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. 2023 Jun;9(6):mgen001026.
doi: 10.1099/mgen.0.001026.

Novel emm 4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022

Boas C L van der Putten  1   2 , Wendy C M Bril-Keijzers  3 , Lidewij W Rumke  4 , Stefan M T Vestjens  4 , Linda A M Koster  1 , Marloes Willemsen  1   5 , Marlies A van Houten  6 , Nynke Y Rots  7 , Bart J M Vlaminckx  8 , Brechje de Gier  7 , Nina M van Sorge  1   3
Affiliations

Novel emm 4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022

Boas C L van der Putten et al. Microb Genom. 2023 Jun.

Abstract

Invasive group A streptococcal (iGAS) disease cases increased in the first half 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-coronavirus disease 2019 (COVID-19) pandemic period 2009-2019 and 26 contemporary isolates from 2022, identified a novel Streptococcus pyogenes lineage (M4NL22), which accounted for 85 % of 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 the results have been promptly communicated to public health officials.

Keywords: Streptococcus pyogenes; emm typing; public health surveillance: outbreak; whole-genome sequencing.

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Conflict of interest statement

N.M.v.S. declares service and consultancy fees paid directly to the institution from MSD and GSK outside the submitted work. N.M.v.S. declares royalties related to a patent (WO 2013/020090 A3) on vaccine development against Streptococcus pyogenes (Vaxcyte; licensee: University of California San Diego with NMvS as co-inventor). N.M.v.S. is a member of the Science advisory Board for the ItsME foundation (unpaid) and Rapua te me ngaro ka tau project (paid to institution; project facilitating Strep A vaccine development for Aotearoa New Zealand). The other authors declare that there are no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Phylogeny of 66 Dutch emm4 isolates and 14 reference genomes . The reference genomes originate from DebRoy et al. [3] and are shown without metadata. The hypervirulent clone lineage is coloured blue and the M4NL22 lineage is coloured red. An interactive version of these data with metadata is available at https://itol.embl.de/tree/92108202133469351670785481#.
See this image and copyright information in PMC

References

    1. van Kempen EB, Bruijning-Verhagen PCJ, Borensztajn D, Vermont CL, Quaak MSW, et al. Increase in invasive group A streptococcal infections in children in the Netherlands, a survey among 7 hospitals in 2022. Pediatr Infect Dis J. 2023;42:e122–e124. doi: 10.1097/INF.0000000000003810. - DOI - PubMed
    1. de Gier B, Marchal N, de Beer-Schuurman I, Te Wierik M, Hooiveld M, et al. Increase in invasive group A streptococcal (Streptococcus pyogenes) infections (iGAS) in young children in the Netherlands, 2022. Euro Surveill. 2023;28:2200941. doi: 10.2807/1560-7917.ES.2023.28.1.2200941. - DOI - PMC - PubMed
    1. DebRoy S, Sanson M, Shah B, Regmi S, Vega LA, et al. Population genomics of emm4 group A streptococcus reveals progressive replacement with a hypervirulent clone in North America. mSystems. 2021;6:e0049521. doi: 10.1128/mSystems.00495-21. - DOI - PMC - PubMed
    1. Bosch AATM, van Houten MA, Bruin JP, Wijmenga-Monsuur AJ, Trzciński K, et al. Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands. Vaccine. 2016;34:531–539. doi: 10.1016/j.vaccine.2015.11.060. - DOI - PubMed
    1. Hendrickx APA, Landman F, de Haan A, Borst D, Witteveen S, et al. Plasmid diversity among genetically related Klebsiella pneumoniae blaKPC-2 and blaKPC-3 isolates collected in the Dutch national surveillance. Sci Rep. 2020;10:16778. doi: 10.1038/s41598-020-73440-2. - DOI - PMC - PubMed

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