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Epidemiology & Monitoring

Session: It’s worth a shot: the Science of stopping a global syphilis epidemic, one genome at a time

O9.1 - The clinical and genomic diversity of Treponema pallidum among early syphilis patients enrolled in a global consortium for syphilis vaccine development

Wednesday, July 26, 2023

10:00 – 10:15 CST

Location: Chicago 10

Primary Presenter(s)

Arlene C. Seña, MD, MPH

Professor of Medicine
Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Chapel Hill, North Carolina, United States

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Background: Understanding the genetic diversity of T. pallidum subsp. pallidum (TPA) is essential for advancing syphilis diagnostics and vaccine development. We established a global clinical consortium to understand TPA population genetics by analyzing clinical data and specimens collected from early syphilis patients worldwide using whole-genome sequencing (WGS), and publicly available WGS data.

Methods: We enrolled patients with primary (PS), secondary (SS) or early latent (ELS) from clinics in the United States, Colombia, China, and Malawi between November 2019 - May 2022. Inclusion criteria included age >18 and laboratory confirmation of syphilis by direct detection methods and/or non-treponemal and treponemal antibody testing. Quantitative TPA polA (tp01021) PCR testing and WGS were conducted on clinical specimens including lesion swabs, skin biopsies or scrapings, whole blood, and/or rabbit-passaged specimens. We compared our TPA WGS data to publicly available genomes. Phylogenetic trees were visualized in R (v4.1.2), and macrolide-resistance mutations (MRM) were analyzed using ARIBA (v2.14.6).

Results: We screened 2820 patients and enrolled 233 participants across sites, including 77 (33%) with PS, 154 (66%) with SS, and 2 (1%) with ELS. The median age of participants was 28 (interquartile range 22 - 35); 66% were male of which 43% were men who have sex with men. HIV co-infection was reported and/or diagnosed at enrollment among 24% of participants. TPA PCR was positive in specimens from 197 (85%) participants. WGS data were available from 113 participants to date, showing a predominance of SS14-lineage strains with geographic clustering among participants with diverse clinical manifestations. The phylogenomic analysis (Figure) confirmed that TPA Nichols-lineage strains have greater genetic diversity than SS14-lineage strains and cluster into more distinct subclades. Half of participants in the Nichols E subclade, consisting mostly of strains from Colombia and China, had HIV co-infection. The prevalence of MRMs ranged from 100% of strains in China to 15% in Malawi. Differences in single nucleotide variants were evident by TPA lineage and geography.

Conclusions: Our study involving different clinical populations in four countries substantiates the global diversity of TPA strains. Further analyses to delineate TPA outer membrane protein variability within strains worldwide will be important for syphilis vaccine development.