{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:43:50Z","timestamp":1785858230137,"version":"3.56.0"},"posted":{"date-parts":[[2026,8,2]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01AI150485"],"award-info":[{"award-number":["R01AI150485"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/023wsvq95","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/037wke960","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Community-based tuberculosis screening can identify asymptomatic tuberculosis, but microbiological confirmation has been sputum-dependent. We evaluated the diagnostic performance, yield, and operational characteristics of centralized qPCR testing of community-collected tongue swabs (TS).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a cross-sectional study among household contacts (HHCs; \u226518 years) of individuals receiving treatment for pulmonary TB in South Africa. During household visits, health workers collected TS specimens and, where possible, sputum, which was tested in participants\u2019 homes using Xpert MTB\/RIF Ultra. TSs were transported non-refrigerated in molecular transport medium to a distant central laboratory for manual qPCR assay. The primary outcome was diagnostic performance of TS qPCR compared with sputum Xpert Ultra using paired results. Secondary outcomes were diagnostic yield by TS and operational indicators of the centralized testing workflow.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>909 HHCs were enrolled; median age 39 years (IQR 28\u201355), 532 (58\u00b75%) were asymptomatic, 617 (67\u00b79%) were sputum scarce. TS were collected from 901\/909 (99\u00b71%) and sputum from 292\/909 (32\u00b71%) participants. Among 271 paired TS\u2013sputum results, TS qPCR sensitivity was 60\u00b79% (95% CI 38\u00b75\u201380\u00b73), specificity 95\u00b72% (91\u00b77\u201397\u00b75), and overall agreement 92\u00b73% (88\u00b75\u201395\u00b70). Yield increased from 1\u00b78% (95% CI 1\u00b70\u20132\u00b78) with symptom-restricted sputum testing to 3\u00b72% (2\u00b71\u20134\u00b75) with symptom-agnostic sputum testing and 5\u00b79% (4\u00b75\u20137\u00b77) when TS testing was implemented among sputum-scarce individuals, identifying 25 additional HHCs with positive molecular test results (86\u00b72% increase). Operational indicators demonstrated successful implementation, with 2\u00b73% specimen loss and valid molecular results for 93\u00b78% who provided a TS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Despite lower per-test sensitivity than sputum testing, TS may provide a scalable strategy for expanding microbiological screening beyond sputum-dependent pathways, thereby substantially increasing tuberculosis detection among HHCs.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>U.S. NIH; Australian Department of Foreign Affairs and Trade; UK Foreign, Commonwealth and Development Office<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESEARCH IN CONTEXT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Evidence before this study<\/jats:title>\n                    <jats:p>\n                      A growing body of evidence suggests that a large proportion of tuberculosis (TB) exists as asymptomatic disease, defined by the World Health Organization as a person with TB disease who does not report symptoms suggestive of TB during screening. However, TB detection strategies have traditionally relied on symptom-based screening of people with presumed disease who present to healthcare facilities for evaluation using sputum-based diagnostic pathways. We searched PubMed, Embase and Google Scholar for studies published in English from January 1, 2010, to July 7, 2026, using combinations of the terms \u201ctuberculosis\u201d or \u201cTB\u201d, \u201ctongue swab\u201d, \u201coral swab\u201d, \u201ccommunity screening\u201d, \u201chousehold contacts\u201d, \u201cactive case finding\u201d, \u201csputum scarce\u201d, \u201casymptomatic\u201d, \u201csubclinical\u201d, \u201cPCR\u201d, \u201cqPCR\u201d, and \u201cXpert\u201d. Community-based screening studies, including household contact investigations, have reported microbiologically detectable TB outside routine facility-based pathways, including among people without symptoms and among those unable to produce sputum. Previous studies and systematic reviews showed that tongue swab testing can detect\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      with high specificity but only moderate sensitivity, generally lower than sputum-based molecular testing and often weaker in paucibacillary and asymptomatic disease. However, the recent evaluation of the near-point-of-care Pluslife MiniDock MTB platform using sputum and tongue swabs met WHO diagnostic accuracy targets for tuberculosis detection. Recent multi-country and in-home prospective tongue swab studies suggested feasibility and diagnostic potential. However, evidence remained limited on centralized workflows, non-refrigerated transport of community-collected swabs, operational implementation indicators, and the incremental contribution of tongue swabs to microbiological case detection in sputum-scarce populations outside traditional clinic-based settings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Added value of this study<\/jats:title>\n                    <jats:p>This study evaluates centralized qPCR testing of community-collected tongue swabs among adult household contacts of people receiving treatment for pulmonary TB in Eastern Cape, South Africa. Relative to paired sputum Xpert MTB\/RIF Ultra, tongue-swab qPCR had sensitivity of 60.9%, specificity of 95\u00b72%, and overall agreement of 92\u00b73%. Across screening strategies, 64 participants were microbiologically detected with TB; 51 were identified by tongue swabs and 29 by sputum, with overlap between modalities. Incorporating tongue swab testing for sputum-scarce participants identified 25 additional people with TB beyond symptom-agnostic sputum testing alone, increasing TB detection by 86\u00b72%. Operationally, tongue swabs were collected from 99\u00b71% of participants, the median shipment-to-receipt time was 47\u00b75 hours, specimen loss during transport was 2\u00b73%, and valid molecular results were generated for 93\u00b78% of participants that provided a tongue swab specimen. To our knowledge, no previous study has combined community-based tongue swab collection, ambient transport, centralized batch qPCR testing, diagnostic performance evaluation, diagnostic-yield comparisons, and operational implementation measures in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications of all the available evidence<\/jats:title>\n                    <jats:p>The available evidence suggests that tongue swabs should be considered not only as an alternative specimen, but also as a programmatic access strategy for microbiological TB testing outside traditional health facilities. Centralized high-throughput tongue swab testing workflows could strengthen community-based screening by extending microbiological testing to asymptomatic and sputum-scarce populations who are not found in traditional health system settings and are often missed by sputum-dependent pathways. Priorities for future research include improving assay sensitivity, evaluating cost-effectiveness and health-system integration, assessing prospective effects on treatment initiation and transmission, and determining generalizability across populations, platforms, and settings.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.30.26359194","type":"posted-content","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:10:15Z","timestamp":1785733815000},"source":"Crossref","is-referenced-by-count":0,"title":["Centralized molecular testing of community-collected tongue swabs for tuberculosis screening among household contacts: a cross-sectional diagnostic performance, yield, and implementation study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-2207","authenticated-orcid":false,"given":"Sharon L.","family":"Olifant","sequence":"first","affiliation":[{"name":"Centre for Tuberculosis Research, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"},{"name":"Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-4141","authenticated-orcid":false,"given":"Andrew","family":"Medina-Marino","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A"},{"name":"Desmond Tutu Health Foundation, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pieruccini","sequence":"additional","affiliation":[{"name":"School of Public Health, Brown University, Providence, Rhode Island, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8785-025X","authenticated-orcid":false,"given":"Kuhle","family":"Fiphaza","sequence":"additional","affiliation":[{"name":"Desmond Tutu Health Foundation, Cape Town, South Africa"},{"name":"Foundation for Professional Development, East London, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7545-6188","authenticated-orcid":false,"given":"Charl","family":"Bezuidenhout","sequence":"additional","affiliation":[{"name":"Foundation for Professional Development, East London, South Africa"},{"name":"Global Health, Boston University School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-441X","authenticated-orcid":false,"given":"Morten","family":"Ruhwald","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"},{"name":"Novo Nordisk Foundation Initiative for Vaccines and Immunity, NIVI, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1883-0059","authenticated-orcid":false,"given":"Adam","family":"Penn-Nicholson","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-7275","authenticated-orcid":false,"given":"Remco P.H.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-3554","authenticated-orcid":false,"given":"P. 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