History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include working/living/travelling in wooded wetlands or swamps in endemic areas, and exposure to mosquitoes.

fever

Reported as a presenting symptom in around 83% to 100% of patients.[33][46]

Usually acute in onset.

Typically resolves in 1 to 2 weeks in the absence of neurological symptoms.[4]

headache

Reported as a presenting symptom in around 64% to 75% of patients.[33][46]

Usually acute in onset and often intense/severe, particularly if there is neurological/central nervous system involvement.

Typically resolves in 1 to 2 weeks in the absence of neurological symptoms.[4]

seizures

Reported on initial presentation in around 25% to 71% of patients.[33][46]​ Children almost always present with seizures.[51]

Seizures are most frequently generalised in nature and less commonly partial complex.[46]

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in those aged over 50 years or under 15 years.[1]

Other diagnostic factors

common

nausea/vomiting

Reported as a presenting symptom in around 61% to 64% of patients.[33][46]

myalgias/arthralgias

Reported as a presenting symptom in around 29% to 36% of patients.[33][46]

neck stiffness (nuchal rigidity)

Reported on initial presentation in around 36% to 64% of patients.[33][46]

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

focal weakness (decreased motor function)

Reported on initial presentation in around 3% to 23% of patients.[33][46]

A sign for neurological/CNS involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

photophobia

Reported as a presenting symptom in around 3% to 29% of patients.[33][46]

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

abdominal pain

Reported as a presenting symptom in around 7% to 22% of patients.[33][46]

altered mental status

Confusion is reported in around 44% of patients.[46]

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

uncommon

cranial nerve palsy

Reported on initial presentation in around 7% to 8% of patients.[33][46]

A sign for neurological/central nervous system (CNS) inolvemnt. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

tremors

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

drowsiness

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

meningismus

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

diarrhoea

Reported in up to 8% of patients.[33][46]

Often accompanied by nausea, vomiting, and abdominal pain.

cerebral oedema

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

intracranial hypertension

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

aseptic meningitis

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

haemophagocytic lymphohistiocytosis

Reported in an infant with acute infection.[3] The infant had neurological injury and died.

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

hemiparesis

A sign for neurological/central nervous system (CNS) involvement. Neurological/CNS involvement occurs in <5% of patients, and is most commonly seen in patients aged over 50 years or under 15 years.[1]

Risk factors

strong

travel/residence in endemic areas

Endemic areas include swamp/wetlands along the east and Gulf Coast of North America.

Case reports have identified exposure to swamp and wetlands along the eastern seaboard and Gulf Coast of North America as a possible risk factor for infection.[34] This is in keeping with the known habitat of mosquito vectors, Culiseta melanura and Coquillettidia perturbans.[35]

working in endemic areas

Endemic areas include swamp/wetlands along the east and Gulf Coast of North America.

Spending long periods working outdoors in endemic areas increases the likelihood of being bitten by mosquitoes, which increases the risk of infection.[1]​​

outdoor recreational activities in endemic areas

Endemic areas include swamp/wetlands along the east or Gulf Coast of North America.

Spending long periods doing outdoor recreational activities in endemic areas increases the likelihood of being bitten by mosquitoes, which increases the risk of infection.[1]​​

homelessness in endemic areas

People experiencing homelessness may be at increased risk of infection due to extensive outdoor exposure and limited financial resources.[1]

seasonal factors favouring breeding of mosquitoes

Most cases occur from late spring through to early autumn, but very rarely cases have been reported in winter in subtropical endemic areas (e.g., the Gulf Coast of the US). Peak incidence occurs between the months of July and September.[1][16]​​​

age <15 years or >50 years

Neurological/central nervous system involvement (e.g., encephalitis) and severe disease is most commonly seen in those aged under 15 years or over 50 years.[1]​

Younger ages are typically more prone to developing encephalitis and cortical involvement likely because adult neurons can successfully suppress viral replication and express apoptosis inhibitors, making them more resistant to apoptosis and subsequent death.[36][37]

occupational exposure (laboratory)

Animal studies have demonstrated that aerosol transmission of eastern equine encephalitis virus, in addition to subcutaneous injection, is possible.[38][39]

Handling high virus concentrations, mouth pipetting, and engaging in activities that generate aerosols (e.g. tissue homogenisation, centrifugation) are risk factors for occupational infection in the laboratory setting.

weak

bioterrorism

Eastern equine encephalitis virus (​EEEV) is considered a potential bioterrorism weapon as it can be produced in large amounts in aerosolised form.

In the US, EEEV (and other alphaviruses) is classified as a Category B agent by the Centers for Disease Control and Prevention (CDC), which is the second highest threat category.[40]

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