Eastern equine encephalitis

Eastern equine encephalitis (EEE), also called triple E and sleeping sickness, is a viral disease caused mainly by the Eastern equine encephalitis virus (EEEV). Most infections in humans are asymptomatic, but about 5% of the time the infection progresses to severe neuroinvasive disease. Symptoms typically appear 3–10 days after being bitten by an infected mosquito and initially include fever, headache, nausea, vomiting, fatigue, muscle pain, and joint pain. Neurological symptoms usually appear a few days later and include altered mental state, encephalitis, <a href="/facts/Photophobia/CEFh6H8t">photophobia</a>, seizures, paralysis, and loss of consciousness and coma. The case fatality rate is 30–75% depending on age, with disease severity greatest in young children and the elderly. About 50 to 90% of survivors experience long-term neurological complications that range from minor to severe. EEE is most common in horses, in which the disease carries a 70–90% case fatality rate and permanent brain damage for survivors.
Most human cases are caused by EEEV. Traditionally, four lineages of EEEV were recognized: I, II, III, and IV. Lineage I corresponds to EEEV and the other lineages are classified as a different virus: Madariaga virus (MADV). EEEV is found in North America, the Caribbean, and Central America, and MADV is found in Central America and South America. While both EEEV and MADV cause disease in horses, it is very rare for MADV to cause disease in humans. EEEV and MADV are single-stranded, positive-sense <a href="/facts/RNA_virus/qwXPeATD">RNA viruses</a> of the genus <a href="/facts/Alphavirus/3SkPGkEd">Alphavirus</a> in the family Togaviridae. Alphaviruses are sorted into Old World alphaviruses and New World alphaviruses, and considered arthritogenic (affecting the joints) or encephalitic (affecting the brain). EEEV and MADV are New World encephalitic alphaviruses. Among encephalitic alphaviruses, EEEV causes the most severe disease in humans.
EEEV is maintained in nature in an enzootic cycle between <a href="/facts/Natural_reservoir/R9nyLwD4">natural reservoirs</a> of the virus and mosquitos that feed on the blood of those animals. In North America, <a href="/facts/Passerine/qby0MANo">passerine</a> birds are the main reservoirs of the virus, and <a href="/facts/Culiseta_melanura/WVMmgCez">Culiseta melanura</a> is the main enzootic <a href="/facts/Disease_vector/bepASE2M">vector</a>. In South America, rodents and marsupials may be reservoirs of MADV, and <a href="/facts/Culex/Ip3x1DJ0">Culex</a> mosquitos of the subgenus Melanoconion are likely the main enzootic vectors. The disease is occasionally transmitted to mammals and other non-reservoir species by other species of mosquitos, called bridge vectors. These mosquitos feed on the blood of both avian and mammalian hosts and include <a href="/facts/Coquillettidia_perturbans/InTTIWIX">Coquillettidia perturbans</a> and various species of the <a href="/facts/Aedes/c5Dd3RIW">Aedes</a>, <a href="/facts/Anopheles/SoWzqURV">Anopheles</a>, and Culex genera. Humans, horses, and other incidental carriers of EEEV are considered dead-end hosts because they cannot transmit the virus back to mosquitos.
EEE is usually diagnosed by using <a href="/facts/Enzyme-linked_immunosorbent_assay/8yvpYDtH">enzyme-linked immunosorbent assay</a> (ELISA) to test for anti-EEEV antibodies in serum or cerebrospinal fluid. The results of ELISA are then verified with <a href="/facts/Plaque_reduction_neutralization_test/IM6tghUh">plaque reduction neutralization tests</a>. Other methods such as <a href="/facts/Viral_culture/2YRCzLSJ">viral cultures</a> and nucleic acid amplification assays may be used post-mortem. <a href="/facts/Neuroimaging/dA5Cteaf">Neuroimaging</a> and <a href="/facts/Electroencephalogram/XGvpcBl5">electroencephalogram</a> (EEG) tests are useful for identify the severity of disease. There are no specific antiviral drugs used to treat EEE, so treatment is supportive in nature and includes <a href="/facts/Corticosteroid/jeL2QeIL">corticosteroids</a>, anti-convulsant drugs, intravenous fluids, <a href="/facts/Tracheal_intubation/5kw0TNxc">tracheal intubation</a>, and fever-reducing drugs. <a href="/facts/Physical_therapy/q24XDqHF">Physical therapy</a>, <a href="/facts/Occupational_therapy/eKTxd7kM">occupational therapy</a>, and <a href="/facts/Speech_therapy/VDaK0JCk">speech therapy</a> are often needed during the recovery process. Prevention methods include <a href="/facts/Insecticide/1xYL3MSD">insecticides</a>, <a href="/facts/Larvicide/dlhj8wkN">larvicides</a>, and eliminating mosquito breeding sites. A vaccine that protects against EEEV, but not MADV, is available for horses.
EEE was first recorded during an outbreak in horses in Massachusetts, USA in 1831. EEEV was first isolated from horse brains and linked to EEE during another outbreak in 1933. The first documented human cases were in 1938 in Massachusetts, and isolation from mosquitos first came in 1949 from Cq. perturbans and then in 1951 from Cs. melanura. The disease occurs along the eastern side of the Americas, mainly in the USA in states bordering the Atlantic Ocean, Gulf of Mexico, and Great Lakes. Fewer than ten human cases occur in a typical year, usually in close proximity to hardwood freshwater swamps and marshes where Cs. melanura and other vectors lives. Periodic outbreaks occur in years following years with heavy rainfall, likely due to creating a favorable environment for Cs. melanura. Outbreaks in horses usually precede those in humans, so an increase in cases in horses may be predictive of an upcoming human outbreak.

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Eastern equine encephalitis