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Viral Infections
Table 1: Diagnostic Testing for Human West Nile Virus Infection
Test Specimen Clinical Setting Comments
Culture Brain tissue WNND Insensitive; requires live cells; BSL-3 lab
NAAT Plasma WNF Rarely positive >7 days after onset of symptoms; cost-effectiveness not proven
WNND Rarely positive at time of presentation; possible exception is immunocompromised patients
CSF WNND Insensitive (<60%); possible exception is immunocompromised patients
Serology Serum WNF Recommended test for diagnosis; IgM typically positive after 1 week of symptoms;
may persist for months to years
WNND IgM typically positive at time of presentation;
can see false-positives due to infection or immunisation with other flaviviruses
CSF WNND Recommended test for diagnosis; IgM typically positive at time of presentation;
finding of intrathecal IgM antibody in a patient with a compatible clinical presentation is diagnostic of infection
BSL = biosafety level; CSF = cerebrospinal fluid; IgM = immunoglobin M; NAAT = nucleic acid amplification testing; WNF = West Nile fever; WNND = West Nile neurological disease.
Serological Testing up to 200 days after donation.
22
WNV IgG antibody typically peaks at
Serology remains the standard method for diagnosis of WNV infection. 100 days after infection,
22
and can remain positive indefinitely. A second
Enzyme-linked immunosorbant assay (EIA) testing is available commercially, consideration in interpreting antibody levels is that WNV cross-reacts
and is highly sensitive.
16
Evidence of intrathecal immunoglobulin M (IgM) serologically with members of the Japanese encephalitis virus serogroup and
antibody in the setting of a compatible clinical illness is highly suggestive of related flaviviruses. These antigenically similar viruses include St Louis
WNV disease. Elevated serum WNV antibodies are suggestive of acute encephalitis, Japanese encephalitis, yellow fever and dengue. A positive
infection, with confirmation by demonstrating a four-fold increase in serological test for WNV, particularly if it is an isolated IgG antibody, should
antibody titre between acute and convalescent samples. The time from prompt consideration of infection with one of these related agents.
23
History
infection to the appearance of detectable WNV antibody is variable. Serial of travel to an endemic area or prior immunisation may provide clues to
testing of asymptomatic blood donors has documented the appearance of infection with a cross-reactive flavivirus. In cases where diagnostic
IgM antibody approximately nine days and IgG antibody approximately two uncertainty persists, plaque reduction neutralisation testing (PRNT) may aid
weeks following viraemia.
17
One study of patients with WNV, most of whom in discriminating between the different flaviviruses. Newer techniques such
had WNF, found IgM antibody in 54% of patients tested during the first as the microspere assay may be useful for differentiating WNV from other
week of symptoms compared with 98% of patients presenting more than flaviviruses, but are not yet widely available.
seven days into their illness.
11
In contrast, most patients with WNND have
detectable antibody in the CSF and serum at the onset of neurological Summary
symptoms.
18
Immunocompromised patients represent the possible Although there is no accepted antiviral treatment for WNV infection,
exception, as this group may demonstrate delayed seroconversion with diagnosis allows discontinuation of antimicrobials directed against
detectable virus in serum and CSF persisting until the development of alternative pathogens, guides discussion of prognosis and allows focused
neutraliaing antibody.
19,20
The finding of an elevated WNV antibody titre on public health interventions such as insecticide campaigns. Serology is the
a single serum specimen should be interpreted with caution. One study recommended initial test for most patients with suspected WNV infection.
identified serum IgM antibody in 58% of WNND cases >500 days following Because of the prolonged seropositivity following infection and serological
clinical illness.
21
IgM antibody persistence has also been reported in a cohort cross-reactivity among related flaviviruses, caution should be exercised
of viraemic blood donors, many of whom had detectable IgM antibody when interpreting a positive result on a single serum specimen. ■
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100 EUROPEAN INFECTIOUS DISEASE 2007
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