eMedicine Specialties > Infectious Diseases > CNS Infections

Eastern Equine Encephalitis

Author: Mohan Nandalur, MD, Staff Physician, Department of Internal Medicine, Section of Cardiovascular Medicine, Washington Hospital Center
Coauthor(s): Andrew W Urban, MD, Chief, Section of Infectious Diseases, Middleton Memorial Veterans Hospital; Clinical Assistant Professor, Department of Internal Medicine, University of Wisconsin at Madison
Contributor Information and Disclosures

Updated: Feb 22, 2010

Introduction

Background

Encephalitis is an acute inflammatory process that primarily involves the brain. The meninges are frequently 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 may also 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 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 via 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 via 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

United States

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

In the United States, EEE is most common east of the Mississippi River (eg, Michigan, Massachusetts, New York, New Jersey, North Carolina, South Carolina, Florida, Louisiana, Georgia). The prevalence is increased in environments with wooded areas adjacent to freshwater swamps and marshes. Most infections occur in summer or early fall. The vector population usually dies in winter, 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 during epizootic outbreaks among horses or caged birds.

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.

International

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 in infected patients 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%.

Race

No race predilection exists.

Sex

No sex predilection exists.

Age

EEE is a summertime disease and most commonly affects 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 permanent neurologic impairment and death are more common in children.

Breed

The alphavirus that causes EEE is found mostly in the mosquito subtype C melanura, as mentioned above. Other infectious subtypes include the Aedes and Coquillettidia species. 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, in which viremia is often 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 viral distribution.

Clinical

History

Eastern equine encephalitis (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 is often short, averaging 5-10 days, and consists of fever, headache, and some abdominal pain with diarrhea. Compared with other alphaviruses, EEE progresses more rapidly 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 can also be risk factors (eg, outdoor activities during peak mosquito activity, most often in rural areas).

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