{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:47:12Z","timestamp":1768567632290,"version":"3.49.0"},"posted":{"date-parts":[[2025,5,15]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Tongue swabs (TS) are novel non-sputum specimens for molecular diagnosis of tuberculosis (TB). Analysis of swabs by using Cepheid Xpert MTB\/RIF Ultra\u00ae (Xpert Ultra) is less sensitive than the use of certain manual qPCR methods but is desirable given the widespread use and familiarity of Xpert Ultra. This study evaluated an easy-to-use protocol for analyzing TS by Xpert Ultra. TS samples from symptomatic South African patients were previously collected and tested by Xpert Ultra using a protocol that requires a heating block (termed Heat+TE). Replicate, paired samples from the same patients were tested by a newly reported method that does not require heating (termed 2:1 SR). The diagnostic accuracy of the two methods was compared. Because the sensitivity of TS testing is lowest in patients with low sputum bacillary loads, the resolving power of this paired comparison was maximized by prioritizing samples from such participants (N=108), 88 of whom were TB-positive by sputum microbiological reference standard (MRS) and 20 were TB-negative. Within this sample set, the Heat+TE method was 42.5% (38\/88; 95CI 33-54%) sensitive and the 2:1 SR method was 52.3% (46\/88; 95CI 41-63%) sensitive relative to sputum MRS. Both methods were 100% (20\/20; 95% CI 83-100%) specific. A secondary analysis compared the sensitivities of single-sample versus dual-sample testing within a cohort (N=241) that included both high- and low-bacillary load participants. Testing of a single sample was 75.5% (182\/241; 95CI 70-81%) sensitive relative to sputum MRS, whereas dual sampling was 81.3% (196\/241; 95CI 76-86%) sensitive.<\/jats:p>","DOI":"10.1101\/2025.05.14.25327613","type":"posted-content","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T19:45:20Z","timestamp":1747338320000},"source":"Crossref","is-referenced-by-count":1,"title":["Testing tongue swab samples by Cepheid Xpert MTB\/RIF Ultra: Comparison of two protocols applied to samples from persons with low-bacillary load TB"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3931-8595","authenticated-orcid":false,"given":"Rachel C.","family":"Wood","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Goodgion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-5025","authenticated-orcid":false,"given":"Alaina M.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-2836","authenticated-orcid":false,"given":"Angelique K.","family":"Luabeya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hatherill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-6520","authenticated-orcid":false,"given":"Gerard A.","family":"Cangelosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025051907001350000_2025.05.14.25327613v1.1","doi-asserted-by":"crossref","first-page":"e1184","DOI":"10.1016\/S2214-109X(24)00148-7","article-title":"Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research","volume":"12","year":"2024","journal-title":"The Lancet Global Health"},{"key":"2025051907001350000_2025.05.14.25327613v1.2","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/s41564-023-01365-3","article-title":"Transforming tuberculosis diagnosis","volume":"8","year":"2023","journal-title":"Nat Microbiol"},{"key":"2025051907001350000_2025.05.14.25327613v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01379-X"},{"key":"2025051907001350000_2025.05.14.25327613v1.4","doi-asserted-by":"crossref","unstructured":"Cangelosi GA , Salfinger M. 2025. Casting a wider net for tuberculosis cases. Eur Respir J 65.","DOI":"10.1183\/13993003.02245-2024"},{"key":"2025051907001350000_2025.05.14.25327613v1.5","first-page":"e01140","article-title":"High-sensitivity detection of Mycobacterium tuberculosis DNA in tongue swab samples","volume":"63","year":"2025","journal-title":"Journal of Clinical Microbiology"},{"key":"2025051907001350000_2025.05.14.25327613v1.6","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-6225530\/v1"},{"key":"2025051907001350000_2025.05.14.25327613v1.7","first-page":"e00019","article-title":"Diagnostic accuracy of tongue swab testing on two automated tuberculosis diagnostic platforms, Cepheid Xpert MTB\/RIF Ultra and Molbio Truenat MTB Ultima","volume":"62","year":"2024","journal-title":"Journal of Clinical Microbiology"},{"key":"2025051907001350000_2025.05.14.25327613v1.8","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00421-22:e0042122"},{"key":"2025051907001350000_2025.05.14.25327613v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0251422"},{"key":"2025051907001350000_2025.05.14.25327613v1.10","first-page":"e01847","article-title":"Noninvasive Detection of Tuberculosis by Oral Swab Analysis","volume":"57","year":"2019","journal-title":"Journal of Clinical Microbiology"},{"key":"2025051907001350000_2025.05.14.25327613v1.11","doi-asserted-by":"crossref","first-page":"10789","DOI":"10.1038\/s41598-019-47302-5","article-title":"Microbiological diagnosis of pulmonary tuberculosis in children by oral swab polymerase chain reaction","volume":"9","year":"2019","journal-title":"Scientific Reports"},{"key":"2025051907001350000_2025.05.14.25327613v1.12","doi-asserted-by":"crossref","unstructured":"Wood RC , Luabeya AK , Weigel KM , Wilbur AK , Jones-Engel L , Hatherill M , Cangelosi GA . 2015. Detection of Mycobacterium tuberculosis DNA on the oral mucosa of tuberculosis patients. Sci Rep 5.","DOI":"10.1038\/srep08668"},{"key":"2025051907001350000_2025.05.14.25327613v1.13","unstructured":"de Vos M , Le H , Marcelo D , Ajide B , Al\u00ed-Francia KG , Borkman AL , Desravines R , Chang HT , Dowling W , Kamulegeya L. Diagnostic Accuracy of Tongue Swabs for Tuberculosis Using a Common Protocol for Xpert MTB\/RIF Ultra Testing: A Multi-Country Assessment."},{"key":"2025051907001350000_2025.05.14.25327613v1.14","doi-asserted-by":"crossref","unstructured":"Wang Y , Cui J , Li Y , Wang M , Han W , Liu A , Wang F , Liu R , Kang S , Zhang J , Zhu S , Lai Z , Guan W , Zou S , Yin X , Qing J , Mu G , Guan L , Li L , Pang Y. 2025. Rapid quantitative PCR on tongue swabs for pulmonary tuberculosis in adults: a prospective multicentre study. 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