{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:41:08Z","timestamp":1791902468633,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,12,17]],"date-time":"2005-12-17T00:00:00Z","timestamp":1134777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Syphilis is a chronic sexually transmitted infection caused by\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    subspecies\n                    <jats:italic>pallidum<\/jats:italic>\n                    . Its protean clinical presentations earned it the name of the \u2018Great Mimicker\u2019. Understanding of disease pathogenesis and how host\u2013pathogen interactions influence the course of disease have been compromised by the facts that the organism cannot be grown\n                    <jats:italic>in vitro<\/jats:italic>\n                    and, as an exclusively human pathogen, inferences made from animal models are of limited applicability. Many questions remain about how\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    biology contributes to distinctive features of syphilis, such as its ability to persist in the presence of a brisk host response or its propensity for neuro\u2010invasion and congenital transmission. In 1998, the genome of\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    was sequenced. The organism has a relatively small genome, suggesting that it utilizes host biosynthesis to fulfil some of its metabolic needs. While biological functions are suggested for only about 55% of\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    's 1041 open reading frames, even these relatively early studies offer important insights into syphilis pathogenesis. A family of repeat genes, the\n                    <jats:italic>Tp<\/jats:italic>\n                    genes, encode proteins homologous to the major sheath proteins of\n                    <jats:italic>T. denticola.<\/jats:italic>\n                    Antibodies to the\n                    <jats:italic>TprK<\/jats:italic>\n                    variable regions are protective in a rabbit model. With successive passage, increasing diversity is observed in the\n                    <jats:italic>TprK<\/jats:italic>\n                    V region genes. Antigenic variation through gene conversion has been hypothesized to be one mechanism of escaping immune surveillance, allowing for prolonged infection and persistence in the presence of a robust host response. Human and animal studies suggest that a Th1 response is elicited in primary syphilis. Progression to the secondary stage is accompanied by a shift to a Th2 response, allowing for incomplete clearance of the pathogen. In pregnancy, intense inflammatory responses and prostaglandins induced by fetal infection may be responsible for fetal death or pre\u2010term delivery and severe growth retardation or other manifestations of congenital syphilis. Understanding of the molecular targets of these immune responses may facilitate the development of vaccines for syphilis. Copyright \u00a9 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.1903","type":"journal-article","created":{"date-parts":[[2005,12,17]],"date-time":"2005-12-17T13:19:32Z","timestamp":1134825572000},"page":"224-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":183,"title":["The pathogenesis of syphilis: the Great Mimicker, revisited"],"prefix":"10.1002","volume":"208","author":[{"given":"Rosanna W","family":"Peeling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Edward W","family":"Hook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,17]]},"reference":[{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.133.1.101-107.1978"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(01)01513-1"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/515247"},{"key":"e_1_2_11_5_2","volume-title":"Fracastoro's Syphilis","author":"Eatough G","year":"1984"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/318158"},{"key":"e_1_2_11_7_2","first-page":"473","volume-title":"Sexually Transmitted Diseases","author":"Sparling PF","year":"1999"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)90001-0"},{"key":"e_1_2_11_9_2","first-page":"479","volume-title":"Sexually Transmitted Diseases","author":"Musher DM","year":"1999"},{"key":"e_1_2_11_10_2","first-page":"467","volume-title":"Sexually Transmitted Diseases","author":"Stamm LV","year":"1999"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.2.187"},{"key":"e_1_2_11_12_2","first-page":"487","volume-title":"Sexually Transmitted Diseases","author":"Swartz MN","year":"1999"},{"key":"e_1_2_11_13_2","first-page":"1165","volume-title":"Sexually Transmitted Diseases","author":"Radolf JD","year":"1999"},{"key":"e_1_2_11_14_2","volume-title":"Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates","author":"World Health Organization"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)01382-2"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.olq.0000149848.03733.c1"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.11.1510"},{"key":"e_1_2_11_18_2","volume-title":"Sexually Transmitted Diseases Surveillance","author":"Centers for Disease Control and Prevention","year":"2001"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.10.3608"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-114-12-1005"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(16)33445-9"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1964.03860120104011"},{"key":"e_1_2_11_23_2","article-title":"Autopsy studies in syphilis. 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