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West Nile virus is transmitted by urban-dwelling mosquitoes to birds and other animals, with occasional “spillover” to humans. While the means by which West Nile virus was introduced into the Americas in 1999 remain unknown, the climatic conditions that amplify diseases that cycle among urban mosquitoes, birds, and humans are warm winters and spring droughts. This information can be useful in generating early warning systems and mobilizing timely and the most environmentally friendly public health interventions. The extreme weather conditions accompanying long-term climate change may also be contributing to the spread of West Nile virus in the United States and Europe.