{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:09:48Z","timestamp":1780088988976,"version":"3.54.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Although the rapid plasma reagin (RPR) test is used to determine treatment efficacy for syphilis, animal studies show that it decreases gradually after an initial increase even without treatment. Pre-treatment changes in RPR titer in humans and its relationship with post-treatment changes in RPR titer are not well known.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We retrospectively analyzed the clinical records of syphilitic patients who underwent automated RPR (Mediace) testing twice before treatment (i.e., at diagnosis and treatment initiation) within 1\u20133 months at an HIV\/AIDS referral hospital in Japan between 2006 and 2018. The RPR values were expressed as the ratio to the value at treatment initiation. The mean monthly relative change in the RPR after treatment was calculated on the log2 scale for each patient and analyzed by multivariable linear regression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Sixty-eight patients were identified. The median age was 45 (interquartile range [IQR], 38\u201350), 98.5% (67\/68) were men, and 97.1% (66\/68) had HIV. The median RPR titer ratio at treatment initiation\/diagnosis was 0.87 (IQR, 0.48\u20131.30). The RPR titer decreased more than twofold in 26.5% (18\/68) and more than fourfold in 10.3% (7\/68) before treatment. In the multivariable analysis, higher age (predicted monthly RPR relative change on the log2 scale 0.23\/10 years [95% confidence interval [CI], 0.090\u20130.37]), history of syphilis (0.36 [95% CI, 0.07\u20130.65]), and a lower ratio of RPR at treatment initiation\/diagnosis (\u22120.52\/every 10-fold increase [95% CI, \u22120.81 to \u22120.22]) were associated with a slower RPR decrease after treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In a mostly HIV patient population, RPR titer can show more than four-fold spontaneous increase or decrease within 1\u20133 months. Pre-treatment spontaneous decrease of RPR titer was associated with a slower decrease in post-treatment RPR titer.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0292044","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T17:39:36Z","timestamp":1695922776000},"page":"e0292044","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Changes in rapid plasma reagin titers in patients with syphilis before and after treatment: A retrospective cohort study in an HIV\/AIDS referral hospital in Tokyo"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-3369","authenticated-orcid":true,"given":"Kazuhiko","family":"Ikeuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-6879","authenticated-orcid":true,"given":"Kazuaki","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishiro","family":"Yajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"issue":"11","key":"pone.0292044.ref001","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1001\/jama.290.11.1510","article-title":"Update on syphilis: resurgence of an old problem","volume":"290","author":"MR Golden","year":"2003","journal-title":"Jama"},{"issue":"2","key":"pone.0292044.ref002","first-page":"134","article-title":"Cerebrospinal fluid findings after treatment of early syphilis with penicillin. A further series of 80 cases.","volume":"44","author":"WL Fernando","year":"1968","journal-title":"Br J Vener Dis"},{"issue":"2","key":"pone.0292044.ref003","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.idc.2023.02.006","article-title":"Syphilis: A Modern Resurgence.","volume":"37","author":"MS Ramchandani","year":"2023","journal-title":"Infect Dis Clin North Am"},{"issue":"18","key":"pone.0292044.ref004","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1001\/jama.2014.13259","article-title":"Treatment of syphilis: a systematic review","volume":"312","author":"ME Clement","year":"2014","journal-title":"Jama"},{"issue":"12","key":"pone.0292044.ref005","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.7326\/0003-4819-114-12-1005","article-title":"Serologic response to treatment of infectious syphilis","volume":"114","author":"B Romanowski","year":"1991","journal-title":"Ann Intern Med"},{"issue":"3","key":"pone.0292044.ref006","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/jdv.16946","article-title":"2020 European guideline on the management of syphilis","volume":"35","author":"M Janier","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"4","key":"pone.0292044.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually Transmitted Infections Treatment Guidelines, 2021.","volume":"70","author":"KA Workowski","year":"2021","journal-title":"MMWR Recomm Rep."},{"issue":"2","key":"pone.0292044.ref008","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cmi.2019.06.004","article-title":"Are nontreponemal tests suitable for monitoring syphilis treatment efficacy? 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Transmitted Disease Centre: A Monocentric Retrospective Study.","volume":"11","author":"V Marchese","year":"2022","journal-title":"J Clin Med."},{"issue":"2","key":"pone.0292044.ref018","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1136\/sextrans-2020-054887","article-title":"Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses.","volume":"98","author":"SA Nieuwenburg","year":"2022","journal-title":"Sex Transm Infect."},{"issue":"6","key":"pone.0292044.ref019","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/OLQ.0000000000001387","article-title":"The Terms \"Serofast\" and \"Serological Nonresponse\" in the Modern Syphilis Era.","volume":"48","author":"KG Ghanem","year":"2021","journal-title":"Sex Transm Dis"},{"key":"pone.0292044.ref020","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1186\/1471-2334-13-605","article-title":"Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging era of universal antiretroviral therapy use.","volume":"13","author":"S Jinno","year":"2013","journal-title":"BMC Infect Dis"},{"issue":"2","key":"pone.0292044.ref021","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1086\/589295","article-title":"Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients","volume":"47","author":"KG Ghanem","year":"2008","journal-title":"Clin Infect Dis"},{"issue":"3","key":"pone.0292044.ref022","doi-asserted-by":"crossref","first-page":"115767","DOI":"10.1016\/j.diagmicrobio.2022.115767","article-title":"Assessment of a fully automated RPR assay (Mediace RPR) for serological diagnosis and follow-up of syphilis: a retrospective study.","volume":"104","author":"AG Leroy","year":"2022","journal-title":"Diagn Microbiol Infect 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