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Insecticides kill mosquitoes, but can they reduce transmission of West Nile virus (WNV) to humans? In Sacramento County, California, a 2005 epidemic of WNV cases prompted aerial spraying of pyrethrin, an insecticide that targets adult mosquitoes. Authorities decided to spray when surveillance indicated escalating risk, based on high mosquito abundance and WNV infection prevalence, elevated seroconversion rates in sentinel chickens, and record numbers of dead birds, infected horses, and confirmed human cases. The main WNV vectors in the area were Culex pipiens (urban) and Culex tarsalis (rural), mosquitoes that feed primarily from dusk to dawn. Aerial spraying, completed during 3 nights in August in each of two urban areas, was mapped to all…