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WEST NILE VIRUSWEST NILE VIRUS

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West Nile Virus: Background

First isolated 1937 Flavivirus Africa, West Asia, Europe and the

Middle East 1999 US isolate similar to a goose

isolate from Israel

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Mosquito vectorIncidental infections

Bird reservoir hosts

Incidental infections

Incubation period -- 3 to 15 days

Incubation period -- 3 to 15 days

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Isolated from over 43 mosquito speciesMostly Culex species:

Cx. univittatus, Cx. perixiguus, Cx. pipiens, Cx. modestus, Cx. quinquefasciatus, Cx. tritaeniorhynchus, and Cx. vishnui

Other mosquito species: Aedes, Aedeomyia, Anopheles, Coquillettidia, Mansonia, Mimomyia

Vectors and Hosts

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Culex tarsalis

Major vector potential WNV vector in Western US

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Epidemiology

Mosquitoes feed on infected birds

Pass the virus to warm-blooded animals.

Horses cannot spread WNV to other horses, people or pets.

Dead-end HostDead-end Host

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Mammals

Infected with WN virus

Mortality:Mortality: bats, rabbit, chipmunk, gray squirrel, horse, cat, alpaca, dog

Seropositive:Seropositive: dog, bears, sheep, goats, wolf

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Clinical Signs

Ataxia 86% Depression 51% Hindlimb weakness 49% Difficulty or inability to rise 46% Muscle tremors 41% Fever only 24% Death in 25-33% of affected horses

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Clinical Signs: Colorado

Clinical signs: Ataxia – 73% Weakness – 69% Lethargy, depression – 61% Muscle fasciculations – 60% Unable to rise on their own – 38%*** Fever – 35% Altered mentation – 31% Hypersesthesia – 30% Cranial nerve deficits – 27%

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Subclinical Infection

Symptomatic:asymptomatic ratio is approximately 1:9

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Epidemiology: Colorado

9 years (3 mos – 35 yrs) No breed, gender predilection 71.4% (344/482) survived Horses that died were older Unvax: 36.6% mortality At least one vax: 20.3% mortality

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Recumbent Horses

Average duration: 2.3 days Range: 1-7 days Onset to recumbency: 2.1 days (range

= 0-14 days) Recumbency as first sign: 4 horses Nonvax 2.4 times more likely to be

unable to rise

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Diagnosis

Clinical signs

CSF: mononuclear pleocytosis, normal to increased protein

IgM antigen-capture ELISA

Plaque reduction neutralization assay

PCR, IHC

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Diagnosis

Serum and CSF results similar Horses do not develop an IgM

response to vaccine

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Treatment

Symptomatic IV fluids Anti-inflammatory medication

Flunixin meglumineDMSOCorticosteroids

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Treatment of WNV

Alpha interferon Hyperimmune plasma

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Prognosis: Colorado

82% considered fully recovered

Some residual signs in 21% (decreased stamina, weight loss)

Estimated 2 unreported cases for every 3 laboratory confirmed cases

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Increased likelihood of survival if:

Steroid treatment (p=0.10)

Hospitalization (p<0.0001)

Vaccination (p=0.0005)

Not recumbent

Affected late in epidemic

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Aged Horses (>18 yrs)

Survivors avg. age = 8.9 yrs

Nonsurvivors avg. age = 10.8 yrs

Aged were 2.6 times as likely to die

Older horses not more likely to be recumbent

Older horses not less likely to be vaccinated

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Treatment of WNV

Anti-inflammatory medicationFlunixin meglumineDMSOCorticosteroids?

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Residual Effects

Florida: 15% Minnesota: 40%

Average followup time 6 months59.2% had no neurologic or

behavioral abnormalitiesAverage duration of signs: 35 days

(1-180)

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Residual Effects

Behavioral changeLoss of muscle massMore frequent stumblingDiminished energyWeak hind limbs “Abnormal” gaitVision lossDysphagiaRelapses (2 wk to 5 mo)

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Prevention of WNV

Eliminate mosquito breeding sites

Control mosquito larvae

Reduce exposure to adult mosquitoes

Vaccinate

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Mosquito Breeding Sites 1. Storm drains

2. Clogged roof gutters

3. Window wells

4. Uncovered containers

5. Leaky faucets and standing water

6. Garden ponds

7. Swimming pools

8. Tires and wheelbarrows

9. Birdbaths and children’s toys

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Control Mosquito Larvae

Stock water tanks with fish that consume mosquito larvae

Use mosquito “dunks” in water tanks

Clean water tanks weekly

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Reduce Exposure to Adult Mosquitoes

Stable horses during active mosquito feeding times

Screen the stables

Fans, barrier cloth, flysheets

Repellants applied frequently

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WNV Vaccine-whole virus

1cc dose, booster 3-6 weeks Induces antibody response Conditional license

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Does the Vaccine Work?

The BEST way to test a vaccine: Experimental Challenge Model

Infect Horse ExperimentallyVaccinate

HorseSee if horse gets

disease

Most horses do not get sick after experimental Most horses do not get sick after experimental infection!infection!

Most horses do not get sick after experimental Most horses do not get sick after experimental infection!infection!

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Vaccine Efficacy

Experimental Challenge

One year after vaccination Controls

9 of 11 infected--82% Vaccinates

1 of 19 infected--5% (95% Protective)

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Infection & Mortality vs. Vaccine Status: Colorado

396

45

7522

97

16268

230

27696

372

0 100 200 300 400

2nd Dose

1st Dose

None

Totals

Vaccination vs. Mortality Status of WNV Horses

Totals

Dead

Alive

(25%)

(30%)

(23%)

(13%)

230 = No Vax

97 = 1 Vax

45 = 2 Vax

372 Total

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California Cases - 2004

Vaccination Status

Cases

(168)

Fatalities

(78)Unvaccinated 110 56

Partially vaccinated

48 16

Fully vaccinated 5 3

Unknown vaccination

5 3

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Post-Approval Reaction Rates:Fort Dodge

<0.025% adverse effects reported lumps and bumps fever lack of efficacy ?

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http://lost-foals-group.4t.com/

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Merial Vaccine

Canarypox vector Mosquito challenge model Similar results for safety, efficacy

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Web site resources

For more information about humans and WNV: www.cdc.gov

For more information about WNV, USDA Website: www.aphis.usda.gov/oa/wnv

For more information about WNV in horses:http://prevmed.vet.ohio-state.edu/