{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T12:20:54Z","timestamp":1793017254322,"version":"4.5.0"},"posted":{"date-parts":[[2024,4,24]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":33,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity \u226590%, specificity \u226570%) for an effective TB triage test.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods\/Measurements<\/jats:title>\n                  <jats:p>Consecutive outpatient adults with cough \u22652 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB\/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg\/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (\u226591%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.04.23.24305228","type":"posted-content","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T19:45:12Z","timestamp":1713987912000},"source":"Crossref","is-referenced-by-count":3,"title":["C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study"],"prefix":"10.64898","author":[{"given":"Brigitta","family":"Derendinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa K.","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danaida","family":"Marcelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Mangeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seda","family":"Yerikaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Worodria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhung Viet","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devasahayam Jesudas","family":"Christopher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Theron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick P.J.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payam","family":"Nahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Denkinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adithya","family":"Cattamanchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024042612401640000_2024.04.23.24305228v1.1","unstructured":"Global Tuberculosis Report 2023 [Internet]. [cited 2024 Feb 2]. Available from: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports\/global-tuberculosis-report-2023"},{"key":"2024042612401640000_2024.04.23.24305228v1.2","unstructured":"WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection, 2021 update [Internet]. [cited 2022 Nov 21]. Available from: https:\/\/www.who.int\/publications-detail-redirect\/9789240029415"},{"key":"2024042612401640000_2024.04.23.24305228v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082786"},{"key":"2024042612401640000_2024.04.23.24305228v1.4","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2013.2284099"},{"issue":"1","key":"2024042612401640000_2024.04.23.24305228v1.5","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.1038\/s41598-020-62148-y","article-title":"Computer aided detection of tuberculosis on chest radiographs: An evaluation of the CAD4TB v6 system","volume":"10","year":"2020","journal-title":"Sci Rep"},{"key":"2024042612401640000_2024.04.23.24305228v1.6","doi-asserted-by":"crossref","unstructured":"Soares TR , Oliveira RD de , Liu YE , Santos A da S , Santos PCP dos , Monte LRS , et al. Evaluation of chest X-ray with automated interpretation algorithms for mass tuberculosis screening in prisons: a cross-sectional study. Lancet Reg Health Am. 2022 Nov 4;17:100388.","DOI":"10.1016\/j.lana.2022.100388"},{"key":"2024042612401640000_2024.04.23.24305228v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00387-X"},{"key":"2024042612401640000_2024.04.23.24305228v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.07.017"},{"issue":"7","key":"2024042612401640000_2024.04.23.24305228v1.9","doi-asserted-by":"crossref","first-page":"e0254002","DOI":"10.1371\/journal.pone.0254002","article-title":"Evaluation of the diagnostic performance of laboratory-based c-reactive protein as a triage test for active pulmonary tuberculosis","volume":"16","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"2024042612401640000_2024.04.23.24305228v1.10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jinf.2022.10.041","article-title":"Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults","volume":"86","year":"2023","journal-title":"J Infect"},{"issue":"2","key":"2024042612401640000_2024.04.23.24305228v1.11","doi-asserted-by":"crossref","first-page":"e226","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","volume":"12","year":"2024","journal-title":"Uganda, and South Africa. The Lancet Global Health"},{"key":"2024042612401640000_2024.04.23.24305228v1.12","doi-asserted-by":"crossref","unstructured":"Bossuyt PM , Reitsma JB , Bruns DE , Gatsonis CA , Glasziou PP , Irwig L , et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015 Oct 28;351:h5527.","DOI":"10.1136\/bmj.h5527"},{"key":"2024042612401640000_2024.04.23.24305228v1.13","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1612-1"},{"issue":"1","key":"2024042612401640000_2024.04.23.24305228v1.14","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1038\/s41598-018-23066-2","article-title":"Correlation of Xpert MTB\/RIF with measures to assess Mycobacterium tuberculosis bacillary burden in high HIV burden areas of Southern Africa","volume":"8","year":"2018","journal-title":"Sci Rep"},{"key":"2024042612401640000_2024.04.23.24305228v1.15","doi-asserted-by":"publisher","DOI":"10.1177\/003335490512000309"},{"issue":"12","key":"2024042612401640000_2024.04.23.24305228v1.16","first-page":"1596","article-title":"Radiological cavitation, sputum mycobacterial load and treatment response in pulmonary tuberculosis","volume":"14","year":"2010","journal-title":"The International Journal of Tuberculosis and Lung Disease"},{"key":"2024042612401640000_2024.04.23.24305228v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm025"},{"key":"2024042612401640000_2024.04.23.24305228v1.18","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.06193-11"},{"key":"2024042612401640000_2024.04.23.24305228v1.19","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01780-07"},{"key":"2024042612401640000_2024.04.23.24305228v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30488-7"},{"issue":"5","key":"2024042612401640000_2024.04.23.24305228v1.21","first-page":"10","article-title":"Diagnostic and prognostic value of serum C-reactive protein for screening for HIV-associated tuberculosis","volume":"17","year":"2013","journal-title":"Int J Tuberc Lung Dis"},{"key":"2024042612401640000_2024.04.23.24305228v1.22","doi-asserted-by":"crossref","unstructured":"Ciccacci F , Floridia M , Bernardini R , Sidumo Z , Mugunhe RJ , Andreotti M , et al. Plasma levels of CRP, neopterin and IP-10 in HIV-infected individuals with and without pulmonary tuberculosis. J Clin Tuberc Other Mycobact Dis. 2019 Jun 5;16:100107.","DOI":"10.1016\/j.jctube.2019.100107"},{"issue":"4","key":"2024042612401640000_2024.04.23.24305228v1.23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4236\/ojrd.2012.24014","article-title":"Correlation of Serum C-Reactive Protein with Disease Severity in Tuberculosis Patients","volume":"2","year":"2012","journal-title":"Open Journal of Respiratory Diseases"},{"issue":"5","key":"2024042612401640000_2024.04.23.24305228v1.24","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/IPC.0b013e3181a4c73d","article-title":"Serum C-Reactive Protein in Pulmonary Tuberculosis: Correlation With Bacteriological Load and Extent of Disease","volume":"17","year":"2009","journal-title":"Infectious Diseases in Clinical Practice"},{"key":"2024042612401640000_2024.04.23.24305228v1.25","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32832c7d61"},{"issue":"Suppl 1","key":"2024042612401640000_2024.04.23.24305228v1.26","first-page":"S3","article-title":"Epidemiology and interaction of diabetes mellitus and tuberculosis and challenges for care: a review","volume":"3","year":"2013","journal-title":"Public Health Action"},{"key":"2024042612401640000_2024.04.23.24305228v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12257"},{"key":"2024042612401640000_2024.04.23.24305228v1.28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050152"},{"issue":"2","key":"2024042612401640000_2024.04.23.24305228v1.29","first-page":"123","article-title":"Gender and tuberculosis: a comparison of prevalence surveys with notification data to explore sex differences in case detection","volume":"4","year":"2000","journal-title":"Int J Tuberc Lung Dis"},{"key":"2024042612401640000_2024.04.23.24305228v1.30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002119"},{"key":"2024042612401640000_2024.04.23.24305228v1.31","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-004818"},{"issue":"3","key":"2024042612401640000_2024.04.23.24305228v1.32","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4103\/2249-4863.222052","article-title":"Diagnostic delay and associated factors among patients with pulmonary tuberculosis in Kerala","volume":"6","year":"2017","journal-title":"J Family Med Prim Care"},{"issue":"8","key":"2024042612401640000_2024.04.23.24305228v1.33","first-page":"635","article-title":"Pulmonary tuberculosis: diagnostic delay in Ghanaian adults","volume":"2","year":"1998","journal-title":"Int J Tuberc Lung Dis"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.04.23.24305228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:59:02Z","timestamp":1768507142000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.04.23.24305228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,24]]},"references-count":33,"URL":"https:\/\/doi.org\/10.1101\/2024.04.23.24305228","relation":{"has-review":[{"id-type":"doi","id":"10.1162\/2e3983f5.0814aeaf","asserted-by":"object"},{"id-type":"doi","id":"10.1162\/2e3983f5.28874cab","asserted-by":"object"},{"id-type":"doi","id":"10.1162\/2e3983f5.2dfe8f8d","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2024,4,24]]},"subtype":"preprint"}}