Streptococcus pyogenes emm Type 3.93 Emergence, the Netherlands and England

Abstract

A global increase in the incidence of invasive group A Streptococcus (iGAS) infections was observed after lifting of COVID-19 related restrictions in 2022, and type M1_UK dominated in many countries. After seasonal declines in iGAS incidence during the summer of 2023, simultaneous, rapid expansion of a previously rare emm type 3.93 was seen beginning in November, increasing to 20% of all cases in England and 60% of all cases in the Netherlands within 4 months. emm3.93 was associated with iGAS in children 6-17 years of age and with increased risk for pneumonia or pleural empyema and meningitis in both countries. No excess risk of death was identified for emm3.93 compared with other types. Genomic analysis of historic and contemporary emm3.93 isolates revealed the emergence of 3 new clades with a potentially advantageous genomic configuration. Our findings demonstrate the value of molecular surveillance, including long-read sequencing, in identifying clinical and public health threats.

Keywords: England; Netherlands; Streptococcus pyogenes; bacteria; epidemiology; genomic inversion; invasive infection; meningitis/encephalitis; pneumonia; streptococci.

Figure 1

Absolute number of Streptococcus pyogenes isolates recovered from patients with invasive group A Streptococcus, by emm type and month, February 1, 2023–March 31, 2024. A) The Netherlands; B) England.

Figure 2

Proportion of emm types 1.0 and 3.93 among all typed invasive Streptococcus pyogenes isolates in the Netherlands and England, February 1, 2023–March 31, 2024.

Figure 3

Genetic information about emm3.93 Streptococcus pyogenes isolates collected in the Netherlands and England, February 1, 2023–March 31, 2024, and reference isolates. A) Maximum-likelihood phylogenetic tree of 114 parsimony informative sites and 255 distinct site patterns from the core genome single-nucleotide polymorphism alignment of 104 emm3.93 isolates from the Netherlands, England, and New Zealand (2009–2024), compared with MGAS315 reference genome (RefSeq accession no. GCF_000007425). The tree was rooted on MGAS315, and colored rings outside the tree represent year of isolation, country, source, and presence of genomic inversion around the ter. Scale bar represents substitutions per site. B) Schematic of the 4 genomic conformations detected in the emm3 lineage. When compared with the consensus reference genome of strain MGAS315, an inversion around both the ori and ter, or around the ter alone (as detected in 11/12 surge isolates) is observed. Genome ABC020055975 indicates a strain lacking prophages MGAS315.1 and MGAS315.2 but with a detected inversion around the ori. G, MGAS315.1; H, MGAS315.2.