{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:57:12Z","timestamp":1789088232038,"version":"build-2803163510"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"name":"Centers for Disease Control and Prevention's Strengthening STD Prevention and Control for Health Departments","award":["PS19-1901"],"award-info":[{"award-number":["PS19-1901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little evidence supports the need for 3 weekly benzathine penicillin G (BPG) injections to treat late or unknown duration syphilis, and completion of the regimen may be difficult. We compared treatment effectiveness of 1 versus 3 doses of BPG and doxycycline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using surveillance data for cases diagnosed with late or unknown duration syphilis between 2016 and 2021 from 6 jurisdictions. We categorized BPG and doxycycline treatment based on the recorded number and timing of doses received. We defined treatment effectiveness as a 4-fold decrease in nontreponemal serum titer by 24 months posttreatment and compared treatment effectiveness using log binomial regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 18 027 cases eligible for inclusion, over half had 3 doses of BPG recorded (11 342, 63%); relatively few had only 1 dose recorded (1928, 11%) or received at least 28 days of doxycycline (3017, 17%). Fourfold titer decreases were observed for 75% and 80% of cases given 3 doses and 1 dose of BPG, respectively, and for the 74% given doxycycline. Treatment effectiveness was similar across all treatment dose\/interval categories and remained comparable when stratified by baseline titer, pregnancy status, and human immunodeficiency virus (HIV) infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We did not observe a difference in treatment effectiveness between 1 and 3 doses of BPG, or between 3 doses of BPG and doxycycline, for late or unknown duration syphilis. Additional observational and clinical studies with more complete treatment and serologic response information are needed to confirm these findings and inform practice recommendations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag099","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:40:59Z","timestamp":1771591259000},"page":"e843-e851","source":"Crossref","is-referenced-by-count":7,"title":["Is 3 Really What We Need? Relative Effectiveness of Benzathine Penicillin G and Doxycycline Treatment Regimens for Late or Unknown Duration Syphilis in 6 US Jurisdictions, 2016\u20132021"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0679-3688","authenticated-orcid":false,"given":"River A","family":"Pugsley","sequence":"first","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"Virginia Department of Health, Division of Disease Prevention , Richmond, Virginia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L","family":"Davis","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-196X","authenticated-orcid":false,"given":"Anna B","family":"Cope","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"North Carolina Division of Public Health , Raleigh, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-7280","authenticated-orcid":false,"given":"Jill C","family":"Diesel","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"Michigan Department of Health and Human Services , Detroit, Michigan ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Matthias","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"Florida Department of Health, STD Section , Tallahassee, Florida ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8101-7012","authenticated-orcid":false,"given":"Brandi","family":"Danforth","sequence":"additional","affiliation":[{"name":"Florida Department of Health, STD Section , Tallahassee, Florida ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-442X","authenticated-orcid":false,"given":"Mohammad","family":"Rahman","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"Louisiana Office of Public Health, STD\/HIV\/Hepatitis Program , New Orleans, Louisiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bell","sequence":"additional","affiliation":[{"name":"Maricopa County Public Health Department , Phoenix, Arizona ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie M","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]},{"name":"Maricopa County Public Health Department , Phoenix, Arizona ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-1163","authenticated-orcid":false,"given":"Felicia M T","family":"Lewis","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7189-5492","authenticated-orcid":false,"given":"Lindley A","family":"Barbee","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention , Atlanta, Georgia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"2026043013150466500_ciag099-B1","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.2105\/AJPH.33.12.1387","article-title":"Penicillin treatment of syphilis","volume":"33","author":"Mahoney","year":"1943","journal-title":"Am J Public Health Nations 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The experience of three decades","volume":"47 Suppl","author":"Idsoe","year":"1972","journal-title":"Bull World Health Organ"},{"key":"2026043013150466500_ciag099-B6","first-page":"143","article-title":"Treatment of latent syphilis","volume":"3","author":"Jaffe","year":"1976","journal-title":"J Am Vener Dis Assoc"},{"key":"2026043013150466500_ciag099-B7","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1001\/jama.2014.13259","article-title":"Treatment of syphilis: a systematic review","volume":"312","author":"Clement","year":"2014","journal-title":"JAMA"},{"key":"2026043013150466500_ciag099-B8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually transmitted infections treatment guidelines, 2021","volume":"70","author":"Workowski","year":"2021","journal-title":"MMWR Recomm Rep"},{"key":"2026043013150466500_ciag099-B9","first-page":"20499361241265941","article-title":"Risk factors for treatment non-completion among patients with syphilis","volume":"11","author":"Clarkson-During","year":"2024","journal-title":"Ther Adv Infect Dis"},{"key":"2026043013150466500_ciag099-B10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/ajo.13424","article-title":"Addressing the crisis of congenital syphilis: key findings from an evaluation of the management of syphilis in pregnancy and the newborn in South-East Queensland","volume":"62","author":"Wu","year":"2022","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"2026043013150466500_ciag099-B11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/OLQ.0000000000001775","article-title":"Treatment completion with three-dose series of benzathine penicillin among people diagnosed with late latent and unknown duration syphilis, Maricopa County, Arizona","volume":"50","author":"Mangone","year":"2023","journal-title":"Sex Transm Dis"},{"key":"2026043013150466500_ciag099-B12","volume-title":"Sexually transmitted infections surveillance 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2024","volume":"73","author":"Papp","year":"2024","journal-title":"MMWR Recomm Rep"},{"key":"2026043013150466500_ciag099-B18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/OLQ.0000000000002148","article-title":"Comparison of three treatment regimens for latent syphilis of late or unknown duration using public health surveillance data","volume":"52","author":"Hunt","year":"2025","journal-title":"Sex Transm Dis"},{"key":"2026043013150466500_ciag099-B19","first-page":"101","article-title":"Syphilis: CDC recommended treatment schedules, 1976","volume":"25","author":"Centers for Disease Control and Prevention","year":"1976","journal-title":"Morb Mortal Wkly Rep"},{"key":"2026043013150466500_ciag099-B20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/OLQ.0000000000002161","article-title":"Is single-dose benzathine penicillin G adequate for late latent syphilis?","volume":"52","author":"Kojima","year":"2025","journal-title":"Sex Transm 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surveillance","volume":"32","author":"Peterman","year":"2005","journal-title":"Sex Transm Dis"},{"key":"2026043013150466500_ciag099-B24","first-page":"3","article-title":"The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material","volume":"35","author":"Gjestland","year":"1955","journal-title":"Acta Derm Venereol Suppl (Stockh)"},{"key":"2026043013150466500_ciag099-B25","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1001\/archinte.160.5.585","article-title":"Unraveling the Tuskegee study of untreated syphilis","volume":"160","author":"White","year":"2000","journal-title":"Arch Intern Med"},{"key":"2026043013150466500_ciag099-B26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/00007435-197910000-00003","article-title":"Serologic responses to treatment of 128 patients with late latent syphilis","volume":"6","author":"Fiumara","year":"1979","journal-title":"Sex Transm Dis"},{"key":"2026043013150466500_ciag099-B27","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":"Romanowski","year":"1991","journal-title":"Ann Intern Med"},{"key":"2026043013150466500_ciag099-B28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1056\/NEJM199707313370504","article-title":"A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection","volume":"337","author":"Rolfs","year":"1997","journal-title":"N Engl J Med"},{"key":"2026043013150466500_ciag099-B29","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1086\/644618","article-title":"Factors determining serologic response to treatment in patients with syphilis","volume":"49","author":"Gonz\u00e1lez-L\u00f3pez","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2026043013150466500_ciag099-B30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/OLQ.0000000000000541","article-title":"Rate of decline in nontreponemal antibody titers and seroreversion after treatment of early syphilis","volume":"44","author":"Se\u00f1a","year":"2017","journal-title":"Sex Transm Dis"},{"key":"2026043013150466500_ciag099-B31","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/sti.2006.021402","article-title":"Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics","volume":"83","author":"Ghanem","year":"2007","journal-title":"Sex Transm Infect"}],"container-title":["Clinical Infectious 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