338 Equine Compendium April 2002

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Equine West Nile Virus:

Diagnosis and Treatment
Corrina S. Snook, VMD
New Bolton Center
School of Veterinary Medicine
University of Pennsylvania
ABSTRACT: West Nile virus was first
identified in the United States in 1999
when it triggered an epizootic of
encephalitis and meningitis, causing
death in humans and horses. Since
1999, both the number of affected
horses and the geographic range have
increased dramatically. West Nile virus
infection in horses may be subclinical, or
signs may range from mild peripheral
neurologic disease to encephalitis. Most
species has been significant, and birds
act as sentinels for virus activity. The
virus, which is an arbovirus (specifi-
cally a flavivirus) of the Japanese
encephalitic complex, was first iso-
lated in Uganda in 1937.1 Its appear-
ance in the United States marked the
first time the virus had been seen in
the western hemisphere.2 Although
WNV can infect many animal
species, including ruminants, camels,
dogs, nonhuman primates, rodents,
bats, pigs, rabbits, and amphibia,1
clinical disease is most
important in birds,
KEY POINTS
which confirmed cases of equine
WNV encephalomyelitis occurred in
2001 include Alabama, Connecticut,
Delaware, Florida, Georgia, Illinois,
Indiana, Kentucky, Louisiana, Mary-
land, Massachusetts, Mississippi,
New Jersey, New York, North Car-
olina, Pennsylvania, Rhode Island,
Tennessee, and Virginia.3 Four hun-
dred sixty-seven cases have been
reported in Florida alone.a Although
final figures for cases occurring in
2001 are not yet available, new cases

affected horses recover. Supportive care
is the only treatment currently available
for horses, although new modalities are
being explored in humans that may be
adapted to horses in the future. Ante-
mortem diagnostic techniques that moni-
tor the serologic status of suspected
cases are improving. An equine vaccine
is available under conditional licensure
and may prove beneficial in decreasing
the incidence of disease. Studies on the
efficacy of this vaccine are still in the
early stages.
horses, and humans.
Birds can develop a
viremic state capable of
infecting mosquitoes,
thereby propagating
the virus.1
Spread of the Virus in the
United States
In 2001, WNV encephalomyelitis
was reported in more than 700
horses in 19 states.a This represents a
significant increase from the 1999
epizootic in which 25 horses were
West Nile virus is currently considered endemic
in the United States.
The virus will likely continue to spread through-
out the country in ensuing vector seasons.
were still being reported in Florida in
December.
The virus isolated in the 1999 epi-
zootic in the United States had a high
degree of genomic sequence similarity
to an isolate that circulated in Israel
between 1997 and 2000.4 To date,
the virus has been found in numerous

W
est Nile virus (WNV)
infection, initially an epi-
zootic occurring in New
York City in 1999, has become
endemic in the United States. The
virus causes encephalitis, meningitis,
and death in both humans and
horses. The death rate in avian
affected in only New York state and
the 2000 outbreak in which 60 horses
in seven states were affected. States in
aPersonal communication: Crom RL,
DVM Veterinary Services, Emergency
Programs Animal and Plant Health
Inspection Service, USDA, Riverdale,
MD, February 2002.
mosquito species in the United
States5 and worldwide. Since hiber-
nating Culex mosquito species were
found to contain the virus in New
York, there is strong evidence to sup-
port the overwintering of the virus as
the means of maintaining an endemic
mosquito population. 6 The exact

SERIES Debra Deem Morris, DVM, MS

EDITOR North Jersey Animal Hospital, PA, Wayne, New Jersey
Compendium April 2002
means of harboring the virus,
whether by transovarial vertical trans-
mission to offspring or by mosquitoes
taking a blood meal just prior to
hibernation, is not well known. 6
Migratory patterns of birds have
likely helped to establish the virus in
other areas of the United States.
Diagnosis
WNV infection in horses may be
subclinical or may produce diseases
ranging from mild peripheral neuri-
tis to encephalitis. Clinical signs
reported include hindlimb and fore-
limb ataxia, recumbency, difficulty
rising, hyperesthesia, altered menta-
tion, hyperresponsiveness to sound,
muscle fasciculations over the muz-
zle and triceps region, drooping
lower lip, stupor, falling to the
knees, blindness, and seizures. 7
Some human patients have low
serum sodium levels that are
thought to result from the syndrome
of inappropriate antidiuretic hor-
mone secretion. 5 To the authors
knowledge, this has not been
reported in horses. Fever has been
reported in less than 25% of affected
horses. This is in direct contrast to
human infection in which fever is
found in a high percentage of cases.
In humans, a cerebrospinal fluid
(CSF) tap is often performed for
diagnostic purposes and to rule out
bacterial meningitis/encephalitis.
Reports of human CSF findings are
consistent with viral infection,
including pleocytosis (often neu-
trophilic) with increased total pro-
tein count.8 There are few reports of
CSF findings in affected horses. In a
study of CSF from four horses with
WNV infection in 2001, CSF was
reported to be normal in three
horses but was xanthochromic with
an increased total protein in one.7
Antemortem diagnosis of WNV
infection is based on serologic evalu-
ation. The serum plaque reduction
neutralizing antibody test measures
virus-neutralizing antibody in CSF
or serum. In equine patients, sero-
conversion from negative to positive
or a fourfold or greater rise in paired
sera taken 10 to 14 days apart indi-
cates recent WNV infection. Neu-
tralizing antibody may persist for
many months in horses and for up to
2 years in humans.9 The IgM-capture
ELISA is a valuable tool for detecting
recent infections. The technique is
species specific but will often cross-
react with other closely related fla-
viviruses. IgM antibodies develop
early after infection with the virus
and do not persist until the next vec-
tor season (antibodies last less than 3
months).9 Hemagglutination inhibi-
tion and complement fixation tests
are also available.9 Virus isolation in
serum or CSF is not routinely per-
formed in horses because their
viremic stage is short and low levels
of virus are present.9 WNV infection
should be suspected in unvaccinated
horses with positive antibody titers.
Postmortem diagnosis by virus isola-
tion on chilled fresh samples of
brainstem, cerebellum, cerebrum,
and spinal cord is possible; histologic
examination of fixed tissues should
also be performed. Because of the
zoonotic potential, practitioners who
perform field necropsies should fol-
low the guidelines established by the
USDA to avoid exposure to the virus
through contact with potentially
infected tissues.9
Treatment
There is no established protocol for
treating WNV encephalitis or menin-
gitis in humans or horses. Supportive
care, which may include fluid therapy
and ventilatory support, is the gener-
ally accepted means of treatment in
humans. Equine patients have been
treated with intravenous dimethyl
sulfoxide (for purported antiinflam-
matory effects on the central nervous
system) and NSAIDs (e.g., phenylbu-
tazone, flunixin meglumine). Intra-
venous fluid and nutritional support
are necessary in somnolent animals
West Nile Virus 339
that are not drinking or eating. The
use of corticosteroids in affected
horses is controversial based on find-
ings in humans. Some cases of
human Streptococcus pneumoniae and
Haemophilus influenzae bacterial
meningitis have benefited from the
use of corticosteroid therapy in con-
junction with appropriate antimicro-
bials.10 One report of viral encephali-
tis in humans indicated a favorable
response to treatment with corticos-
teroids when the CSF contained
more than 15% of CD4+ CD26+
memory helper T cells, supporting
the involvement of autoimmune
mechanisms. 11 Other reports state
that the use of corticosteroids may be
contraindicated in patients with viral
central nervous system infections.12
New therapeutic modalities being
explored in humans with WNV
encephalitis include intravenous
immunoglobulin containing high
titers for WNV antibody and rib-
avirin. Ribavirin, a guanosine ana-
logue, has in vitro antiviral activity
against a broad spectrum of RNA
and DNA viruses. High doses of rib-
avirin have been shown to inhibit
WNV cytopathogenicity and viral
replication in human neural cells in
vitro.13 One report has shown rib-
avirin therapy to be a factor associ-
ated with death in Israeli patients
with WNV encephalitis. 14 Con-
trolled studies demonstrating in vivo
efficacy have not been performed.
Specific antiviral or immunoglobulin
therapies for equine WNV enceph-
alitis are not likely to be available
soon. The single most important
treatment of equine patients is to
prevent severely ataxic animals from
injuring themselves. Sling support
may be beneficial in horses that have
difficulty rising. With supportive
care, the prognosis for clinically
affected horses has been fairly good,
with a total death rate of 39%
reported for 1999 through 2000.7 An
accurate death rate for the year 2001
is not yet available. Most reports
340 Equine
indicate that surviving horses return
to complete function within a few
weeks to months after the onset of
disease. Horses with rapid progres-
sion of clinical signs to recumbency
have shown an unfavorable outcome.
Prevention and Control
Prevention and control measures
recommended by the USDA for
WNV include reduction of mosquito
breeding sites on farms, thereby
decreasing the exposure of horses to
adult mosquitoes, and vaccination.15
Steps to reduce mosquito breeding
sites include eliminating standing
pools of water, maintaining cleanli-
ness of watering troughs, and apply-
ing larvicidals to any pools of water
that are difficult or impossible to
remove. Screened housing, use of
mosquito repellents, and reducing
the horses access to the outdoors may
help prevent exposure to adult mos-
quitoes.15 The mosquito vector and
the times at which animals are most
at risk of virus exposure have not
been definitively determined in
horses. In 2000, the Culex pipiens and
Culex restuans mosquito species were
most frequently identified as WNV
positive.16 The 2001 USDA report
suggested that horses infected with
WNV are more likely to be turned
out at night or used as pleasure
mounts.4 The presence of blackbird
roosts and waterfowl aggregations
within a half mile of the affected
horses premises was of marginal sig-
nificance.4 The incidence of WNV in
birds and humans may prove as sen-
tinels for equine cases. WNV has
been found in birds at least 3 months
prior to infections in humans.17 Dur-
ing the 1999 and 2000 U.S. out-
breaks, WNV infections in humans
and horses peaked in August and
September, respectively.16
On August 1, 2001 the USDA
issued a conditional license to Fort
Dodge Animal Health, Fort Dodge,
Iowa, for production of a WNV vac-
cine for use in horses. Since the con-
ditional vaccine was released in early
fall 2001, over one million doses have
been distributed throughout the
United States. To date, adverse effects
of the vaccine are few and are com-
monly seen with other killed virus
vaccines. Challenge studies are
required for full licensure but have
not yet been performed. Fort Dodge
has submitted an application to the
USDA to perform challenge studies
designed to demonstrate the efficacy
and potency of the vaccine. Unpub-
lished data demonstrate an increase
in neutralizing antibody in horses
vaccinated intramuscularly with the
WNV vaccine twice, 3 to 6 weeks
apart.b Each state has restrictions on
the distribution and sale of the vac-
cine, and individual state veterinari-
ans should be contacted prior to vac-
cine procurement and use. This is
especially important in states in
which the virus has not yet been
known to circulate and the serologic
status of horses has not been assessed.
It is likely that WNV will persist in
the western hemisphere and continue
to spread throughout the United
States. Diagnosis of the disease has
greatly improved since the virus was
first seen in this country, and vaccina-
tion may prove helpful in preventing
the disease in horses.
References
1. Peiris JS, Amerasinghe FP: West Nile
fever, in Beran GW, Steele JH (eds):
Handbook of Zoonoses. Section B: Viral,
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2. Centers for Disease Control and Pre-
vention: Update: West Nile-like viral
encephalitisNew York, 1999.
MMWR Morb Mortal Wkly Rep
48:944946, 1999.
3. USDA Animal and Plant Health In-
spection Service: Update on the current
status of West Nile virus. Available at:
www.aphis.usda.gov/oa/wnv/wnvstats.
html; updated November 20, 2001.
4. USDA Animal and Plant Health
bPersonal communication: Carlson M,
Fort Dodge Industries, Fort Dodge, IA,
January 2002.
Compendium April 2002
Inspection Service: West Nile virus in
equids in the northeastern United
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usda.gov/vs/ceah/wnvreport.pdf;
updated August 2001.
5. Craven RB, Roehrig JT: West Nile
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11. Matsui M: Infection in the central
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Available at: www.aphis.usda.gov/oa/
wnv/prv.html; updated 2001.
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