Epidemiological and genomic characterisation of an outbreak of Streptococcus pyogenes emm5.23

Objectives: This retrospective cross-sectional study examined the epidemiology, clinical presentations, and genomics of Streptococcus pyogenes genotype emm5.23, linked to severe outcomes in Scotland. Methods: Between 2014 and 2022, 58 cases of invasive Group A Streptococcus (iGAS) disease associated with emm5.23 were reported in Scotland. Surveillance data from 45 cases were analysed for clinical characteristics and risk factors. Whole-genome sequencing (WGS) included all available emm5.23 strains from Scotland (n=58), a subset from England (n=29), and emm5 strains of non-5.23 subtypes from Scotland (n=10), England (n=2), and Canada (n=1). Results: Nearly all cases (96%, 43/45) were hospitalised, of whom 33% (15/45) required intensive care and 20% (9/45) died with iGAS. The most common presentations were bacteraemia (51%, 23/45) and pneumonia (24%, 11/45). WGS identified an emerging emm5.23 clade in Scotland, encompassing most isolates, which shared highly similar genomes and three non-synonymous polymorphisms. Conclusions: Although genomic traits known to increase GAS virulence potential were not found, polymorphisms that may affect the emm5.23 phenotype were detected. This suggests this emm5.23 genotype was transiently successful rather than hypervirulent, with low population-level immunity contributing to its spread. This study emphasises the need for integration of real-time genomic data in public health surveillance to enhance source attribution and guide interventions.