West Nile Virus Information for Professionals

 

Epidemiology

  • Infectious agent – flavivirus, single-stranded RNA virus
  • Transmission – primarily through the bite of an infective mosquito, but other routes have been identified that include organ transplant, blood transfusion, consumption of breast milk from infected mother, transplacental transmission, and occupational (laboratory) exposure.
  • Incubation period – typically 3 to 14 days after exposure
  • Risk factors - anyone is at risk for developing WNV infection, but several groups are at an increased risk. Those individuals who have a higher probability of being bitten by a mosquito are at risk for acquiring WNV infection (i.e. people who spend time outdoors for work or recreation). Other groups at an increased risk include people over age 50, organ transplant recipients, and the immunocompromised. These groups are at an increased risk of developing severe disease

Clinical Description

West Nile virus infection can cause a wide range of symptoms depending on its severity. Human infection can range from asymptomatic illness to West Nile neuroinvasive illness (encephalitis, meningitis, and poliomyelitis). An estimated 80% of people infected with WNV never developed symptoms.

 

West Nile Fever (Non-neuroinvasive disease)

Of those individuals who do develop illness from WNV infection, the majority will develop what is called West Nile fever or West Nile non-neuroinvasive disease. Although most cases of West Nile fever are mild, recent studies have shown that West Nile fever may be more clinically significant than we once thought. Some patients may experience symptoms for weeks or months. One study found that 63% of patients with West Nile fever continued to have symptoms at 30 days or longer, and approximately one-third of West Nile fever cases were hospitalized (Watson, et al. Ann Int Med. 141(5): 360-365, Sep 7, 2004).

Symptoms of West Nile fever may include

  • Fever (not present in all cases of WNV non-neuroinvasive disease)
  • Headache
  • Fatigue
  • Maculopapular skin rash
  • Myalgia
  • Nausea
  • Vomiting
  • Lymphadenopathy
  • Eye pain
  • Memory/concentration deficits

Please note that some cases of West Nile fever may progress to West Nile neuroinvasive disease.

 

West Nile Neuroinvasive Disease (encephalitis, meningitis, poliomyelitis)

WNV infection can cause significant neuroinvasive illness of the central nervous system (CNS). Severe WNV infection can result in several different clinical syndromes ranging from febrile headache to aseptic meningitis to encephalitis. Many times, these syndromes are indistinguishable from similar syndromes caused by other viruses. These syndromes are characterized by persistent neurocognitive sequelae. It is not uncommon for individuals with severe WNV infection to have persistent symptoms 6-18 months post onset (Pepperell, et al. CMAJ. 168(11):1399-1405, May 27, 2003). Klee, et al. found that only 37% of cases of WNV neuroinvasive disease had fully recovered 12 months post onset (Klee, et al. EID. 10(8):1405-1411, Aug 2004).

  • West Nile encephalitis and meningitis: may be characterized by altered mental status, focal neurologic findings, meningeal signs, and other neurologic abnormalities. Approximately 25-35% of cases with neuroinvasive WNV infection have meningitis without evidence of encephalitis. WNV encephalitis is the most severe form or WNV neuroinvasive disease and may involve fever, headache, loss of consciousness, lethargy, confusion, and coma.
  • West Nile poliomyelitis: characterized by acute onset of asymmetric limb weakness or paralysis in the absence of sensory loss. Occasionally, pain precedes paralysis. Recent studies suggest that paralysis can occur in the absence of fever, headache, or other common symptoms. Respiratory paralysis causes death in 50% of fatal WNV infections. Common symptoms of respiratory paralysis syndrome include respiratory weakness, dysarthria, and dysphasia. Many times, these deaths occurred 6-8 months post-onset.

Symptoms of West Nile neuroinvasive disease may include:

  • Fever
  • Headache
  • Altered mental status
  • Weakness
  • Ataxia and extrapyramidal signs
  • Parkinsonism
  • Balance rigidity
  • Neurokinesia
  • Gastrointestinal symptoms
  • Optic neuritis
  • Seizures
  • Myelitis
  • Polyradiculitis
  • Maculopapular or morbilliform rash involving the neck, trunk, arms, or legs
  • Flaccid paralysis
  • Myocarditis, pancreatitis, and fulminant hepatitis (infrequently observed)
  • Respiratory paralysis

Common laboratory findings in cases of severe WNV disease

  • Total leukocyte counts in peripheral blood are mostly normal or elevated with lymphocytopenia and anemia also occurring.
  • Hyponatremia is sometimes present, particularly among patients with encephalitis.
  • Examination of cerebrospinal fluid (CSF) shows pleocytosis, usually with a predominance of lymphocytes. Protein is universally elevated. Glucose is normal.
  • Computed tomography is not useful specifically in the diagnosis of WNV infection, but is useful in excluding other etiologies of acute meningoencephalitis. Brain MRI is often normal, but will sometimes display leptomeningeal enhancement or parenchymal signal changes.

West Nile Virus, Pregnancy, and Breast-feeding

Current Recommendations

  • Pregnant women who have meningitis, encephalitis, acute flaccid paralysis, or unexplained fever in an area of ongoing WNV transmission should have serum (and cerebrospinal fluid [CSF], if clinically indicated) tested for antibody to WNV.
  • If laboratory tests indicate recent infection with WNV, these infections should be reported immediately to the state health department, and the women should be followed to determine the outcomes of their pregnancies.
  • If the patient has pregnancy-associated WNV disease and wishes to be part of the registry to track intrauterine infections and birth outcomes, the Wyoming Department of Health (WDH) can provide you with appropriate contact information.
  • If, in the unfortunate event of miscarriage in a WNV-infected patient, products of conception are available, it would be important to ask the patient if she is willing to submit the products for WNV testing. If she consents to testing, store the products by freezing and notify the WDH as soon as possible.
  • WNV may be transmitted through breast milk. Because the health benefits of breast-feeding are well established, and the true risk for WNV transmission through breast-feeding is unknown, the new findings do not suggest a change in breast-feeding recommendations.

Laboratory Testing for WNV

Indications for WNV Testing

The diagnosis of WNV infection relies on a high index of clinical suspicion and on the results of specific laboratory tests. WNV or other arboviral diseases (Western Equine encephalitis, St. Louis encephalitis, etc.) should be seriously considered in patients who have onset of unexplained encephalitis or meningitis in summer or early fall. The local presence of WNV enzootic activity or other human cases should further raise the index of suspicion.

Testing for WNV is indicated when:

  • There is evidence of clinically compatible illness (as indicated in the Clinical Description section above) during transmission season (May through October).
  • Pregnant or breast-feeding women with a compatible febrile illness and exposure history
  • WDH does NOT recommend testing of asymptomatic persons concerned about exposure, or screening of asymptomatic pregnant or breast-feeding women.
  • Click HERE for form to Request WNV Serology

Availability of WNV Testing

All WNV tests must be referred to the lab by a healthcare professional. The Wyoming Public Health Laboratory now requires a fee for WNV testing. Please see http://health.wyo.gov/phsd/lab/testingfees.html for fee information.  Serologic testing for WNV is available; both serum and CSF samples are tested using the IgM antibody-capture ELISA serology test, which looks for the presence of IgM antibody in the specimen. For more diagnostic testing guidlines, click HERE.

  • A new diagnostic method may be implemented later this year called Luminex. It is a bead based technology which is a slightly different form of immunoassay that will give similar results as the traditional ELISA system (positive vs. negative). The Luminex bead system is compatible with both serum and CSF samples but is easier to work with and takes less time to perform.
  • Serum samples will be tested Monday through Thursday. Serum samples received on Friday will be run on the following Monday as the test protocol indicates overnight incubation.
  • CSF samples will be tested Monday through Friday.
  • Expected turnaround time is approximately 48 hours.
  • All CSF results will be phoned upon completion. Positive and borderline results for serum samples will be phoned upon completion. Negative serum results will be mailed upon completion.

 

In recent years, commercially available WNV diagnostic assays have been offered at an increasing number of commercial laboratories. Positive test results obtained using these assays help provide a presumptive diagnosis of WNV infection in patients with neuroinvasive disease; however, all positive results using these assays should be confirmed by further laboratory testing at a state health department or CDC.

 

Ideal Timing for WNV Specimen Collection

It is important to understand the ideal timing of specimen collection in order to optimize testing and interpretation of results. Improper timing of specimen collection may result in the patient needing to be re-tested.

  • CSF specimens for IgM should be collected between 2 and 8 days post onset of illness.
  • Acute serum specimens should ideally be collected 8 days post onset of illness or later.
  • Convalescent specimens should be collected 2-3 weeks after collection of acute serum.

Specimens should be transported on cold pack by overnight carrier or USPS ground. Submitters in Cheyenne can hand deliver samples to the WPHL (5th floor Hathaway Bldg) at room temperature. Please note that the submitter is responsible for all shipping costs.

For additional information on WNV testing, visit the WPHL website at: http://wdh.state.wy.us/lab/WPHL-WNV.asp
or call the Wyoming Public Health Laboratory:
During business hours: (307) 777-7431

 

Laboratory criteria for diagnosis

  • Fourfold or greater change in virus-specific serum antibody titer, or
  • Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, CSF, or other body fluid, or
  • Virus-specific IgM antibodies demonstrated in CSF or serum by antibody-capture enzyme immunoassay (EIA)

Reporting WNV Cases to WDH

West Nile virus is a reportable disease in Wyoming. Please report all cases of confirmed and suspected West Nile virus infections (fever, encephalitis, meningitis, poliomyelitis) to the Wyoming Department of Health. Rapid reporting of cases to the health department is essential to guide public health control efforts. Future funding for mosquito control efforts may depend on accurate reporting of human cases that are considered a reflection of WNV activity in the area.
When reporting, please be sure to indicate the manifestation of the West Nile virus infection by specifying the following:

  • Asymptomatic blood donor: confirmed viremic blood donor who does not develop a compatible illness within two weeks of the positive donation.
  • West Nile non-neuroinvasive disease (with or without fever): mild to moderate illness without clinical or laboratory evidence of central nervous system involvement, and with a positive IgM in serum. If a case is originally reported as West Nile non-neuroinvasive disease and progresses to West Nile neuroinvasive disease, please submit an updated report.
  • WNV meningitis: physician diagnosis of meningitis or abnormal CSF findings consistent with viral meningitis, and a positive IgM in serum or CSF, characterized by fever, headache, stiff neck, and pleocytosis.
  • WNV encephalitis: physician diagnosis of encephalitis and clinical presentation of encephalitis characterized by fever, headache, and altered mental status ranging from confusion to coma with or without additional signs of brain dysfunction (e.g. paresis, paralysis, cranial nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, or abnormal movements), and a positive IgM in serum or CSF.
  • WNV poliomyelitis: physician diagnosis of acute flaccid paralysis and/or respiratory paralysis syndrome with or without additional symptoms and a positive IgM in serum or CSF.

If the patient is pregnant, breast-feeding, or has donated blood in the last two weeks, this should be indicated on the report.

SEND REPORTS TO THE EPIDEMIOLOGY SECTION BY FAX OR PHONE:
FAX: (307) 777-5573
PHONE: (307) 777-3593
TOLL-FREE: 1-877-996-9000 (during business hours)

 

Treatment of WNV

At this time, no specific treatment of human WNV infections is available. In severe cases, treatment consists of supportive care that often involves hospitalization, intravenous fluids, respiratory support, and prevention of secondary infections. There are several ongoing clinical trials for treatments of WNV infection. A list of these clinical trials may be found on the CDC’s website at: http://www.cdc.gov/ncidod/dvbid/westnile/clinicalTrials.htm.

 

Animal Health Care Professionals

Laboratory guidance and information for animal sample submissions can be obtained from the University of Wyoming State Veterinary Laboratory’s website at http://wyovet.uwyo.edu/. You may also call the Wyoming State Veterinary Laboratory at 1-800-442-8331.

Information on West Nile virus and animals can be obtained from the American Veterinary Medical Association

Additional information can be obtained from the United States Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS).

 

Additional Resources

Recent research articles

  • Watson JT, Pertel PE, Jones RC, et al. Clinical characteristics and functional outcomes of West Nile fever. Annals of Internal Medicine. Sept 2004. 141(5):360-365.
  • Pepperell C, Rau N, Krajden S, et al. West Nile virus in 2002: Morbidity and mortality among patients admitted to the hospital in southcentral Ontario. Canadian Medical Association Journal. May 2003. 168(11):1399-1405.
  • Yim R, Posfay-Barbe KM, Nolt D, et al. Spectrum of clinical manifestations of WNV infection in children. Pediatrics. Aug 2004. 114(6):1673-1675.
  • Klee AL, Maidin B, Edwin B, et al. Long-term prognosis for clinical West Nile virus infection. Emerging Infectious Diseases. Aug 2004. 10(8):1405-1411.