In a recent study published in Eurosurveillance, researchers investigated whether a change in variant structure might be responsible for the increased incidence of group A streptococci (GAS) infections of invasive (iGAS) and non-invasive (nGAS) types in winter 2023 or whether this can be better understood through the effect of coronavirus disease 2019 (COVID-19)-associated limitations on group A streptococci transmission and immunity in the population.
Study: Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023. Image Credit: Jezper/Shutterstock.com
Background
Several European nations have reported increases in iGAS and nGAS infections in the 2022 and 2023 winter months. From the end of 2022, a virulent sub-variant of the Streptococcus pyogenes M1 clone will rapidly propagate across Denmark, contributing to 30.0% of aggressive GAS infections.
New variants with higher virulence capacity majorly contribute to iGAS prevalence. Even indels or single nucleotide polymorphisms (SNPs) can impact iGAS virulence, emphasizing the necessity of monitoring genetic trends and identifying new variants.
About the study
In the present study, researchers examined current genetic advancements and the effect of new strain emergence on iGAS infection incidence in 2023.
Whole genome sequencing (WGS) data were examined for nationwide iGAS surveillance among Danish individuals in 2018.
Invasive GAS was not required to be documented in the nation of Denmark, except in meningitis cases; nonetheless, test data from all ten Departments of Clinical Microbiology (DCMs) reported to the Microbiology Database (MiBa) of the nation were evaluated to monitor disease incidence.
In addition, the team analyzed published WGS information on invasive GAS infection cases detected in 2022-2023 in Iceland, a nation with a greater iGAS incidence at the beginning of 2023.
The researchers collected GAS-positive cell culture reports from 2018 onward and grouped them as invasive GAS if the specimen originated from synovial fluid, blood, peritoneum, pleural fluid, spinal fluid, or sterile tissue, and non-invasive GAS if the strain in question had been of any other type of specimen or non-sterile tissue.
Repeated positive laboratory test reports from a subject in a month were treated as one instance. WGS information from 43 isolates collected from individuals hospitalized with severe illness in 2023 was evaluated to characterize iGAS genomes in Iceland.
The team gathered mortality data from the Civil Registration System of Denmark and data on the durations of hospitalizations and intensive care unit (ICU) treatment from the National Patient Registry for invasive GAS infections in Denmark.
The researchers analyzed the present genetic patterns for invasive GAS (257 strains) and non-invasive GAS (152 strains) isolates obtained by DCMs among patients selected between January and February 2023.
Results
In total, 1,265.0 iGAS infections were identified between 2018 and May 2023 among six million Danish individuals.
During the COVID-19 pandemic, the Danish nation witnessed historically low invasive GAS infection rates. Still, the cases began to rise rapidly in November 2022, with a peak in January 2023.
The monthly incidence of GAS infections was 118.0 cases among 100,000 individuals (3.50-fold higher than the incidence peak between 2018 and 2019), and that of invasive GAS infections was 1.70 cases among 100,000 individuals (3.0-fold higher than the rates between 2018 and 2019).
The highest invasive GAS infection incidence rates were observed among individuals aged ≥85 years, with a peak of 7.40 cases among 100,000 individuals each month.
However, the highest rise relative to pre-pandemic limitations was noted among pediatric individuals under five years, peaking at 3.20 cases among 100,000 children in March of 2023. Death rates were comparable to those observed in prior years across ages, with 30.0% among older individuals aged ≥85 and below 5.0% among those under five years.
Among Icelanders, 46 invasive GAS infections were documented through 7 May 2023, higher than the yearly mean of 15.0 cases between 2010 and 2019. A noteworthy increase was observed in children, with those under five years accounting for 17% (12 of 69) of infections versus 11% (47 of 436) between 1975 and 2021.
Individuals aged ≥60 years contributed to 33.0% (23 of 69) of infections, lower than that documented between 1975 and 2022 (214 of 434 infections, 49%).
High-quality WGS data were accessible for 839 from 1,019.0 (82%) invasive GAS infections identified between January 2018 and February 2023, vs. 11% (47 of 436) infections between 1975 and 2021.
The M1 ST28/EMM-1 and the ST36/EMM-12 clones were identified most frequently as the etiological agents of invasive GAS infections in winter 2023, responsible for 57% (n=87) and 24% (n=36) infections, respectively, from January to February of 2023.
Among Danish individuals, the M1UK strain was the most predominant causative strain of invasive GAS infections before COVID-19-associated limitations’ implementation. Across ages, except among individuals aged between 15 and 44 years, among whom ST36 infections were more frequently reported.
The recent upsurge in infections coincided with the novel M1DK strain emergence, responsible for 30.0% of the sequenced invasive GAS strains in 2023.
M1DK was more common among iGAS than among nGAS, while ST36 was overrepresented in nGAS. Although the novel M1DK lineage was overrepresented in invasive cases and carried the highest risk of requiring ICU treatment, its virulence was similar to other M1 variants associated with more severe infections.
The M1DK strain was distinguished from the M1UK and M1global lineages by obtaining a phage carrying the speC endotoxin.
Conclusion
Overall, the study findings showed an increase in GAS infections in Denmark in the winter months of 2023. The increase in invasive GAS infections could be due to the rapid spread of the M1DK lineage and the shift towards more virulent M1 variants.
The rapid expansion of M1DK is primarily driven by the unique circumstances surrounding COVID-19-related restrictions. Low immunity and reduced GAS transmission during lockdowns may have enhanced the development of individual lineages.
The M1UK strain is the leading cause of invasive GAS infections in a few European nations, indicating that the drastic increase in cases was also driven by factors beyond genomic developments.
