Genomic epidemiology of syphilis in England: a population- based study

Background Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum subspecies pallidum. Since 2012, syphilis rates have risen dramatically in many high-income countries, including England. Although this increase in syphilis prevalence is known to be associated with high-risk sexual activity in gay, bisexual, and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women. The transmission dynamics within and between sexual networks of GBMSM and heterosexual people are not well understood. We aimed to investigate if whole genome sequencing could be used to supplement or enhance epidemiological insights around syphilis transmission.Methods We linked national patient demographic, geospatial, and behavioural metadata to whole T pallidum genome sequences previously generated from patient samples collected from across England between Jan 1, 2012, and Oct 31, 2018, and performed detailed phylogenomic analyses.Findings Of 497 English samples submitted for sequencing, we recovered 240 genomes (198 from the UK Health Security Agency reference laboratory and 42 from other laboratories). Three duplicate samples (same patient and collection date) were included in the main phylogenies, but removed from further analyses of English populations, leaving 237 genomes. 220 (92 center dot 8%) of 237 samples were from men, nine (3 center dot 8%) were from women, and eight (3 center dot 4%) were of unknown gender. Samples were mostly from London (n=118 [49 center dot 8%]), followed by southeast England (n=29 [12 center dot 2%]), northeast England (n=24 [10 center dot 1%]), and southwest England (n=15 [6 center dot 3%]). 180 (76 center dot 0%) of 237 genomes came from GBMSM, compared with 25 (10 center dot 5%) from those identifying as men who have sex with women, 15 (6 center dot 3%) from men with unrecorded sexual orientation, nine (3 center dot 8%) from those identifying as women who have sex with men, and eight (3 center dot 4%) from people of unknown gender and sexual orientation. Phylogenomic analysis and clustering revealed two dominant T pallidum sublineages in England. Sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in GBMSM older than 34 years and was absent from samples sequenced from the north of England. These different spatiotemporal trends, linked to demography or behaviour in the dominant sublineages, suggest they represent different sexual networks. By focusing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission in GBMSM.Interpretation These findings show that, despite extremely close genetic relationships between T pallidum genomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up. This could be of value for deconvoluting putative outbreaks and for informing public health interventions. Crown Copyright (c) 2023 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.