A new rapid lipoarabinomannan urine assay for tuberculosis: a two-centre diagnostic accuracy evaluation in outpatients with and without HIV

A new rapid lipoarabinomannan urine assay for tuberculosis: a two-centre diagnostic accuracy evaluation in outpatients with and without HIV | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A new rapid lipoarabinomannan urine assay for tuberculosis: a two-centre diagnostic accuracy evaluation in outpatients with and without HIV Beston Hamasur, Anna O. Okunola, James Sserubiri, Welile V. Dube-Nwamba, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5386988/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Introduction: Non-sputum tests for people attending primary care with symptoms of tuberculosis (TB) are a global priority. Methods: We performed a cross-sectional two-centre diagnostic accuracy study of a next-generation urine lipoarabinomannan assay (Biopromic TB LAM, BP-LAM) and the lateral flow Determine TB LAM Ag assay (LF-LAM) on urine from 629 adults with presumptive pulmonary TB (315 with TB) attending primary care in South Africa and Uganda. An extended sputum microbiological reference standard (eMRS) was used and, in South Africa, sputum induction done. Results: BP-LAM had higher sensitivity than LF-LAM [95% confidence interval (CI) 63% (58, 69) vs. 22% (18, 27)] and similar specificity [93% (90, 96) vs. 89% (85, 92)]. BP-LAM sensitivity did not differ in HIV-positive vs. -negative people nor by CD4 counts. Specificity was diminished in PLHIV [90% (83, 94) vs. 96% (92, 99)]. The design-locked version of BP-LAM had improved specificity than the prototype [93% (90, 96) vs. 85% (80, 88)]. In people with TB who could not expectorate sputum, 67% (55, 79) were BP-LAM-positive; resulting in similar yield to sputum Xpert MTB/RIF Ultra [64% (49, 78)] in a programmatic scenario where sputum induction is unavailable. BP-LAM false-negatives had, vs. true-positives, less severe disease and were more likely to have previous TB. False-positive results were more likely to be from people who cultured only non-tuberculous mycobacteria [19% (4/21) vs. 4% (12/293) for true-negatives]. Conclusions: BP-LAM has higher sensitivity than LF-LAM, including in HIV-negative people, potentially permitting the expansion of urine LAM testing beyond people with advanced immunosuppression. Funding: The Global Health Technology Fund (GHIT) programs RFP-TRP-2018-001 and RFP-PD-2020-002, EDCTP2 (RIA2020I-3305, CAGE-TB; TMA2020CDF-3209, RADIANT). Molecular Biology Infectious Diseases Laboratory Diagnostics tuberculosis HIV diagnosis urine lipoarabinomannan Full Text Additional Declarations The authors declare no competing interests. Supplementary Files UrineLAMsupplementaryfile13112024.xlsx Individual level data UrineLAMsupplemetary10022025.docx Supplement Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5386988","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":374806243,"identity":"e569ca37-fa18-442b-9a8a-95ebc551cd04","order_by":0,"name":"Beston Hamasur","email":"","orcid":"","institution":"Biopromic AB, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute","correspondingAuthor":false,"prefix":"","firstName":"Beston","middleName":"","lastName":"Hamasur","suffix":""},{"id":374806244,"identity":"5e44834c-d186-4ed8-8164-0e9dabe12751","order_by":1,"name":"Anna O. 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An extended sputum microbiological reference standard (eMRS) was used and, in South Africa, sputum induction done.\u003c/p\u003e\n\u003cp\u003eResults: BP-LAM had higher sensitivity than LF-LAM [95% confidence interval (CI) 63% (58, 69) vs. 22% (18, 27)] and similar specificity [93% (90, 96) vs. 89% (85, 92)]. BP-LAM sensitivity did not differ in HIV-positive vs. -negative people nor by CD4 counts. Specificity was diminished in PLHIV [90% (83, 94) vs. 96% (92, 99)]. The design-locked version of BP-LAM had improved specificity than the prototype [93% (90, 96) vs. 85% (80, 88)]. In people with TB who could not expectorate sputum, 67% (55, 79) were BP-LAM-positive; resulting in similar yield to sputum Xpert MTB/RIF Ultra [64% (49, 78)] in a programmatic scenario where sputum induction is unavailable. BP-LAM false-negatives had, vs. true-positives, less severe disease and were more likely to have previous TB. False-positive results were more likely to be from people who cultured only non-tuberculous mycobacteria [19% (4/21) vs. 4% (12/293) for true-negatives].\u003c/p\u003e\n\u003cp\u003eConclusions: BP-LAM has higher sensitivity than LF-LAM, including in HIV-negative people, potentially permitting the expansion of urine LAM testing beyond people with advanced immunosuppression.\u003c/p\u003e\n\u003cp\u003eFunding: The Global Health Technology Fund (GHIT) programs RFP-TRP-2018-001 and RFP-PD-2020-002, EDCTP2 (RIA2020I-3305, CAGE-TB; TMA2020CDF-3209, RADIANT).\u003c/p\u003e","manuscriptTitle":"A new rapid lipoarabinomannan urine assay for tuberculosis: a two-centre diagnostic accuracy evaluation in outpatients with and without HIV","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-02-18 23:00:31","doi":"10.21203/rs.3.rs-5386988/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2024-11-06 11:11:02","doi":"10.21203/rs.3.rs-5386988/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f38af029-6ac9-432b-ac64-e32a1c55b802","owner":[],"postedDate":"February 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44178006,"name":"Molecular Biology"},{"id":44178007,"name":"Infectious Diseases"},{"id":44178008,"name":"Laboratory Diagnostics"}],"tags":[],"updatedAt":"2024-11-06T11:11:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-18 23:00:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-5386988","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5386988","identity":"rs-5386988","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}