Case Study

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
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)

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)
• gt1 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.