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

Since 2022, many countries have reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in carriage rates or emergence of strains with potentially altered virulence, such as 1 variants M1 and M1, contributed to the 2022/2023 surge in the Netherlands. We determined (sub)type distribution for 2,698 invasive and 351 . carriage isolates collected between January 2009 and March 2023. Genetic evolution of 1 was analyzed by whole-genome sequencing of 497 1 isolates. The nationwide iGAS upsurge coincided with a sharp increase of 1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher's exact test, < 0.0001). M1 became dominant among invasive 1 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 M1 clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of 1 isolates. carriage rates and 1 proportions in carriage isolates remained stable during this surge, and the expansion of M1 in iGAS was not reflected in carriage isolates. During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1 clades was observed among invasive isolates, but not carriage isolates, suggesting increased virulence and fitness of M1 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.IMPORTANCEThis study describes the molecular epidemiology of invasive group A streptococcal (iGAS) infections in the Netherlands based on >3,000 isolates from both asymptomatic carriers and iGAS patients collected before, during, and after the COVID-19 pandemic period (2009-2023) and is the first to assess whether changes in carriage rates or carried types contributed to the alarming post-COVID-19 upsurge in iGAS infections. We show that the 2022/2023 iGAS surge coincided with a sharp increase of 1, particularly the toxicogenic M1 variant, in invasive isolates, but not in carriage isolates. These findings suggest that increased virulence and fitness of M1 likely contributes to an increased dissemination between hosts. The emergence of a more virulent and fit lineage has important implications for iGAS control interventions such as antibiotic prophylaxis for close contacts of iGAS patients and calls for a reappraisal of iGAS control interventions and guidelines.