Case Study #9West Nile Virus

Sara HalasziYoonhee ChoiDaniella 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 WNVEncephalitis 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

Year Total Cases Cases of WNV fever

Case of WNVneurological

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

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

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 infectionSome 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.