A genomic approach to understand the phylodynamics of infectious syphilis in Canada and to develop novel immuno-reagents for rapid diagnostic testing

Funding period: 2023-2025
Lead: Raymond Tsang
Total GRDI funding: $1,025,500

Syphilis is a sexually transmitted infection (STI) caused by the “non-culturable” bacterium Treponema pallidum subsp. pallidum (referred hereto as T. pallidum). Since decades of low incidence in Canada, infectious syphilis is on the rise, leading to an unprecedented number of cases, including congenital syphilis in babies resulting from infection occurring in pregnant women. Diagnosis of syphilis is challenging as it has been called the “great imitator”, and current laboratory methods to confirm a diagnosis takes days to provide results to the health care provider, thus delaying treatment to halt the transmission of the disease. Rapid innovative diagnostics that can be applied at the site where vulnerable populations encounter their health care providers, including in remote northern locations, are required. Also, current surveillance of the disease is limited to case counting in different demographic groups, and very little is known about the strain type causing disease in both past and current outbreaks. Syphilis continues to be treatable by parenteral penicillin antibiotic. However, individuals with penicillin allergies or in regions that lack readily available access to parenteral treatment, it is vital that a viable alternative treatment option is available. Genetic information is needed to effectively track syphilis diversity and distribution as well as gather information on antimicrobial resistance to inform on alternative treatments options, leading to better patient and public health outcomes. T. pallidum genomic data is essential for phylodynamics (combines knowledge of epidemiology and evolution), a method that will help us understand the evolutionary histories of T. pallidum populations, outbreak potential, and transmission dynamics of syphilis in Canada. Genomes are also needed for immuno-informatics analysis that will identify unique B-cell determinants (epitopes) for development of antigen and antibody detection-based rapid diagnostic tests. This research aims to develop a meta-genomics, immuno-informatics, and novel phylodynamic pipeline to (a) fill the knowledge gap of T. pallidum strain types circulating in Canada, (b) track antimicrobial resistance, and (c) identify and evaluate B-cell epitopes for the development of a rapid diagnostic tests. implementing e-requisitions and reporting to modernize infectious disease detection and surveillance.