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.

Signs and symptoms

The incubation period from mosquito bite to onset of WNV disease symptoms is typically 2–6 days but ranges from 2–14 days and may longer in immunocompromised patients.

Asymptomatic infection

An estimated 80% of human WNV infections are subclinical or asymptomatic.

Non-neuroinvasive disease

If symptomatic, most people develop an acute systemic febrile illness, referred to as non-neuroinvasive disease or West Nile fever. Non-neuroinvasive disease often includes fever, fatigue, headache, myalgia, arthralgia, transient maculopapular rash, or gastrointestinal symptoms like vomiting or diarrhea.

Neuroinvasive disease

Less than 1% of infected patients develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or acute flaccid myelitis. Risk of neuroinvasive disease is higher among older individuals and those with immunocompromising conditions.

Meningitis

WNV meningitis is clinically indistinguishable from other viral meningitides and typically presents with fever, headache, photophobia, and meningismus.

Encephalitis

WNV encephalitis is a more severe clinical syndrome that often manifests with fever, altered mental status, and movement disorders such as tremors, myoclonus, parkinsonism, and cerebellar ataxia.

Acute flaccid myelitis

WNV acute flaccid myelitis can develop concurrently with meningitis or encephalitis and can cause limb weakness, paralysis, areflexia, cranial neuropathies, and neuromuscular respiratory failure. WNV acute flaccid myelitis typically develops within 24-48 hours of illness onset and is clinically and pathologically identical to poliovirus-associated poliomyelitis, with damage of anterior horn cells of the spinal cord.

WNV-associated Guillain-Barré syndrome (acute demyelinating polyradiculoneuropathy) can occur 1-8 weeks following acute WNV infection and is characterized by ascending, symmetric weakness and sensory and autonomic dysfunction. It can be distinguished from WNV acute flaccid myelitis by clinical manifestations, timing of onset, and electrophysiologic testing.

Other complications

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

Pregnancy and breastfeeding

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 27th week of gestation, and her neonate was born with cystic lesions in brain tissue and chorioretinitis. One infant who might have acquired WNV infection through breastfeeding remained asymptomatic.

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. Protein levels are elevated, and glucose is generally normal. 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.

Risk factors

Age

Anyone can develop neuroinvasive disease following WNV infection, but the risk increases with age.

• Based on blood donor studies, about 2% of people aged ≥65 years develop neuroinvasive disease compared with <0.5% of people <65 years.
• Patients aged 60–69 years are twice as likely, and patients aged ≥70 years are more than 6 times as likely to be hospitalized with WNV disease compared with younger adults.

Underlying health conditions

Risk of neuroinvasive disease is also increased for patients with cancer, diabetes, hypertension, renal disease, or immunosuppression.

Outcomes

Most patients with non-neuroinvasive 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. Many patients have long-term physical, cognitive, and functional sequelae after being hospitalized for WNV disease, with 30-40% of patients being discharged to long-term care or rehabilitation facilities, and >50% having ongoing symptoms for over a year after illness.

Mortality

Among patients with neuroinvasive disease, the overall case-fatality is approximately 10% but is significantly higher for patients who are older or immunocompromised.

• Mortality is ~20% for patients aged ≥70 years compared with ~2% for people <50 years.
• Mortality is 30–40% for patients with hematologic malignancies, recipients of stem cell and solid organ transplants, and patients receiving anti-CD20 monoclonal antibody therapies.

Immunity

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.