Associations between the 2022 global mpox outbreak and multifaceted factors: A multi-geographical retrospective study.

Unlike prior travel-related mpox cases, the 2022 outbreak of mpox virus (MPXV) clade IIb outside endemic regions posed a significant global health threat. Despite growing recognition of the One Health relevance of mpox, the factors driving this unprecedented outbreak and their quantitative effects remain not fully understood. This study aims to identify key factors across various geographical scales to inform future mpox mitigation policies within One Health framework. We built logistic regression models to assess the association of 18 covariates-including socioeconomic, demographic, and human behaviors (e.g., urbanization, sexual behavior, immunity, mobility and contact intensity) -with mpox outbreak probability in the United States, England, Brazil, and globally. We also examined temporal trends over the past decade. Our analysis revealed positive associations between mpox cases and urbanization rates (United States: R = 0.43; England: R = 0.25; Brazil: R = 0.52; all P < 0.05) and the proportion of lesbian, gay, bisexual, and transgender (LGBT) individuals (United States: R = 0.39; England: R = 0.72; both P < 0.05; Brazil: R = 0.26, P = 0.18). Conversely, smallpox vaccination coverage showed a negative association with mpox cases (United States: R = -0.25, P = 0.08; England: R = -0.52). Similar trends were observed globally. Mpox outbreak probability increased globally over the past decade. Our findings highlight the role of long-term human behavior changes in MPXV clade IIb outbreaks. From a One Health perspective, these results suggest that ongoing attention to behavioral factors, alongside ecological and social contexts, may help improve understanding and prediction of outbreak dynamics.