Mortality among patients with invasive group A streptococcal infections caused by the M1UK lineage: a retrospective cohort study in England and Wales
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
The M1UK sublineage of Streptococcus pyogenes has driven recent post-pandemic surges in invasive group A streptococcal (iGAS) disease. We assessed case fatality rate (CFR) among patients with emm1 iGAS in England and Wales, and then compared outcomes associated with M1UK and ancestral emm1 lineages.
Methods
We linked emm1 iGAS cases (December 2009–July 2022) with demographic and mortality records. Lineage was determined for isolates collected in 2010, 2013–2016, and 2020 via whole-genome sequencing or allele-specific PCR. Seven- and 30-day all-cause CFRs were estimated. Univariate and multivariate models assessed the association between lineage and risk of death.
Results
Among 4,952 emm1 iGAS cases, lineage was assigned to 1,356. The 30-day CFR was 24.4% for M1UK, 22.3% for M1global, 10.5% for M123SNP, and 10.3% for M113SNP. After adjustment for age and sex, lineage was not a significant predictor of 7- or 30-day mortality. Survival analysis showed rapid progression to death in both M1UK and M1global cases: 63.7% of deaths occurred within 1 day of diagnostic sampling. Among children under 15 years, 56.3% of fatal cases died before sampling, and 95.6% within 1 day of sampling.
Conclusions
Mortality did not differ significantly between M1UK and M1global lineages but more studies are required. Overall mortality from emm1 S. pyogenes remains strikingly high. The rapid time to death underscores the need for preventive measures and rapid diagnostic tools that act prior to culture-based confirmation, and highlights challenges for clinical trial design in iGAS.
The M1UK sublineage of Streptococcus pyogenes has driven recent post-pandemic surges in invasive group A streptococcal (iGAS) disease. We assessed case fatality rate (CFR) among patients with emm1 iGAS in England and Wales, and then compared outcomes associated with M1UK and ancestral emm1 lineages.
Methods
We linked emm1 iGAS cases (December 2009–July 2022) with demographic and mortality records. Lineage was determined for isolates collected in 2010, 2013–2016, and 2020 via whole-genome sequencing or allele-specific PCR. Seven- and 30-day all-cause CFRs were estimated. Univariate and multivariate models assessed the association between lineage and risk of death.
Results
Among 4,952 emm1 iGAS cases, lineage was assigned to 1,356. The 30-day CFR was 24.4% for M1UK, 22.3% for M1global, 10.5% for M123SNP, and 10.3% for M113SNP. After adjustment for age and sex, lineage was not a significant predictor of 7- or 30-day mortality. Survival analysis showed rapid progression to death in both M1UK and M1global cases: 63.7% of deaths occurred within 1 day of diagnostic sampling. Among children under 15 years, 56.3% of fatal cases died before sampling, and 95.6% within 1 day of sampling.
Conclusions
Mortality did not differ significantly between M1UK and M1global lineages but more studies are required. Overall mortality from emm1 S. pyogenes remains strikingly high. The rapid time to death underscores the need for preventive measures and rapid diagnostic tools that act prior to culture-based confirmation, and highlights challenges for clinical trial design in iGAS.
Date Issued
2025-11-15
Date Acceptance
2025-08-27
Citation
Clinical Infectious Diseases, 2025, 81 (5), pp.e277-e284
ISSN
1058-4838
Publisher
Oxford University Press
Start Page
e277
End Page
e284
Journal / Book Title
Clinical Infectious Diseases
Volume
81
Issue
5
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distri bution, and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Date Publish Online
2025-10-16