{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:44:50Z","timestamp":1789670690541,"version":"4.0.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute for Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007565","name":"CRDF","doi-asserted-by":"publisher","award":["DAA3-18-64075"],"award-info":[{"award-number":["DAA3-18-64075"]}],"id":[{"id":"10.13039\/100007565","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RePORT India and South Africa Consortium"},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["RFA-EMU-02-2017"],"award-info":[{"award-number":["RFA-EMU-02-2017"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"European & Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["TMA-2015SF-1043"],"award-info":[{"award-number":["TMA-2015SF-1043"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"European & Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["TMA-1051-TESAII"],"award-info":[{"award-number":["TMA-1051-TESAII"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S03563X\/1"],"award-info":[{"award-number":["MR\/S03563X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["MR\/S027777\/1"],"award-info":[{"award-number":["MR\/S027777\/1"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"EDCTP","doi-asserted-by":"publisher","award":["TMA-2015CDF-1052"],"award-info":[{"award-number":["TMA-2015CDF-1052"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tuberculous pleural effusion (TPE) is the most common form of extrapulmonary tuberculosis in many settings. The diagnostic performance of the frontline polymerase chain reaction\u2013based GeneXpert MTB\/RIF Ultra (Xpert Ultra) remains suboptimal (sensitivity of \u223c30%), but data are limited. Improved diagnostic approaches are urgently needed to detect extrapulmonary tuberculosis (EPTB) in tuberculosis (TB)-endemic settings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This multicenter, prospective cohort study evaluated the diagnostic performance of a rapid (same-day) interferon gamma rapid immunosuspension assay (IRISA-TB) in patients with presumed TPE from South Africa and India. Participants underwent pleural biopsy, and testing with other available same-day diagnostic assays (adenosine deaminase [ADA], Xpert Ultra, and IRISA-TB) was concurrently undertaken. The reference standard for TB was microbiological and\/or histopathological confirmation using pleural fluid and\/or pleural biopsy samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 217 participants with presumed TPE were recruited (106 from South Africa, 111 from India). The sensitivity of IRISA-TB (cut-point 20.5\u2005pg\/mL) was significantly better than that of Xpert Ultra (81.8% [70.4\u201390.2] vs 32.9% [22.1\u201345.1]; P &amp;lt; .001) and ADA at the 40 IU\/mL cut-point used in India (81.8% [70.4\u201390.2] vs 53.8% [41.0\u201366.3]; P \u00a0= .002). Compared with ADA at the 30 IU\/mL cut-point used in South Africa, IRISA-TB had a higher specificity (96.6% [90.3\u201399.3] vs 87.1% [78.6\u201393.2]) and a higher positive predictive value (94.7% [85.5\u201397.3] vs 81.8% [72.4\u201388.5]). The negative predictive value (NPV; rule-out value) of IRISA-TB was significantly better than that of Xpert Ultra (87.5% [83.2\u201393.0] vs 64.9% [61.1\u201368.6]; P &amp;lt; .001) and ADA at the 40 IU\/mL cut-point (87.5% [83.2\u201393.0] vs 74.1% [68.7\u201379.0]; P &amp;lt; .001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IRISA-TB demonstrated markedly better sensitivity and NPV than Xpert Ultra and excellent specificity for the diagnosis of TPE. These data have implications for clinical practice in TB-endemic settings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofae533","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T18:10:42Z","timestamp":1727201442000},"source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic Performance of Unstimulated IFN-\u03b3 (IRISA-TB) for Pleural Tuberculosis: A Prospective Study in South Africa and India"],"prefix":"10.1093","volume":"11","author":[{"given":"Devasahayam J","family":"Christopher","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Christian Medical College , Vellore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1835-9252","authenticated-orcid":false,"given":"Aliasgar","family":"Esmail","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-607X","authenticated-orcid":false,"given":"Alex J","family":"Scott","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-0536","authenticated-orcid":false,"given":"Philippa","family":"Randall","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balamugesh","family":"Thangakunam","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Christian Medical College , Vellore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Shankar","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Christian Medical College , Vellore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekar","family":"Rajasekar","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Christian Medical College , Vellore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christhunesa S","family":"Christudass","sequence":"additional","affiliation":[{"name":"Division of Neurochemistry, Department of Neurological Sciences, Christian Medical College , Vellore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loui\u00e9","family":"K\u00fchn","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremi","family":"Swanepoel","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahlia","family":"Perumal","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Pooran","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzette","family":"Oelofse","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7709-5341","authenticated-orcid":false,"given":"Keertan","family":"Dheda","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute , Cape Town ,","place":["South Africa"]},{"name":"South African MRC\/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town , Cape Town ,","place":["South Africa"]},{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"2024102921291043000_ofae533-B1","author":"World Health Organization. Global Tuberculosis Report 2023. World Health Organization","year":"2023"},{"key":"2024102921291043000_ofae533-B2","author":"World Health Organization. WHO COVID-19 dashboard","year":"2020"},{"key":"2024102921291043000_ofae533-B3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7196\/samj.6374","article-title":"Extrapulmonary tuberculosis among adults: experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa","volume":"104","author":"Karstaedt","year":"2013","journal-title":"S Afr Med J"},{"key":"2024102921291043000_ofae533-B4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/17476348.2019.1637737","article-title":"Tuberculous pleural effusion: diagnosis & management","volume":"13","author":"Antonangelo","year":"2019","journal-title":"Expert Rev Respir Med"},{"key":"2024102921291043000_ofae533-B5","doi-asserted-by":"crossref","first-page":"32924","DOI":"10.1038\/srep32924","article-title":"The diagnostic accuracy of pericardial and urinary lipoarabinomannan (LAM) assays in patients with suspected tuberculous pericarditis","volume":"6","author":"Pandie","year":"2016","journal-title":"Sci Rep"},{"key":"2024102921291043000_ofae533-B6","doi-asserted-by":"crossref","first-page":"e4689","DOI":"10.1371\/journal.pone.0004689","article-title":"Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting","volume":"4","author":"Dheda","year":"2009","journal-title":"PLoS One"},{"key":"2024102921291043000_ofae533-B7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1471-2466-14-58","article-title":"Comparison of same day diagnostic tools including GeneXpert and unstimulated IFN-\u03b3 for the evaluation of pleural tuberculosis: a prospective cohort study","volume":"14","author":"Meldau","year":"2014","journal-title":"BMC Pulm Med"},{"key":"2024102921291043000_ofae533-B8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S1473-3099(17)30691-6","article-title":"Xpert MTB\/RIF ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study","volume":"18","author":"Dorman","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2024102921291043000_ofae533-B9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ijid.2020.03.025","article-title":"Comparison of Xpert MTB\/RIF (G4) and Xpert Ultra, including trace readouts, for the diagnosis of pulmonary tuberculosis in a TB and HIV endemic setting","volume":"95","author":"Esmail","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2024102921291043000_ofae533-B10","doi-asserted-by":"crossref","first-page":"e00614","DOI":"10.1128\/JCM.00614-19","article-title":"Same-day tools, including Xpert Ultra and IRISA-TB, for rapid diagnosis of pleural tuberculosis: a prospective observational study","volume":"57","author":"Meldau","year":"2019","journal-title":"J Clin Microbiol"},{"key":"2024102921291043000_ofae533-B11","doi-asserted-by":"crossref","first-page":"e0213728","DOI":"10.1371\/journal.pone.0213728","article-title":"Adenosine deaminase for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis","volume":"14","author":"Aggarwal","year":"2019","journal-title":"PLoS One"},{"key":"2024102921291043000_ofae533-B12","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1128\/JCM.01128-11","article-title":"Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis","volume":"49","author":"Patel","year":"2011","journal-title":"J Clin Microbiol"},{"key":"2024102921291043000_ofae533-B13","first-page":"777","article-title":"Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis","volume":"7","author":"Greco","year":"2003","journal-title":"Int J Tuberc Lung Dis"},{"key":"2024102921291043000_ofae533-B14","doi-asserted-by":"crossref","first-page":"e0202481","DOI":"10.1371\/journal.pone.0202481","article-title":"Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-\u03b3, IP-10 and adenosine deaminase","volume":"13","author":"Santos","year":"2018","journal-title":"PLoS One"},{"key":"2024102921291043000_ofae533-B15","doi-asserted-by":"crossref","first-page":"e02112","DOI":"10.1128\/JCM.02112-20","article-title":"Unstimulated pleural fluid interferon gamma for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis","volume":"59","author":"Aggarwal","year":"2021","journal-title":"J Clin Microbiol"},{"key":"2024102921291043000_ofae533-B16","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1183\/09031936.00005309","article-title":"Utility of quantitative T-cell responses versus unstimulated interferon-\u03b3 for the diagnosis of pleural tuberculosis","volume":"34","author":"Dheda","year":"2009","journal-title":"Eur Respir J"},{"key":"2024102921291043000_ofae533-B17","volume-title":"National Tuberculosis Management Guidelines","author":"TB DOTS Strategy Coordination","year":"2014"},{"key":"2024102921291043000_ofae533-B18","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/S0140-6736(15)01316-1","article-title":"A blood RNA signature for tuberculosis disease risk: a prospective cohort study","volume":"387","author":"Zak","year":"2016","journal-title":"Lancet"},{"key":"2024102921291043000_ofae533-B19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1183\/13993003.00263-2015","article-title":"Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study","volume":"46","author":"Rakotosamimanana","year":"2015","journal-title":"Eur Respir J"},{"key":"2024102921291043000_ofae533-B20","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nature09247","article-title":"An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis","volume":"466","author":"Berry","year":"2010","journal-title":"Nature"},{"key":"2024102921291043000_ofae533-B21","doi-asserted-by":"crossref","first-page":"e00927","DOI":"10.1128\/JCM.00927-19","article-title":"Predominance of th1 immune response in pleural effusion of patients with tuberculosis among other exudative etiologies","volume":"58","author":"da Cunha Lisboa","year":"2019","journal-title":"J Clin Microbiol"},{"key":"2024102921291043000_ofae533-B22","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/1741-7015-12-101","article-title":"Diagnostic accuracy of quantitative PCR (Xpert MTB\/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-\u03b3 in a high burden setting: a prospective study","volume":"12","author":"Pandie","year":"2014","journal-title":"BMC Med"},{"key":"2024102921291043000_ofae533-B23","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.21037\/jtd-22-106","article-title":"Economic evaluation of microbiological and host biomarker-based tests for the diagnosis of pleural tuberculosis in a high burden setting","volume":"14","author":"Pooran","year":"2022","journal-title":"J Thorac Dis"},{"key":"2024102921291043000_ofae533-B24","first-page":"172","article-title":"Effusions related to TB","volume":"87","author":"Shaw","year":"2020","journal-title":"Eur Respir Monogr"},{"key":"2024102921291043000_ofae533-B25","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1378\/chest.109.2.414","article-title":"Combined use of pleural adenosine deaminase with lymphocyte\/neutrophil ratio: increased specificity for the diagnosis of tuberculous pleuritis","volume":"109","author":"Burgess","year":"1996","journal-title":"Chest"},{"key":"2024102921291043000_ofae533-B26","doi-asserted-by":"crossref","first-page":"e38729","DOI":"10.1371\/journal.pone.0038729","article-title":"Diagnostic accuracy of adenosine deaminase and lymphocyte proportion in pleural fluid for tuberculous pleurisy in different prevalence scenarios","volume":"7","author":"Garcia-Zamalloa","year":"2012","journal-title":"PLoS One"},{"key":"2024102921291043000_ofae533-B27"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofae533\/59316743\/ofae533.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/11\/10\/ofae533\/60198101\/ofae533.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/11\/10\/ofae533\/60198101\/ofae533.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T21:29:28Z","timestamp":1730237368000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofae533\/7774037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,9,27]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofae533","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,9,24]]},"article-number":"ofae533"}}