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Preferred test for the laboratory diagnosis of WNV meningitis or
encephalitis
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 of WNV is best achieved by demonstration
of specific IgG and IgM class antibodies in serum specimens from
patients. By the 8th 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. By 3 weeks
postinfection, virtually all infected persons should have developed
serum IgG antibodies to WNV.
The specific identification of WNV by detection of IgM
in cerebrospinal fluid (CSF) is the recommended test to document
central nervous system disease, but this test may be falsely
negative in CSF collected <8 days after the onset of symptoms.
PCR (#86197 "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 PCR sensitivity in CSF is
approximately 55%, and in blood, about 10% in patients with known
WNV infection.
IgG: negative
IgM: negative
Reference values apply to all ages
IgM:
A positive result is consistent with the acute phase of WNV
meningitis or encephalitis. In the very early stages of acute WNV
infection, IgM may be detectable in CSF before it becomes
detectable in serum.
A negative result may indicate the absence of disease. However,
specimens drawn too early in the acute phase may be negative
for IgM-specific antibodies to WNV. If WNV central nervous system
(CNS) infection is suspected, a second specimen should be
collected in 1 to 2 weeks and tested.
IgG:
A positive result is consistent with CNS infection with WNV some
time in the past.
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.
False-negative results due to competition by high levels of IgG,
while theoretically possible, have not been observed.
WNV antibody results for 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