Basics
Description
- Viruses transmitted by an arthropod vector that can cause CNS infections, undifferentiated febrile illness, acute polyarthropathy, and hemorrhagic fevers
- Most arboviral infections are asymptomatic.
- West Nile virus (WNV) is an arbovirus in the flavivirus family.
- WNV was first recognized in the United States in 1999 during an outbreak of encephalitis in New York City.
- More than 150 arboviruses are known to cause human disease.
- Other arboviruses can produce similar syndromes or acute hemorrhagic fevers.
Epidemiology
- Arboviruses are spread by mosquitoes, ticks, and sand flies. The major vector for WNV in the United States is the Culex mosquito. WNV has been spread through blood transfusions, transplanted organs, and, rarely, intrauterine.
- Arboviruses are maintained in nature through cycles of transmission among birds, horses, and small animals. Humans and domestic animals are infected incidentally as "dead-end " hosts.
- Disease among birds has been a hallmark of WNV in the United States and has served as a sensitive surveillance indicator of WNV activity.
- Each North American arbovirus has specific geographic distributions and is associated with a different ratio of asymptomatic to clinical infections. These agents cause disease of variable severity and have distinct age-dependent effects. WNV has now been identified throughout the United States and is also found in Europe, Africa, and Asia.
Incidence
- The peak incidence of arboviral encephalitis occurs during the late summer and early fall. Seasonality depends on the breeding and feeding seasons of the arthropod host.
- WNV is the leading cause of arboviral CNS disease. Encephalitis is most commonly seen in older adults, generally aged >60 years. Cases of WNV in children are unusual.
- Fewer than 10 cases each of Eastern equine encephalitis and Western equine encephalitis are reported nationally each year. Eastern equine encephalitis tends to produce a more fulminant illness than LaCrosse or Western equine encephalitis.
General Prevention
- Public health department efforts focus on surveillance of viral activity to predict and prevent outbreaks:
- Active bird surveillance to detect the presence of WNV activity
- Active mosquito surveillance to detect viral activity in mosquito populations
- Passive surveillance by veterinarians and human health care professionals to detect neurologic illnesses consistent with encephalitis
- Screening of blood and organ donors
- Personal precautions to avoid mosquito bites including use of repellents, protective clothing, and screens; avoiding peak feeding times (dawn and dusk); and installation of air conditioners
- Coordination of mosquito control programs in endemic infection areas
- Vaccines for prevention of most arbovirus infections are not available. A vaccine is available for Japanese encephalitis and yellow fever (YF) for travelers to endemic areas who are planning prolonged stays.
- Infection control measures
- Standard precautions are recommended for the hospitalized patient.
- Respiratory precautions are recommended when vector mosquitoes are present.
- Patients with dengue and YF can be viremic and should be protected against vector mosquitoes to avoid potential transmission.
Pathophysiology
- The incubation period for WNV and other arboviral encephalitis agents is 2 " 14 days (up to 21 days in immunocompromised hosts).
- The incubation period reflects the time necessary for viral replication, viremia, and subsequent invasion of the CNS.
- Virus replication begins locally at the site of the insect bite; transient viremia leads to spread of virus to liver, spleen, and lymph nodes. With continued viral replication and viremia, seeding of other organs including the CNS occurs.
- Virus can rarely be recovered from blood within the 1st week of onset of illness but not after neurologic symptoms have developed.
Etiology
- Arboviruses can be divided into 2 groups based on the predominant clinical syndrome.
- In the United States, 7 arboviruses are important causes of encephalitis: WNV, California encephalitis virus (LaCrosse strain), Eastern equine encephalitis, Western equine encephalitis, St. Louis encephalitis, Powassan encephalitis virus, and Venezuelan equine encephalitis virus.
- Arboviruses such as YF, dengue fever, and Colorado tick fever typically cause acute febrile diseases and hemorrhagic fevers and are not characterized by encephalitis.
- Clinical manifestations of WNV
- Asymptomatic: most common
- Self-limited febrile illness: 67% of symptomatic cases
- Neuroinvasive disease: aseptic meningitis, encephalitis, or flaccid paralysis " <1% cases
Diagnosis
History
- The diagnosis of arboviral infections of the CNS is difficult.
- Characteristic epidemiology that suggests a specific etiology is an important part of the history.
- The season of disease, prevalent diseases within the community, and animal exposures may provide clues to the diagnosis:
- Enteroviral infections are seen in the warmer months (summer and early fall) in temperate climates.
- Mosquito propagation in damp climates or standing water during the summer months may increase the likelihood of arthropod-borne viruses.
- History of an animal bite or bat exposure may suggest the possibility of rabies.
- WNV (symptomatic infection) is characterized by sudden onset of fever, headache, myalgias, muscle weakness, and GI symptoms (nausea, vomiting, or diarrhea).
- Neuroinvasive WNV can be characterized by neck stiffness and headache, mental status changes, movement disorders, or flaccid paralysis.
- Encephalitis caused by arboviruses is characterized by acute onset of fever and headache in almost all patients. Associated symptoms may include seizures, altered consciousness, disorientation, and behavioral disturbances.
Physical Exam
- Neurologic signs are more commonly diffuse but may be focal. These clinical findings can help to distinguish patients with meningitis, which is characterized by nuchal rigidity and fever usually without an altered sensorium.
- Other signs possibly observed in WNV infection:
- A rash is seen in ’ Ό50% of patients and is described as nonpruritic, roseolar, or maculopapular on the chest, back, and arms, which lasts 1 week.
- Diffuse lymphadenopathy is also common.
- Neurologic examination in WNV infection may reveal motor weakness or flaccid paralysis, increased deep tendon reflexes and extensor plantar responses, and tremor or abnormal movement of extremities.
Diagnostic Tests & Interpretation
The diagnosis of arboviral encephalitis depends on the recognition of epidemiologic risk factors and typical signs and symptoms with the aid of laboratory and radiographic studies.
Lab
- Routine laboratory tests
- CBC typically reveals a mild leukocytosis.
- Mild increase in erythrocyte sedimentation rate (ESR)
- Mild to moderate CSF pleocytosis, predominately mononuclear cells
- Elevated CSF protein
- Normal CSF glucose
- Serology
- IgM and IgG enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA) for WNV and other arboviruses
- The diagnosis of arbovirus encephalitis is made by 1 of the following:
- Detection of virus-specific IgM antibodies in the CSF is confirmatory.
- A 4-fold rise in serum antibody titers is confirmatory. Acute-phase titers should be collected 0 " 8 days after onset of symptoms. Convalescent phase titers should be collected 14 " 21 days after acute specimen. A single negative acute-phase specimen is inadequate for diagnosis, but a positive test can provide evidence of recent infection.
- Isolation of the virus from tissue, blood, or CSF
- Polymerase chain reaction (PCR) to detect viral RNA
Imaging
- Imaging studies such as MRI or CT can assist in ruling out other potential causes of encephalopathy or encephalitis.
- MRI has proved useful in differentiating postinfectious encephalomyelitis from acute viral encephalitis. The former is characterized by enhancement of multifocal white matter lesions.
Diagnostic Procedures/Other
- EEG
- Diffuse generalized slowing of brain waves
- Periodic high-voltage spike waves originating in the temporal lobe region and slow-wave complexes at 2 " 3-second intervals are suggestive of herpes simplex virus infection.
Differential Diagnosis
Infectious
- Viral
- Herpes simplex virus
- Enterovirus
- HIV
- HHV-6
- Epstein-Barr virus
- Cytomegalovirus
- Lymphocytic choriomeningitis virus
- Rabies
- Mumps
- Influenza
- Adenovirus
- Nonviral
- Cat-scratch disease (Bartonella henselae)
- Mycoplasma pneumoniae
- Postinfectious encephalomyelitis: generally follows a vague viral syndrome, usually upper respiratory tract, by days to weeks
- Abscess/subdural empyema
- Meningitis
- Tuberculous
- Cryptococcal or other fungal (histoplasmosis, coccidioidomycoses, blastomycoses)
- Bacterial
- Listeria
- Toxoplasmosis
- Plasmodium falciparum infection (malaria)
- Parasites (cysticercosis, echinococcus, amebiasis, trypanosomiasis)
Noninfectious: tumor, carcinomatous meningitis, systemic lupus erythematosus, sarcoidosis, vasculitis, hemorrhage, toxic encephalopathy, metabolic disorders
Treatment
General Measures
- No specific antiviral therapy is available.
- Supportive therapy including cardiorespiratory function, fluid and electrolyte balance, seizure control, and reduction of intracranial pressure is important.
- Consider intravenous immunoglobulin (IVIG)/plasmapheresis for associated Guillain-Barre syndrome; IVIG has been used in cases of flaccid paralysis with some response.
- Recovery can be seen after prolonged periods of coma.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Neurobehavioral follow-up should be considered in children with severe or complicated disease.
- If WNV is diagnosed during pregnancy, detailed fetal ultrasound (US) should be considered 2 " 4 weeks after illness onset with evaluation for congenital anomalies and neurologic deficits.
- Infant serum should be tested for WNV IgM at birth and 6 months with IgG at 6 months.
Prognosis
- Prognosis for recovery depends on the specific infecting agent and host factors such as age and underlying illness.
- Eastern equine and Japanese encephalitis have the worst prognoses, with mortality occurring in 30% of cases.
Complications
- Optic neuritis
- Seizures
- Coma
- Death
- Guillain-Barre syndrome
- Severe neurologic sequelae
- Myocarditis
- Pancreatitis
- Hepatitis
Additional Reading
- Asnis DS, Conetta R, Teixeira AA, et al. The West Nile virus outbreak of 1999 in New York: the Flushing Hospital experience. Clin Infect Dis. 2000;30(3):413 " 418. [View Abstract]
- Hayes EB. West Nile virus disease in children. Pediatr Infect Dis J. 2006;25(11):1065 " 1066. [View Abstract]
- Lindsey NP, Hayes EB, Staples JE, et al. West Nile virus disease in children, United States, 1999-2007. Pediatrics. 2009;123(6):e1084 " e1089. [View Abstract]
- Rizzo C, Esposito S, Azzari S, et al. West Nile virus infections in children: a disease pediatricians should think about. Pediatr Infect Dis J. 2011;30(1):65 " 66. [View Abstract]
- Romero JR, Newland JG. Viral meningitis and encephalitis: traditional and emerging viral agents. Semin Pediatr Infect Dis. 2003;14(2):72 " 82. [View Abstract]
Codes
ICD09
- 066.40 West Nile Fever, unspecified
- 066.41 West Nile Fever with encephalitis
- 064 Viral encephalitis transmitted by other and unspecified arthropods
- 062.2 Eastern equine encephalitis
- 062.3 St. Louis encephalitis
- 062.5 California virus encephalitis
- 062.1 Western equine encephalitis
ICD10
- A92.30 West Nile virus infection, unspecified
- A92.31 West Nile virus infection with encephalitis
- A85.2 Arthropod-borne viral encephalitis, unspecified
- A83.2 Eastern equine encephalitis
- A83.3 St Louis encephalitis
- A83.1 Western equine encephalitis
- A83.5 California encephalitis
SNOMED
- 417093003 Disease due to West Nile virus (disorder)
- 392662004 West Nile encephalitis (disorder)
- 192687008 Arbovirus encephalitis (disorder)
- 416925005 Eastern equine encephalitis virus infection (disorder)
- 417192005 St. Louis encephalitis virus infection (disorder)
- 416442006 California encephalitis virus infection (disorder)
- 47523006 Western equine encephalitis (disorder)
FAQ
- Q: Should testing for arboviruses, including WNV, be performed on all patients with encephalitis?
- A: Diagnostic testing for arboviruses is not recommended for all patients with encephalitis. The prevalence of these diseases is low, and the diagnosis of more common causes of childhood encephalitis (e.g., herpes simplex virus) should be pursued initially. Patients with no other identifiable cause of encephalitis who have epidemiologic risk factors such as geographic location, season, and exposure history suggestive of arbovirus encephalitis should be evaluated. Testing of patients with aseptic meningitis or Guillain-Barre syndrome is low yield.