show Abstracthide AbstractSyphilis is an important sexually transmitted infection (STI) caused by the spirochaete bacterium Treponema pallidum subspecies pallidum (TPA). Through systematic testing and recording of positive cases, syphilis rates have been seen to be increasing substantially over the last decade in many high income countries. This contrasts most other parts of the world, particularly in Africa and Latin America, where STIs are largely managed syndromically and there is a complete lack of comprehensive serological or molecular diagnostic use or data. A deep understanding of the genetic diversity of a pathogen is crucial for designing and developing globally representative 'equitable' vaccines and molecular or serological diagnostics, as well as supporting epidemiological surveillance. Although we now have a good understanding of TPA genetic diversity in high income countries, we still have major knowledge gaps for much of the world – in our recent global analysis of 726 genomes, only 19 were from Africa (Zimbabwe 18, South Africa 1), and 25 from Asia (China 15, central Russia 10). Despite this, our sampling from Zimbabwe detected novel sublineages that were genetically related but distinct from those circulating elsewhere in the world. The same was true of sublineages circulating in central Russia, and of individual samples sequenced from South Africa and Cuba. Therefore, it is clear that we have not yet captured the full extent of the genetic diversity that exists for TPA.Our genomic analyses to date have made use of existing samples collected primarily as part of routine care for patients, including those with high TPA load from a recently published study on syphilis in Southern Africa. However, in low and middle income settings such sample banks do not exist, reflecting the use of a syndromic management approach to STIs which does not require sample collection or diagnostic testing. To close this gap, we will prospectively collect and test samples from patients with genital ulcer disease in multiple countries in poorly represented parts of Africa and Latin America; all TPA positive samples will be sent for WGS using established pipelines