Human Disease

EEE virus is maintained in a cycle between Culiseta melanura mosquitoes and avian hosts in freshwater hardwood swamps. Culiseta melanura is not considered to be an important vector of EEE virus to people because it feeds almost exclusively on birds. Transmission to people requires another mosquito species to create a bridge between infected birds and uninfected mammals, such as people or horses (Morris 1988). Most of the bridge species are within the Aedes, Coquillettidia, and Culex genera. EEE virus has been documented to be transmitted through organ transplantation with one organ donor transmitting the infection to three organ transplant recipients (Pouch et al. 2019). Although not documented, EEE virus likely can be transmitted from person-to-person through blood transfusions.

Most persons infected with EEE virus have no apparent illness (Davis et al. 2008; Calisher 1994). Among those who develop symptoms, the incubation period typically ranges from 4 to 10 days but can be several weeks in people who are immunocompromised (CDC 2021; Sherwood and Oliver 2013).

Symptomatic infection is characterized by fever, chills, malaise, arthralgia, and myalgia (Calisher 1994). Most people recover completely in 1 to 2 weeks unless central nervous system involvement is present. Less than 5% of infected individuals develop meningitis or encephalitis (Morris 1988; Goldfield et al.1968). In infants, neurologic disease often occurs soon after onset; in older children and adults, encephalitis may occur after several days of systemic illness. Signs and symptoms in patients with neuroinvasive disease include headache, confusion, focal neurologic deficits, meningismus, seizures, or coma (Feemster 1938; Przelomski et al.1988; Deresiewicz et al. 1997; Clarke 1961; Letson et al. 1993; Ayers and Feemster 1949). Cerebrospinal fluid (CSF) findings include an initial neutrophil-predominant pleocytosis, shifting to a lymphocyte-predominance, and elevated protein levels; glucose levels are normal (Przelomski et al. 1988; Deresiewicz et al. 1997; Silverman et al. 2013). Neuroimaging shows brain lesions consistent with encephalitis, including neuronal destruction and vasculitis in the cortex, midbrain, and brain stem (Przelomski et al. 1988; Silverman et al. 2013). Magnetic resonance imaging using T2-weighted images often show areas of increased signal in basal ganglia and thalami (Deresiewicz et al. 1997).

Persons aged >50 and <15 years seem to be at greatest risk for developing severe disease when infected with EEE virus. EEE neuroinvasive disease is estimated to have a 30% case fatality rate and results in neurologic sequelae in >50% of survivors (Feemster 1938; Goldfield and Sussman 1968; Deresiewicz et al. 1997; Letson et al. 1993; Ayers and Feemster 1949; Silverman et al. 2013; Gaensbauer et al. 2014). Death typically occurs 2 to 10 days after symptom onset but can occur much later. The neurologic sequelae can range from mild brain dysfunction to severe intellectual impairment, personality disorders, seizures, paralysis, and cranial nerve dysfunction. Many patients with severe sequelae require long-term care and die within a few years.

EEE virus disease should be considered in any person with a febrile or acute neurologic illness with a potential for recent exposure to mosquitoes, organ transplantation, or potentially blood transfusion, particularly during the summer months in areas where virus activity has been reported. In addition to other more common causes of encephalitis and aseptic meningitis (e.g., herpes simplex virus and enteroviruses), other arthropod-borne viruses (e.g., West Nile, La Crosse, St Louis encephalitis, and Powassan viruses) should also be considered in the differential diagnosis of suspected EEE.

References

Ayres JC and Feemster RF. The sequelae of eastern equine encephalomyelitis. N Engl J Med 1949;240: 960–962.

Calisher CH. Medically important arboviruses of the United States and Canada. Clin Microbiol Rev 1994;7:89–116.

CDC. Eastern equine encephalitis: Clinical Evaluation & Disease. Fort Collins; 2021. https://www.cdc.gov/easternequineencephalitis/healthcare-providers/clinical-evaluation-disease.html.

Clarke DH. Two nonfatal human infections with the virus of eastern encephalitis. Am J Trop Med Hyg 1961;10:67–70.

Davis LE, et al. North American encephalitic arboviruses. Neurol Clin 2008;26:727–57, ix.

Deresiewicz RL, et al. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 1997;336:1867–1874.

Feemster RF. Outbreak of encephalitis in man due to the eastern virus of equine encephalomyelitis. Am J Public Health Nations Health 1938;28:1403–1410.

Gaensbauer JT, et al. Neuroinvasive arboviral disease in the United States: 2003 to 2012. Pediatrics 2014;134:e642–e650.

Goldfield M, et al. The 1959 outbreak of eastern encephalitis in New Jersey. The inapparent infection: Disease ratio. Am J Epidemiol 1968;87:32–38.

Goldfield M and Sussman O. The 1959 outbreak of eastern encephalitis in New Jersey. I. Introduction and description of outbreak. Am J Epidemiol 1968;87:1–10.

Letson GW, et al. Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent epidemiologic trends, and the association of rainfall with EEE occurrence. Am J Trop Med Hyg 1993;49:677–85.

Morris CD. Eastern equine encephalitis. Monath TP, ed. The Arboviruses: Epidemiology and Ecology, Vol. 3. Boca Raton (FL): CRC Press; 1988. p. 1–20.

Pouch SM, et al. Transmission of eastern equine encephalitis virus from an organ donor to 3 transplant recipients. Clin Infect Dis 2019;69:450–458.

Przelomski MM, et al. Eastern equine encephalitis in Massachusetts: a report of 16 cases, 1970–1984. Neurology 1988;38:736–739.

Sherwood JA and Oliver J. Eastern equine encephalitis incubation time periods of 5 and 8 days. Pediatr Infect Dis J 2015;34:459–60.

Silverman MA, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970–2010. Emerg Infect Dis 2013;19:194–201.