{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T23:54:33Z","timestamp":1770422073976,"version":"3.49.0"},"posted":{"date-parts":[[2023,7,24]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":30,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,7,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    The continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to explore\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    subsp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    (\n                    <jats:italic>TPA<\/jats:italic>\n                    ) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We enrolled patients with primary (PS), secondary (SS) or early latent (ELS) syphilis from clinics in China, Colombia, Malawi and the United States between November 2019 - May 2022. Inclusion criteria included age \u226518 years, and syphilis confirmation by direct detection methods and\/or serological testing.\n                    <jats:italic>TPA<\/jats:italic>\n                    detection and WGS were conducted on lesion swabs, skin biopsies\/scrapings, whole blood, and\/or rabbit-passaged isolates. We compared our WGS data to publicly available genomes, and analysed\n                    <jats:italic>TPA<\/jats:italic>\n                    populations to identify mutations associated with lineage and geography.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>\n                    We screened 2,820 patients and enrolled 233 participants - 77 (33%) with PS, 154 (66%) with SS, and two (1%) with ELS. Median age of participants was 28; 66% were\n                    <jats:italic>cis<\/jats:italic>\n                    -gender male, of which 43% reported identifying as \u201cgay\u201d, \u201cbisexual\u201d, or \u201cother sexuality\u201d. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants demonstrated a predominance of SS14-lineage strains with geographic clustering. Phylogenomic analysis confirmed that Nichols-lineage strains are more genetically diverse than SS14-lineage strains and cluster into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by\n                    <jats:italic>TPA<\/jats:italic>\n                    lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models demonstrated population-specific substitutions, some in outer membrane proteins (OMPs) of interest.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>\n                    Our study involving participants from four countries substantiates the global diversity of\n                    <jats:italic>TPA<\/jats:italic>\n                    strains. Additional analyses to explore\n                    <jats:italic>TPA<\/jats:italic>\n                    OMP variability within strains will be vital for vaccine development and improved understanding of syphilis pathogenesis on a population level.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>National Institutes of Health, Bill and Melinda Gates Foundation<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.07.19.23291250","type":"posted-content","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T14:25:11Z","timestamp":1690208711000},"source":"Crossref","is-referenced-by-count":5,"title":["Clinical and genomic diversity of\n                  <i>Treponema pallidum subsp. pallidum:<\/i>\n                  A global, multi-center study of early syphilis to inform vaccine research"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1206-2175","authenticated-orcid":false,"given":"Arlene C.","family":"Se\u00f1a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitch M.","family":"Matoga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Lopez-Medina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhang","family":"Aghakanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane S.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Everton B.","family":"Bettin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonny A.","family":"Garcia-Luna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Hennelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinbo","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Posp\u00ed\u0161ilov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lady","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"\u0160majs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-1181","authenticated-orcid":false,"given":"Joseph D.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio Vargas","family":"Cely","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irving F.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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