Reservoir host community and vector density predict human tick-borne diseases across the Eastern United States.

Tick-borne disease (TBD) incidence is rising globally, underscoring the need for prevention strategies that consider ecological drivers of transmission. We analyzed associations between human reported cases of four TBDs and ecological and climatic factors across 24 eastern U.S. counties. Mean reported cases per 100,000 people were 0.0274 for Lyme disease, 0.0045 for anaplasmosis, 0.0012 for ehrlichiosis, and 0.0005 for babesiosis. Babesiosis was negatively associated with mean annual temperature, whereas ehrlichiosis increased with nymphal tick density. Anaplasmosis was positively linked to tick density, with the abundance of competent hosts mediating the effects of small-mammal richness. Lyme disease was positively associated with deer density and negatively associated with precipitation, temperature, and small-mammal richness. We also found a positive interaction between competent host abundance and tick density as drivers of Lyme disease. Our results support the dilution-effect hypothesis for Lyme disease and a mediating effect of host composition for anaplasmosis dilution or amplification. Our findings highlight that ecological context strongly shapes TBD risk, suggesting that the effectiveness of intervention strategies depends on interactions among ticks, hosts, and climate.