Eastern Equine Encephalitis (EEE)

Updated: Aug 21, 2023
  • Author: Mohan Nandalur, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Encephalitis is an acute inflammatory process that primarily involves the brain. The meninges frequently are involved (meningoencephalitis). Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. The incidence of encephalitis is 1 case per 200,000 population in the United States, with herpes simplex virus (HSV) being the most common cause. The arboviruses account for 10% of cases; occasionally, during an epidemic, they can account for as many as 50%.

Five types of arborviral encephalitis are found in the United States: eastern equine encephalitis (EEE), [1, 2, 3] western equine encephalitis (WEE), St Louis encephalitis, La Crosse encephalitis, and West Nile encephalitis (WNE). [4] This article focuses on EEE, which is caused by an arthropod-borne alphavirus. In equines, EEE is invariably fatal. In humans, EEE is uncommon but likewise is associated with a high rate of morbidity and mortality. Initial symptoms often progress rapidly to confusion, somnolence, or even coma.

In North America, the enzootic vector for EEE is the mosquito Culiseta melanura, which is responsible for the spring-summer amplification of the virus in the mosquito-bird-mosquito cycle. Occasionally, other mosquito types (eg, Coquillettidia perturbans and the ubiquitous Aedes canadensis species) may act as bridges in the horse-to-human transmission.

The viral reservoir varies depending on climate and habitat changes and often exhibits an annual fluctuation between avirulent and virulent strains. The degree of virulence is related to the host specifics of a given epizootic outbreak.

Initial medical care focuses on making a prompt diagnosis that differentiates EEE from potentially treatable causes. Like all diseases caused by alphaviruses, EEE has no specific treatment. Management of this condition primarily rests on supportive and preventive measures.

See the following for more information:

Patient education

For patient education resources, see the Brain and Nervous System Center, as well as Encephalitis.



EEE is characterized by diffuse central nervous system (CNS) involvement. [1, 2] A large number of immunologically active cells enter the brain parenchyma and perivascular areas and mediate much of the damage. Infiltrating neutrophils and macrophages cause neuronal destruction, neuronophagia, focal necrosis, and spotty demyelination. Vascular inflammation with endothelial proliferation, small vessel thrombosis, and perivascular cuffing also may develop.

Antigenic studies reveal that EEE primarily affects the perikaryon and dendrites of neurons, with minimal findings in glial cells. Occasionally, secondary glial proliferation and the formation of glial nodules occur. Cell death by apoptosis occurs primarily among the glial and inflammatory cells. Gross inspection on autopsy reveals edema, leptomeningeal vascular congestion, hemorrhage, and encephalomalacia. Patients who die late in the disease may exhibit diffuse cerebral atrophy, particularly of the cortex.

The mosquito injects the agent of EEE into the subcutaneous and cutaneous tissues of the host. EEE is not transmitted via the aerosol route. It may cross the placenta and infect the fetus. Because of low viral titers in the donor’s blood, EEE is unlikely to be transmitted via transfusion. The prodrome of fevers, chills, weakness, headache, and myalgias represents replication of the virus in nonneural tissues (tissue adjacent to the mosquito’s bite or the lymphatic system).

The virus then binds to specific tissue receptors, undergoes endocytosis, and initiates an RNA-dependent RNA and protein synthetic process. [5] If the original inoculum is large enough, secondary viremia occurs, with eventual viral migration into the CNS via cerebral capillary endothelial cells. Poorly described features of the virus increase microvascular permeability of the brain. Cell-to-cell spread then occurs via dendrites and axons.



EEE is caused by a virus from the Alphavirus genus, which is part of the antigenically similar family of viruses known as Togaviridae. [1, 3] (Alphaviruses are also responsible for WEE and VEE.) These alphaviruses are spherical and have a diameter of 60-65 nm. The outer layer consists of a glycoprotein shell with protruding glycoprotein spikes found beneath the lipid bilayer. The nucleocapsid core contains the single-stranded RNA genome.

The alphavirus that causes EEE is found mostly in the mosquito subtype C melanura; other infectious subtypes include the Aedes and Coquillettidia species. C melanura mosquitoes breed in freshwater swamps and feed on passerine birds. The infected birds subsequently exhibit high levels of viremia, which differs from human and equine cases, in which viremia often is low.

Passerine birds serve as an effective reservoir for continued mosquito infection. Regardless of the extent of viremia in the birds, the outcome varies, ranging from asymptomatic states to death. With low viremia in horses and humans, neither of these species acts as a reservoir for further viral distribution.

The only individual risk factor for EEE is age; however, certain behaviors can also be risk factors (eg, outdoor activities during peak mosquito activity, most often in rural areas).



United States statistics

EEE was first recognized in 1938. From 1955-1997, 256 cases, both sporadic and epidemic types, were reported to the US Centers for Disease Control and Prevention (CDC). From 2009-2018, 72 cases were reported to the CDC, averaging 7 cases per year (range, 3-15 annually). [6]

As of October 3, 2019, 30 cases of EEE had been reported in the United States for the year, including 11 deaths. Affected states have included Tennessee, Michigan, Massachusetts, North Carolina, Connecticut, New Jersey, and Rhode Island. [7]

Because alphaviruses depend on arthropod vectors, their distribution is geographically limited. The EEE virus is divided into North and South American variants on the basis of results from hemagglutinin inhibition testing. North American isolates have a highly conserved lineage, as noted in comparisons of outbreaks in Mexico and Texas.

In the United States, EEE is most common east of the Mississippi River (eg, in Michigan, Massachusetts, New York, New Jersey, North Carolina, South Carolina, Florida, Louisiana, and Georgia). [8] The prevalence is increased in environments with wooded areas adjacent to freshwater swamps and marshes.

Most infections occur in summer or early fall. The vector population usually dies in winter, and cases of EEE are almost nonexistent in winter months; however, after winter, a repetitive endemic locus of infection may persist. An additional risk increase occurs during epizootic outbreaks among horses or caged birds. 

There have a been a stable number of cases with limited outbreaks amongst horses in Florida, Michigan, and Massachussets in recent years, but no documented human infections. 

International statistics

EEE also is prevalent in gulf coastal areas (eg, Mexico, northern coast of South America, Caribbean). The EEE virus in these regions is an antigenic variant of the North American form.

Age-, sex-, and race-related demographics

EEE is a summertime disease and most commonly affects people younger than 15 years and older than 55 years. The exact reason for this pattern is not known, but the preference for extremes of age is a characteristic common to many species of the alphavirus family. Patient age does not affect prognosis, but permanent neurologic impairment and death are more common in children.

No sexual or racial predilection exists for EEE.



EEE has an infection rate of 33%. The average duration of hospitalization is 16-20 days. The prognosis in infected patients is extremely poor; 50-70% of patients die. The morbidity rate is approximately 90%, representing a wide range of mild to severe impairment. Only 10% of patients fully recover.

Currently, no clinical or radiographic prognostic indicators are available for EEE. The location and the type of lesion on imaging do not correlate with long-term sequelae or mortality. Additionally, although younger patients with longer prodromes tend to have better outcomes, no study has proven any statistical significance. The initial history and physical examination often do not reveal any prognostic variables.

Changes in treatment regimens do not commonly affect outcome; in fact, one series revealed a poorer outcome with the use of steroids and anticonvulsants, but many confounding variables were involved in this determination.

Certain laboratory findings may have some significance. The expected outcome in a patient with an elevated white blood cell (WBC) count (>500/μL) in cerebrospinal fluid (CSF) is poorer than that in a patient with a lower CSF WBC count (ie, < 500 cells/μL). In addition, the prognosis in a hyponatremic patient with a sodium level lower than 130 mmol/L is poorer than that in a patient with a higher sodium level.