Abstract

BackgroundDuring a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Isolates were collected to provide geographical representation, for approximately 5% SF isolates from each region from 1st April 2014 to 18th June 2014. Contemporaneous iGAS isolates for which genomic data were available were included for comparison. Data were analysed in order to determine emm gene sequence type, phylogenetic lineage and genomic clade representation, the presence of known prophage elements and the presence of genes known to confer pathogenicity and resistance to antibiotics.Results555 isolates were analysed, 303 from patients with SF and 252 from patients with iGAS. Isolates from patients with SF were of multiple distinct emm sequence types and phylogenetic lineages. Prior to data normalisation, emm3 was the predominant type (accounting for 42.9% of SF isolates, 130/303 95%CI 37.5–48.5; 14.7% higher than the percentage of emm3 isolates found in the iGAS isolates). Post-normalisation emm types, 4 and 12, were found to be over-represented in patients with SF versus iGAS (p < 0.001). A single gene, ssa, was over-represented in isolates from patients with SF. No single phage was found to be over represented in SF vs iGAS. However, a “meta-ssa” phage defined by the presence of :315.2, SPsP6, MGAS10750.3 or HK360ssa, was found to be over represented. The HKU360.vir phage was not detected yet the HKU360.ssa phage was present in 43/63 emm12 isolates but not found to be over-represented in isolates from patients with SF.ConclusionsThere is no evidence that the increased number of SF cases was a strain-specific or known mobile element specific phenomenon, as the increase in SF cases was associated with multiple lineages of GAS.

Highlights

  • During a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, Lancefield group A streptococcus (GAS)) isolates from patients with SF with comparison to isolates from patients with invasive disease to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF

  • Due to the unprecedented increase in the incidence of SF in England and Wales, a national incident management team was convened by PHE which initiated investigation of isolates of GAS from patients with SF, with the intention of collating a representative selection of SF isolates from all regions of England for genomic analysis

  • A total of 555 isolates of which 303 were from SF patients and 252 from invasive GAS (iGAS) patients were included in the analysis

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Summary

Introduction

During a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Due to the unprecedented increase in the incidence of SF in England and Wales, a national incident management team was convened by PHE which initiated investigation of isolates of GAS from patients with SF, with the intention of collating a representative selection of SF isolates from all regions of England for genomic analysis. This was undertaken to determine whether the increase in SF was due to the introduction of new/ emerging strain/s into the population or transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF

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