Re: *NEWS* Eastern Equine Encephalitis (EEE)

http://www.emedicine.com/MED/topic3155.htm


Background: Encephalitis is an acute inflammatory process primarily involving the brain. Frequently, the meninges are involved (meningoencephalitis). Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. The incidence rate of encephalitis is 1 case per 200,000 population in the United States, with herpes simplex being the most common cause. The arboviruses account for 10% of cases and occasionally can account for 50% during an epidemic.

Five types of arborviral encephalitis are found in the United States, including eastern equine encephalitis (EEE), western equine encephalitis, St Louis encephalitis, La Crosse encephalitis, and West Nile encephalitis. This article focuses on EEE. This infection is caused by an arthropod-borne alphavirus of the Togaviridae family. In equines, the disease is invariably fatal. The disease is uncommon in humans and is likewise associated with a high rate of morbidity and mortality.

In North America, the enzootic vector is the mosquito Culiseta melanura, which is responsible for the spring-summer amplification of the virus in the mosquito-bird-mosquito cycle. Occasionally, other mosquito types (eg, Coquillettidia perturbans and the very ubiquitous Aedes canadensis species) may act as bridges in the horse-to-human transmission. 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.

EEE is a member of the antigenically similar family of viruses known as Togaviridae, which also includes western equine encephalitis and Venezuelan equine encephalitis. These alphaviruses are spherical and have a diameter of 60-65 nm. The outer layer consists of a glycoprotein shell with protruding glycoprotein spikes found beneath the lipid bilayer. The nucleocapsid core contains the single-stranded RNA genome.

Pathophysiology: EEE is characterized by diffuse CNS involvement. A large number of immunologically active cells enter the brain parenchyma and perivascular areas and mediate much of the damage. Infiltrating neutrophils and macrophages cause neuronal destruction, neuronophagia, focal necrosis, and spotty demyelination. Vascular inflammation with endothelial proliferation, small vessel thrombosis, and perivascular cuffing also may develop. Antigenic studies reveal that EEE primarily affects the perikaryon and dendrites of neurons, with minimal findings in glial cells. Occasionally, secondary glial proliferation and the formation of glial nodules can occur. Cell death by apoptosis occurs primarily among the glial and inflammatory cells. Gross inspection on autopsy reveals edema, leptomeningeal vascular congestion, hemorrhage, and encephalomalacia. Patients who die late in the disease may exhibit diffuse cerebral atrophy, particularly of the cortex.

The mosquito injects the agent of EEE into the subcutaneous and cutaneous tissues of the host. EEE is not transmitted by the aerosol route. It may cross the placenta and infect the fetus. Because of low viral titers in the donor's blood, EEE is unlikely to be transmitted by transfusion. The prodrome of fevers, chills, weakness, headache, and myalgias represents replication of the virus in nonneural tissues (tissue adjacent to the mosquito's bite or the lymphatic system). The virus then binds to specific tissue receptors, undergoes endocytosis, and initiates an RNA-dependent RNA and protein synthetic process. If the original inoculum is large enough, secondary viremia occurs, with eventual viral migration into the CNS via cerebral capillary endothelial cells. Poorly described features of the virus increase microvascular permeability of the brain. Cell-to-cell spread then occurs via dendrites and axons.

These initial symptoms often progress rapidly to confusion, somnolence, or even coma.

Frequency:

In the US: Because alphaviruses are dependent on arthropod vectors, their distribution is geographically limited. The EEE virus is divided into North and South American variants, based on hemagglutinin inhibition tests. North American isolates have a highly conserved lineage, as noted through comparisons of outbreaks in Mexico and Texas.

EEE most commonly occurs east of the Mississippi (eg, Michigan, Massachusetts, New York, New Jersey, North Carolina, South Carolina, Florida, Louisiana, Georgia). An environment with wooded areas adjacent to freshwater swamps and marshes shows an increased prevalence. Most infections occur in summer or early fall. The vector population usually dies in the wintertime, and cases of EEE are almost nonexistent in winter months; however, after winter, a repetitive, endemic locus of infection may persist. An additional risk increase occurs when an epizootic outbreak in horses or caged birds occurs.

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 North Carolina, where 26 cases were reported in 2003.

Internationally: EEE also is prevalent in gulf coastal areas (eg, Mexico, northern coast of South America, Caribbean). The EEE virus in these regions is an antigenic variant of the North American form.
Mortality/Morbidity:

The prognosis for the infected patient is extremely poor; 50-70% of patients die. The morbidity rate is approximately 90%, representing a wide range of mild to severe impairment. Only 10% of patients fully recover.
The average duration of hospitalization is 16-20 days. Most patients die within a few days.

EEE has an infection rate of 33%.
Breed: The alphavirus causing EEE is found mostly in the mosquito subtype C melanura, as previously mentioned. Other infectious subtypes are the Aedes and Coquillettidia species. The C melanura mosquitoes breed in freshwater swamps and feed on passerine birds. The infected birds subsequently exhibit high levels of viremia, which differs from human and equine cases where viremia often is low. Passerine birds serve as an effective reservoir for continued mosquito infection. Regardless of the extent of viremia in the birds, the outcome varies, ranging from asymptomatic states to death. With low viremia in horses and humans, neither of these species acts as a reservoir for further virus distribution.

Race: No race predilection exists.

Sex: No sex predilection exists.

Age: EEE is a summertime disease and occurs most often in people younger than 15 years and older than 55 years. The exact reason for this is not known but is a characteristic common to many species of the alphavirus family. Patient age does not affect prognosis, but children tend to have higher frequency of permanent neurologic impairment or death.

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History: EEE is difficult to diagnose because of the lack of specific symptoms. A rewarding diagnostic approach is to determine the extent of the patient's illness and to determine whether CNS infection is present. The prodromal phase often is short, averaging 5-10 days, and consists of fever, headache, and some abdominal pain with diarrhea. Compared to other alphaviruses, EEE more rapidly progresses to both CNS involvement and death. Once symptoms arise, the patient often deteriorates rapidly.

Neurologic symptomology
Headache - Most prevalent symptom
Nausea or vomiting - Present in both the prodromal and active stages of the infection
Confusion
Focal neurologic deficits - Sensory or motor loss (relatively low prevalence of focal deficits)
Seizures - Occur in roughly half of the patients (most often generalized tonic clonic with occasional partial complex seizures)
Somnolence
Neck stiffness
Malaise and weakness
Cranial nerve palsies - Often develop either directly from the disease or secondary to elevated cerebrospinal fluid (CSF) pressure (most commonly affected are cranial nerves VI, VII, and occasionally XII)
Photophobia
Autonomic disturbances (ie, sialorrhea)
Other associated symptoms
Fever - Almost invariably present at some point
Chills
Abdominal pain
Diarrhea
Sore throat
Arthralgia or myalgia
Respiratory difficulty
Social history
Recent travel to endemic areas
Outdoor exposure history
Work related to the care of horses or work located in marshes
Recent insect bites
Work or home in areas with high mosquito counts
Physical: The physical examination for EEE also is nonspecific and is similar to many other encephalitides.
Changes in vital signs
Fever
Tachycardia
Possible tachypnea
Neurologic findings
Bilateral papilledema
Nuchal rigidity
Focal sensory or motor deficit
Depressed or hyperactive reflexes
Tremors
Fasciculations
Seizure activity
Spastic paralysis
Other findings
Cyanosis - With respiratory compromise
Facial, periorbital, or generalized edema
Lymphadenopathy - Not necessarily present
Possible pharyngeal erythema
Causes: The only individual risk factor is age; however, certain behaviors also can be a risk factor (eg, outdoor activities during peak mosquito activity, most often in rural areas).

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