{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T15:05:44Z","timestamp":1772031944164,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,23]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Household contact investigation for tuberculosis (TB) is limited by referral for clinic-based testing services. We evaluated the performance of in-home tongue swab (TS) testing among symptom-agnostic household contacts (HHC) to inform HCI screening strategies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a prospective cohort study among HHC of TB patients in Eastern Cape, South Africa. In-home testing of sputum and TSs, with TSs pooled from up to three HHCs, was performed using Xpert Ultra on portable GeneExpert devices. Outcomes included diagnostic performance of TS testing relative to sputum and linkage-to-care outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>Between June 2021 and October 2024, 909 HHC were enrolled; 99\u00b71% provided s TS, 31\u00b76% provided sputum. Overall sensitivity and specificity of TS testing was 61\u00b79% (95% CI: 38\u00b74%\u201381\u00b79%) and 100% (98\u00b79%\u2013100%), respectively; sensitivity was 100% (47\u00b78%\u2013100%) for individually tested swabs. Among two-swab and three-swab pools where 21 individual was sputum positive, 55\u00b76% (21\u00b72%\u201386\u00b73%) and 42\u00b79% (9\u00b79%\u201381\u00b76%) tested positive, respectively; TS sensitivity declined with decreasing sputum Ultra semi-quantitative category. 27 of 439 (6\u00b72%) households had an indictation of secondary TB; 13 (3\u00b70%) by sputum and TS, 11 (2\u00b75%) by sputum only, 3 (0\u00b77%) by TS only. Sputum testing identified 29 HHC with TB (yield=3\u00b72%); 25\/29 (86\u00b72%) linked to care (median 1 day [IQR 1\u20132]).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>While in-home molecular testing of sputum supported rapid linkage-to-care, and TSs enabled near-universal testing of symptom-agnostic HHCs, efficiency gains through pooled TS testing must be balance against sensitivity trade-offs.<\/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>Household contacts (HHCs) of people with TB are prioritized for active case-finding (ACF) strategies due to their increased risk of developing TB disease. Household contact investigation (HCI), a widely recommended ACF strategy, is constrained by attrition from referral-based cascades and sputum-based testing. We searched PubMed and Embase for studies published in English from January 1, 2010 to January 31, 2026, using combinations of the terms \u201ctuberculosis\u201d or \u201cTB\u201d with \u201chousehold contact,\u201d \u201ccontact tracing,\u201d \u201ccontact investigation,\u201d \u201cscreening,\u201d \u201ctriage,\u201d \u201cin-home testing,\u201d \u201cmolecular testing,\u201d and \u201ctongue swab.\u201d We also reviewed references listed in relevant articles. There are limited data describing microbiological testing strategies targeting HHCs conducted outside clinic settings, and fewer still that explore the integration of HCI and in-home molecular TB testing. Tongue swabs have emerged as a promising non-invasive, non-sputum specimen type for molecular TB diagnosis. However, most tongue swab performance data have been generated in clinic-based or symptom-prompted populations, with a marked paucity of data generated in populations at high risk for asymptomatic or paucibacillary TB, including HHC. Before this study, published work exploring the use of tongue swabs within in-home TB testing strategies was limited to two papers, both from our group, which focused on acceptability, feasibility, and preliminary costing and modeling analyses. To date, no published studies have assessed the diagnostic performance of tongue swab\u2013based molecular testing relative to sputum-based testing among HHC, the use of tongue swab specimens as part of in-home testing strategies, nor the implication of pooled tongue swab testing to inform household-level screening and diagnostic escalation strategies. In addition, evidence describing verified linkage to TB treatment services following in-home sputum molecular testing was limited to one pilot study paper.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Added Value of This Study<\/jats:title>\n                    <jats:p>This study is the first to evaluate in-home molecular TB testing using tongue swab specimens, and to incorporate household-level pooling of tongue swabs from multiple household members as a primary screening strategy. Near-universal swab collection substantially expanded access to microbiological testing in a population with limited sputum production. Although pooled swab testing exhibited reduced sensitivity compared with individual-level sputum testing, stratified analyses of tongue swab tests by sputum Xpert Ultra semi-quantitative categories demonstrate that this reduction reflects a biological gradient associated with low mycobacterial burden. Importantly, pooled swab testing identified TB among contacts unable to produce sputum, increasing diagnostic yield beyond sputum-dependent approaches. The study also documents the increase in diagnostic yield when implementing a symptom-agnostic testing strategy among HHC, and rapid, verified linkage to clinic-based TB treatment services following in-home sputum testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications of All the Available Evidence<\/jats:title>\n                    <jats:p>Collectively, the available evidence supports reframing TB household contact investigation from individual-level referral for clinic-based testing toward in-home testing models, including the use of household-level screening with diagnostic escalation. Near-universal, in-home collection of tongue swab specimens enables substantially broader microbiological assessment than sputum-dependent strategies and facilitates detection of TB among asymptomatic and sputum-scarce HHCs, individuals frequently missed by referral-based approaches for clinic-based sputum collection and testing. Our findings show that the reduced sensitivity associated with pooled tongue swab testing follows a predictable biological gradient related to mycobacterial burden rather than a technical failure of pooling. Pooled swab testing should therefore be understood as a household-level screening strategy within a sequential diagnostic algorithm, not a replacement for individual diagnosis. For TB programs, efficiency gains and expanded coverage achieved through pooling must be balance against sensitivity trade-offs. Household-level screening using pooled specimens can focus downstream referrals and may improve programmatic efficiency without requiring universal individual testing. Future research should evaluate optimized diagnostic algorithms that integrate pooled, non-sputum testing with diagnostic escalation, assess impact on linkage-to-care and prevention outcomes, and define the role of pooled testing within scalable, community-based TB case-finding strategies.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.19.26346589","type":"posted-content","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T01:20:25Z","timestamp":1771896025000},"source":"Crossref","is-referenced-by-count":0,"title":["In-home molecular testing of tongue swabs and sputum to inform household-level screening with diagnostic escalation strategies for tuberculosis contact investigation: a prospective cohort study in South Africa"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-982X","authenticated-orcid":false,"given":"Andrew","family":"Medina-Marino","sequence":"first","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Centre for Tuberculosis Research, 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, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-2207","authenticated-orcid":false,"given":"Sharon","family":"Olifant","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pieruccini","sequence":"additional","affiliation":[{"name":"School of Public Health, Brown University, Providence, Rhode Island, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8785-025X","authenticated-orcid":false,"given":"Kuhle","family":"Fiphaza","sequence":"additional","affiliation":[{"name":"Research Unit, Foundation for Professional Development, East London, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nondumiso","family":"Ngcelwane","sequence":"additional","affiliation":[{"name":"Buffalo City Metro Health District, Eastern Cape Provincial Department of Health, Bisho, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-441X","authenticated-orcid":false,"given":"Morten","family":"Ruhwald","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-4141","authenticated-orcid":false,"given":"Adam","family":"Penn-Nicholson","sequence":"additional","affiliation":[{"name":"FIND, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-3554","authenticated-orcid":false,"given":"Bernard","family":"Fourie","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026022505351216000_2026.02.19.26346589v1.1","doi-asserted-by":"crossref","first-page":"100337","DOI":"10.1016\/j.jctube.2022.100337","article-title":"Tuberculosis in household contacts of tuberculosis patients in sub-Saharan African countries: A systematic review and meta-analysis","volume":"29","year":"2022","journal-title":"Journal of Clinical Tuberculosis and Other Mycobacterial Diseases"},{"key":"2026022505351216000_2026.02.19.26346589v1.2","doi-asserted-by":"crossref","first-page":"101206","DOI":"10.1016\/j.eclinm.2021.101206","article-title":"Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis","volume":"42","year":"2021","journal-title":"eClinicalMedicine"},{"issue":"4","key":"2026022505351216000_2026.02.19.26346589v1.3","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.4269\/ajtmh.20-0809","article-title":"Evaluating the Quality of Tuberculosis Contact Investigation in Cali, Colombia: A Retrospective Cohort Study","volume":"104","year":"2021","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"2026022505351216000_2026.02.19.26346589v1.4","doi-asserted-by":"crossref","unstructured":"Velen K , Shingde RV , Ho J , Fox GJ . 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