Clinical Signs and Symptoms of West Nile Virus Disease

Clinical presentation

WNV disease should be considered in any person with an acute febrile or neurologic illness who has had recent exposure to mosquitoes, blood transfusion, or organ transplantation, especially during the summer months in areas where virus activity has been reported. The diagnosis should also be considered in any infant born to a mother infected with WNV during pregnancy or while breastfeeding. See West Nile and Pregnancy and West Nile and Breastfeeding for more information.

Other causes of encephalitis and aseptic meningitis should also be considered, as appropriate (e.g., herpes simplex viruses, enteroviruses, Powassan virus, St. Louis encephalitis virus, La Crosse virus, eastern equine encephalitis virus).

Signs and symptoms

The incubation period for WNV disease is typically 2 to 6 days but ranges from 2 to 14 days and can be several weeks in immunocompromised people.

An estimated 70-80% of human WNV infections are subclinical or asymptomatic. Most symptomatic persons experience an acute systemic febrile illness that often includes headache, weakness, myalgia, or arthralgia; gastrointestinal symptoms and a transient maculopapular rash also are commonly reported. Less than 1% of infected persons develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or acute flaccid myelitis.

• WNV meningitis is clinically indistinguishable from viral meningitis due to other etiologies and typically presents with fever, headache, and nuchal rigidity.
• WNV encephalitis is a more severe clinical syndrome that usually manifests with fever and altered mental status, seizures, focal neurologic deficits, or movement disorders such as tremor or parkinsonism.
• WNV acute flaccid myelitis is usually clinically and pathologically identical to poliovirus-associated poliomyelitis, with damage of anterior horn cells, and may progress to respiratory paralysis requiring mechanical ventilation. WNV acute flaccid myelitis often presents as isolated limb paresis or paralysis and can occur without fever or apparent viral prodrome. WNV-associated Guillain-Barré syndrome and radiculopathy have also been reported and can be distinguished from WNV acute flaccid myelitis by clinical manifestations, timing of onset, and electrophysiologic testing.

Rarely, cardiac dysrhythmias, myocarditis, rhabdomyolysis, optic neuritis, uveitis, chorioretinitis, orchitis, pancreatitis, and hepatitis have been described in patients with WNV disease.

Most women known to have been infected with WNV during pregnancy have delivered infants without evidence of infection or clinical abnormalities. In the best-documented, confirmed congenital WNV infection, the mother developed neuroinvasive WNV disease during the twenty-seventh week of gestation, and her neonate was born with cystic lesions in brain tissue and chorioretinitis. One infant who apparently acquired WNV infection through breastfeeding remained asymptomatic. See Interim guidelines for the evaluation of infants born to mothers infected with West Nile virus during pregnancy for more information.

Clinical assessment

Routine clinical laboratory studies are generally nonspecific. In patients with neuroinvasive disease, cerebrospinal fluid (CSF) examination generally shows lymphocytic pleocytosis, but neutrophils may predominate early in the course of illness. Brain magnetic resonance imaging (MRI) is frequently normal, but signal abnormalities in the basal ganglia, thalamus, and brainstem may be seen in patients with encephalitis, and in the anterior spinal cord in patients with acute flaccid myelitis.

Outcomes

Most patients with nonneuroinvasive WNV disease or WNV meningitis recover completely, but fatigue, malaise, and weakness can linger for weeks or months. Patients who recover from WNV encephalitis or acute flaccid myelitis often have residual neurologic deficits. Among patients with neuroinvasive disease, the overall case-fatality ratio is approximately 10%, but it is significantly higher for patients with WNV encephalitis and acute flaccid myelitis than WNV meningitis.

Recent studies have raised questions about the possible persistence of WNV infection and subsequent renal disease.

Most people infected with WNV are believed to have lifelong immunity from getting the disease again. Some people who have weakened immune systems from certain conditions or medications might not have a strong immune response to the initial infection or their immunity may wane over time. However, most people are protected from getting WNV disease again once they have had it.