Case Study #9 West Nile Virus

1. Case Study #9West Nile Virus Sara Halaszi Yoonhee Choi Daniella Ross November 15, 2007

2. (www.geocities.com/.../PagelsTom/02westnile.jpg)

3. The Case: • In late August 1999, an outbreak of mosquito-borne encephalitis occurs in NY state • August 23, 1999: infectious-disease doctor reports 2 cases of encephalitis in NYC (Queens) • Health Dept. then identifies 6 patients with encephalitis, 5 with extreme muscle weakness requiring respiratory support • First suspected to be St. Louis Encephalitis virus strain • Outbreak confirmed as West Nile-like virus based on identification of the virus in human, avian and mosquito samples. • Increased fatalities observed with NYC birds, especially crows, before and concurrent with this outbreak. . .

4. Family Flaviviridae, genus Flavivirus First discovered in 1937 Uganda, West Nile region 40-60 nm in diameter Enveloped, icosahedral One molecule of + sense SS RNA (10,000-11,000 bases) Member of the Japanese encephalitis virus antigentic complex Close antigentic relationship with other Flaviviruses (serologic cross-reactions) West Nile Virus www.lib.uiowa.edu/hardin/md/cdc/2290.html

5. Primary Mode of Transmission • Main route of human infection through bites from infected mosquitoes, mostly Culex species (vector) • Mosquitoes become infected when they feed on infected birds (reservoirs) and carry virus particles in their salivary glands • Corvidae birds (i.e. crows) are especially susceptible to WNV infection • Bird reservoirs sustain infectious viremia after exposure (1-4 days) and if they survive, develop life-long immunity

6. Primary Modes of Transmission • People, horses, and most other mammals are not known to develop infectious-level viremias very often, and thus are probably "dead-end" or incidental hosts.

7. Primary Mode of Transmission (www.ci.greenfield.ca.us/Public_Health_Info.htm)

8. Alternate Modes of Transmission • WNV is not spread via casual contact, but can be transmitted (less frequently) by: • Organ transplantation • Blood transfusion • Breast milk and transplacental (mother-child) • Occupational exposure (lab accidents)

9. WNV Infection • 2-14 day incubation period • ~80% of individuals infected with WNV are asymptomatic • ~20% experience flu-like symptoms (fever, fatigue, headache, muscle and joint pain) • >1% experience severe symptoms (encephalitis, meningitis, profound muscle weakness, high fever, seizures, paralysis)

10. WNV Infection • 60-75% of people with neuroinvasive WNV infections have encephalitis or meningoencephalitis (with most fatalities from encephalitis) • The elderly and immuno-compromised are at a higher risk for developing encephalitis and other severe neuroinvasive infections

11. Schematic of Virologic and Serologic Tests in WNV Encephalitis (http://www.annals.org/cgi/content /full/140/7/545)

12. Progression of WNVEncephalitis in deep gray nuclei (http://www.annals.org/cgi/content /full/140/7/545)

13. WNV Epidemiology • The spread of WNV infection in the U.S. has been very well documented • Excellent case study of how a virus can enter a new territory and spread rapidly through a population. . . • Case figures reflect changes in methods of detection (rise in case number indicative of improved and widespread testing for infection)

14. WNV Infection Statistics Cases of WNV infection in humans in the USA (Figures taken from the Centers for Disease Control)

15. WNV Infection Statistics West Nile Virus Activity in United States (1999)

16. WNV Infection Statistics West Nile Virus Activity in United States (2007)

17. Methods for Minimizing WNV Impact • Prevention of mosquito bites is the best way to avoid WNV infection Some tips: • Use insect repellent (i.e. DEET or other EPA approved insect repellent) • Elimination of mosquito breeding sites (standing pools of water) • Use extra caution when out during peak times of mosquito activity: dawn and dusk, summer months • Proper window screens • Very careful handling of dead animals (if you must)

18. Prevention and Treatment of WNV • No specific therapies for WNV infection currently exist • Supportive care is generally the only treatment available (IV fluids, ventilator, prevention of secondary infection)

19. Prevention and Treatment (cont.) • Recombinant vaccine and DNA vaccine available for equine WNV infection A horse being vaccinated against West Nile virus. Photo courtesy of CDC.

20. Vaccines and Antivirals • What about humans?? • No antiviral agents or vaccines officially approved, but research in the field is currently underway. . . • Chimeric vaccines (combination of genes from more than one virus in a single vaccine) • Naked DNA vaccines • “cocktail” vaccines (individual WNV proteins)

21. Vaccines and Antivirals (in development) • 1) Acambis vaccine: (entered human clinical trials in 2006) combines yellow fever genes and WNV surface proteins. • 2) Attenuated dengue virus backbone to carry WNV protective antigens. • 3) NIAID/Vical vaccine: uses an existing codon-modified gene-based DNA plasmid vector to express WNV proteins

22. Antiviral Peptides Targeting WNV Envelop Protein • P1 and P9 inhibited WNV infection in mice cells • Peptides inhibitory effects depend on their capacity to bind to target E protein • P9 binds to WNV E protein and interferes with virus attachment (concentration dependent) (Bai, Fengwei et al, “Antiviral Peptides Targeting the West Nile Virus Envelope Protein.” Journal of Virology, Feb. 2007, p. 2047-2055)

23. Vaccines and Antivirals (in development) • Antiviral peptides targeting WNV envelope proteins • Antibodies from individuals who have recovered from WNV infection • Use of animal models to study how prior infection with related viruses may confer partial or complete immunity will likewise be useful for vaccine research and treatment.