Phenotypic and genomic analysis of a large-scale Corynebacterium diphtheriae outbreak among migrant populations in Europe

Abstract

Background. Increased numbers of cases of Corynebacterium diphtheriae infections were diagnosed in migrant-related facilities of Europe since summer 2022. Most cases involved cutaneous diphtheria, although some respiratory cases and fatalities were reported. A pan-European consortium was created to assess the clinical, epidemiological and microbiological features of this outbreak. Methods. All 363 toxigenic C. diphtheriae infection cases from ten European countries were included. Data from case interviews regarding countries of origin and transit routes of migrants were collected. Bacterial isolates underwent whole genome sequencing and antibiotic susceptibility testing. Phylogenetic relationships of outbreak isolates and their antimicrobial resistance genes were studied. Results. Four major genomic clusters were identified, revealing the multiclonal nature of the outbreak. Genes ermX, coding for erythromycin resistance, and genes pbp2m and blaOXA-2 for beta-lactam resistance, were detected in a subset of isolates. Isolates harboring ermX were resistant to erythromycin, and isolates carrying pbp2m were resistant to penicillin, but susceptible to amoxicillin, whereas those carrying blaOXA-2 remained susceptible to beta-lactams. Genomic variation within the four genomic clusters led to estimate their most recent common ancestors between 2017 and 2020. Conclusions. The multi-country distribution of each cluster demonstrated repeated cross-border spread. The increased number of C. diphtheriae cases among migrants is a cause for concern, particularly considering antimicrobial resistance phenotypes that threaten the efficacy of first-line treatments. This work provides important knowledge on modern C. diphtheriae infections, useful for addressing the reemergence of diphtheria in vulnerable populations and to guide clinical management and measures to control further dissemination.