Approach

EEEV infection is a notifiable condition in the US and some other countries; therefore, all cases of EEEV infection should be reported to the local health authority in these countries.

There is no specific antiviral treatment for EEEV infection. Patients may be asymptomatic, or have symptoms that resemble influenza or dengue fever (e.g., acute onset fever, malaise, headache, chills, arthralgias, myalgias) with or without neurological (encephalitic) symptoms. Nausea, vomiting, and diarrhoea may also occur in symptomatic patients.

Asymptomatic patients do not require treatment. Patients with febrile illness require supportive care. In the absence of neurological symptoms, febrile illness usually resolves in 1 to 2 weeks.[5] If neurological symptoms are present, they tend to appear several days into the course of illness and include irritability, drowsiness, altered mental status, seizures, cranial nerve palsies, focal weakness, and meningismus. Patients with neurological symptoms should be hospitalised, if possible. If the patient develops seizures, anticonvulsants should be administered and airway protection instituted.

Supportive care for symptomatic patients

Supportive care for patients with febrile illness includes ample oral fluid intake (i.e., enough fluids to be passing clear urine) and use of analgesics and/or anti-pyretics (e.g., paracetamol).

If there is severe dehydration due to vomiting and diarrhoea, the patient is hospitalised, if possible, and treated with oral or intravenous fluids, along with an anti-emetic agent (e.g., ondansetron). Initial administration of a single oral dose of ondansetron may obviate the need for intravenous fluids or hospitalisation in children.[42] Other anti-emetics are not recommended due to lack of benefit and risk of adverse effects.

Management of neurological symptoms

Neurological/central nervous system involvement is most commonly seen in patients aged over 50 years or under 15 years. However, neurological involvement due to South American EEEV/Madariaga virus (MADV) is more prevalent in children.[16]

Patients exhibiting neurological symptoms (e.g., altered mental status, disorientation, ataxia, seizures, paresis) are admitted to hospital, if possible, and evaluated for seizures, cerebral oedema, and intracranial hypertension. Anticonvulsants are administered if there is seizure activity or a history of seizures. Benzodiazepines are preferred for the initial management of seizures, with lorazepam being most effective due to its long half-life. Phenytoin is recommended if a second drug is needed to terminate seizures. In pregnant women, phenytoin is only used in life-threatening infection, because it is potentially teratogenic. If a patiet is taking certain anticonvulsants, serum drug levels are monitored to ensure that therapeutic levels are achieved. The airway is secured by intubation if the patient has altered mental status (e.g., obtundation) and mechanical ventilation is initiated.

A cranial nerve examination, fundoscopic exam, and head CT or brain MRI is performed to evaluate for cerebral oedema and elevated intracranial pressure. If intracranial pressure is elevated, head elevation, hyperventilation, and intravenous mannitol may be considered to reduce pressure.[43] In such instances, the placement of an external ventricular device should be considered.

Treatment with intravenous aciclovir, to cover for possible herpes simplex virus infection, is recommended in patients with cerebrospinal fluid or imaging findings suggesting viral encephalitis; or if these results will not be available within 6 hours; or if the patient is deteriorating.[39]

Empirical antibiotic therapy should also be started until bacterial encephalitis has been ruled out.[38]

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