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

2. (

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. West Nile Virus 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)

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(

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
( /full/140/7/545)

12. Progression of WNV Encephalitis in deep gray nuclei
( /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)
Year
Total Cases
Cases of WNV fever
Case of WNV
neurological disease
WNV deaths
1999 62 3 59 7
2000 21 2 19
2001 66 64 9
2002
4156
1162
2946
284
2003
9862
6830
2860
264
2004
2539
1269
1142
100
2005
3000
1607
1294
119
Total
19,706
10,875
8464
785

15. WNV Infection Statistics
Initial source of infection-- Introduced into US from importation of infected bird (illegally?)
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
National institute of allergy and infectious disease

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 )
Receptor mediated endocytosis, acidification, fusion, disassembly, release of viral genome in cytoplasm

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.