AUTHOR=Mangioni Davide , Fox Valeria , Saltini Paola , Lombardi Andrea , Bussini Linda , Carella Francesco , Cariani Lisa , Comelli Agnese , Matinato Caterina , Muscatello Antonio , Teri Antonio , Terranova Leonardo , Cento Valeria , Carloni Sara , Bartoletti Michele , Alteri Claudia , Bandera Alessandra 

TITLE=Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1287522

DOI=10.3389/fmicb.2023.1287522

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.</p></sec><sec><title>Methods</title><p>GAS strains collected in 09/2022–03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between <italic>emm-</italic>types and clinical severity.</p></sec><sec><title>Results</title><p>Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen <italic>emm</italic>-types were detected, the most prevalent being <italic>emm</italic>1 and <italic>emm</italic>12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of <italic>emm</italic>1.0 and <italic>emm</italic>12.0 strains revealed pairwise SNP distance always &gt;10, inconsistent with unique transmission chains. <italic>Emm</italic>12.0-type, found to almost exclusively carry virulence factors <italic>spe</italic>H and <italic>spe</italic>I, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, <italic>p</italic> = 0.007 and 66.7 vs. 0.0%, <italic>p</italic> &lt; 0.001, respectively), while <italic>emm</italic>1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, <italic>p</italic> = 0.045).</p></sec><sec><title>Conclusions</title><p>This study showed that multiple <italic>emm</italic>-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific <italic>emm</italic>-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.</p></sec>