{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:13:20Z","timestamp":1760422400754,"version":"build-2065373602"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Tuberculosis (TB) still remains the world\u2019s leading infectious disease killer. New screening and diagnostic tests are urgently needed. We have previously identified a 3-marker host protein signature with high accuracy for TB in sputum from adult Gambian patients. The aim of this project was to analyse host sputum markers in a larger cohort of adults and children with presumptive TB from The Gambia, and to determine the global applicability of such a signature in samples from South Africa, Vietnam and Peru.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sputum samples were collected at baseline from all symptomatic participants and used for routine diagnostics and biomarker evaluation. Samples were also collected at 1 and 2 months after anti-TB treatment initiation from those who were subsequently found to have TB. For biomarker evaluation, an aliquot of sputum was digested with an equal volume of Sputolysin<jats:sup>\u00ae<\/jats:sup>, incubated for 15 minutes at RT, centrifuged, and the supernatant analysed using multiplex cytokine arrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For Gambian participants (n=428 TB and n=313 other respiratory diseases (ORD)) an 8-marker signature was able to differentiate between smear and culture positive TB from ORD with an AUC of 0.77, while a 3-marker signature classified smear negative TB with an AUC of 0.74. Additionally, a 4-marker signature could discriminate between children (&amp;lt;18 years) with TB (n=17) and those with ORD (n=23) with an AUC of 0.87, sensitivity of 82% and specificity of 87%. A 5-marker global signature was identified with an AUC of 0.71.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study describes the use of host markers in sputum for development of a rapid triage test for pulmonary TB in adults and children. Whilst the results are promising for regional-specific and treatment response signatures, our pilot data do not support development of a global test for TB triage based on sputum host signatures.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1652719","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:28:37Z","timestamp":1760419717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sputum host cytokine signatures for diagnosis of TB in children and adults"],"prefix":"10.3389","volume":"16","author":[{"given":"Joseph","family":"Mendy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Coker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"3rd","given":"January","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian","family":"van der Spuy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Novel N.","family":"Chegou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayne S.","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","unstructured":"WHO Global TB report\n          \n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.TBTB2-0019-2016","article-title":"Tuberculosis diagnostics: state of the art and future directions","volume":"4","author":"Pai","year":"2016","journal-title":"Microbiol Spectr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"ciae549","DOI":"10.1093\/cid\/ciae549","article-title":"Diagnostic accuracy of TB screening tests in a prospective multinational cohort: Chest-X-ray with computer-aided detection, Xpert TB host response, and C-reactive protein","author":"Crowder","year":"2024","journal-title":"Clin Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab839","article-title":"Diagnostic accuracy of the cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results","volume":"74","author":"Sutherland","year":"2022","journal-title":"Clin Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(23)00541-7","article-title":"Evaluation of the Xpert MTB Host Response assay for the triage of patients with presumed pulmonary tuberculosis: a prospective diagnostic accuracy study in Viet Nam, India, the Philippines, Uganda, and South Africa","volume":"12","author":"Gupta-Wright","year":"2024","journal-title":"Lancet Glob Health"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00491-7","article-title":"Diagnostic accuracy of a three-gene Mycobacterium tuberculosis host response cartridge using fingerstick blood for childhood tuberculosis: a multicentre prospective study in low-income and middle-income countries","volume":"24","author":"Olbrich","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"8868","DOI":"10.1038\/s41598-017-07803-7","article-title":"Field-friendly serological tests for determination of M. leprae-specific antibodies","volume":"7","author":"van Hooij","year":"2017","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"105873","DOI":"10.1016\/j.isci.2022.105873","article-title":"Host biomarker-based quantitative rapid tests for detection and treatment monitoring of tuberculosis and COVID-19","volume":"26","author":"Pierneef","year":"2023","journal-title":"iScience"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00209913","article-title":"Rapid diagnosis of tuberculosis using ex vivo host biomarkers in sputum","volume":"44","author":"Ota","year":"2014","journal-title":"Eur Respir J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-214238","article-title":"Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay","volume":"75","author":"Sabiiti","year":"2020","journal-title":"Thorax"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4419-9863-7_1215","article-title":"Benjamini\u2013hochberg method","author":"Haynes","year":"2013","journal-title":"Encyclopedia Syst Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"102909","DOI":"10.1016\/j.ebiom.2020.102909","article-title":"A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children","volume":"58","author":"Togun","year":"2020","journal-title":"EBioMedicine"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1652719\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:28:50Z","timestamp":1760419730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1652719\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":12,"alternative-id":["10.3389\/fimmu.2025.1652719"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1652719","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"article-number":"1652719"}}