Venezuelan equine encephalitis (VEE) is caused by the VEE virus, which belongs to the Togaviridae family and Alphavirus genus. VEE virus is one of the North American encephalitic arboviruses that is transmitted to humans by mosquito bites. There are 6 subtypes (I through VI) in the VEE virus complex. VEE virus subtype I consists of 5 antigenic variants (I-AB, I-C, I-D, I-E, I-F). These subtypes and variants are responsible for 2 distinct VEE virus transmission phases, known as enzootic and epizootic cycles.

The enzootic cycle is caused by VEE virus strains I-D, I-E, I-F, and II through VI, and is maintained with rodents as primary reservoirs and Culex (Melanoconion) iolambdis mosquitoes as primary vectors. The enzootic VEE virus strains are considered to be of low pathogenicity for horses and cause sporadic disease in humans throughout Central and South America. Infection is usually asymptomatic. Notably, the type II enzootic strain, called Everglades virus, is known to cause VEE in the US state of Florida and can cause clinical encephalitis in humans.

VEE virus variants I-AB and I-C are responsible for the epizootic cycle and cause outbreaks of encephalitis in horses in countries in South America (Venezuela, Colombia, Ecuador, and Peru), Mexico, and the US state of Texas. These variants are transmitted from horses to humans through the bites of mosquitoes, Aedes taeniorhynchus and Psorophora spp, causing a neuroinvasive form of VEE infection. In contrast to other arbovirus infections in humans, viremia in humans is thought to be sufficient to infect mosquitoes and maintain the epizootic cycle. Direct transmission between horses, horse-to-human transmission, and human-to-human transmission have not been confirmed. However, transmission via aerosols among laboratory personnel has been reported and poses an occupational risk to laboratory workers; aerosol transmission is also regarded as a potential biowarfare weapon.

It should be noted that studies of viral evolution have demonstrated that the existing epizootic strains have evolved from enzootic strains under appropriate climatic and ecological conditions. Expansion of human habitats and concurrent reduction in regional biodiversity may increase the probability of the emergence / evolution of new enzootic or epidemic strains.

After a 1- to 5-day incubation period, infected patients usually present with a flu-like syndrome, often accompanied by pharyngitis and cervical lymphadenopathy. Most patients (> 96% of children and 99% of adults) recover completely after a week. Up to 4% of affected children and 0.4% of affected adults progress to encephalitis syndrome with altered mental status, tremors, convulsions, or paralysis. The case fatality rate of encephalitis is 10%-25%, and it could be as high as 35% in children younger than 5 years. Neurologic sequelae are uncommon, and the prognosis for full recovery is excellent among survivors of encephalitis.