals with TBI is critical since diagnosis and treatment of TBI are essential in controlling the TB burden. It is important to identify high-risk individuals with TBI who are more likely to progress to active TB disease. There are two diagnostic methods for identifying TBI. These include the conventional tuberculin skin test (TST) and interferon-\u03b3 release assay (IGRA). However, these methods are not the \u201cgold standard\u201d. Furthermore, all of these methods are indirect, relying on the host\u2019s adaptive immune response to Mycobacterium tuberculosis-derived protein antigens. This review will describe the various tests for TBI, such as TST, IGRAs, newer skin and blood tests, methods for performing IGRAs, interpretation strategies, and limitations.<\/jats:p>","DOI":"10.4081\/monaldi.2025.3258","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T12:29:56Z","timestamp":1756729796000},"source":"Crossref","is-referenced-by-count":1,"title":["Interferon-\u03b3 release assay"],"prefix":"10.4081","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-2750","authenticated-orcid":false,"given":"Malay","family":"Sarkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-6988","authenticated-orcid":false,"given":"Jasmine","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"61900","unstructured":"WHO. Global tuberculosis report 2023. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240083851."},{"key":"61901","doi-asserted-by":"publisher","DOI":"10.14745\/ccdr.v43i34a01"},{"key":"61902","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00120908"},{"key":"61903","unstructured":"WHO. WHO Global tuberculosis report 2018. Available from: https:\/\/www.who.int\/publications-detail-redirect\/9789240013131."},{"key":"61904","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002152"},{"key":"61905","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwy094"},{"key":"61906","doi-asserted-by":"publisher","DOI":"10.1016\/S0174-3031(82)80100-5"},{"key":"61907","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2006.08.006"},{"key":"61908","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2012.01002.x"},{"key":"61909","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-303641"},{"key":"61910","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.6.968"},{"key":"61911","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-119-3-199308010-00002"},{"key":"61912","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9801120"},{"key":"61913","unstructured":"Streeton JA, Desem N, Jones SL. Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection. Int J Tuberc Lung Dis 1998;2:443-50."},{"key":"61914","unstructured":"Food and Drug Administration, Center for Devices and Radiological Health. QuantiFERON\u00ae-TB - P010033 [Letter]. Rockville, MD: Food and Drug Administration, 2002. Available from: https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfpma\/pma.cfm?ID=P010033."},{"key":"61915","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70118-3"},{"key":"61916","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.5.1274-1282.1996"},{"key":"61917","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02742-2"},{"key":"61918","unstructured":"Prevention Committee of the Japanese Society for Tuberculosis. Guidelines for using QuantiFERON\u00ae TB Gold In-Tube August 2011. Kekkaku 2013;88:33-7."},{"key":"61919","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.6.2379-2387.2004"},{"key":"61920","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.12.012"},{"key":"61921","unstructured":"QIAGEN GmbH. QuantiFERON-TB Gold Plus, ELISA Package Insert. Available from: https:\/\/www.quantiferon.com\/wp-content\/uploads\/2017\/04\/English_QFTPlus_ELISA_R04_022016.pdf."},{"key":"61922","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2019.07.007"},{"key":"61923","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.8.3.247"},{"key":"61924","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.4.2009100"},{"key":"61925","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05115-1"},{"key":"61926","unstructured":"Revvity. T-SPOT technology (ELISPOT). Available from: https:\/\/www.oxfordimmunotec.com\/international\/products-services\/t-cell-select\/."},{"key":"61927","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22253"},{"key":"61928","unstructured":"WHO. WHO operational handbook on tuberculosis. Module 3: diagnosis. Tests for TB infection. 2022. Available from: https:\/\/iris.who.int\/bitstream\/handle\/10665\/363237\/9789240058361-eng.pdf."},{"key":"61929","unstructured":"WHO. ELISA-based WANTAI TB-IGRA. Available from: https:\/\/tbksp.org\/en\/node\/2427."},{"key":"61930","unstructured":"WHO. Use of alternative interferon-gamma release assays for the diagnosis of TB infection. WHO policy statement. Available from: https:\/\/iris.who.int\/bitstream\/handle\/10665\/351180\/9789240042360-eng.pdf."},{"key":"61931","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200402-179OC"},{"key":"61932","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-149-3-200808050-00241"},{"key":"61933","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00115110"},{"key":"61934","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002814"},{"key":"61935","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2019.08.018"},{"key":"61936","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2019.09.001"},{"key":"61937","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01870-21"},{"key":"61938","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2023-0293"},{"key":"61939","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00985-19"},{"key":"61940","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201905-0969OC"},{"key":"61941","unstructured":"WHO. Consensus meeting report: development of a target product profile (TPP) and a framework for evaluation for a test for predicting progression from tuberculosis infection to active disease. Available from: http:\/\/www.who.int\/iris\/handle\/10665\/259176."},{"key":"61942","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1439OC"},{"key":"61943","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283188415"},{"key":"61944","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00045509"},{"key":"61945","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31820b07ab"},{"key":"61946","unstructured":"Laboratory Procedure Manual. Tuberculosis (TB) QUANTIFERON gold plus (Interferon-gamma). Available from: https:\/\/www.quantiferon.com\/wp-content\/uploads\/2017\/04\/English_QFTPlus_ELISA_R04_022016.pdf."},{"key":"61947","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2014.02.007"},{"key":"61948","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2023.03.003"},{"key":"61949","unstructured":"Revvity. T-SPOT technology (ELISPOT). Available from: https:\/\/www.oxfordimmunotec.com\/international\/wp-content\/uploads\/sites\/3\/Final-File-PI-TB-US-V6.pdf."},{"key":"61950","unstructured":"Testing for TB infection video: tuberculin skin test & IGRA blood test Available from: https:\/\/www.michigan.gov\/-\/media\/Project\/Websites\/mdhhs\/Folder2\/Folder90\/Folder1\/Folder190\/6_Participant_Guide_Testing_for_TB_Infection_Video_-_2017.pdf?rev=65b6c1708ee14792ab6467636d22e4f1."},{"key":"61951","unstructured":"WHO. South-East Asia immunizes a record-high number of children in 2024. Available from: http:\/\/www.searo.who.int\/india\/mediacentre\/events\/2014\/stci_book.pdf."},{"key":"61952","doi-asserted-by":"publisher","DOI":"10.4103\/0970-2113.156210"},{"key":"61953","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00114810"},{"key":"61954","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00683-09"},{"key":"61955","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5419.1520"},{"key":"61956","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00120214"},{"key":"61957","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.JJID.2009.300"},{"key":"61958","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-1995"},{"key":"61959","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023806"},{"key":"61960","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58459-9"},{"key":"61961","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.18-0684"},{"key":"61962","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2017.0072"},{"key":"61963","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1170579"},{"key":"61964","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-2350"},{"key":"61965","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2011.02.001"},{"key":"61966","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.09.012"},{"key":"61967","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00811-21"},{"key":"61968","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.11.0017"},{"key":"61969","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy184"},{"key":"61970","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00040007"},{"key":"61971","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1621CI"},{"key":"61972","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2019.01.048"},{"key":"61973","unstructured":"Ewer K, Deeks J, Alvearez L, et al. Longitudinal tracking of M. tuberculosis-specific T cells ex vivo in latently infected, tuberculin skin test-negative tuberculosis contacts. In: Tuberculosis: integrating host and pathogen biology. Keystone Symposia 2003 Abstract Book; Abstract 317. Silverthorne, CO: Keystone Symposia"},{"key":"61974","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir068"},{"key":"61975","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201310-378OC"},{"key":"61976","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-472OC"},{"key":"61977","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/291294"},{"key":"61978","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0365OC"},{"key":"61979","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.201178"},{"key":"61980","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008517"},{"key":"61981","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00034-13"},{"key":"61982","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02803-15"},{"key":"61983","unstructured":"Menzies D. Use of interferon-gamma release assays for diagnosis of tuberculosis infection (tuberculosis screening) in adults. Available from: https:\/\/www.uptodate.com\/contents\/use-of-interferon-gamma-release-assays-for-diagnosis-of-tuberculosis-infection-tuberculosis-screening-in-adults."},{"key":"61984","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01136-11"},{"key":"61985","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201405-188OC"},{"key":"61986","doi-asserted-by":"publisher","DOI":"10.1093\/occmed\/kqt105"},{"key":"61987","unstructured":"Canadian Tuberculosis Committee (CTC). Updated recommendations on interferon gamma release assays for latent tuberculosis infection. An Advisory Committee Statement (ACS). Can Commun Dis Rep 2008;34:1-13."},{"key":"61988","unstructured":"Tuberculosis blood test: interferon gamma release assay (IGRA). Available from: https:\/\/www.dhs.wisconsin.gov\/publications\/p01182.pdf."},{"key":"61989","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00089510"},{"key":"61990","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1083"},{"key":"61991","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2007.04.006"},{"key":"61992","unstructured":"WHO. Rapid communication: TB antigen-based skin tests for the diagnosis of TB infection. Available from: https:\/\/www.who.int\/publications\/i\/item\/WHO-UCN-TB-2022.1."},{"key":"61993","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30436-2"},{"key":"61994","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064215"},{"key":"61995","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00167-2021"},{"key":"61996","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01464-2015"},{"key":"61997","doi-asserted-by":"publisher","DOI":"10.4103\/ijmy.ijmy_131_20"},{"key":"61998","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-020-05413-9"},{"key":"61999","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab472"},{"key":"62000","unstructured":"DiaSorin. LIAISON\u00ae QuantiFERON\u00ae-TB Gold Plus ([REF] 311020). Avaialable from: https:\/\/www.accessdata.fda.gov\/cdrh_docs\/pdf18\/P180047D.pdf."},{"key":"62001","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00603-21"},{"key":"62002","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00780-20"},{"key":"62003","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2023.04.010"},{"key":"62004","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfab012"},{"key":"62005","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01067-23"},{"key":"62006","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02563-2021"},{"key":"62007","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.21.0391"},{"key":"62008","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0279882"},{"key":"62009","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-65663-4"},{"key":"62010","doi-asserted-by":"publisher","DOI":"10.1101\/2022.04.01.22271763"},{"key":"62011","unstructured":"Lionex. LIOFeron\u00aeTB\/LTBI IGRA. Avaialble from: https:\/\/lionex.de\/product\/lioferon\/."},{"key":"62012","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01549.x"},{"key":"62013","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2412-2415.2004"},{"key":"62014","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22101"},{"key":"62015","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2019.12.012"},{"key":"62016","unstructured":"Ichroma\u2122 IGRA-TB 25. Available from: https:\/\/labindustrias.com\/wp-content\/uploads\/2023\/10\/INS-TBE-EN-ichroma-IGRA-TB-25_Rev.00_2002111.pdf."},{"key":"62017","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2021.05.007"},{"key":"62018","unstructured":"SD Biosensor STANDARD F TB-Feron FIA. Available from: https:\/\/www.sdbiosensor.com\/product\/product_view? product_no=167."},{"key":"62019","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.0079-2021"},{"key":"62020","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01347-19"},{"key":"62021","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11091659"},{"key":"62022","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2020.40.1.33"},{"key":"62023","unstructured":"TB diagnostics pipeline: needs & solutions by Samuel Schumacher, Deputy Head TB. FIND & NDWG joint symposium, 50th Union World Conference, 30 October 2019. https:\/\/www.stoptb.org\/sites\/default\/files\/imported\/article\/oldweb\/wg\/new_diagnostics\/assets\/documents\/TB_diagnostics_pipeline_needs_and_solutions.pdf."},{"key":"62024","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad030"}],"container-title":["Monaldi Archives for Chest Disease"],"original-title":[],"link":[{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/download\/3258\/2124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/download\/3258\/2124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:54:10Z","timestamp":1784282050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.monaldi-archives.org\/macd\/article\/view\/3258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":125,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,5,7]]}},"URL":"https:\/\/doi.org\/10.4081\/monaldi.2025.3258","relation":{},"ISSN":["2532-5264","1122-0643"],"issn-type":[{"value":"2532-5264","type":"electronic"},{"value":"1122-0643","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}