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

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

doi:10.3389/fmicb.2023.1287522

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

Front Microbiol. 2024 Jan 11:14:1287522. doi: 10.3389/fmicb.2023.1287522. eCollection 2023.

Authors

Davide Mangioni^#^{1

2}, Valeria Fox^#³, Paola Saltini^{1

2}, Andrea Lombardi^{1

2}, Linda Bussini^{4

5}, Francesco Carella^{4

5}, Lisa Cariani⁶, Agnese Comelli¹, Caterina Matinato⁶, Antonio Muscatello¹, Antonio Teri⁶, Leonardo Terranova⁷, Valeria Cento^{5

8}, Sara Carloni^{5

9}, Michele Bartoletti^{4

5}, Claudia Alteri³, Alessandra Bandera^{1

2}

Affiliations

¹ Infectious Diseases Unit, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
² Department of Pathophysiology and Transplantation, University of Milano, Milan, Italy.
³ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
⁴ Infectious Disease Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Milan, Italy.
⁵ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁶ Microbiology Laboratory, Clinical Pathology, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁷ Respiratory Unit and Adult Cystic Fibrosis Center, Department of Internal Medicine, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁸ Microbiology and Virology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Milan, Italy.
⁹ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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 emm-types and clinical severity.

Results: 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 emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p < 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045).

Conclusions: This study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-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.

Keywords: GAS; Streptococcus pyogenes; WGS; genomic surveillance; necrotizing fasciitis; virulence factors.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was partially funded by the Italian Ministry of Health—Current research IRCCS, by project STOP COVID financed by COVID-19 emergency donations and by EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).