eMedicine Specialties > Infectious Diseases > CNS Infections

Eastern Equine Encephalitis

Mohan Nandalur, MD, Staff Physician, Department of Internal Medicine, Section of Cardiovascular Medicine, Washington Hospital Center
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

Updated: Oct 31, 2007

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).

Differential Diagnoses

Other Problems to Be Considered

Mumps
Stroke
Metabolic encephalopathy
Reye syndrome
Bartonella infection
Cytomegalovirus
Ebstein-Barr virus
Prion disease
Toxic ingestions
AIDS

Workup

Laboratory Studies

• Because of the numerous organisms that can produce signs and symptoms similar to those of eastern equine encephalitis (EEE), clinical diagnosis is difficult. Likewise, laboratory confirmation is challenging because it requires either specific serologic findings or virus isolation in brain tissue or CSF. If the possibility of EEE is considered early, recovery of the virus from the serum during the prodromal phase is possible; however, isolation from either the blood or CSF is often difficult.
• Blood cultures reveal nothing in this particular disease but may be performed if suspicion of bacterial infection is high.
• The current CDC diagnosis guidelines of an arbovirus require the presence of an acute febrile illness with encephalitis during a time when viral transmission is likely and one of the following criteria are evident:
  • Greater than 4-fold increase in the viral antibody titer between acute and convalescent sera (often 10 wk apart)
  • Viral isolation from the CSF, blood, or tissue
  • Immunoglobulin M (IgM) positive to the organism in the CSF: Presumptive positives can be made from the remaining biochemical assays (eg, hemoagglutinin inhibition, immunofluorescence, neutralization, complement fixation).
• Biochemical assays are valuable for EEE diagnosis. With early suspicion, obtain sera at 2- to 3-day intervals. A potential drawback is the slow turnaround time for these test results. Additionally, VecTest antigen assays and Vero cell plaque assays have been in use for arthropod surveillance programs and have also been effective in human diagnosis.¹ Potential assays for isolation include the following:
  • Enzyme-linked immunosorbent assay (ELISA) is used to detect IgM, primarily during convalescent stages or prolonged courses.
  • ELISA may be used to detect antiarboviral immunoglobulin G (IgG), which has similar results to the neutralization assay (current use primarily as an adjunct to the IgM ELISA).²
  • Serum hemoagglutinin-inhibition titer of at least 1:320 is most common.
  • Complement fixation titer of at least 1:128 primarily occurs in convalescing patients.
  • Immunofluorescence titer of at least 1:256 is uncommon.
  • Neutralization assay titer of at least 1:160 is common.
• Few laboratory test abnormalities are particular to EEE. The following are abnormal findings:
  • Leukocytosis has a 95% prevalence rate, with a median of 15,000 cells/µL. It is predominantly neutrophilic, but bands or lymphocytosis may not necessarily be visualized.
  • Hyponatremia often develops, but the exact relationship between the virus being directly responsible and a secondary syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has not been outlined.
• CSF findings
  • Increases in protein and protein concentration in the CSF, approximately 100 mg/dL, are common.
  • The CSF RBC count may be elevated.
  • The CSF WBC count may be elevated (initial WBC count 500-2000/µL with a median of 600 WBC/µL with a predominance of neutrophils).
  • Hypoglycorrhachia is not present.
• EEE-specific TaqMan reverse transcriptase polymerase chain reaction (PCR) analysis
  • Use this as a final alternative to analyze the various organisms known to cause encephalitis.
  • This analysis will hopefully provide rapid diagnosis in the future.
  • Recent studies are more promising for PCR because they indicate higher accuracy rates than the 10% likelihood of serological diagnostics for yielding positive virus results.
  • Other current advantages include the ability to target antiviral therapy, the ability to reduce the need for brain biopsies, and the ability to increase the speed of diagnosis (obtaining the panel can occur in 72 hours).
  • The current limitation is that this study likely requires a state or national effort, which may not be available for EEE.

Imaging Studies

Neuroimaging studies (eg, CT scanning, MRI) may aid in early virus identification and are routinely performed in patients with CNS symptoms. Relatively recent advances in imaging show that previous neuroradiographic manifestations of EEE were not precisely defined. Early studies (not entirely sensitive) revealed a predilection for the thalamic nuclei and the basal ganglia³ ; however, these changes are also common in infections with Japanese encephalitis, measles, mumps, echovirus 25, conjunctivitis (CJ) disease, cyanide poisoning, and carbon monoxide (CO) poisoning. Both CT scanning and MRI may play an important role in the early identification of EEE. Of note, most radiographic changes resolve in those patients who recover.

• CT scanning
• Perform this test to monitor the evolution of lesions or to determine primary areas of disease.
• The most common finding is a lesion of the basal ganglia.
• Lesions vary in size and may exhibit a secondary mass effect with edema.
• A CT scan may reveal areas of punctate hemorrhage, focal edema with a mass effect, poorly marginated lesions, or interventricular hemorrhage.
• In elderly patients, the findings can mimic early infarction or they may be nonspecific, which is common in elderly patients.
• Occasionally, meningeal enhancement may also be present, indicating a subarachnoid hemorrhage or meningitis.
• MRI
• MRI often is sensitive to early changes secondary to EEE and aids in a more prompt diagnosis in up to 60% of patients. Compared with CT scanning, MRI is more sensitive and reveals more abnormalities with increased detail.
• Use a T2-weighted image to best observe the lesions, which appear as areas of increased signal intensity.
• The most commonly affected areas of the CNS include the basal ganglia (unilateral or asymmetric with occasional internal capsule involvement) and thalamic nuclei. Other areas include the brain stem (often the midbrain), periventricular white matter, and cortex (most often temporally).
• The MRI findings are abnormal in all comatose patients, and normal MRI findings may indicate the need to consider another diagnosis.
• MRI also provides critical information in differentiating EEE from herpes encephalitis because EEE is common in the basal ganglia and herpes is not. If attenuation is present in the basal ganglia, herpes tends to occur laterally, whereas EEE has a medial preponderance.

Other Tests

• EEG: This test often reveals a generalized slowing and disorganization of the background. Later, this condition is followed by epileptiform activity that varies from isolated discharges to gross seizure activity.
• Culture growth: Previously, the recovery of EEE was limited because only a few facilities had the resources to amplify the virus. Recent studies indicate excellent growth of the virus recovered from patient CSF in A549 and MRC-5 cell cultures, which are mediums that virology laboratories routinely use to recover adenovirus, herpes simplex virus (HSV), and enterovirus.⁴
• Brain biopsy: This is rarely indicated and is simply a last resort for diagnosis.

Procedures

• Obtain a lumbar puncture (LP) as soon as possible when EEE is strongly suspected. Assess the CSF for elevated opening pressures and obtain a CBC count with differential, Gram stain, glucose, protein, bacterial culture, viral culture, fungal culture, acid-fast bacillus, India ink stain, and Venereal Disease Research Laboratory (VDRL) test.

Histologic Findings

CNS histopathology

The perikaryon and dendrites are primarily affected and demonstrate evidence of cytoplasmic swelling, eosinophilia, and nuclear pyknosis. Occasionally, mature viral particles are observed in extracellular spaces. The brain is grossly edematous, and inflammation is evident both parenchymally and perivascularly, as outlined above. Perivascular inflammation, vasculitis, thrombi, neurolysis, neuronophagia, and demyelination may be observed. The predominance of neutrophils in the inflammatory cell type is particularly important.

Treatment

Medical Care

Focus initial medical care on making a prompt diagnosis that differentiates this condition from potentially treatable causes. Because eastern equine encephalitis (EEE) mimics other encephalitides, meningitis, or meningoencephalitis, 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 HSV infection should be started until these diseases are ruled out.

• Like all alphaviruses, EEE has no specific treatment. Focus management primarily on supportive and preventive measures.
• Although ribavirin has in vitro activity against this virus, the benefit of administering it in the early viremic stage has not been established.
• Once the patient is comatose, undertake obvious measures (eg, respiratory maintenance with ventilator support in a critical care unit). Additionally, maintain patient nutritional status appropriately.
• If SIADH is present, treat accordingly (see Syndrome of Inappropriate Antidiuretic Hormone Secretion).
• Pharmacologic therapy consists primarily of antipyretics, analgesics, and anticonvulsants.
• Although no current medical therapies exist for EEE, recent research reveals some possibilities. An antibody with appropriate specificity attenuates the intracellular processes necessary for viral replication in animal models. The antibody binds to cell-specific markers of infected cells and initiates an intracellular cascade, which interferes with viral reproduction. Cytotoxic T cells also play an important part in the recovery from CNS lesions in mice. Early studies attempted to use pyrimidine derivatives and isoprinosine, a derivative of inosine, for treatment, but in vivo results were poor.⁵ Nucleoside analogs (eg, ribavirin) also have in vitro activity, but no clinical application is apparent. Whether or not these therapies can be productive in humans remains questionable.

Surgical Care

No direct surgical treatments for this disease are available except for appropriate neurologic measures necessary to deal with significant CNS bleeding or the consequences of markedly elevated CNS pressure.

Consultations

Consultations are primarily for supportive measures.

• Infectious disease specialist - Particularly relevant when the etiology of the encephalitis or meningoencephalitis is difficult to determine (most important contribution will likely be the ability to rapidly determine a potentially reversible cause of the patient’s symptoms)
• Neurologist - May provide early insightful information and aid with the diagnosis (EEG) and treatment of complications
• Critical care specialist - Valuable for coordinating intensive care unit (ICU) care if general practitioner is treating patient
• Neurosurgeon - Needed only for treatment of complications or brain biopsy

Diet

No special dietary restrictions exist. As with all critically ill patients, carefully provide adequate nutritional support.

Medication

Drugs currently used are those capable of ameliorating neurologic complications. No current studies provide support for or against prophylactic use. Potentially used medications include phenytoin, phenobarbital, or a benzodiazepine drip. Use antipyretics as needed. Additionally, appropriate analgesics and amnestics can be used once the patient is intubated. Antibiotics are not of value in these situations and may predispose patients to superinfections. After determining that the patient does not have a bacterial infection, discontinue antibiotics.

Anticonvulsants

Because of the high prevalence of seizures in patients with eastern equine encephalitis (EEE), these drugs are appropriate.

Dilantin (phenytoin)

May act in motor cortex where may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures also may be inhibited. Individualize dose and administer a larger dose before retiring if dose cannot be divided equally. Rate of infusion must not exceed 50 mg/min to avoid hypotension and arrhythmia.

Dosing

Adult

Loading dose: 15-20 mg/kg PO/IV single or divided doses, followed by 100-150 mg/dose at 30-min intervals
Initial dose: 100 mg (125 mg suspension) PO/IV tid
Maintenance dosage: 300-400 mg/d PO/IV divided tid or qd/bid if using extended release; increase to 600 mg/d (625 mg/d suspension) may be necessary; not to exceed 1500 mg q24h

Pediatric

Loading dose: 15-20 mg/kg PO/IV single or divided doses
Initial dose: 5 mg/kg/d PO/IV divided bid/tid
Maintenance dose: 4-8 mg/kg PO/IV divided bid/tid
< 6 years: Not established
> 6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d

Interactions

Please consult pharmacist because of multiple drug interactions; amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase phenytoin toxicity; phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; phenytoin may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid

Contraindications

Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Perform blood counts and urinalyses at start of therapy and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if a skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugar); discontinue use if hepatic dysfunction occurs

Diazepam (Valium)

Any of the benzodiazepines may be effective in the short term. Most often, diazepam or lorazepam is recommended. Diazepam depresses all levels of CNS (eg, limbic, reticular formation), possibly by increasing activity of GABA. Individualize dosage and increase cautiously to avoid adverse effects.

Dosing

Adult

5-15 mg IV q5min, repeat prn titrating to effect; not to exceed 30 mg in 8 h

Pediatric

0.05-0.3 mg/kg/dose IV/IM over 2-3 min q15-30min; repeat in 2-4 h prn; not to exceed 10 mg

Interactions

Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Sedation, hypotension; caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)

Corticosteroids

Early initiation serves multiple purposes (eg, decreases inflammation, decreases cerebral edema, treats potential adrenocortical dysfunction).

Dexamethasone (Decadron, AK-Dex, Alba-Dex)

Potent corticosteroid usually administered IV in these situations. For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Dosing

Adult

16 mg IV, then 4-10 mg IV q6h

Pediatric

0.08-0.3 mg/kg/d or 2.5-10 mg/m²/d divided q6-12h

Interactions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effect of salicylates and vaccines used for immunization

Contraindications

Documented hypersensitivity; active bacterial or fungal infection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Methylprednisolone (Solu-Medrol)

IV steroid often used early. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Dosing

Adult

100-150 mg IV, then 60-120 mg IV q6h or 30 mg/kg IV over 15 min followed in 45 min by 5.4 mg/kg/h IV

Pediatric

30 mg/kg IV over 15 min followed in 45 min by 5.4 mg/kg/h IV

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Follow-up

Further Inpatient Care

• Transfer an infected patient to the ICU when appropriate.
• Assess the many issues secondary to the high mortality rate of the disease.
• Ensure that a social worker and appropriate hospital services staff are available to the patient's family.

Further Outpatient Care

• Patients who survive infection usually need extensive rehabilitation.
• Based on the duration of symptoms and the extent of neurospasticity, schedule the patient for physical therapy upon recovery.
• Also, based on the specific defect, a patient may need consultations with speech and auditory therapists.
• Because of the potential for high neurologic morbidity, arrange coordinated care and quality follow-up care.
• Patients often require close neurodiagnostic follow-up care. The primary care physician must also be aware of subtle changes in behavior, intelligence, and motor skills.

Deterrence/Prevention

• Environmental animal control
  • Monitoring the sources of infection may be possible by assessing serology of antibodies to eastern equine encephalitis (EEE) in certain wild birds or caged flocks of sentinel birds (eg, chickens).
  • The virus may also be recovered from adult mosquitoes and may provide an opportunity for screening in possible vector habitats.
  • Officials should control the vector mosquito population in areas where the virus has been isolated or where the risk of infection is high.
• Environmental: Global factors also play a role in future prevention and spread. If global temperatures continue to rise and sea levels rise, the swampy breeding habitat of the C melanura mosquito and other bridge vectors may expand.
• Public information: Warn individuals who live in high-risk areas to take the necessary precautions. This includes wearing appropriate clothing (eg, long pants, long-sleeved shirts), wearing mosquito repellant, avoiding areas with high mosquito activity, and avoiding outside activity during times of day when mosquitos are active. Mosquito netting at nighttime can also be used if appropriate.
  • Permethrin 5% cream on exposed skin areas can prevent arthropod bites for up to a week. The drug is not an effective repellant of arthropods, but it deters biting and causes the insect to die after contact with the treated skin.⁶
  • Permethrin rinse in clothing has been shown to be partially effective in the prevention of arthropod bites.
• Future prevention: Currently, a vaccine is available for the North American subtype of EEE is not in widespread use and may not be effective against certain antigenic variants that are found primarily in other countries. Current use is limited to environmental workers at high risk of exposure. Recent advances in experimental vaccination have yielded equivocal results. The current vaccine has a weak antigen and requires multiple immunizations to achieve protection.
• Surveillance: EEE is reportable under the National Notifiable Diseases Surveillance System. Additionally, electronic surveillance is conducted through ArboNet, a CDC site used to assist states in tracking mosquito-borne viruses.
• Screening: To enable appropriate precautions, states with known mosquito-borne illnesses are now also screening vectors to determine if certain counties contain an increased number of carriers.

Complications

• The primary complication, other than death, is often a variable level of CNS impairment. Numerous factors, including location and specific inflammatory cell response may determine the result.
• Demyelination is a known by-product of this disease and can be radiologically detected. Often, these areas heal well, unless overlying fibrosis is present or cell death occurs.
• Additional complications
  • Mental retardation
  • Behavioral changes
  • Paralysis
  • Permanent focal neurologic deficits
  • Seizure disorders
  • Emotional lability
  • Adjustment disorders

Prognosis

• Currently, no clinical or radiographic prognostic indicators are available for EEE. The location and the type of lesion on imaging do not correlate with long-term sequelae or mortality.
• Additionally, although younger patients with longer prodromes tend to have better outcomes, no study has proven any statistical significance.
• The initial history and physical examination often do not reveal any prognostic variables.
• Changes in treatment regimens do not commonly affect outcome; in fact, one series revealed a poorer outcome with the use of steroids and anticonvulsants, but many confounding variables were involved in this determination.
• Certain laboratory findings may have some significance. The outcome in a patient with an elevated CSF WBC count (>500 cells/μL) is poorer than in a patient with a CSF WBC count of less than 500 cells/μL. Also, the prognosis in a patient with hyponatremia whose sodium level is less than 130 mmol/L is poorer than in patients with a higher sodium level.

Patient Education

• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Encephalitis.

Miscellaneous

Medicolegal Pitfalls

• Failure to carefully stabilize the patient before any other activity, as with all critically ill patients
• Because of the similarity in presentation between encephalitis and meningitis, failure to implement broad-spectrum antibiotics and antivirals in patients with eastern equine encephalitis (EEE)

References

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Keywords

eastern equine encephalitis, EEE, western equine encephalitis, WEE, St Louis encephalitis, La Crosse encephalitis, West Nile encephalitis, meningoencephalitis, viral encephalitis, herpes simplex virus, arboviruses, alphavirus, Togaviridae family, Culiseta melanura, Coquillettidia perturbans, Aedes canadensis, Venezuelan equine encephalitis, North American eastern equine encephalitis, South American eastern equine encephalitis

Contributor Information and Disclosures

Author

Mohan Nandalur, MD, Staff Physician, Department of Internal Medicine, Section of Cardiovascular Medicine, Washington Hospital Center
Mohan Nandalur, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Physicians-American Society of Internal Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

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
Andrew W Urban, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine
Disclosure: Nothing to disclose.

Medical Editor

Gary L Gorby, MD, Program Director of Adult Infectious Diseases Fellowship, Associate Professor, Department of Internal Medicine, Division of Infectious Disease, St Joseph Medical Center, Creighton University School of Medicine
Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance
John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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