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West Nile Encephalitis Last Updated: June 9, 2006 |
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| Synonyms and related keywords: WNE, West Nile virus, viral encephalitis, western equine encephalitis, WEE, eastern equine encephalitis, EEE, Japanese encephalitis, Venezuelan encephalitis
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: Burke A Cunha, MD, MACP, 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, MACP, is a member of the following medical societies:
American College of Chest Physicians,
American College of Physicians, and
Infectious Diseases Society of America |
| Editor(s): Wesley W Emmons, MD, FACP, Assistant Professor, Department of Medicine, Thomas Jefferson University; Consulting Staff, Infectious Diseases Section, Department of Internal Medicine, Christiana Care, Newark, DE; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance;
Eleftherios Mylonakis, MD, PhD, Assistant Professor of Medicine, Harvard Medical School, Clinical Assistant in Medicine, Division of Infectious Disease, Massachusetts General Hospital;
and Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: West Nile encephalitis (WNE) is distinguished from other arthropod-borne causes of viral encephalitis (eg, western equine encephalitis, eastern equine encephalitis [EEE], Japanese encephalitis, Venezuelan encephalitis) by its geographic distribution, clinical features, and laboratory findings. WNE virus is endemic in the Middle East, Africa, and Asia. In North America, WNE first occurred in the northeast United States along the eastern seaboard and now extends nationwide. WNE may have existed in antiquity in the Middle East. Some have suggested that Alexander the Great may have died from WNE.
Seventeen species of wild birds transmit WNE to humans via the Culex, Aedes, and Anopheles mosquitoes. WNE first causes symptomatic or asymptomatic illness in wild migratory birds that act as viral replication factories. Wild birds infected with WNE contain high titers of the virus and remain viremic for 1-2 weeks, making them ideal hosts to perpetuate the disease. Mosquitoes transmit WNE from birds to humans. Horses, dogs, and other small animals may harbor WNE after being bitten; however, they are inefficient transmitters because viral titers are relatively low, and WNE viremia is short-lived in these animals. Pathophysiology: WNE, as with other arthropod-borne viral encephalitides, traverses the blood-brain barrier and infects the brain parenchyma, clinically manifesting as viral encephalitis. WNE may also affect the leptomeninges, resulting in a clinical presentation of aseptic meningitis (viral meningitis). Patients with WNE may present with features of both encephalitis and aseptic meningitis (meningoencephalitis). Frequency:
- In the US: Cases initially occurred in the greater New York area, but cases have now occurred in western states. Wild birds with WNE virus have been found in many states and in Canada.
Furthermore, the cluster of recent outbreaks in Romania, Russia, the Congo, and the United States is characterized by a low frequency of classic WNE features but a high rate of encephalitis and death.
- Internationally: WNE seropositivity of children in Egypt is approximately 50%. WNE is the most common cause of viral aseptic meningitis or encephalitis in patients presenting to emergency departments in Cairo. WNE is common in the Middle East, Asia, and Africa.
Mortality/Morbidity: Most cases in children from Asia and Africa have a benign course and only rarely result in fatality. In the United States, most fatal cases have occurred in elderly patients.
Race: No racial predisposition exists.
Sex: Males and females are affected equally.
Age: Most US cases occur in elderly patients. Worldwide, most cases occur in young children or young adults; however, elderly patients are affected more severely.
History: - Mosquito bites: Patients may not provide a mosquito bite history. The incubation period of WNE is 1-6 days.
- Patients with WNE may present with features of encephalitis, aseptic meningitis (meningoencephalitis), or both.
- Complaints include a mild febrile illness accompanied by headache, mental confusion, tremors, or flaccid paralysis.
- Symptoms are most prominent in people who are very young and people who are elderly.
- Most people who are infected (at least most children) are asymptomatic or have a nonspecific flulike illness. A minority of people develop neurologic disease.
Physical: - The extent and severity of viral invasion of the central nervous system (CNS) determine the clinical expression of WNE.
- Most patients are febrile or have low-grade fevers.
- Patients presenting with encephalitis have mental confusion or disorientation and may have decreased consciousness. Patients with severe cases of WNE may present with stupor or coma.
- Multifocal chorioretinitis is the most common ophthalmologic manifestation of WNE.
- Of patients, 10% have an enlarged liver. Splenomegaly is present in approximately 20% of patients.
- CNS findings include a stiff neck with meningeal signs, including positive Kernig or Brudzinski signs in patients with aseptic meningitis or meningoencephalitis.
- Some cases are accompanied by mild nonexudative pharyngitis.
- The following are additional findings outside the United States:
- A truncal maculopapular rash may be present in nearly half of patients (overseas experience), but this is not a common feature in the United States (New York experience).
- Generalized adenopathy and an enlarged submental node are common.
- Consider WNE in patients who have encephalitis and otherwise unexplained extremity weakness and/or paralysis.
Causes: - WNE usually occurs in the summer when mosquitoes, wild migratory birds, and humans are in close proximity outdoors.
- Mosquito bites, which are particularly prone to occur during feeding times (dawn and dusk) in the summer months, transmit WNE.
- Prolonged contact or multiple mosquito bites enhances risk.
- WNE may be transmitted in organ transplants.
- WNE virus has been found in breast milk.
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DIFFERENTIALS
| Section 4 of 11 |
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Encephalopathy, Hypertensive
Epidural Abscess
Other Problems to be Considered:
Encephalopathy from systemic illnesses
Encephalopathy is a feature of many systemic illnesses that the clinician should consider in patients presenting with encephalitis. Most of these patients have extra-CNS findings that suggest the underlying disease process. Common disorders with CNS manifestations that may mimic WNE include subacute bacterial endocarditis, Legionnaires Disease, Rocky Mountain Spotted Fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus 6, and systemic lupus erythematosus cerebritis.
Other arthropod-borne viral encephalitides
The clinical presentation of WNE is not dissimilar from other causes of arthropod-borne viral encephalitis (eg, Japanese equine encephalitis, St Louis encephalitis), including mental confusion, stupor, or coma. However, the clinical presentation of arthropod-borne viral encephalitis is characterized by rapid onset and severe headache. Arthropod-borne viral encephalitis has some distinctive features that indicate a prospective clinical diagnosis (see Image 1, Image 2).
The differential diagnosis for aseptic meningitis is extensive but may be reduced to 2 common clinical entities.
Enteroviral aseptic meningitis
The most common cause of aseptic meningitis encountered during the summer months is enteroviral meningitis. Enteroviral aseptic meningitis is most commonly due to coxsackieviruses but may also be due to enterocytopathogenic human orphan virus or nonparalytic strains of poliovirus. Enteroviral meningitis may occur after water exposure in swimming pools, lakes, streams, or oceans as well as after contact with infected individuals.
Acute enteroviral CNS infections usually manifest as aseptic meningitis, uncommonly as meningoencephalitis, or rarely as encephalitis. Nonexudative pharyngitis, maculopapular extremity rash, loose stools, and even diarrhea often accompany enteroviral aseptic meningitis, which provides clues to its presence.
Enteroviral meningitis is not accompanied by paralysis or prolonged and/or profound lymphopenia.
Herpesvirus type 1 encephalitis
Herpes simplex virus encephalitis due to herpesvirus type 1 (HSV-1) is the most common cause of non–arthropod-borne (nonseasonal) encephalitis in the United States. HSV-1 usually manifests as encephalitis, uncommonly as meningoencephalitis, or rarely as aseptic meningitis (see Image 3).
Nonsteroidal anti-inflammatory drugs
In patients presenting with aseptic meningitis, consider drug-induced aseptic meningitis, most commonly due to nonsteroidal anti-inflammatory drugs (NSAIDs). A patient presenting with aseptic meningitis with no predisposing risk factors may have recently been taking NSAIDs or may be currently taking NSAIDs. |
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Lab Studies:
- Many viral illnesses may manifest as mild leukopenia or borderline/low normal white blood cell count.
- In patients presenting with acute encephalitis, leukocytosis should suggest EEE, California encephalitis, or St Louis encephalitis.
- Although lymphopenia is not specific for WNE, it is a helpful diagnostic finding if present in a patient with aseptic meningitis, meningoencephalitis, or encephalitis of unknown cause.
- Although patients with HIV or Venezuelan equine encephalitis often present with encephalitis and lymphopenia, lymphopenia with WNE is profound and prolonged, which should suggest the diagnosis.
- Mild serum glutamic-oxaloacetic transaminase (SGOT) elevations are not a feature of most encephalitides due to arboviral causes.
- Mild elevations of the SGOT/serum glutamic-pyruvic transaminase (SGPT) in a patient with encephalitis should suggest Epstein-Barr virus, Rocky Mountain spotted fever, ehrlichiosis, human herpesvirus 6, or Legionnaires disease in addition to WNE.
- Serum amylase/lipase levels are increased in some cases of WNE.
- WNE may be cultured from the blood within the first 2 weeks after infection, but it is not usually culturable from cerebrospinal fluid (CSF).
- A specific diagnosis can be confirmed by serum testing. A variety of serologic methods are available, but enzyme immunoassay (EIA) with plaque reduction neutralization test is the best test currently available. Polymerase chain reaction is also available at selected research centers.
- A highly elevated acute titer or a 4-fold or greater rise between acute and convalescent titer is diagnostic of WNE.
Imaging Studies:
- Computed tomography scan and magnetic resonance imaging
- Since the differential diagnosis of WNE includes HSV-1 meningoencephalitis or encephalitis, a head CT scan or MRI is helpful to exclude HSV-1, the only treatable cause of viral encephalitis.
- CT scan or MRI may exhibit changes in one temporal lobe, which is highly characteristic of HSV-1 encephalitis. CT scan and MRI findings are often negative early.
- CT scans are less sensitive and may not detect abnormalities if obtained very early in the disease process.
- All other causes of aseptic meningitis, meningoencephalitis, or encephalitis, including systemic disorders with an encephalitic component, have negative findings (nonfocal temporal lobe findings) on CT scan or MRI.
- CNS lupus may be suggested by the diffuse uptake over the cerebral cortex, suggesting cerebritis.
Other Tests:
- This is the most sensitive way to make a presumptive diagnosis of HSV-1 encephalitis. An abnormal temporal lobe focus is present on EEG as early as the first few days of the disease.
- EEG shows unilateral focal electrical abnormalities in the temporal lobe.
Procedures:
- CSF reveals mild-to-moderate pleocytosis with a lymphocytic predominance in WNE. CSF protein is variably elevated, and the CSF glucose level is not decreased.
- The CSF lactic acid level is not elevated, and RBCs, excluding traumatic taps, are not present in WNE. CSF Gram stain and bacterial culture findings are negative.
Histologic Findings: Brain biopsy findings exhibit diffuse encephalitis, which is nonspecific and nondiagnostic for WNE.
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TREATMENT
| Section 6 of 11 |
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Medical Care: - Provide supportive care to minimize the potential for cerebral edema.
- In comatose patients, pay special attention to maintaining a clear airway.
- Replace fluids and electrolytes as they are lost through insensible losses due to fever and decreased or absent intake.
Surgical Care: - No surgical care is necessary.
Consultations: - Consult an infectious disease specialist.
Diet: - A normal diet, as tolerated by the patient, is acceptable.
Activity: - Normal activity, as tolerated by the patient, is acceptable.
- Many patients recover quickly, but some experience prolonged malaise.
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MEDICATION
| Section 7 of 11 |
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No specific drug treatment exists for WNE.
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FOLLOW-UP
| Section 8 of 11 |
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Further Inpatient Care:
- In patients with WNE, repeat testing for lymphopenia or increased serum transaminases until levels return to normal.
- A repeat lumbar puncture is usually not necessary.
- Patients who are unconscious may need ventilation support in an intensive care unit (ICU) until consciousness is restored.
Further Outpatient Care:
- Further outpatient care is usually unnecessary.
In/Out Patient Meds:
- No medications are indicated.
Transfer:
- Transfer is usually not necessary.
Deterrence/Prevention:
- Avoid exposure to mosquitoes.
Complications:
- Severe cases may result in death; however, recovery is usually complete and does not result in neurologic sequelae.
Prognosis:
- Prognosis is excellent in all patients except those who are elderly or debilitated.
Patient Education:
- Avoid exposure, particularly from dawn to dusk, in areas where mosquitoes and WNE are present.
- Mosquito netting and mosquito repellents may also be used.
- Avoid wearing bright colors and highly aromatic perfumes, deodorants, and hair products that attract mosquitoes.
- Avoid handling dead or diseased wild birds without proper aseptic precautions.
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MISCELLANEOUS
| Section 9 of 11 |
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Medical/Legal Pitfalls:
- Excluding systemic illnesses (eg, subacute bacterial endocarditis, Legionnaires disease) with encephalopathy is important so that the underlying infection or disorder may be treated properly.
- Specifically question patients presenting with aseptic meningitis about NSAIDs, which may cause similar symptoms. Discontinue NSAIDs if the patient is taking them.
- The most important infection to exclude in the differential is HSV-1 encephalitis because it is the only treatable viral encephalitis. HSV-1 encephalitis is suggested by temporal lobe abnormalities on EEG and later on CT scans and MRI.
- Early in the course of HSV-1 encephalitis, CSF may initially show a polymorphonuclear predominance, frequently has red blood cells, and may be associated with a decreased CSF glucose level in contrast to the CSF in WNE, which does not have any of these features.
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PICTURES
| Section 10 of 11 |
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| Caption: Picture 4. The Culex mosquito, common to the eastern United States, is the primary vector responsible for infecting humans with West Nile virus. Prevention of West Nile virus is primarily directed at reducing the mosquito population from May to October and by taking precautions to limit human exposure during these months of high mosquito activity. Image courtesy of the Centers for Disease Control and Prevention.
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| Caption: Picture 5. The geographic distribution of the Japanese encephalitis servocomplex of the family Flaviridae, 2000. Image courtesy of the Centers for Disease Control and Prevention.
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| Caption: Picture 6. States reporting laboratory-positive West Nile virus infection in birds, mosquitoes, animals, or humans between January 1 and August 28, 2002. Image courtesy of the Centers for Disease Control and Prevention.
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| Section 11 of 11 |
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