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Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study
AC. Seña, MM. Matoga, L. Yang, E. Lopez-Medina, F. Aghakhanian, JS. Chen, EB. Bettin, MJ. Caimano, W. Chen, JA. Garcia-Luna, CM. Hennelly, E. Jere, Y. Jiang, JJ. Juliano, P. Pospíšilová, L. Ramirez, D. Šmajs, JD. Tucker, F. Vargas Cely, H. Zheng,...
Language English Country England, Great Britain
Document type Journal Article, Multicenter Study
Grant support
T32 AI007151
NIAID NIH HHS - United States
P41 GM103311
NIGMS NIH HHS - United States
D43 TW006589
FIC NIH HHS - United States
U19 AI144177
NIAID NIH HHS - United States
Wellcome Trust - United Kingdom
INV-036560
Bill & Melinda Gates Foundation - United States
NLK
Directory of Open Access Journals
from 2020
ROAD: Directory of Open Access Scholarly Resources
from 2020
- MeSH
- Bacterial Vaccines immunology administration & dosage MeSH
- Adult MeSH
- Phylogeny MeSH
- Genetic Variation genetics MeSH
- Genome, Bacterial MeSH
- Genomics MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Molecular Epidemiology * MeSH
- Cross-Sectional Studies MeSH
- Whole Genome Sequencing * MeSH
- Syphilis * epidemiology microbiology MeSH
- Treponema pallidum * genetics immunology MeSH
- Treponema MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- United States MeSH
BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.
Connecticut Children's Hartford CT USA
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Immunology UConn Health Farmington CT USA
Department of Integrative Immunology Duke University Medical Center Durham NC USA
Department of Medicine UConn Health Farmington CT USA
Department of Pediatrics UConn Health Farmington CT USA
Department of Pediatrics Universidad del Valle Cali Colombia
Duke Human Vaccine Institute Durham NC USA
References provided by Crossref.org
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- $a Seña, Arlene C $u Department of Medicine, Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: idrod@med.unc.edu
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