Transcript Case Study #9 West Nile Virus

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
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)
www.lib.uiowa.edu/hardin/md/cdc/2290.html
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

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 Transmission
(www.ci.greenfield.ca.us/Public_Health_Info.htm)
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
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 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
(http://www.annals.org/cgi/content /full/140/7/545)
Progression of WNV
Encephalitis in deep gray nuclei
(http://www.annals.org/cgi/content /full/140/7/545)
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
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
2
2001
66
2
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
WNV Infection Statistics
West Nile Virus Activity in United States (1999)
WNV Infection Statistics
West Nile Virus Activity in United States (2007)
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


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.)

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





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)



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



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 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.