{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T02:18:04Z","timestamp":1776824284159,"version":"3.51.2"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009250","name":"New Partnership for Africa's Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009250","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South African Network of Biosciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%\u201389.4%] vs 25% [8.9%\u201353.3%]; P = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%\u201393.4%] vs 86.9% [83.4%\u201389.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)\u2013infected versus uninfected participants (85.8% vs 66.7%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB\/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofae496","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T21:13:44Z","timestamp":1724966024000},"source":"Crossref","is-referenced-by-count":2,"title":["Utility of Cerebrospinal Fluid Unstimulated Interferon-Gamma (IRISA-TB) as a Same-Day Test for Tuberculous Meningitis in a Tuberculosis-Endemic, Resource-Poor Setting"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-0536","authenticated-orcid":false,"given":"Philippa","family":"Randall","sequence":"first","affiliation":[{"name":"Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]},{"name":"Antrum Biotech (Pty) Ltd , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junior","family":"Mutsvangwa","sequence":"additional","affiliation":[{"name":"Biomedical Research and Training Institute , Harare ,","place":["Zimbabwe"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marriott","family":"Nliwasa","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Malawi , Blantyre ,","place":["Malawi"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beauty","family":"Makamure","sequence":"additional","affiliation":[{"name":"Biomedical Research and Training Institute , Harare ,","place":["Zimbabwe"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edson","family":"Makambwa","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Meldau","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]},{"name":"Department of Infection Biology, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shungu","family":"Munyati","sequence":"additional","affiliation":[{"name":"Biomedical Research and Training Institute , Harare ,","place":["Zimbabwe"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Division of Neuro-Virology, Beth Israel Deaconess Medical Center , Boston, Massachusetts ,","place":["USA"]},{"name":"Department of Internal Medicine, University of Zambia School of Medicine , Lusaka ,","place":["Zambia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Corbett","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Malawi , Blantyre ,","place":["Malawi"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Esmail","sequence":"additional","affiliation":[{"name":"Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"2025031914255732800_ofae496-B1","volume-title":"Global tuberculosis report 2023","author":"World Health Organization (WHO)","year":"2023"},{"key":"2025031914255732800_ofae496-B2","doi-asserted-by":"crossref","first-page":"e0000069","DOI":"10.1371\/journal.pgph.0000069","article-title":"The global burden of tuberculous meningitis in adults: a modelling study","volume":"1","author":"Dodd","year":"2021","journal-title":"PLoS Glob Public 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