Early underdetected dissemination followed by extensive local transmission propelled the 2022 mpox epidemic and limited impact of vaccination.

The World Health Organization (WHO) declared mpox a public health emergency of international concern in July 2022. It is still unclear to what extent international travel contributed to the explosive spread of mpox and the degree to which national vaccination campaigns were responsible for controlling the epidemic. We built phylogeographic and phylodynamic models to analyze MPXV genomes sampled between March 2022 and January 2023 from five global regions together with air traffic and epidemiological data to analyze the global spread of mpox. Our models reveal community transmission prior to detection by local surveillance, changes in case-reporting throughout the epidemic, and a large degree of transmission heterogeneity. Additionally, we find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that the time-varying effective reproductive number in North America declines below one before more than 10% of individuals at high risk individuals in the USA had vaccine-induced immunity, suggesting little impact of vaccination in controlling the epidemic. Given that cases quickly declined after detection most likely due to behavioral modifications, our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases.