Abstract
Background: England is experiencing scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular-epidemiological investigation of these events and emergence of a new emm1 lineage. Methods: We analysed changes in S. pyogenes emm-genotypes, and notifications of scarlet fever and invasive disease 2014-2016 using regional and national data. We analysed genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-2016, and compared 2800 global emm1 sequences. Expression of Streptococcal pyrogenic exotoxin (Spe)A by sequenced non-invasive emm1 isolates was quantified. Findings: Coincident with national increases in scarlet fever and invasive disease, emm1 S. pyogenes infections increased significantly, accounting for 32·6% (47/144) of pharyngeal isolates in North West London and 41·9% (267/637) of invasive isolates nationally in March-May 2016. Sequences of emm1 isolates from 2009-2016 demonstrated emergence of a new emm1 lineage (M1UK), with overlap of pharyngitis, scarlet fever, and invasive M1UK strains, that could be genotypically distinguished from pandemic emm1 isolates (M1global). Compared with M1global , median expression of SpeA increased 9-fold in M1UK isolates. M1UK expanded nationally to represent 84% (252/299) of all emm1, genomes in 2016; analysis identified two M1UK isolates outside the UK. Interpretation: A dominant new emm1 S. pyogenes lineage characterized by increased SpeA production has emerged during increased S. pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S. pyogenes provide plausible explanation for increased invasive disease, and rationale for global surveillance. Funding Statement: Supported by grants from Medical Research Council (MR/P022669/1); NIHR Health Protection Unit in AMR and HCAI (HPRU-2012-10047); NIHR BRC SpyVAC; Conor Kerin Foundation. NNL is a Sir Henry Wellcome Postdoctoral Research Fellow funded by the Wellcome Trust (103197/Z/13/Z); EJ is a Rosetrees/Stoneygate 2017 Imperial College Research Fellow (M683). Declaration of Interests: JP is a consultant to Next Gen Diagnostics LLC; other authors declare no interests. Ethics Approval Statement: Clinical data were linked to isolates and anonymized in accordance with Research Ethics approval 06/Q0406/20.
Highlights
Scarlet fever is a classic exanthem of childhood caused by the bacterium Streptococcus pyogenes that, until the beginning of the 20th century, was associated with frequent loss of life among children.[1]
Added value of this study Our study provides a molecular explanation for the association between increased incidence of scarlet fever and increased incidence of invasive S pyogenes infections, by identifying an emergent lineage of M1T1 S pyogenes (M1UK) that expanded rapidly to become the largest single contributor to both non-invasive and invasive infections in 2016
We compared notifications of invasive S pyogenes infections in northwest London with national data, which showed a marked increase in S pyogenes invasive disease in 2016 in northwest London during the scarlet fever season that mirrored the national pattern of increased notifications in 2016
Summary
Scarlet fever is a classic exanthem of childhood caused by the bacterium Streptococcus pyogenes (group A strepto coccus) that, until the beginning of the 20th century, was associated with frequent loss of life among children.[1]. Since the 1940s, scarlet fever has followed a seasonal springtime pattern—peaking between March and May while remaining less frequent throughout the rest of the year—without the major cyclical epidemics observed in the early 20th century.[3] Surges in invasive infections can periodically follow a similar seasonal pattern for reasons that are incompletely understood. In 2014, England had an unexpected surge in scarlet fever infections, with over 15 000 disease notifications—a marked increase in inci dence compared with previous decades.[3,4] Despite having a major impact on public health resources,[3] the increase in infections was not associated with any rise in the incidence of invasive disease.
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