{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:40:16Z","timestamp":1781840416270,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010197","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000}}],"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>In yaws-endemic areas, children with <jats:italic>Treponema pallidum subsp<\/jats:italic>. <jats:italic>pertenue<\/jats:italic> infection may suffer recurrent episodes due to either reinfection or relapse. However, the possibility of infection with other cutaneous ulcer causative agents and difficulties in interpreting standard laboratory results challenges the estimation of yaws recurrence rates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We estimated the rates of yaws recurrences in the Lihir Island (Papua New Guinea) using two approaches: passive surveillance based on a retrospective screening of electronic medical records of cutaneous ulcers diagnosed using serological testing between 2005 and 2016, and active surveillance conducted during a cross-sectional prevalence study which included PCR analyses of ulcers of all suspected cases of yaws. The risk of recurrent infection was assessed based on data from the passive surveillance analysis and using two Cox regression models (crude and multivariate), stratified by year of index episode. Data gathered from the active surveillance was used to characterize the recurrences and no hypothesis testing was performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The electronic medical records included 6,125 patients (7,889 ulcer episodes) with documented serological results of cutaneous ulcers of which1,486 were diagnosed with yaws. Overall, 1,246\/6,125 patients (20.3%) presented more than once with a cutaneous ulcer, and 103\/1,486 (6.7%) patients had multiple episodes of yaws. The risk of yaws recurrence significantly increased with age and was higher in patients with \u22653 recurrent episodes. In the active surveillance, we identified 50 individuals with recurrent cutaneous ulcer that had PCR results available for both the index and recurrent episode. Of 12 individuals with <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> in the index ulcer, 8 (66%) had <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> in subsequent assessments, relapse related to macrolide-resistance was identified in two of these cases.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results confirm the need for active follow-up of yaws patients after treatment, particularly children and individuals with a history of recurrence.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0010197","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T17:42:17Z","timestamp":1647884537000},"page":"e0010197","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Yaws recurrence in children at continued risk of infection"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-0748","authenticated-orcid":true,"given":"Camila G.","family":"Beiras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7585-4743","authenticated-orcid":true,"given":"Michael","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-6951","authenticated-orcid":true,"given":"Lloren\u00e7","family":"Quint\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Gavil\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reman","family":"Kolmau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ubals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marti","family":"Vall-Mayans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Mitj\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"pntd.0010197.ref001","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/S0140-6736(18)30204-6","article-title":"Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study","volume":"391","author":"O Mitj\u00e0","year":"2018","journal-title":"Lancet"},{"key":"pntd.0010197.ref002","first-page":"17","article-title":"Non-specific factors in the epidemiology of yaws","volume":"8","author":"KR Hill","year":"1953","journal-title":"Bull World Health Organ"},{"key":"pntd.0010197.ref003","first-page":"1206","article-title":"Immunity in experimental syphilis. VI. Successful vaccination of rabbits with Treponema pallidum, Nichols strain, attenuated by g- irradiation","volume":"110","author":"JN Miller","year":"1973","journal-title":"J Immunol"},{"key":"pntd.0010197.ref004","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1128\/iai.21.2.430-435.1978","article-title":"Passive transfer of resistance to frambesial infection in hamsters","volume":"21","author":"RF Schell","year":"1978","journal-title":"Infect Immun"},{"key":"pntd.0010197.ref005","first-page":"237","article-title":"The Effect of Repeated Cured Infections on the Develop-ment of Acquired Homologous Strain Immunity in Experimental Syphilis.","volume":"36","author":"HJ Magnuson","year":"1952","journal-title":"Am J Syph"},{"key":"pntd.0010197.ref006","doi-asserted-by":"crossref","first-page":"6244","DOI":"10.1128\/IAI.00827-06","article-title":"Antigenic variation of TprK V regions abrogates specific antibody binding in syphilis","volume":"74","author":"RE LaFond","year":"2006","journal-title":"Infect Immun"},{"key":"pntd.0010197.ref007","doi-asserted-by":"crossref","first-page":"e0007621","DOI":"10.1371\/journal.pntd.0007621","article-title":"Insights into the genetic variation profile of tprK in Treponema pallidum during the development of natural human syphilis infection","volume":"13","author":"D Liu","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010197.ref008","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1128\/IAI.02236-14","article-title":"Antigenic variation of TprK facilitates development of secondary syphilis","volume":"82","author":"TB Reid","year":"2014","journal-title":"Infect Immun"},{"key":"pntd.0010197.ref009","doi-asserted-by":"crossref","first-page":"e235","DOI":"10.1016\/S2214-109X(14)70019-1","article-title":"Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study","volume":"2","author":"O Mitj\u00e0","year":"2014","journal-title":"Lancet Glob Heal"},{"key":"pntd.0010197.ref010","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3201\/eid\/1706.101575","article-title":"Outcome predictors in treatment of yaws","volume":"17","author":"O Mitj\u00e0","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"pntd.0010197.ref011","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/ije\/dyu222","article-title":"Modelling recurrent events: A tutorial for analysis in epidemiology.","volume":"44","author":"LDAF Amorim","year":"2015","journal-title":"Int J Epidemiol."},{"key":"pntd.0010197.ref012","volume-title":"Stata Statistical Software. Release 16.[software].","author":"StataCorp LLC"},{"key":"pntd.0010197.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-018-3399-8","article-title":"Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study.","volume":"18","author":"C Kenyon","year":"2018","journal-title":"BMC Infect Dis"},{"key":"pntd.0010197.ref014","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/OLQ.0b013e3181e9afc7","article-title":"Reinfections during the Florida syphilis epidemic, 2000\u20132008.","volume":"38","author":"TH Brewer","year":"2011","journal-title":"Sex Transm Dis"},{"key":"pntd.0010197.ref015","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1177\/0956462418757554","article-title":"Factors associated with repeat diagnosis of syphilis in genitourinary medicine (GUM) clinic attendees in the North East of England, 2002\u20132014.","volume":"29","author":"G Dolan","year":"2018","journal-title":"Int J STD AIDS"},{"key":"pntd.0010197.ref016","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/OLQ.0b013e3181fe650b","article-title":"Repeat syphilis among men who have sex with men\u2014San Diego County, 2004\u20132009.","volume":"38","author":"KA Katz","year":"2011","journal-title":"Sex Transm Dis"},{"key":"pntd.0010197.ref017","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1016\/S2666-5247(20)30113-0","article-title":"Yaws re-emergence and bacterial drug resistance selection after mass administration of azithromycin: a genomic epidemiology investigation","volume":"1","author":"MA Beale","year":"2020","journal-title":"The Lancet Microbe"},{"key":"pntd.0010197.ref018","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1001\/jama.1972.03200180015003","article-title":"Treatment for early syphilis and reactivity of serologic tests","volume":"221","author":"AL Schroeter","year":"1972","journal-title":"Jama"},{"key":"pntd.0010197.ref019","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S0140-6736(11)61624-3","article-title":"Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: An open-label, non-inferiority, randomised trial","volume":"379","author":"O Mitj\u00e0","year":"2012","journal-title":"Lancet"},{"key":"pntd.0010197.ref020","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1093\/aje\/kwx305","article-title":"Targeted Treatment of Yaws with Household Contact Tracing: How Much Do We Miss?","volume":"187","author":"L Dyson","year":"2018","journal-title":"Am J Epidemiol"},{"key":"pntd.0010197.ref021","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.3201\/eid2611.191491","article-title":"Modeling treatment strategies to inform yaws eradication","volume":"26","author":"A Holmes","year":"2020","journal-title":"Emerg Infect Dis"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010197","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T18:14:16Z","timestamp":1648750456000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010197"}},"subtitle":[],"editor":[{"given":"Stuart Robert","family":"Ainsworth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010197","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0010197","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]}}}