Invasive Streptococcus dysgalactiae subspecies equisimilis compared with Streptococcus pyogenes in Australia, 2011-23, and the emergence of a multi-continent stG62647 lineage: a retrospective clinical and genomic epidemiology study.
BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is closely related to Streptococcus pyogenes, with overlapping disease manifestations. We compared the clinical and genomic epidemiology of invasive SDSE with invasive S pyogenes across different settings in Australia and phylogenetically contextualised the SDSE sequences within a global cohort of genomes. METHODS: In this retrospective clinical and genomic epidemiology study, cases of invasive SDSE isolated from normally sterile sites were identified and whole-genome sequenced across five hospital networks in temperate southeast Australia (Melbourne and Sydney) and the tropical Top End of the Northern Territory. SDSE disease incidence, case demographics, clinical outcomes, and longitudinal lineage dynamics were compared between southeast Australia and the Top End and to co-collected invasive S pyogenes cases in each region. SDSE genomes and lineages were also contextualised within 1166 global SDSE sequences. Genomic transmission clusters (not necessarily direct transmission) were inferred between isolates from different individuals by single-linkage clustering at a single nucleotide polymorphism threshold of less than or equal to seven for SDSE and less than or equal to five for S pyogenes based on previous transmission analyses. FINDINGS: Between Jan 1, 2011, and Feb 28, 2023, there were 693 invasive SDSE cases and 995 invasive S pyogenes cases. Invasive SDSE occurred almost exclusively in adults. The overall invasive SDSE incidence in southeast Australia was similar to invasive S pyogenes (incidence rate ratio [IRR] 1·15, 95% CI 0·91-1·46; p=0·26) and increased over the study period (IRR 1·06 per year, 95% CI 1·05-1·08; p<0·0001) from 1·30 cases per 10 000 admissions in 2011 to 3·72 cases per 10 000 admissions in the first 2 months of 2023 (95% CI 2·13-6·07). In southeast Australia, where stringent COVID-19 non-pharmaceutical interventions (NPIs) were implemented between 2020 and 2021, the SDSE incidence plateaued during 2020-21 but did not significantly decline (IRR 1·09 compared with 2017-19, 95% CI 0·88-1·35; p=0·47). By contrast, S pyogenes incidence substantially declined in 2020-21 in southeast Australia (IRR 0·35 compared to 2017-19, 95% CI 0·22-0·52; p=0·017). In the Top End, SDSE incidence was lower than S pyogenes (IRR 0·24, 95% CI 0·19-0·31; p<0·0001). However, crude incidence remained higher than southeast Australia (crude IRR 1·24, 95% CI 1·07-1·42; p=0·0037) and disproportionately affected First Nations Australians in the Top End compared with non-First Nations individuals (IRR 3·36, 95% CI 2·33-4·85; p<0·0001). Comparing 2020-21 with 2017-19, there was no decline in SDSE (IRR 1·27, 95% CI 0·73-2·24; p=0·45) or S pyogenes (IRR 0·97, 95% CI 0·80-1·18; p=0·81) incidence in the Top End, which did not implement prolonged stringent COVID-19 NPIs. Analysing the available genomes of invasive cases and in lineages for which more than or equal to five invasive cases occurred, only 24 (6%) of 384 SDSE cases were assigned to genomic transmission clusters, compared with 271 (52%) of 524 S pyogenes cases. An stG62647 lineage encompassed 113 (26%) of 436 sequenced SDSE genomes. Analysis of available SDSE sequences from Australia, western Europe, and North America inferred concurrent international expansion of the stG62647 lineage in all three regions between 1990 and 2005. INTERPRETATION: We identified a substantial burden of invasive SDSE, dominated by the emergent stG62647 lineage. The contrasting epidemiology between species in the different Australian regions, during COVID-19 NPIs, and genomic infection patterns indicates transmission dynamic, pathogen population, and host-pathogen interaction differences between SDSE and S pyogenes and indicates implications for disease control measures. FUNDING: Australian National Health and Medical Research Council.