Eastern equine encephalitis virus (EEE) commonly called Triple E or, sleeping sickness (not to be confused with Trypanosomiasis) is a zoonotic alphavirus and arbovirus present in North, Central and South America and the Caribbean. EEE was first recognized in Massachusetts, USA in 1831 when 75 horses died mysteriously of viral encephalitis. Epizootics in horses have continued to occur regularly in the United States. EEE is found today in the eastern part of the country and is often associated with coastal plains. EEEV is closely related to Venezuelan equine encephalitis virus and Western equine encephalitis virus. 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. The incubation period for Eastern equine encephalitis virus (EEEV) disease (the time from infected mosquito bite to onset of illness) ranges from 4 to 10 days. EEEV infection can result in one of two types of illness, systemic or encephalitic (involving swelling of the brain, referred to below as EEE). The type of illness will depend on the age of the person and other host factors. It is possible that some people who become infected with EEEV may be asymptomatic (will not develop any symptoms). Systemic infection has an abrupt onset and is characterized by chills, fever, malaise, arthralgia, and myalgia. The illness lasts 1 to 2 weeks, and recovery is complete when there is no central nervous system involvement. In infants, the encephalitic form is characterized by abrupt onset; in older children and adults, encephalitis is manifested after a few days of systemic illness. Signs and symptoms in encephalitic patients are fever, headache, irritability, restlessness, drowsiness, anorexia, vomiting, diarrhoea, cyanosis, convulsions, and coma. Nervous signs appear during the fever that include sensitivity to sound, periods of excitement, and restlessness. Brain lesions appear, causing drowsiness, drooping ears, circling, aimless wandering, head pressing, inability to swallow, and abnormal gait. Paralysis follows, causing the horse to have difficulty raising its head. The horse usually suffers complete paralysis and death two to four days after symptoms appear. Mortality rates among horses with the eastern strain range from 70 to 90%.
Outbreaks of eastern equine encephalitis observed from May 2008 to August 2009 in the Brazilian states of Pernambuco, Ceará, and Paraíba are reported. The disease occurred in 93 farms affecting 229 equids with a case fatality rate of 72.92%. Main clinical signs were circling, depression or hyperexcitability, ataxia, and progressive paralysis with a clinical manifestation period of 3-15 days. Main histologic lesions were a diffuse lymphocytic encephalomyelitis with neuronal death, satellitosis, neuronophagia, and hemorrhages being more severe in the cerebral gray matter of the telencephalon, diencephalon, and mesencephalon. Some animals also had areas of malacia in the telencephalon, thalamus, and basal nuclei. From 1 case, the virus was isolated by mice inoculation, and in other 13 cases was identified as Eastern equine encephalitis virus by semi-nested reverse transcription polymerase chain reaction. After DNA sequencing, all samples were identified as eastern equine encephalitis through the BLASTn analysis, but samples from the Ceará and Paraíba states corresponded to the same cluster, while the sample from the state of Pernambuco corresponded to a different cluster 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). Incidence in the United States is roughly 12-17 cases per year. The CDC reported only 4 cases in 1997. The most recent epidemic occurred in 2003 in North Carolina, where 26 cases were reported. Several states in the northeast US have seen increased virus activity since 2004. Between 2004 and 2006, there were at least 10 human cases of EEE reported in Massachusetts. In 2006, approximately 500,000 acres (2,000 km2) in southeastern Massachusetts were treated with mosquito adulticides to reduce the risk of humans contracting EEE. There have been several human cases reported in New Hampshire as well. In October 2007, a citizen of Livingston, West Lothian, Scotland became the first European victim of this disease. The man had visited New Hampshire during the summer of 2007 on a fishing vacation, and was diagnosed as having EEEV on 13 September 2007. He fell ill with the disease on 31 August 2007, just one day after flying home.
There is no cure for EEE. Treatment consists of corticosteroids, anticonvulsants, and supportive measures (treating symptoms) such as intravenous fluids, tracheal intubation, and antipyretics. About four % of humans known to be infected develop symptoms, with a total of about six cases per year in the US. A third of these cases die, and many survivors suffer permanent brain damage. No human vaccine against EEEV infection or specific antiviral treatment for clinical EEEV infections is available. Patients with suspected EEE should be evaluated by a healthcare provider, appropriate serologic and other diagnostic tests ordered, and supportive treatment provided. Like all disease caused by alpha viruses, eastern equine encephalitis (EEE) has no specific treatment. Focus management primarily on supportive and preventive measures. Pharmacologic therapy consists primarily of antipyretics, analgesics, and anticonvulsants. If the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is present, treat accordingly. Carefully stabilize the patient before any other activity. Once the patient is comatose, undertake obvious measures (eg, respiratory maintenance with ventilator support in a critical care unit [CCU]). Additionally, as with all critically ill patients, carefully provide adequate nutritional support. No special dietary restrictions exist. Transfer an infected patient to the intensive care unit (ICU) when appropriate. The therapy is of two types: i. Pharmacologic Therapy, ii. Empiric drug therapy. Pharmacologic Therapy: There is no specific pharmacologic therapy for EEE. Drugs currently used are those capable of ameliorating neurologic complications (eg, anticonvulsants). No current studies provide convincing evidence for or against prophylactic use. Medications that may be given include phenytoin, phenobarbital, and a benzodiazepine drip. Use antipyretics as needed. Additionally, appropriate analgesics and amnestics may be used once the patient is intubated. Antibiotics are not of value in these situations and may predispose patients to super infections. After determining that the patient does not have a bacterial infection, discontinue antibiotics. Empiric drug therapy: Because EEE can mimic other encephalitides, meningitis, or meningo encephalitis, empiric drug therapy for these conditions should be implemented promptly. Antibiotic therapy for generalized coverage of bacterial meningitis (as appropriate for age and antibiotic resistance patterns) and acyclovir to treat herpes simplex virus (HSV) infection should be started until these diseases are ruled out. Although ribavirin has in vitro activity against this virus, the benefit of administering it in the early viremic stage has not been established.