Viral introductions and return to baseline sexual behaviors maintain low-level mpox incidence in Los Angeles County, USA, 2023-2024

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 expected accumulation of immunity within queer sexual networks, mpox continues to persist at low incidence in North America without extinction, raising concerns of future outbreaks. We combined phylodynamic inference and microsimulation modeling to understand the heterogeneous dynamics governing local mpox persistence in Los Angeles County (LAC) from 2023–2024. Our Bayesian phylodynamic analysis revealed a time-varying pattern of viral importations into the county that seeded a heavy-tailed distribution of mpox outbreak clusters that display a ″stuttering chains″ dynamic. Our phylodynamics–informed microsimulation model demonstrated that the persistent number of mpox cases in LAC can be explained by a combination of waves of viral introductions and a return to near-baseline sexual behaviors that were altered during the 2022 epidemic. Finally, our counterfactual scenario modeling showed that public health interventions that either promote increased isolation of symptomatic, infectious individuals or enact behavior–modifying campaigns during the periods with the highest viral importation intensity are both actionable and effective at curbing mpox cases. Our work highlights the heterogeneous factors that maintain present-day mpox dynamics in a large, urban US county and describes how to leverage these results to design timely and community–centered public health interventions