{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:05:29Z","timestamp":1791821129082,"version":"4.3.4"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"crossref","award":["8029802812"],"award-info":[{"award-number":["8029802812"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"crossref","award":["8029802812"],"award-info":[{"award-number":["8029802812"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2024,11,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Non-sputum tests are needed to improve tuberculosis (TB) diagnosis and close the diagnostic gap. The World Health Organization\u2019s target product profile (TPP) for point-of-care (POC) screening tests requires a minimum sensitivity of 90% and a specificity of 70%. Our objective was to identify host blood protein biomarkers meeting TPP criteria. A systematic review was conducted and reported following PRISMA guidelines. Data extraction and quality assessment with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were completed for the included studies. Heterogeneity was assessed. For biomarkers reporting sensitivity and specificity in at least four studies, a random-effects meta-analysis was performed for biomarkers with similar cut-offs. We screened 4,651 citations and included 65 studies that enrolled 16,010 participants and evaluated 156 host proteins. Most (47\/65) studies enrolled adult pulmonary TB (PTB), with 15 studies in adult extra-pulmonary TB and 5 in children. Small early-stage discovery studies with case-control design were common (24\/65) and had a high risk of bias. For adult PTB, CRP, IP-10, NCAM-1, and SAA met TPP criteria in high-quality studies. There was a high degree of heterogeneity in biomarker cut-offs and study design. CRP at 10 mg\/L cut-off was meta-analyzed from 10 studies; pooled sensitivity 86% [95% confidence interval (CI): 80\u201395] and pooled specificity 67% (95% CI: 54\u201379). In people living with HIV (six studies), CRP pooled sensitivity was 93% (95% CI: 90\u201395), and pooled specificity was 59% (95% CI: 40\u201378). We identified promising biomarkers that performed well in high-quality studies. Data overall are limited and highly heterogenous. Further standardized validation across subgroups in prospective studies is needed before translating into POC assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>To our knowledge, this is the first comprehensive systematic review of host blood protein biomarkers for tuberculosis (TB), and we identified promising biomarkers for a TB screening test.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jcm.00786-24","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T09:00:21Z","timestamp":1729760421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Host blood protein biomarkers to screen for tuberculosis disease: a systematic review and 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