Monkeypox is a zoonotic disease with clinical manifestations similar to smallpox in humans. Since May 13, 2022, an increasing number of suspected and confirmed cases have been reported, affecting non-endemic regions across the globe. More strikingly, reports from the current outbreak reveal unique aspects regarding transmission dynamics and an unprecedented, rapidly expanding and sustained community transmission. As demonstrated through the still-ongoing COVID-19 pandemic, genomic surveillance has been an essential resource for monitoring and tracking the evolution of pathogens of public health relevance. Herein, we performed a phylogenomic analysis of available Monkeypox virus (MPXV) genomes to determine their evolution and diversity. Our analysis revealed that all MPXV genomes grouped into three monophyletic clades: two previously characterized clades and a newly emerging clade harboring genomes from the ongoing 2022 multi-country outbreak with 286 genomes comprising the hMPXV-1A clade and the newly classified lineages: A.1 (n = 6), A.1.1 (n = 1), A.2 (n = 3) and B.1 (n = 262), where lineage B.1 includes all MPXV genomes from the 2022 outbreak. Finally, it was estimated that B.1 lineage of this clade emerged in Europe on 03/02/2022 [95%CI = 11/13/2021 to 05/10/2022]. The exceptional surge of cases and the broader geographical expansion suggest multifactorial factors as drivers of the current outbreak dynamics. Such factors may include the cessation of smallpox vaccination and its potential spread across particular networks. Integrating pertinent epidemiological information with genomic surveillance information will help generate real-time data to help implement adequate preventive and control measures by optimizing public health decisions to mitigate this outbreak.
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