Eastern Equine Encephalitis

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Continuing Education Activity

Eastern equine encephalitis (EEE) is one of the most severe arboviral encephalitis affecting America. Currently considered an emerging disease showing consistently increase incidence across a wider population. In the United States, between six to eight cases are annually reported, predominantly between May through October, mostly in Florida, Georgia, Maryland, Wisconsin, and New Jersey. This virus has also been considered a potential bioterrorism weapon given its airborne transmission. The case-fatality rate described is 30%, with neurologic sequelae seen in 50% of survivors. This activity describes the epidemiology pathophysiology, diagnosis, treatment, and outcome of Eastern equine encephalitis. It highlights the importance of an interprofessional team in detecting outbreaks and also in managing this complex and uncommon condition.


  • Identify the etiology of Eastern equine encephalitis medical conditions and emergencies.
  • Outline the appropriate evaluation of Eastern equine encephalitis.
  • Review the management options available for Eastern equine encephalitis
  • Describe interprofessional team strategies for improving care coordination and communication to advance Eastern equine encephalitis care and improve outcomes.


Eastern equine encephalitis (EEE) is one of the most severe arboviral encephalitis affecting America. Currently considered an emerging disease showing consistently increase incidence across a wider population. In the United States, between six to eight cases are annually reported, predominantly between May through October, mostly in Florida, Georgia, Maryland, Wisconsin, and New Jersey.[1][2][3] This virus has also been considered a potential bioterrorism weapon, given its airborne transmission.[4] The case-fatality rate described is 30%, with neurologic sequelae seen in 50% of survivors.[3]


Eastern equine encephalitis virus (EEEV) is an arbovirus from the Togaviridae family, genus alphavirus. Maintained by a cycle between birds and predominantly Culiseta melanura mosquitoes associated with freshwater hardwood swamps.[5] Recent data suggest other mosquitoes species also involved in EEBV transmission include Coquillettidia perturbans, Aedes cinereus, and Aedes canadensis.[6][7] The mosquitoes get infected and transmit EEV during blood feeding to passerine (tree-perching) birds and opportunistic mammals, reptiles, or amphibians. This virus can escape its usual reservoir to infect dead-end hosts (humans, swine, equids, pheasants). Humans are described as dead-end hosts since viremia levels are not usually reached to a level to allow the transmission to the feeding mosquitoes.[6] This cross-transmission happens unpredictably, but changes in weather and global warming may have an effect on this rising incidence. Other factors include environmental perturbations, movement of birds, and human interaction with the environment.[8] In 2017, EEEV transmission was reported for the first time via organ transplantation.[9][1]


The first identification of Eastern equine encephalitis virus in humans dates from 1938 during an important outbreak affecting Massachusetts, U.S. As previously described, humans do not usually participate in the natural cycle but rather get affected sporadically in the geographic region along the Atlantic, and Gulf coasts of the U.S. The largest EEEV outbreak recorded is from 1959 in New Jersey, U.S., and involved 32 cases during 8 weeks. E.E.E. is now a nationally notifiable condition and is monitor through ArboNET, a national arboviral disease surveillance disease system since 2003.[5] The latest data reflects EEEV was present in 20 states. Massachusetts, Florida, and New Hampshire as the states with more reported cases nationwide, but new states have been now included in this list, such as Arkansas, Connecticut, Maine, Tennessee, North Carolina, and Vermont showing a larger geographic range affected by this viral encephalitis.[10] Annual incidence reflects a mean of 8 cases in the U.S. Neuroinvassive disease is 2 times higher among males. The incidence of EEEV also has shown a bimodal presentation with the highest risk among the population less than 5 years of age and above 60 years of age.[1] Data from Lindsey et al. also described a fatality rate as high as 41%, with 50% of long-term neurological sequelae. 

As per ArboNET reports, non-human active areas are much greater than what human data suggests. Some researchers hypothesize this is likely due to the lack of necessary conditions for the EEBV to escape the enzootic cycle (non-human animal endemic) and then enter the epizootic cycle (non-human animal epidemic). It could also be related to surveillance and/or testing biases.[5][6]


After a bite from an infected mosquito, Eastern equine encephalitis virus is inoculated carried by mosquito saliva into dermal tissue, it starts affecting dendritic and Langerhans cells, which migrate to lymphoid tissue, where viral replication occurs translating into viremia or systemic virus seeding. The incubation period ranges from 3 to 10 days.[8]


Research has shown the mesenchymal cell tropism of Eastern equine encephalitis virus with early replication in bones, tendons, and myocardium. Lungs, stomach, kidneys, and spleen have also been described in EEEV infection.[9] Brain histopathology is unspecific, including perivascular lymphohistiocytic cuffing, as noted with other viral encephalitides. Other findings include leptomeningeal vascular congestion, hemorrhage, encephalomalacia, and rarely pyogenic meningeal exudate.[11][12] Immunostaining of EEEV antigen can be detected in affected tissues.[13] A case report from Duke University also described optic histopathologic findings consistent with brain findings in a case of EEE.[11] Some authors also described focal infiltration of neutrophils and macrophages in the brain parenchyma, causing neuronal destruction, focal necrosis, and local demyelination, resulting in glial nodules. Cortical atrophy described in the autopsy of patients dying later in the course of illness.[12] 

History and Physical

Human arboviral disease, when symptomatic, can be divided into three different syndromes: Febrile systemic illness (seen in uncomplicated Dengue fever), Hemorrhagic fever (seen in dengue hemorrhagic fever and yellow fever) and encephalitis. This last category includes EEE but also Venezuelan equine encephalitis, Japanese encephalitis, and La Crosse encephalitis.[8] Nearly 96% of infected patients remain asymptomatic. Those with symptoms usually start with non-specific symptomatology, fever, headache, malaise, chills, arthralgias, nausea, and vomiting also reported.[8] Less than 5% of the infected population will develop meningitis or encephalitis. Neurologic symptoms appear in the first 5 days and are indistinguishable from other encephalitides, usually described as altered mental status and seizures. Less frequently, paresthesia and focal weakness have also be seen.[8][5][12] Many authors emphasize the correlation between length of prodrome symptoms and the clinical outcome. A short prodrome seems to be associated with a fatality or neurological disability, while a mild or moderate prodrome was associated with full recovery and moderate disability, especially noted in the pediatric population.[14][8]


Basic laboratory findings include peripheral leukocytosis. Cerebrospinal fluid (CSF) usually reports neutrophilic pleocytosis and absent hypoglycorrhachia.[9] Specific diagnostic tests (polymerase-chain-reaction analysis from blood or CSF, or serology) may be normal at the onset of symptoms. These can be positive within a week when neurological damage has already occurred.[8] General recommendations point to obtain repeated samples for serum antibodies in patients with encephalitis and a high index of suspicion of viral etiology. Antibodies can increase by 4-fold within 4 days. In cases were CSF nucleic acid test is negative, a positive serum titer should be not disregarded, as this can happen early in the course. On the other hand, in cases with negative nucleic acid testing, serial titer testing may be helpful for definite diagnosis when it is not possible to repeat a lumbar puncture.[15] Both antibodies and nucleic acid tests are equally important in the diagnosis of EEE. Currently, available testing techniques include ELISA and IFA.[16]

Radiologic findings usually involve basal ganglia, thalami, and cerebral cortex. Neuroimage, specifically brain MRI T2/FLAIR can report a pattern of focal lesions (also described in children) without significant edema as opposed to common autopsy findings, which include severe edema, peaking around day 12 in 60% of the patients with encephalitis. In children, the predominantly affected area seems to be the cortex.[14][12] Early involvement of thalami and basal ganglia can help distinguish EEEV from Herpes simplex encephalitis.[12] On computerized tomography, basal ganglia lesions are also more commonly seen, but MRI is preferred as is more sensitive to identify common changes.[12] 

Treatment / Management

Thus far, no antiviral drug has proven to be beneficial in treating Eastern equine encephalitis. Supportive care continues to be the general approach, and this often includes intensive care unit admission requiring ventilatory support. There is no need to isolate patients.[8] In patients with worsening encephalitis, routine monitor of intracranial pressure and cerebral pressure-directed therapies have been described, including decompressive craniotomy, reserved for refractory cases.[14] Anecdotal reports suggest worse outcomes after corticosteroid use and possibly benefit from immunoglobulin therapy.

Since a vaccine is currently not available, prevention represents the main strategy to control this emergent disease. Prevention then depends on efforts to reduce vectors, such as reducing potential breeding sites and the use of insecticides along with personal protective measures (e.g., protective clothing and use of repellents).[5]

Differential Diagnosis

In areas with greater risk of Eastern equine encephalitis virus transmission, EEE should be considered by health-care professionals in any case with aseptic meningitis or encephalitis. Suspected infections should also be reported to the local health department. Differential diagnosis includes other viral encephalitides, such as measles, mumps, echovirus, and less likely prion disease such as Creutzfeldt–Jakob disease.[12]

Pertinent Studies and Ongoing Trials

Currently, only veterinary Eastern equine encephalitis virus vaccines are available, especially for use in horses. There are no licensed vaccines available or EEE at the time. There is an inactivated Vero cell vaccine for Japanese encephalitis approved since 2009. Some studies have identified cross-protection with Yellow fever, but no association has been documented with EEE.[17] 

Some researchers are currently working on a possible live-virus vaccine potentially effective against multiple mosquito-borne diseases, but more research is granted.[18]


The fatality rate is described as high as 41%. Around 50% of the affected patients will develop some neurological disability. Poor predictive factors identified include severe hyponatremia, electroencephalogram abnormalities, and high initial CSF pleocytosis.[19][12] These findings are possibly inflammatory markers, but curiously patients treated with corticosteroids had worse outcomes than patients not treated with corticosteroids.[12]


Several complications have been described, more frequently involving the central nervous system resulting in cognitive, motor, or sensory deficits. Associated neurological sequelae include most commonly seizures (63%), but also paralysis, intellectual disability, and behavioral changes. Late diagnosis and intervention can result in multiorgan failure and autonomic dysfunction, and ultimately death.[20][21] A rare case reported hemophagocytic lymphohistiocytosis in a 5 month-old infant secondary to EEE.[22] Behavioral changes are also described, specifically psychosis.[23]

Deterrence and Patient Education

Eastern equine encephalitis is caused by a virus transmitted by a particular mosquito usually found in freshwater swamps. Symptoms include fever, chills, headache, myalgias, arthralgias. Diagnosis is made by serology and viral identification by PCR on a cerebrospinal fluid obtained after a lumbar puncture. Currently, treatment is supportive care and close monitoring. The fatality rate can be as high as 41%, and early diagnosis is key. Neurologic sequelae are seen in up to 50% of the patients, including seizures, paralysis, behavioral changes as psychosis, intellectual disability. There is no vaccine available. Prevention is critical to avoid EEE by limiting exposure to mosquitos. The center for disease control and prevention (CDC) recommends the use of insect repellent containing one of the following: DEET, picaridin, IR3535, oil of lemon eucalyptus, para-menthane-diol, or 2-undecanone. It also recommends wearing long-sleeve shirts and long pants and mosquito-control both indoors and outdoors.

Enhancing Healthcare Team Outcomes

An interprofessional approach is very important in the management of Eastern equine encephalitis. This is a nationally notifiable condition, communication between epidemiologists and the health department is vital to understand changing trends and raise awareness if a new outbreak is taking place, especially among physicians, to diagnose EEE promptly. Neurology evaluation could also be considered, depending on the level of confidence of the primary team and the complexity of the case. 

Article Details

Article Author

Cecilia Banda

Article Editor:

Debopam Samanta


8/2/2021 11:22:27 AM



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