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Objectives: We attempted to establish a molecular investigation by Next Generation sequencing of the measles virus (MeV) strains circulating in Marseille-France during the last outbreak that occurred between 2017 and 2019.Methods: The circulating MeV were isolated from clinical samples using cell culture method and whole genomes were sequenced by Illumina Miseq Next Generation. Genotyping and comparative analyses were assessed by phylogenetic reconstructions. Clinical and epidemiological data from cases were also recorded.Results: A total of 110 MeV strains were isolated in cell culture. Our analysis based on whole genome sequences of 98 isolates confirmed that 93 strains belonged to the genotype D8 and 5 to the genotype B3. Phylogenetic analyses revealed 4 distinct MeV circulating clones in Marseille. Measles mostly occured in children < 5 years-old and in adults 30-50 years-old. Measles infection also occurred in 2 adequately vaccinated cases (2 doses). Among 63 measles cases of whom we had available clinical data informations, a total of 35 patients were hospitalized and 19 developed complications including one death case recorded.Conclusions: Whole Genome Sequencing seems to be a useful tool for more refined genomic characterization of large measles outbreak. Vaccination strategies for measles eradication need to be re-evaluated in the current context. [ABSTRACT FROM AUTHOR]