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 (≥37.5°C)
headache
seizures
Reported on initial presentation in around 25% to 71% of patients with EEEV infection.[2][36]
A sign for neurological/CNS involvement.
Seizures are most frequently generalised in nature and less commonly partial complex.[36]
Neurological/CNS involvement is most commonly seen in those aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
Other diagnostic factors
common
nausea/vomiting
myalgias/arthralgias
neck stiffness (nuchal rigidity)
Reported on initial presentation in around 36% to 64% of patients with EEEV infection.[2][36]
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
focal weakness (decreased motor function)
Reported on initial presentation in around 3% to 23% of patients with EEEV infection.[2][36]
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
photophobia
Reported as a presenting symptom in around 3% to 29% of patients with EEEV infection.[2][36]
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
abdominal pain
altered mental status
Confusion is reported in around 44% of patients with EEEV infection.[36]
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
uncommon
cranial nerve palsy
Reported on initial presentation in around 7% to 8% of patients with EEEV infection.[2][36]
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
tremors
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
drowsiness
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
meningismus
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
diarrhoea
cerebral oedema
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
intracranial hypertension
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
aseptic meningitis
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
haemophagocytic lymphohistiocytosis
Reported in an infant with acute EEEV infection.[4] The infant had neurological injury and died.
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
hemiparesis
A sign for neurological/CNS involvement.
Neurological/CNS involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
Risk factors
strong
travel/residence in endemic areas
Endemic areas include swamp/wetlands along the east coast of North America or rural/tropical areas of Central and South America.
Case reports have identified exposure to swamp and wetlands along the eastern seaboard of North America as a possible risk factor for EEEV infection.[28] This is in keeping with the known habitat of North American EEEV mosquito vectors, Culiseta melanura and Coquillettidia perturbans.[29]
EEEV has also been found in South America where it has caused human disease in eastern Panama and other Latin American countries, albeit very rarely. South American EEEV (now known as the Madariaga virus [MADV]) has a different genetic lineage to North American EEEV. It is also less virulent than North American EEEV and associated with significantly less mortality.
No epidemiological studies have been conducted to determine the risk factors for EEEV disease.
working in endemic areas
Endemic areas include swamp/wetlands along the east coast of North America or rural/tropical areas of Central and South America.
Spending long periods working outdoors in endemic areas increases the likelihood of being bitten by mosquito, which increases the risk of EEEV infection.[15]
In a serosurvey conducted in Panama, cattle ranching for >20 hours/week was found to be associated with seropositivity for Madariaga virus (MADV) infection (odds ratio [OR] 2.4 [95% CI 1.0 to 5.6]).[17]
In the same serosurvey conducted in Panama, farming was also found to be associated with seropositivity for MADV infection (OR 3.1 [95% CI 1.3 to 7.4]).[17]
No epidemiological studies have been conducted to determine the risk factors for EEEV disease.
outdoor recreational activities in endemic areas
Endemic areas include swamp/wetlands along the east coast of North America or rural/tropical areas of Central and South America.
Spending long periods doing outdoor recreational activities in endemic areas increases the likelihood of being bitten by mosquito, which increases the risk of EEEV infection.[15]
In a serosurvey conducted in Panama, fishing >10 hours/week was found to be associated with seropositivity for Madariaga virus (MADV) infection.[17]
No epidemiological studies have been conducted to determine the risk factors for EEEV disease.
seasonal factors favouring breeding of mosquitoes
Most cases of EEEV infection 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).[15]
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. However, neurological involvement due to Madariaga virus (MADV) infection is more prevalent in children.[16]
occupational exposure (laboratory)
Animal studies have demonstrated that aerosol transmission of EEEV, in addition to subcutaneous injection, is possible.[30][31]
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
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.
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