Approach
Diagnosis is generally based on the history and physical exam; however, serologic testing and neuroimaging are recommended in patients with suspected neuroinvasive disease. West Nile virus infection should be considered in any person with a febrile or acute neurologic illness who has had recent mosquito exposure, organ transplantation, or a blood transfusion in areas where virus activity has been reported, especially during the summer months.[21]
As the clinical features of infection are relatively nonspecific, exposure history and public health information regarding outbreaks aids interpretation of the clinical findings. Other causes of encephalitis and meningitis should be considered in the differential diagnosis. West Nile virus encephalitis, meningitis, and poliomyelitis are clinically indistinguishable from encephalitis, meningitis, and poliomyelitis due to other etiologies.[21]
West Nile virus infection is a notifiable condition in the US.
History
Ask the patient about a history of exposure to mosquitoes in areas of known West Nile virus (WNV) transmission. Cases have been reported in Europe, the Middle East, Africa, parts of Asia including India, North America, parts of Central America, and the Caribbean. Cases have also been reported in Australia; however, infection is due to the Kunjin virus, a WNV subtype. Rarely, there may be a history of blood transfusion, needlestick injury, organ transplant, or illness in neonates whose mothers were infected with WNV during pregnancy or while breastfeeding.[3][4][33]
Approximately 70% to 80% of people who are infected remain asymptomatic or subclinical.[21] Most of the remaining patients develop an influenza-like illness that usually lasts 3 to 6 days, but can persist for weeks or months (known as West Nile fever or WNF). Symptoms include headache, malaise, fever, anorexia, abdominal pain, nausea, vomiting, generalized muscle weakness, myalgia and arthralgia, and pharyngitis. The patient may also complain of visual disturbances, such as visual blurring, floaters, or eye pain.[1]
West Nile neuroinvasive disease (WNND) occurs in <1% of patients with WNF, and can present with signs and symptoms of encephalitis, meningitis, or poliomyelitis (acute flaccid paralysis).[21] Symptoms include sudden onset of fever, severe headache, photophobia, seizures, mental status changes (e.g., depression, confusion, disorientation, memory loss), severe muscle weakness, or respiratory distress.[1] Older or immunocompromised people are at higher risk of developing neuroinvasive disease.[13]
Hepatitis, pancreatitis, and myocarditis are all rare complications. Symptoms include right upper quadrant abdominal pain (hepatitis), epigastric pain (pancreatitis), or chest pain, dyspnea, and palpitations (myocarditis).
Cases of congenital infection have been reported in pregnant women who are infected with West Nile virus during pregnancy; however, the risk for adverse pregnancy and newborn outcomes appears to be low.[2]
Physical exam
Patients with WNF may present with a morbilliform or maculopapular rash over the trunk and extremities. Lymphadenopathy (typically submental) and splenomegaly may be present. Epigastric pain or tenderness may indicate pancreatitis, while jaundice usually indicates hepatitis.
Perform an ophthalmoscopic exam in all suspected cases. This may reveal conjunctival injection, retinal hemorrhages, multifocal chorioretinal lesions (clustered in temporal and nasal regions of the fundus periphery), chorioretinitis, and inflammatory vitritis.[34]
Movement disorders, including tremors, ataxia, myoclonus, and parkinsonism, are suggestive of neuroinvasive disease. Neck stiffness and positive Kernig and Brudzinski signs indicate meningitis. Confusion, which can progress to stupor or coma, indicates encephalitis. While generalized muscle weakness occurs in patients with WNF, the paralysis in West Nile poliomyelitis is usually an asymmetric, flaccid paralysis that affects the extremities and respiratory muscles. Cranial nerve palsies and bladder/bowel dysfunction can occur in patients with poliomyelitis.[35]
Laboratory investigations
Serologic testing is recommended in patients with suspected disease. Test serum and/or cerebrospinal fluid (CSF) for the presence of WNV-specific immunoglobulin M (IgM) antibodies using a commercially available immunoassay. Serum and CSF samples are recommended if neurologic symptoms are present.[36][37]
Presence of WNV-specific IgM antibodies in serum and/or CSF provides good evidence of recent infection. The detection of IgM antibodies in the CSF indicates CNS infection. IgM antibodies are detectable for 3-8 days after symptom onset, and may persist for up to 3 months, or in some cases, up to 12 months or longer.
A positive result may indicate past infection with WNV or antibody cross-reactivity to other flaviviruses (e.g., yellow fever virus, Japanese encephalitis virus, dengue virus) from exposure via infection or vaccination.
A negative result does not rule out the diagnosis. A false-negative result is possible if the sample was collected in the first few weeks after symptom onset, and the test may need to be repeated on a later sample.
Immunoglobulin G (IgG) antibodies may persist for years following asymptomatic or symptomatic infection, and the presence of IgG antibodies alone only provides evidence of previous infection. Clinically compatible cases with a positive IgG result, but not IgM, should be assessed for other diagnoses.
Confirmatory testing is required in certain circumstances (e.g., possible exposure to cross-reactive flaviviruses, atypical or unusually severe clinical presentation or death, presentation outside typical arboviral season, unusual route of transmission suspected such as an organ transplant or blood transfusion).[36][37]
Plaque reduction neutralization test (PRNT) is recommended for confirmatory testing and to determine the specific flavivirus.
PRNT on acute and convalescent serum specimens is recommended. A fourfold or greater change in WNV-specific neutralizing antibody titer between acute and convalescent serum samples collected 7-10 days apart (or some sources recommend 2-3 weeks apart) confirms an acute infection.
If neutralizing antibodies are not detected, consider an alternative diagnosis.
Molecular testing (e.g., reverse transcriptase-polymerase chain reaction [RT-PCR]) may be recommended to confirm the diagnosis in certain circumstances.[36][37]
Molecular testing is recommended in conjunction with serologic testing for immunocompromised patients (including those on B-cell depleting immunotherapies such as rituximab) to confirm the diagnosis, as immunocompromised patients can have prolonged viremia and delayed antibody responses.
Molecular testing can be performed on serum, plasma, CSF, or tissue specimens. A positive result confirms the diagnosis. However, a negative result does not necessarily rule out infection.
Viral RNA is usually negative by the time patients present with symptoms, and so is only useful early in the course of illness. One study found that RT-PCR can identify WNV RNA in 86% of whole-blood samples during acute infection.[38]
Sensitivity is <60% in immunocompetent patients, and the likelihood of detecting an infection with molecular testing in an immunocompetent patient is fairly low.
Viral cultures and immunohistochemistry are other diagnostic options. However, these tests are difficult to perform, have low yield, and require laboratories with proper biosafety containment facilities, so are generally not recommended.
Routine clinical laboratory investigations are generally nonspecific.[21] Order liver function tests and serum amylase/lipase in patients with suspected hepatitis or pancreatitis (i.e., patients with abdominal pain or jaundice). Order a complete blood count in patients with symptoms of neuroinvasive disease. This may show leukocytosis, anemia, lymphopenia, or thrombocytopenia. Serum electrolytes may reveal hyponatremia. Perform a lumbar puncture in patients with suspected neuroinvasive disease.[39]
Imaging
Cranial imaging is necessary only to rule out other causes of neurologic symptoms. Although MRI is preferable, a CT scan is usually more readily available. Neuroimaging cannot confirm infection or neuroinvasive disease, but it can help exclude other causes of meningitis, encephalitis, and flaccid paralysis. CT scan of the head is usually normal. Brain MRI may be normal, even in severe encephalitis, or demonstrate prominent signal abnormalities in the deep gray matter (posterior thalami and basal ganglia) and/or cerebellum.[40]
Use of this content is subject to our disclaimer