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Laboratory diagnosis of acute phase infection with West Nile virus
West Nile virus (WNV) is a mosquito-borne flavivirus (single-stranded RNA) that primarily infects birds but occasionally infects horses and humans. WNV was first isolated in 1937 from an infected person in the West Nile district of Uganda. Until the viral infection was recognized in 1999 in birds in New York City, WNV was found only in the Eastern Hemisphere, with wide distribution in Africa, Asia, the Middle East, and Europe.(1-3) In 2002, a total of 3,389 human cases of WNV infection were reported from 37 states (794 cases in Illinois); 2,354 (69%) presented with meningoencephalitis, 704 (21%) had West Nile fever, and 331 (10%) had an unspecified illness.(2) Overall, the WNV epidemic in the United States was the largest arboviral meningoencephalitis outbreak documented in the Western hemisphere. In addition, 33 cases of probable WNV infection occurred among persons who had received blood components in the month before illness onset.(3)
Most people who are infected with WNV will not have any type of illness. It is estimated that about 20% of those who become infected will develop West Nile fever with mild symptoms, including fever, headache, myalgia, and occasionally a skin rash on the trunk of the body. About 1 of 150 WNV infections (<1%) result in meningitis or encephalitis. Case fatality rates among patients hospitalized during recent outbreaks have ranged from 4% to 14%. Advanced age is the most important risk factor for death, and patients older than 70 years of age are at particularly high risk.(1)
Laboratory diagnosis is best achieved by demonstration of specific IgG and IgM class antibodies in serum specimens. PCR (LCWNV / West Nile Virus [WNV] RNA Detection by Rapid PCR) can detect WNV RNA in specimens from patients with WNV infection when specific antibodies to the virus are not present. However, the likelihood of detection is relatively low as the sensitivity of PCR detection is approximately 55% in cerebrospinal fluid and approximately 10% in blood, from patients with known WNV infection.
Reference values apply to all ages.
Presence of specific IgM class antibodies in a serum specimen is consistent with acute-phase infection with West Nile virus (WNV).
By the eighth day of illness, most infected persons will have detectable serum IgM antibody to WNV; in most cases it will be detectable for at least 1 to 2 months after onset of illness, in some cases it will be detectable for 12 months or longer.
Absence of IgM class antibodies to WNV is consistent with lack of acute-phase infection with this virus. Specimens drawn too early in the acute phase (eg, before 8 days postinfection) may be negative for IgM-specific antibodies to WNV. If WNV infection is suspected, a second specimen drawn approximately 14 days postinfection should be tested.
Presence of specific IgG class antibodies in a serum specimen indicates infection with WNV sometime in the past. By 3 weeks postinfection, virtually all infected persons should have developed IgG antibodies to WNV. If acute-phase infection is suspected, serum specimens drawn within approximately 7 days postinfection should be compared with a specimen drawn approximately 14 to 21 days after infection to demonstrate rising IgG antibody levels between the 2 serum specimens.
In the very early stages of acute WNV infection, IgM may be detectable in cerebrospinal fluid before it becomes detectable in serum.
Test results should be used in conjunction with a clinical evaluation and other available diagnostic procedures.
The significance of negative test results in immunosuppressed patients is uncertain.
Positive test results may not be valid in persons who have received blood transfusions or other blood products within the past several months.
False-negative results due to competition by high levels of IgG, while theoretically possible, have not been observed.
False-positive results may occur with persons vaccinated for flaviviruses (eg, yellow fever, Japanese encephalitis, dengue), with persons infected with other flaviviruses, and with persons previously infected with West Nile virus (WNV). Because closely related arboviruses exhibit serologic cross-reactivity, it sometimes may be epidemiologically important to attempt to pinpoint the infecting virus by conducting cross-neutralization tests using an appropriate battery of closely related viruses.
WNV antibody results for cerebrospinal fluid (CSF) should be interpreted with caution. Complicating factors include low antibody levels found in CSF, passive transfer of antibody from blood, and contamination via bloody taps.
Cross-reactivity has been noted with some specimens containing IgM antibody to enteroviruses.
1. Petersen LR, Marafin AA: West Nile Virus: a primer for the clinician. Ann Intern Med 2002;137:173-179
2. Petersen LR, Roehrig JT: West Nile Virus: a reemerging global pathogen. Emerg Infect Dis 2001;7(4):611-614
3. Brinton MA: The molecular biology of West Nile Virus: a new invader of the western hemisphere. Ann Rev Microbiol 2002;56:371-402
4. Centers for Disease Control and Prevention (CDC). Provisional Surveillance Summary of the West Nile Virus epidemic. United States, January-November 2002. MMWR Morb Mortal Wkly Rep 2002;51(50):1129-1133
5. Centers for Disease Control and Prevention (CDC). Investigations of West Nile Virus infections in recipients of blood transfusions. MMWR Morb Mortal Wkly Rep 2002;51(43):973-974