{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:47Z","timestamp":1792785947877,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Canada Research Chair Program"},{"name":"Canadian Institutes of Health Research Foundation","award":["FDN-148439"],"award-info":[{"award-number":["FDN-148439"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004489","name":"Mitacs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP-1022128"],"award-info":[{"award-number":["OPP-1022128"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Host circulating biomarkers may enhance access to tuberculosis (TB) diagnostics in low-resource settings. We sought to identify host plasma proteins that differentiate TB disease from other infectious causes of fever.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This secondary analysis of a prospective cohort included outpatients \u226518 years old in urban Tanzania presenting with \u22647 days of fever. Fourteen plasma proteins reflecting endothelial and immunoregulatory pathways were evaluated against a composite reference standard including sputum Xpert MTB\/RIF, urine lipoarabinomannan, and\/or chest radiography. Multivariable models assessed proteins and symptoms associated with TB diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 507 participants, 40 (7.9%) had TB disease and 467 (92.1%) had other causes of fever. Eight proteins were significantly elevated (P &amp;lt; .05) in people with TB. Regression modeling identified a 4-protein biosignature (soluble triggering receptor expressed on myeloid cells 1 [sTREM-1], chitinase 3\u2013like protein 1, soluble tumor necrosis factor receptor 1, and C-reactive protein) with a cross-validated median area under the receiver operating characteristic curve (AUC) of 0.81 (2.5th\u201397.5th percentiles, 0.65\u20130.93), sensitivity of 80.0% (41.4%\u2013100%), and specificity of 65.5% (54.2%\u201376.6%); however, discrimination was lower in people living with human immunodeficiency virus (AUC, 0.71 [95% confidence interval, .61\u2013.81]). Classification and regression tree analysis yielded a simplified algorithm incorporating cough and sTREM-1, with a cross-validated AUC of 0.79 (95% confidence interval, .69\u2013.88), sensitivity of 77.5% (61.6%\u201389.2%), and specificity of 84.2% (80.5%\u201387.4%); this approach may be more pragmatic for low-resource settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory analysis identified a parsimonious biosignature and biomarker-based algorithm for TB evaluation among febrile adults in a high-burden setting. With further development, host protein-based assays may enhance TB case detection in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag238","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:30:38Z","timestamp":1777980638000},"page":"e881-e890","source":"Crossref","is-referenced-by-count":0,"title":["Host Plasma Protein Biomarkers for Tuberculosis Disease Screening in Febrile Adults in Tanzania"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-5301","authenticated-orcid":false,"given":"Michael","family":"Prodanuk","sequence":"first","affiliation":[{"name":"Centre for Global Child Health, The Hospital for Sick Children , Toronto, Ontario ,","place":["Canada"]},{"name":"Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children and University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Institute for Health 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