Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak

Abstract

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1_UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1_global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates.

Importance: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.

Keywords: GAS; M1UK; Streptococcus pyogenes; children; invasive disease; outbreak.

Fig 1

Population structure of Streptococcus pyogenes isolates from this study: minimum-spanning tree. Distances shown are based on cgMLST of 1168 genes using the parameter “pairwise ignoring missing values.” Fill colors in each circle indicate emm types, color of the dashed line in circles indicates the origin from cases or controls.

Fig 2

Types of Streptococcus pyogenes identified in patients with clinical data. (A) Types of controls compared to the total number of cases. (B) Types of cases by diagnoses.

Fig 3

Evolution of the main clonal lineages of Streptococcus pyogenes during the 2022–2023 outbreak in Spain. Bar and linear chart that represents the temporal evolution of the total, emm1 (global plus UK clones), M1_UK, emm1.0, emm1.3, emm12.0, and emm12.37 isolates. y-Axis represents the number of isolates and x-axis shows the studied period (months).

Fig 4

Population structure of Streptococcus pyogenes serotype M1 including isolates from this study and a well-characterized collection of 631 genomes that belong to M1_UK, M1_global, and M1inter (reference). (A) Maximum-likelihood tree showing the relationship between isolates; branch lengths are indicative of the number of SNPs. Colored branches indicate the variants of serotype M1. (B) Minimum-spanning tree showing distance based on cgMLST of 1,168 genes using the parameter “pairwise ignoring missing values.” Each circle is named with the MLST type of the isolates and colors indicate the variants of serotype M1.