ABSTRACT
Background Since 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.
Methods We 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.
Findings The 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 (Fisher’s 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.
Interpretation During 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.
Competing Interest Statement
NMvS reports fee for service and presentations from MSD, GSK and grants from the Dutch Health Council (ZonMW; all directly paid to the institution), contract research with Argenx (unrelated to this work), a patent on vaccine development against S. pyogenes (licensee: University of California San Diego, inventors Nina van Sorge and Victor Nizet; licensed by Vaxcyte; personal revenue), participation in the science advisory board of the ItsME foundation (no honorarium; https://itsme-foundation.com/en/) and Rapua te me ngaro ka tau, a project facilitating Strep A vaccine development for Aotearoa New Zealand (honorarium paid directly to the institution). Other authors have nothing to disclose.
Funding Statement
The study has been funded by a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) research grant to LWR in 2022, St. Antonius hospital research grant in 2020, and Amsterdam UMC Innovation Grant (2023-26) in 2023, and by the DRESSCODE project (project number 09150181910001) of the Vici Talent program to NMvS, which is financed by ZonMW.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Invasive S. pyogenes isolates were collected as part of routine care. Carriage isolates were collected after written informed consent from all adults and parents or legal guardians of the included children. Ethical approval was obtained from The Central Committee on Research Involving Human Subjects (CCMO), the Netherlands (OKIDOKI-1; NL24116.000.08), the Medical Ethics Testing Committee (METC Noord-Holland), The Netherlands (OKIDOKI-3; NL40288.094.12 and OKIDOKI-4; NL53027.094.15) and Medical Research Ethics Committees United (MEC-U), Nieuwegein, The Netherlands (OKIDOKI-5; NL65919.100.18). Ethical approval was waived for OKIDOKI-2 performed in 2009 by Stichting Therapeutische Evaluatie Geneesmiddelen (STEG), Arnhem, The Netherlands (NVI-257) and for OKIDOKI-6 by the Centre for Clinical Expertise at the RIVM, Bilthoven, the Netherlands (ISRCTN31549735) because these studies do not fulfill both conditions stated in the law for medical research involving human subjects (WMO) and therefore were exempted for further approval by the ethical research committee. All were conducted in accordance with the European Statements for Good Clinical Practice and the Declaration of Helsinki of the World Medical Association. Only fully anonymized data was used.
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Data Availability
Whole genome sequence data will be publically available through the PubMLST database: https://pubmlst.org/organisms/streptococcus-pyogenes
