Venezuelan equine encephalitis (VEE) is caused by the VEE virus, which belongs to the Togaviridae family and genus Alphavirus. 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. Notably, the type II enzootic strain, called Everglades virus, is known to cause VEE in the US state of Florida.
On the other hand, 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 Texas. They 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 enough 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.
After a 1-5 day incubation period, infected patients usually present with a flu-like syndrome, often accompanied by pharyngitis and cervical lymphadenopathy. Most patients 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.
ICD10CM: A92.2 – Venezuelan equine fever
SNOMEDCT: 417702007 – Disorder due to Venezuelan equine encephalitis virus
Differential Diagnosis & Pitfalls
The major differential diagnoses include several mosquito-borne arboviral encephalitides commonly seen in the United States.
West Nile virus (WNV) encephalitis (see WNV, viral encephalitides) – There is widespread distribution in the continental United States, and it is the most common arboviral infection in the United States. The majority of cases occur in late summer through fall. Neuroinvasive WNV can present as encephalitis, meningitis, flaccid paralysis, or a mixed pattern.
St. Louis encephalitis (SLE) – Elderly patients are more prone to symptomatic infections. Prior to the onset of neurologic symptoms, patients experience fever, generalized malaise, and myalgias. Some have patients have dysuria, hematuria, or sterile pyuria. Neurologic manifestations include meningitis and encephalitis. Patients may present with myoclonus, tremors, opsoclonus, ataxia, or nystagmus. Cerebrospinal fluid (CSF) studies show lymphocytic pleocytosis, and magnetic resonance imaging (MRI) findings are nonspecific, although MRI may show T2 signal intensity in the substantia nigra.
Eastern equine encephalitis (EEE) – Most human cases in the United States occur along the Atlantic and Gulf coasts during summer. It has the highest mortality rate (as high as 75%) among arboviral encephalitides in the United States. Typical MRI brain findings include hyperintense signal abnormalities in bilateral symmetric basal ganglia, thalami, and brain stem.
Western equine encephalitis (WEE) – Occurs mainly in the western and Midwestern United States and in western Canada. Human cases of WEE are now exceedingly rare, with only 5 confirmed cases in the last 20 years. Focal temporal activity on electroencephalography (EEG) mimicking herpes simplex encephalitis has been reported in patients with WEE.