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West Nile Virus
Diagnostic Features of West Nile Virus Infection for Clinical Physicians
a report by
Rajeev Vaidyanathan, PhD
and Erol Fikrig, MD
1. Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine; 2.SRI CADRE Vector-borne and Zoonotic Disease Research
West Nile virus (WNV) is the most common cause of arboviral encephalitis in supply of Mexico, with 0.03% of donors viremic.
Kidney, stem cell, liver,
North America. From 1999 to 2007, over 25,000 human cases and 1,000 lung, pancreas, and bone marrow transplants have been implicated in WNV
human deaths were reported in the US. WNV is a mosquito-borne, infection and death.
Neurological sequelae and encephalitis in
neurotropic flavivirus antigenically similar to Japanese encephalitis and immunocompromised recipients of organ transplants are more severe than
St Louis encephalitis viruses.
WNV has caused epidemics of febrile illness and in non-immunocompromised individuals.
WNV should be considered in
encephalitis in Africa, the Mediterranean, Europe, India, and Australia.
WNV renal transplant recipients who present with febrile illness and neurological
was first detected in North America in dead birds from New York City in 1999, symptoms.
In addition, transplant recipients who do not contract WNV by
and has spread in the last eight years to all 48 contiguous states, seven transplant or transfusion are still at greater risk of severe neurological
Canadian provinces, and Mexico.
Yearly case and fatality rates, state-by- disease following mosquito bite than the general population.
state distribution, and a breakdown of clinical syndromes are available at
www.cdc.gov/ncidod/dvbid/westnile/index.htm. Several recent reviews have Clinical Symptoms
superbly summarized the epidemiology and clinical features of WNV, Over 80% of WNV infections are asymptomatic, 20% result in self-limiting
specifically with clinical physicians in mind.
West Nile fever (WNF), and <1% result in West Nile neuroinvasive disease
(WNND), such as viral aseptic meningitis or meningoencephalitis, which is
Transmission associated with high mortality.
Muscle weakness, fatigue, headache,
The most common route of human infection is by mosquito bite. WNV is difficulty concentrating, and fever are the most commonly reported
enzootic in birds, and a mosquito may acquire infection after feeding on an symptoms.
About 25–30% of patients may have vomiting and diarrhea.
infected bird. The virus replicates in the mosquito, which then bites a Some cases of infection may resolve within a week, but severe cases of
human and transmits the virus in its saliva.
The original genotype isolated fatigue and myalgia may persist for over a month.
in 1999, known as NY99, is being displaced in North America by a newly involvement may manifest as loss of bowel and bladder control or acute
emergent genotype, WN02, which requires a shorter replication period in respiratory failure requiring mechanical ventilation.
the mosquito before transmission.
Shorter gaps between blood feeding conductance studies can reveal a critical reduction in the amplitudes
increase the number of mosquito–host contacts, leading to more infected of compound muscle action potentials in affected limbs, but nerve
birds. This, in turn, increases the probability of a naïve mosquito acquiring conduction velocities are usually unimpaired.
an infectious blood meal. Birds are the most common reservoirs of WNV, symptoms include acute flaccid paralysis or poliomyelitis, tremor, and
especially corvids (crows and jays), sparrows, finches, and grackles.
Severe diffuse axonal polyneuropathy is revealed by nerve
mammals—including primates, horses, dogs, and cats—are not competent conduction studies and electromyography. The prognosis for most patients
reservoirs, although rodents and rabbits may develop a sufficiently high with meningitis or encephalitis is positive, but patients with acute flaccid
viremia to infect mosquitoes.
Juvenile alligators may also act as amplifying paralysis do not recover their strength.
Electroencephalograms may reveal
hosts in areas of high alligator and mosquito density.
severe toxic metabolic encephalopathy. Most patients with WNND have
normal neuroimaging studies, but there may be abnormalities in the basal
Intra-uterine infection of the fetus with WNV has been documented. In ganglia, thalamus, cerebellum, and brainstem.
Fatal hemorrhagic fever
mice, embryos are susceptible to WNV infection after the formation of the and rhabdomyolysis with elevated creatine kinase levels
have been reported
trophectoderm until formation of the placenta.
Pregnancy in the mouse as part of the clinical spectrum of WNND. A case of fatal fulminant WNV
model greatly increases the risk of severe WNV infection and maternal meningoencephalitis resulted in coma, ventilator dependence, and loss of
Congenital WNV infections in human neonates may manifest as brain function within 10 days of admission.
meningitis, encephalitis, and, possibly, death.
Vertical transmission of WNV
during breastfeeding appears to be rare.
WNV can be transmitted by WNV infection often results in ocular symptoms such as chorioretinitis,
human blood transfusion. The risk of transmission has decreased since vitritis, and intraretinal hemorrhage.
Multifocal chorioretinitis is common
screening with minipool nucleic acid-amplification testing (MP-NAT) began in acute cases and, with associated febrile and neuralgia symptoms,
in 2002, but a slight risk of transmission by this route still exists.
Seasonal specifically indicates WNV infection. Other clinical symptoms of WNV have
screening of individual samples and restricting screening to blood donations included maculopapular exanthema,
vocal fold paralysis,
intended for immunocompromised recipients has been found to be cost- and diffuse lymphadenopathy.
These latter two symptoms may require the
Physicians should also be aware that WNV is present in the blood attention of an otolaryngologist. The spectrum of symptoms in children
© T OUCH BRIEFINGS 2007