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Genomic Epidemiology of Syphilis in England Reveals Sexual Networks, Drug Resistance Patterns

NEW YORK — By combining whole-genome sequence (WGS) analysis of syphilis-causing bacteria with patient demographics and sexual behaviors, UK-based researchers have gained an insight into the disease's transmission patterns in England.

In a paper published this week in the Lancet Microbe, a team led by scientists at the Wellcome Sanger Institute used WGS data from Treponema pallidum to identify different spatiotemporal and genomic disease transmission patterns among gay, bisexual, and other men who have sex with men (GBMSM), as well as heterosexual individuals.

While WGS analysis has been used for pathogens such as SARS-CoV-2 and mpox, it has traditionally not been used for T. pallidum because its genome mutates very slowly, making it challenging to track samples based on mutation differences, lead author Mathew Beale, a staff scientist at the Wellcome Sanger Institute, said in an email.

"Despite those limitations, our findings show that it is possible to identify syphilis cases as potentially part of a transmission cluster, especially when combined with additional patient information," he said.

For their study, Beale and colleagues studied previously published WGS data of T. pallidum from 237 syphilis patients diagnosed between 2012 and 2018 across England. These samples were collected and sequenced mainly by the UK Health Security Agency.

Out of these samples, 180 came from GBMSM, while 25 were from heterosexual males. The remaining were from men with unrecorded sexual orientation, those identifying as women who have sex with men, and people of unknown gender and sexual orientation, the researchers noted. 

Subsequent phylogenomic analysis of the samples and spatiotemporal and sociodemographic metadata of the patients acquired from the national STI surveillance system revealed the circulation of two dominant T. pallidum sublineages in England: sublineages 1 and 14.

While sublineage 1 was noted throughout England and patient groups, sublineage 14 was seen predominantly in GBMSM older than 34 years and was absent from samples sequenced from the north of England.

"Our identification of discrete clusters associated with sexual behavior suggests WGS combined with detailed epidemiological data can resolve some local transmission chains for T. pallidum. This could offer opportunities to intervene or educate sexual networks and to determine or exclude outbreak membership," the authors concluded.

Meanwhile, they also highlighted that both these sublineages are predicted to be resistant to antibiotic macrolides, which are used to treat syphilis. This is consistent with the high percentage of macrolide-resistant samples in the UK, the authors wrote.

Cases of syphilis have risen in many high-income countries since 2012, and England has seen an astounding increase. There were 8,700 patients in England in 2022, the highest since 1948, the Guardian reported in June 2023.

According to Beale, one of the main implications of these findings is that genomics can be integrated with routine syphilis public health surveillance. "A combination of epidemiological surveillance based on case numbers with genomics, therefore, offers an alternative approach for the toolkit when inferring chains of transmission," he said.

Meanwhile, highlighting one of the several limitations of the study, the authors wrote that the sample size was small compared to the total number of syphilis cases during the period and the overrepresentation of models from GBMSM in the national genome collection. Pointing out a technical limitation, Beale highlighted that using long-read sequencing instead of the short-read sequencing used in this study may improve the ability to determine transmission clusters.