Unravelling the mystery of Treponema pallidum: Novel insights in to syphilis to accelerate development of effective and accessible syphilis control strategies

Background Syphilis is a sexually transmitted infection (STI) caused by Treponema pallidum. The UK is experiencing a syphilis epidemic, in particular amongst men who have sex with men, and individuals from racially minoritised groups. Cases are at their highest since World War Two with >7,000 cases annually. Syphilis causes significant morbidity, including an increased risk of stillbirth. Current strategies have proved insufficient to control the epidemic. I have established collaborations to develop novel approaches to controlling syphilis including genomics, self-testing and accelerating development of syphilis vaccines. These, and other promising strategies, including doxycycline prophylaxis (DoxyPEP), require evaluation to understand how they can best be deployed to stem the syphilis epidemic in the UK and ultimately worldwide. Aims and objectives Aim: Enhance understanding of syphilis transmission, evaluate novel diagnostic strategies, determine the best way to maximise uptake and establish a framework for predicting the impact of new control strategies. Specific objectives: Utilise next-generation genomic epidemiology to understand syphilis transmission Determine the accuracy of oral-fluid compared to blood-based syphilis self-testing and identify whether adding syphilis PCR to routine STI screening detects cases of infectious syphilis currently classified as non-infectious Establish the preferences for, acceptability of, feasibility and likely uptake of novel syphilis control strategies among key stakeholders and affected communities Using data from Objectives 1-3 and linked projects develop a UK mathematical model of syphilis transmission to simulate the impact and cost-effectiveness of DoxyPEP, self-testing and vaccines on disease. Methods Workstream 1: Utilise whole-genome sequencing linked to spatiotemporal and sociodemographic metadata to perform fine-scale phylogenetic analyses and establish distinct transmission networks clusters. Workstream 2: Enrol a cohort to establish the sensitivity and specificity of self-testing using oral fluid. Use samples from asymptomatic individuals to establish the prevalence of infectious syphilis detected by adding syphilis PCR testing to screening for other STIs. Workstream 3: Establish a PPIE advisory group. Key stakeholder interviews, focus group discussions and discrete choice experiments with affected communities to assess preferences and likely uptake of new interventions. Workstream 4: Development and parameterisation of a UK focused mathematical model of syphilis using data from Workstream 1. Utilise simulation experiments to explore novel control strategies informed by Workstream 2 & 3 alongside existing studies on vaccines and collaborations of DoxyPEP. Timelines for delivery Workstream 1 will run throughout. Workstream 2 will run for the first three years. Both will be embedded alongside Gates funded projects on syphilis genomics and vaccine development. Workstream 3 will run throughout, whilst Workstream 4 will run between years three to five. All workstreams will be underpinned by meaningful engagement with the PPIE panel throughout. Anticipated impact and dissemination In this professorship, syphilis will be used as an exemplar to develop approaches to tackle STIs in the UK more broadly. Studies will produce data to inform strategy on syphilis control and help end the syphilis epidemic both in the UK and globally. Outputs will include high quality scientific papers, policy briefs and patient and community focused outputs co-developed with the PPIE advisory board.