Clinical characterization of an emm1-dominant group A Streptococcus outbreak in Chile in the context of the previous 6 years

TL;DR

Chile experienced a 2024 outbreak of group A Streptococcus infections dominated by the emm1 lineage, which likely spread due to clonal expansion rather than increased virulence.

Contribution

The study provides genomic and clinical evidence that the Chilean iGAS outbreak was driven by emm1 lineage expansion, not increased virulence.

Findings

emm1 became dominant in 2024, with reduced emm diversity and increased clindamycin resistance among iGAS cases.

Whole-genome sequencing showed emm1 isolates carried more virulence genes and were closely related to strains from the UK, Argentina, and the US.

h-niGAS cases required more surgical procedures and medical evaluations compared to other niGAS cases.

Abstract

In 2024, Chile experienced an outbreak of invasive group A Streptococcus (iGAS) infections. Although increasing reports of GAS outbreaks have been described worldwide, it remains unclear whether these events are driven by increased virulence of circulating lineages or by lineage replacement. In parallel, the burden of hospitalized noninvasive GAS infections (h-niGAS), which may present with severe disease, remains poorly characterized. This study aimed to compare epidemiological, clinical, antimicrobial resistance, and genomic features of iGAS and h-niGAS infections in Chile over a six-year period.

We analyzed 2,307 GAS isolates collected between 2018 and 2024, including 2,249 noninvasive isolates and 58 iGAS isolates. Noninvasive cases were classified as outpatient niGAS or hospitalized niGAS (h-niGAS). Antimicrobial susceptibility testing was performed for all isolates. emm typing was performed on isolates from hospitalized patients (28 iGAS and 94 h-niGAS). Whole-genome sequencing was performed on outbreak-related isolates, followed by virulence gene profiling and phylogenetic analysis. Clinical characteristics were compared between iGAS and non-iGAS cases and across time periods.

Among niGAS isolates, 2,119 were obtained from outpatients and 130 from hospitalized patients. h-niGAS isolates showed the highest proportion of clindamycin resistance (42%), whereas iGAS isolates showed the lowest (16%). Notably, clindamycin resistance among iGAS increased from 0% during 2020–2023 to nearly 20% in 2024. The most frequent emm types were emm1, emm12, and emm4. The frequency of emm1 increased from 0% in 2020–2023 to 10% in 2024, while overall emm diversity declined markedly (Simpson’s reciprocal index from 17.3 to 6.63). Clinically, iGAS infections were associated with immunosuppression, chronic liver disease, viral coinfection, and trauma. During the 2024 outbreak, iGAS cases did not differ clinically from those reported in 2018–2023; however, h-niGAS cases required more surgical procedures (p = 0.005) and medical evaluations (p = 0.025). Whole-genome sequencing revealed predominance of emm1, including three M1UK strains harboring all 27 defining single-nucleotide polymorphisms. emm1 isolates carried a higher number of virulence-associated genes compared with non-emm1 isolates (p < 0.05). Phylogenetic analysis showed close relatedness to strains from the United Kingdom, Argentina, and the United States.

These findings suggest that the Chilean outbreak was driven by the expansion of the emm1 lineage rather than an increase in strain virulence. The identification of M1UK strains and the reduced emm diversity support a model of lineage introduction and clonal expansion. The significant clinical burden observed among h-niGAS cases underscores the importance of including hospitalized noninvasive infections in surveillance efforts. Ongoing integrated clinical and genomic surveillance of both iGAS and h-niGAS is essential to monitor emerging lineages and antimicrobial resistance trends.

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