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Case Study #9 West Nile Virus . Sara Halaszi Yoonhee Choi Daniella Ross November 15, 2007 . (www.geocities.com/.../PagelsTom/02westnile.jpg). The Case: . In late August 1999, an outbreak of mosquito-borne encephalitis occurs in NY state

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case study 9 west nile virus

Case Study #9West Nile Virus

Sara Halaszi

Yoonhee Choi

Daniella Ross

November 15, 2007

the case
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. . .
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)

West Nile Virus

www.lib.uiowa.edu/hardin/md/cdc/2290.html

primary mode of transmission
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
primary modes of transmission
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.
primary mode of transmission1
Primary Mode of Transmission

(www.ci.greenfield.ca.us/Public_Health_Info.htm)

alternate modes of transmission
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)
wnv infection
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)

wnv infection1
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
schematic of virologic and serologic tests in wnv encephalitis
Schematic of Virologic and Serologic Tests in WNV Encephalitis

(http://www.annals.org/cgi/content /full/140/7/545)

progression of wnv encephalitis in deep gray nuclei
Progression of WNVEncephalitis in deep gray nuclei

(http://www.annals.org/cgi/content /full/140/7/545)

wnv epidemiology
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)
wnv infection statistics
WNV Infection Statistics

Cases of WNV infection in humans in the USA

(Figures taken from the Centers for Disease Control)

wnv infection statistics1
WNV Infection Statistics

West Nile Virus Activity in United States (1999)

wnv infection statistics2
WNV Infection Statistics

West Nile Virus Activity in United States (2007)

methods for minimizing wnv impact
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)
prevention and treatment of wnv
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)
prevention and treatment cont
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.

vaccines and antivirals
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)
vaccines and antivirals in development
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

antiviral peptides targeting wnv envelop protein
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)

vaccines and antivirals in development1
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.
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