1. 1 WEST NILE VIRUS

2. 2 West Nile Virus: Background l First isolated 1937 l Flavivirus l Africa, West Asia, Europe and the Middle East l 1999 US isolate similar to a goose isolate from Israel

3. 3 Mosquito vector Incidental infections Bird reservoir hosts Incidental infections Incubation period -- 3 to 15 days

4. 4 l Isolated from over 43 mosquito species ã Mostly Culex species: 4 Cx. univittatus, Cx. perixiguus, Cx. pipiens, Cx. modestus, Cx. quinquefasciatus, Cx. tritaeniorhynchus, and Cx. vishnui ã Other mosquito species: 4 Aedes, Aedeomyia, Anopheles, 4 Coquillettidia, Mansonia, Mimomyia Vectors and Hosts

5. 5 Culex tarsalis Major vector potential WNV vector in Western US

6. 6 Epidemiology l Mosquitoes feed on infected birds l Pass the virus to warm-blooded animals. l Horses cannot spread WNV to other horses, people or pets. Dead-end Host

7. 7 Mammals l Infected with WN virus ã Mortality: ã Mortality: bats, rabbit, chipmunk, gray squirrel, horse, cat, alpaca, dog ã Seropositive: ã Seropositive: dog, bears, sheep, goats, wolf

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14. 14 Clinical Signs l Ataxia 86% l Depression 51% l Hindlimb weakness 49% l Difficulty or inability to rise 46% l Muscle tremors 41% l Fever only 24% l Death in 25-33% of affected horses

15. 15 Clinical Signs: Colorado l Clinical signs: ã Ataxia – 73% ã Weakness – 69% ã Lethargy, depression – 61% ã Muscle fasciculations – 60% ã Unable to rise on their own – 38%*** ã Fever – 35% ã Altered mentation – 31% ã Hypersesthesia – 30% ã Cranial nerve deficits – 27%

16. 16 Subclinical Infection l Symptomatic:asymptomatic ratio is approximately 1:9

17. 17 Epidemiology: Colorado l 9 years (3 mos – 35 yrs) l No breed, gender predilection l 71.4% (344/482) survived l Horses that died were older l Unvax: 36.6% mortality l At least one vax: 20.3% mortality

18. 18 Recumbent Horses l Average duration: 2.3 days l Range: 1-7 days l Onset to recumbency: 2.1 days (range = 0-14 days) l Recumbency as first sign: 4 horses l Nonvax 2.4 times more likely to be unable to rise

19. 19 Diagnosis l Clinical signs l CSF: mononuclear pleocytosis, normal to increased protein l IgM antigen-capture ELISA l Plaque reduction neutralization assay l PCR, IHC

20. 20 Diagnosis l Serum and CSF results similar l Horses do not develop an IgM response to vaccine

21. 21 Treatment l Symptomatic l IV fluids l Anti-inflammatory medication ã Flunixin meglumine ã DMSO ã Corticosteroids

22. 22 Treatment of WNV l Alpha interferon l Hyperimmune plasma

23. 23 Prognosis: Colorado l 82% considered fully recovered l Some residual signs in 21% (decreased stamina, weight loss) l Estimated 2 unreported cases for every 3 laboratory confirmed cases

24. 24 Increased likelihood of survival if: l Steroid treatment (p=0.10) l Hospitalization (p<0.0001) l Vaccination (p=0.0005) l Not recumbent l Affected late in epidemic

25. 25 Aged Horses (>18 yrs) l Survivors avg. age = 8.9 yrs l Nonsurvivors avg. age = 10.8 yrs l Aged were 2.6 times as likely to die l Older horses not more likely to be recumbent l Older horses not less likely to be vaccinated

26. 26 Treatment of WNV l Anti-inflammatory medication ã Flunixin meglumine ã DMSO ã Corticosteroids?

27. 27 Residual Effects l Florida: 15% l Minnesota: 40% ã Average followup time 6 months ã 59.2% had no neurologic or behavioral abnormalities ã Average duration of signs: 35 days (1-180)

28. 28 Residual Effects ã Behavioral change ã Loss of muscle mass ã More frequent stumbling ã Diminished energy ã Weak hind limbs ã “Abnormal” gait ã Vision loss ã Dysphagia ã Relapses (2 wk to 5 mo)

29. 29 Prevention of WNV l Eliminate mosquito breeding sites l Control mosquito larvae l Reduce exposure to adult mosquitoes l Vaccinate

30. 30 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

31. 31 Control Mosquito Larvae l Stock water tanks with fish that consume mosquito larvae l Use mosquito “dunks” in water tanks l Clean water tanks weekly

32. 32 Reduce Exposure to Adult Mosquitoes l Stable horses during active mosquito feeding times l Screen the stables l Fans, barrier cloth, flysheets l Repellants applied frequently

33. 33 WNV Vaccine-whole virus l 1cc dose, booster 3-6 weeks l Induces antibody response l Conditional license

34. 34 Does the Vaccine Work? The BEST way to test a vaccine: Experimental Challenge Model Infect Horse Experimentally Vaccinate Horse See if horse gets disease Most horses do not get sick after experimental infection!

35. 35 Vaccine Efficacy Experimental Challenge l One year after vaccination l Controls ã 9 of 11 infected--82% l Vaccinates ã 1 of 19 infected--5% (95% Protective)

36. 36 Infection & Mortality vs. Vaccine Status: Colorado 230 = No Vax 97 = 1 Vax 45 = 2 Vax 372 Total

37. 37 California Cases - 2004 Vaccination Status Cases (168) Fatalities (78) Unvaccinated11056 Partially vaccinated 4816 Fully vaccinated53 Unknown vaccination 53

38. 38 Post-Approval Reaction Rates: Fort Dodge l <0.025% adverse effects reported l lumps and bumps l fever l lack of efficacy ?

39. 39 http://lost-foals-group.4t.com /

40. 40 Merial Vaccine l Canarypox vector l Mosquito challenge model l Similar results for safety, efficacy

41. 41 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/