Abstract

In 2022, mpox clade IIb disseminated around the world, causing outbreaks in more than 117 countries. Despite the decay of the 2022 epidemic and the increased immunity within sexual networks, mpox continues to persist in North America without extinction, raising concerns of future outbreaks. We combined phylodyamic inference and microsimulation modeling to understand the heterogeneous dynamics governing local mpox persistence in Los Angeles County (LAC) from 2023 to 2024. Our Bayesian phylodynamic analysis revealed a time-varying pattern of viral importations into the county, which seeded mpox outbreak clusters that display “stuttering chains” dynamics. Our phylodynamics-informed microsimulation model demonstrated that the mpox cases in LAC can be explained by a combination of waves of viral introductions, a median effective reproductive rate below one, and a return to near-baseline sexual behaviors after the 2022 epidemic. Our counterfactual scenario modeling showed that frequent public health interventions that either promote increased isolation of infectious individuals or enact behavior-modifying campaigns during the periods with the highest viral importation intensity are actionable and effective at curbing mpox cases. Our work highlights the factors that maintain present-day mpox dynamics in a large, urban US county and describes how to leverage these results into community-centered public health interventions.