Targeted County-Level Interventions Achieve Epidemic Control Without Statewide Lockdowns

When a new pathogen emerges, public health authorities must act rapidly to mitigate its spread while minimizing socioeconomic disruption. Despite extensive debate on localized epidemic control, no model-based study has systematically evaluated county-level interventions for statewide epidemic suppression in the United States. We present a metapopulation model that integrates county-level mobility data to identify epidemic hotspots and assess targeted intervention strategies for pandemic preparedness. We identify epidemic hotspots as counties that generate disproportionately large statewide epidemics when serving as outbreak origins. These hotspots align with population-dense and highly connected locations but provide sharper spatial contrast than traditional centrality metrics. Targeted interventions reducing the basic reproduction number (R0) only at hotspots achieve substantial epidemic control, reducing statewide epidemics by 60-90% in four representative states (Oklahoma, New York, Florida, and California), without requiring broad lockdown measures. Hybrid strategies combining moderate reductions in R0 (10-30%) with partial mobility restrictions (30-80%) from hotspot counties, while preserving activity elsewhere, achieve control equivalent to full suppression at hotspots. This framework demonstrates that strategic, location-specific interventions can replace blanket pandemic responses. It provides state and county decision makers with a quantitative tool for prospective pandemic planning, enabling rapid hotspot identification and intervention design grounded in empirical mobility networks.