Nationwide upsurge in invasive disease in the context of longitudinal surveillance of carriage and invasive Streptococcus pyogenes 2009-2023, the Netherlands: a molecular epidemiological study

BackgroundSince 2022, many countries reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in S. pyogenes carriage rates or emergence of more virulent strains, such as emm1 variants M1UK and M1DK, contributed to the 2022/2023 surge in the Netherlands. MethodsWe determined emm (sub)type distribution for 2,698 invasive and 351 S. pyogenes carriage isolates collected between January 2009 - March 2023. Genetic evolution of emm1 was analyzed by whole-genome sequencing of 497 emm1 isolates. FindingsThe nationwide iGAS upsurge coincided with a sharp increase of emm1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fishers exact, p<0.0001). M1UK became dominant among invasive emm1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1UK clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of emm1 isolates. S. pyogenes carriage rates and emm1 proportions in carriage isolates remained stable during this surge and the expansion of M1UK in iGAS was not reflected in carriage isolates. InterpretationDuring the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1UK clades was observed among invasive isolates but not carriage isolates, suggesting increased virulence and fitness of M1UK compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.