Phenotypic and genomic analysis of a large-scaleCorynebacterium diphtheriaeoutbreak among migrant populations in Europe

Abstract

BackgroundIncreased numbers of cases ofCorynebacterium diphtheriaeinfections 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.MethodsAll 363 toxigenicC. diphtheriaeinfection 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.ResultsFour 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.ConclusionsThe multi-country distribution of each cluster demonstrated repeated cross-border spread. The increased number ofC. diphtheriaecases 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 modernC. diphtheriaeinfections, useful for addressing the reemergence of diphtheria in vulnerable populations and to guide clinical management and measures to control further dissemination.