{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:33:51Z","timestamp":1784590431331,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004666","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-143350"],"award-info":[{"award-number":["FDN-143350"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016178","name":"Instituto Nacional de Ci\u00c3\u00aancia e Tecnologia dos Hymenoptera Parasit\u00c3\u00b3ides da Regi\u00c3\u00a3o Sudeste Brasileira","doi-asserted-by":"publisher","award":["parecer t\u00e9cnico 3\/2021, NUP 25000.012788\/2021-61"],"award-info":[{"award-number":["parecer t\u00e9cnico 3\/2021, NUP 25000.012788\/2021-61"]}],"id":[{"id":"10.13039\/501100016178","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chair","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Desenvolvimento Cient\u00c3fico e Tecnol\u00c3\u00b3gico of Brazil"},{"name":"Desenvolvimento Cient\u00c3fico e Tecnol\u00c3\u00b3gico of Brazil"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The World Health Organization recommends evaluation of all household contacts (HHC) of index tuberculosis (TB) patients for TB disease (TBD) and TB infection (TBI). Tests to identify TBI and TBD are preferred but can be skipped in persons living with HIV and children &lt;5 years. There is equipoise on the need for these tests in other HHC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a superiority, open label cluster-randomized trial in Benin and Brazil to compare three strategies to evaluate HHC aged 5\u201350 of persons newly diagnosed with drug susceptible pulmonary TBD: Standard: tuberculin skin testing (TST) for TBI and if positive, chest X-ray (CXR) to rule out TBD; rapid molecular test (RMT): same as Standard, except CXR replaced by an RMT; and No-TST: CXR for all but no TST. Randomization was computer-generated and stratified by country, in blocks of variable length. The primary outcome was TB preventive therapy (TPT) initiation among HHC considered eligible (positive TST, if done, and no evidence of TBD on CXR or RMT). Secondary outcomes were: completion of investigations to detect TBI and TBD, detection of TBD, TPT completion, severe adverse events, and societal costs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among 1,589 participating HHC enrolled from 29 January 2020, to 30 November 2022, 474 were randomized to the standard, 583 to the RMT, and 532 to the no-TST strategies; all were included in the analyses. Of 848 HHC considered eligible for TPT, 802 (94.6%) initiated TPT, with no difference between strategies (95%, 94%, and 95% for the standard, RMT, and no-TST strategies, respectively). Of the secondary outcomes, protocol-mandated investigations to detect TBI and exclude possible TBD were completed for 93.4% overall, with slight differences between arms (93%, 95%, and 93% for the standard, RMT, and no-TST strategies, respectively). Adverse events resulting in discontinuation of TPT occurred in 3 (0.4%) participants in total (with 1, 0, and 2 events among participants in the Standard, RMT, and no-TST arms, respectively). The proportion completing TPT was similar with Standard and RMT strategies but was 13% lower (95% confidence interval: 3% to 23% lower) with the No-TST strategy. Societal costs per HHC completing investigations were $61 ($56\u2013$65) with the standard strategy, compared to $52 ($49\u2013$55) with the RMT strategy and $74 ($72\u2013$77) with the no-TST strategy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This randomized trial provides <jats:strike>high-quality<\/jats:strike> evidence that TST followed by selected use of CXR or an RMT to exclude disease can achieve high rates of TPT initiation at reasonable costs. A limitation of the trial is the potential study effect, which may have affected adherence by providers and HHCs. RMT could replace CXR in the management of HHC in resource limited settings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Registration<\/jats:title>\n<jats:p>clinicaltrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04528823\" xlink:type=\"simple\">NCT04528823<\/jats:ext-link><\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004666","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T17:52:06Z","timestamp":1753725126000},"page":"e1004666","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rapid molecular testing or chest X-ray or tuberculin skin testing for household contact assessment of tuberculosis infection: A cluster-randomized trial"],"prefix":"10.1371","volume":"22","author":[{"given":"Menonli","family":"Adjobimey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-4984","authenticated-orcid":true,"given":"Anete","family":"Trajman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-8870","authenticated-orcid":true,"given":"Mayara Lisboa","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Valiquette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6960-7482","authenticated-orcid":true,"given":"Diana","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6114-0906","authenticated-orcid":true,"given":"Frimege","family":"Djohoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-8327","authenticated-orcid":true,"given":"Olivia","family":"Oxlade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-4583","authenticated-orcid":true,"given":"Federica","family":"Fregonese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dissou","family":"Affolabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Kouchade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-0485","authenticated-orcid":true,"given":"Elisa","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3913-9985","authenticated-orcid":true,"given":"Renata","family":"Spener-Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Cordeiro-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato T.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Scotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-9497","authenticated-orcid":true,"given":"Andrea","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-4514","authenticated-orcid":true,"given":"Dick","family":"Menzies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"pmed.1004666.ref001","volume-title":"Global Tuberculosis Report 2023","author":"World Health Organization.","year":"2024"},{"issue":"9979","key":"pmed.1004666.ref002","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/S0140-6736(15)60570-0","article-title":"WHO\u2019s new end TB strategy","volume":"385","author":"M Uplekar","year":"2015","journal-title":"Lancet"},{"issue":"10","key":"pmed.1004666.ref003","article-title":"The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling","volume":"13","author":"RMGJ Houben","year":"2016","journal-title":"PLoS Med"},{"key":"pmed.1004666.ref004","first-page":"10","volume-title":"Political declaration of the high-level meeting of the general assembly on the fight against tuberculosis: draft resolution","author":"United Nations General Assembly.","year":"2023"},{"key":"pmed.1004666.ref005","volume-title":"WHO consolidated guidelines on tuberculosis. 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