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West Nile Virus
infected with WNV includes fever, meningitis, encephalitis, rash, nausea, require up to three days for replication, followed by nucleic acid
and vomiting.
45
Prolonged encephalitis, fulminant hepatitis, and vitritis have sequencing. Serum plaque reduction–neutralization tests (PRNTs) can
also been reported in children 12 years of age and younger.
46
confirm acute WNV infection. Histological analysis and transmission
electron microscopy of the brain and spinal cord may reveal severe non-
Diagnosis necrotizing polio-meningoencephalitis or diffuse edema,
34
although virus
Patients most commonly reported their symptoms as “headache, new particles themselves may not be found. Immunohistochemistry can be used
rash, and generalized weakness.”
44
WNV infection should be a to confirm the presence of WNV in the neuronal cytoplasm,
34
and may be
differential diagnosis in a patient who manifests acute febrile or most useful during the first week of infection, when antigen levels are
neurological illness and has been exposed to mosquitoes in an enzootic high.
60
Viral antigens are focal in the CNS of most patients, but diffuse in
or rural area during the summer or fall. WNV infection should also be the CNS of immunosuppressed patients.
60
considered in a patient who has received a recent blood transfusion or
organ transplant. Groups at high risk for infection include children, the Treatment
elderly, diabetics, and immunocompromised persons. The course of Current treatment for WNV infection and encephalitis is supportive. There
encephalitis, however, is similar for otherwise healthy and is no present therapy for WNND, but several vaccines, antiviral–antibody
immunocompromised patients. For elderly or diabetic patients who treatments, antisense oligonucleotides, and interferon preparations are
present with high fever during the summer, an ocular evaluation should undergoing clinical human trials.
31
A recent review has summarized the state
include a dilated fundus examination and fluorescein angiography,
36,37
of therapy development.
61
searching specifically for multifocal chorioretinitis. One study suggests
that focal neurological injury may occur independently of patient age or Interferon alpha, imiquimod (an interferon-inducer), and ribavirin (in
pre-infection health.
47
Persons with diabetes, a history of alcohol abuse, combination with interferon) have successfully protected mice from
chronic renal or cardiovascular disease, hypertension, or hepatitis C mortality induced by WNV injection.
62
However, ribavarin has limited success
infection may be at increased risk for WNV encephalitis, and encephalitic in humans. Interferon alpha-2b inhibits WNV replication in vitro, and has
patients with a history of stroke or who require mechanical ventilation been used successfully to treat patients with WNND within one week of
are more likely to die.
48,49
hospital admission. One case successfully resolved even after starting
interferon alpha-2b three weeks after disease presentation.
63
Efficacy may
Standard serological diagnosis of WNV infection is performed with samples be compromised, however, if the patient is elderly.
64
of serum or cerebrospinal fluid (CSF) tested with an immunoglobin M (IgM)-
capture enzyme linked immunosorbent assay (ELISA) or an indirect IgG Tumor necrosis factor (TNF) is effective against WNV in vitro. Treatment with
ELISA for WNV antibodies.
32,50
Because IgM does not normally cross the infliximab, a TNF-inhibitor used to treat autoimmune disorders, may result
blood–brain barrier, the presence of WNV-specific IgM in the CSF indicates in WNV penetration into the CNS and fulminant meningoencephalitis.
65
WNV central nervous system (CNS) infection. WNV-specific IgM and IgA can Individuals with Crohn’s disease, psoriasis, or rheumatoid arthritis who are
persist for six months to a year after the acute phase of the infection.
51
undergoing infliximab therapy must be made aware of their increased risk
Because IgM persists for so long, patients with an unrelated illness can for severe WNV encephalitis.
still test positive for circulating WNV-specific IgM.
52
In such cases, IgG avidity
testing can distinguish between recent and past exposure.
52
Previous vaccination against yellow fever or Japanese encephalitis (JE)
viruses does not exacerbate the course of WNV infection
66
and, in fact,
Electroencephalograms of patients with WNV encephalitis show prominent vaccination with either results in homologous and cross-reactive WNV
slowing in the anterior regions, which is uncommon in other viral antibody responses.
67
ChimeriVax-WN02—a live, attenuated, recombinant
encephalitides.
53
Diagnosis of WNND is also confirmed by the WNV vaccine constructed from an infectious yellow fever virus—elicited a
demonstration of WNV-specific IgM antibodies in the CSF,
31
which presents strong immune response in humans after a single dose.
68
The cost per case
as pleocytosis with a predominance of neutrophils.
31,54
Persistent of WNV illness prevented by vaccination was calculated to be $20–59,000
lymphopenia (lymphocytes <10%) and elevated serum ferritin levels (mean $36,000), which means that universal vaccination against WNV is
(>500ng/ml) are typical of WNV encephalitis, and the more prolonged the unlikely to materialize unless disease incidence increases substantially.
69
lymphopenia, the worse the prognosis.
53
Both of these parameters may be
helpful in diagnosing WNV encephalitis in the absence of serological tests. Pregnant women with WNV should undergo regular pre-natal check-ups,
including ultrasound examinations to assess fetal development, and should
Other diagnostic tools include TaqMan reverse transcriptase–polymerase understand the risks to the baby. While children under 18 years of age are
chain reaction (RT–PCR) to detect viral ribonucleic acid (RNA),
55
nucleic acid at higher risk for exposure and infection than adults, children have shorter
amplification testing (NAAT) of plasma in parallel with WNV-specific IgM hospitalization stays, fewer neurological symptoms, better neurological
assays,
56
and quantitative PCR to titrate virus levels in plasma.
32
RT–PCR of outcomes, and lower mortality.
70
However, acute lymphocytic leukemia
infected tissue is significantly more sensitive than immunohistochemistry, in children and adolescents may render the patient more susceptible to
especially for patients who die soon after disease onset and for whom WNV encephalitis.
71
Immunosuppressed patients infected with WNV have
serology may be negative.
57,58
For example, serology results for WNV were been treated successfully with intravenous immunoglobulin (IVIg)
negative in an infected, immunocompromised patient treated with containing WNV-neutralizing antibodies.
72
Flaccid paralysis in WNV patients
rituximab/fludarabine for non-Hodgkin’s lymphoma.
59
Viral culture may be may be confused with Guillain-Barré syndrome or stroke. However, Guillain-
performed on post mortem spleen, kidney, or brain,
34
although this may Barré syndrome produces symmetrical, ascending limb weakness, and CSF
42 US INFECTIOUS DISEASE 2007