Genomics uncovers syphilis transmission networks

Genomics has helped to reveal distinct sexual networks for syphilis transmission – showing how drug resistance develops, according to a major UK study.

Researchers from the Wellcome Sanger Institute and the UK Health Security Agency (UKHSA) sequenced 237 whole genome samples and integrated this with epidemiological data to map the bacterium’s evolution and spread through a population.

They show distinct transmission chains between individuals as well as significant resistance to a commonly prescribed class of antibiotics in England.

Writing in Lancet Microbe, they say by grouping closely related strains of Treponema pallidum, the bacterium that causes syphilis, they have demonstrated how a large number of cases are linked together.

They add that using genomic surveillance could help identify high-risk areas or populations and inform targeted public health strategies to break the chains of transmission.

In this new study, the team combined anonymised patient demographic and epidemiological data with whole genome sequencing analysis of T. pallidum genomes from 237 patients diagnosed with syphilis in England between 2012 and 2018.

By comparing the bacterial genomes from different individuals, they identified single nucleotide polymorphisms (SNPs) to distinguish one strain of T. pallidum from another.

The team identified multiple features of transmission networks of T. pallidum in England, affecting GBMSM (gay and bisexual men and other men who have sex with men) and heterosexuals at national and regional levels. They were able to make inferences of recent transmission based on how related T. pallidum genomes were across different individuals. These inferences were later verified by epidemiological data.

While previous work has grouped T. pallidum lineages separated by many years with a large number of SNPs, the new study goes down to the identical gene level with zero SNPs, indicating recent transmission.

This, say the report authors, could enable public health authorities to map syphilis spread in an ongoing outbreak.

Their analysis of genetic diversity also revealed the extent of drug resistance in England. Many of the 237 genome samples sequenced showed resistance to macrolides.

First study author Dr Mathew Beale, of the Wellcome Sanger Institute, said: “The Covid-19 pandemic has reimagined what scale is possible in genomic surveillance and this study capitalises on that, providing important background information on how fast the genomes of T. pallidum evolve as syphilis spreads through a population. We should explore with future sampling work whether these evolutionary baselines are representative and if the approach can be used robustly in settings outside of England. Syphilis genome diversity is poorly understood in countries where STI control programmes are most needed.”

Dr Helen Fifer, senior author and lead microbiologist for bacterial sexually transmitted infections at the UK Health Security Agency, said with record levels of STIs including syphilis, genomics provides another tool for understanding chains of transmission of syphilis and predicting response to treatments.

“We must also focus on readily available prevention strategies and STI services, such as condoms, including information about their limitations, effective follow-up of people with new STI diagnoses and self-monitoring for symptoms when necessary,” she added.

Dr Ana Cehovin, senior research manager, infectious disease at Wellcome, said: “Genomic surveillance is an invaluable tool for understanding how diseases are spreading, what populations are at increased risk and which strains are developing drug resistance.

“Using this knowledge, we can spot outbreaks or incidences of drug resistance earlier, and therefore take action to protect at-risk communities.”

Beale MA, Fifer H, Thomson NR et al. Genomic epidemiology of syphilis in England: a population-based study. Lancet Microbe 16 September 2023; doi: 10.1016/S2666-5247(23)00154-4.


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