Novel emm4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022

Invasive group A streptococcal (iGAS) disease cases increased in the first half year of 2022 in the Netherlands with a remarkably high proportion of emm4 isolates. Whole-genome sequence analysis of 66 emm4 isolates, 40 isolates from the pre-COVID-19-pandemic period 2009-2019 and 26 contemporary isolates from 2022, identified a novel Streptococcus pyogenes lineage (M4NL22), which accounted for 85% emm4 iGAS cases in 2022. Surprisingly, we detected few isolates of the emm4 hypervirulent clone, which has replaced nearly all other emm4 in the USA and the UK. M4NL22 displayed genetic differences compared to other emm4 strains, although these were of unclear biological significance. In publicly available data, we identified a single Norwegian isolate belonging to M4NL22, which was sampled after the isolates from this study, possibly suggesting export of M4NL22 to Norway. In conclusion, our study identified a novel S. pyogenes emm4 lineage underlying an increase of iGAS disease in early 2022 in the Netherlands and results have been promptly communicated with public health officials. Impact statementGroup A Streptococcus (predominantly comprising Streptococcus pyogenes) has a long history of causing disease in humans. Over the past decades, researchers have described various changes in the S. pyogenes population circulating in humans. In this study, we describe a shift in the S. pyogenes population within type emm4 in the Netherlands in early 2022. A novel lineage, which we termed M4NL22, became the predominant emm4 lineage during this period. This was surprising, as in other countries such as the USA and the UK, another recently emerged lineage became dominant. Our work informed public health officials on the possible causes of increased S. pyogenes cases in the Netherlands and underlines the added value of continued active bacteriological surveillance. Data summaryCode is freely available from https://github.com/boasvdp/GAS_M4. All sequencing data is freely available from BioProject PRJEB58654.