In the United States, the leading cause of epidemic flaviviral encephalitis is St. Louis encephalitis (SLE) virus.

SLE is the most common mosquito-transmitted human pathogen in the U.S. While periodic SLE epidemics have occurred only in the Midwest and southeast, SLE virus is distributed throughout the lower 48 states.

Since 1964, there have been 4,437 confirmed cases of SLE with an average of 193 cases per year (range 4 – 1,967). However, less than 1% of SLE viral infections are clinically apparent and the vast majority of infections remain undiagnosed.

Illness ranges in severity from a simple febrile headache to meningoencephalitis, with an overall case-fatality ratio of 5-15 %. The disease is generally milder in children than in adults, but in those children who do have disease, there is a high rate of encephalitis. The elderly are at highest risk for severe disease and death.

During the summer season, SLE virus is maintained in a mosquito-bird-mosquito cycle, with periodic amplification by peridomestic birds and Culex mosquitoes. In Florida, the principal vector is Cx. nigripalpus, in the Midwest, Cx. pipiens pipiens and Cx. p. quinquefasciatus and in the western United States, Cx. tarsalis and members of the Cx. pipiens complex.