West Nile virus 2009: from emerging to endemic in 10 short years.

The first West Nile virus (WNV) cases that made chilling headline news in 1999 brought only questions: What is causing birds and humans to become ill and die? An unknown pathogen? How is it transmitted? How deadly? Today we know that WNV is mosquito-borne, transmitted by a variety of mosquito species, and supported by numerous mammal hosts, including animals and migratory birds. WNV is also now known to be transmitted via transfusion, organs/tissue transplant, and in utero and through breastfeeding. In just 10 years, WNV has gone from "emerging" to "endemic" and joined the ranks of other arboviruses (ARthropod-BOrne viruses) that periodically plague different regions of North America, although at a much lower frequency than WNV.

Joining the ranks of the arboviruses

West Nile virus is a flavivirus closely related to Japanese encephalitis, St. Louis encephalitis (SLE), and Dengue viruses. Not a newly discovered pathogen after all, WNV was simply new to the United States in 1999. Because of its rapid and persistent spread across the country, WNV is probably the most notorious U.S. virus since HIV and the blood-borne hepatitis viruses. The peak incidence for WNV was in 2003, with 9,862 cases reported and 264 deaths. Most summers, some half-dozen viruses, collectively known as arboviruses, infect individuals from coast to coast in the Americas. Encephalitis is the most severe form of arboviral disease and the most commonly reported. The exception is WNV, for which both mild (West Nile fever) and neuroinvasive disease (meningitis and encephalitis are reported.

Laboratory diagnosis

Fortunately, most WNV infections tend to be mild or self-limiting--the individual with a slight fever, headache, and body ache might diagnose himself as having the "flu." Only 20% of infections are symptomatic, and less than 1% of individuals will develop neuroinvasive disease. (The mortality rate for EEE is much higher at around 30%.) Based on symptoms alone, it is rarely possible to diagnose accurately the exact cause of febrile illness. Laboratory testing is important for establishing an accurate diagnosis and providing accurate epidemiological information about which viruses are being passed in a given region. A number of tests are currently in use or available:

Serological tests:

* IgM Capture ELISA or IFA--indicates acute infection in serum or cerebrospinal fluid;

* IgG ELISA or IFA--indicates previous exposure; fourfold increase indicates recent infection;

* Plaque reduction neutralization (PRNT)--confirmatory test for WNV in that it differentiates WNV antibodies from those directed toward SLE, a closely related but less common virus; and

* IgG aviditiy test--can help distinguish between recent and past infection.

Virus-detection tests:

* PCR--detects viral RNA; useful for detecting virus in blood products, but less useful as a diagnostic test because the window for RNA detection is short (a few days) in most patients; and

* Viral culture--not used for diagnostic testing.

New information pending publication: A recent study (data presented in abstract at the 2009 West Nile National Conference. Feb. 19-20, 2009, in Savannah, GA) has shown that some acute infections may be missed by performing only IgM or PCR testing. This suggests that there is a window when it would be of value to perform both serological and molecular testing (i.e., in the transition from viremia to immune response).

Table 1: Cases of arboviral disease reported to Centers for Disease
Control and Prevention

         Major US arboviruses that cause encephalitis

      Virus           Primary mosquito       Geographic area
                           vector

West Nile virus     Culex and other       48 states (continenal
(WNV)                                     U.S.)

Eastern Equine      Culiseta melanura     Eastern seaboard,
encephalitis (EEE)                        Gulf Coast, Midwest
virus

Western Equine      Culex tarsalis; also  Western U. S. and
encephalitis (WEE)  Aedes spp.            Canada
virus

St. Louis           Culex and others      48 states
encephalitis (SLE)                        (continental U.S.)
virus

LaCrosse (LAC)      Aedes triseriatus     Midwestern,
encephalitis virus                        mid-Atlantic states

Confirmed and probable cases reported to the CDC (fatalities available
                           for WNV only *)

          Virus             1989-1998  1999  2000-2007       2008

West Nile virus (WNV)            0      62    27,543     1,338
                                        (7)   (1,080) *  1,338 (43) *

Eastern Equine                  61       5        75     Not available
encephalitis (EEE) virus

Western Equine                   3       1         0     Not available
encephalitis (WEE) virus

St. Louis encephalitis         475       4       187     Not available
(SLE) virus

LaCrosse (LAC)                 739      70       830     Not available
encephalitis virus

Total human WNV cases reported to the CDC: These numbers reflect both
mild and severe human disease cases occurring each year as reported to
ArboNET by state and local health departments. ArboNET is the national,
electronic surveillance system established by CDC to assist states in
tracking West Nile virus and other mosquito-borne viruses.

Vaccine on the horizon?

West Nile vaccines for human use have been in development since 2000 and in clinical trials since 2005 under funding by the National Institute of Allergy and infectious Disease or NIAID. The first vaccine is anticipated for approval sometime in 2009. Vaccine scientists have taken advantage of the close genetic relationship between WNV and yellow fever virus--both flaviviruses--to design a vaccine that can be used to protect humans against WNV infection. While there are no human vaccines to date, vaccines for veterinary use have been available for a number of years.

On the alert: Chikungunya virus

Travelers from outside the United States can enter the country or return home with other vector-borne infections that are not currently endemic in the Americas. Whether the virus is able to spread or remains an isolated event depends on the makeup of the local mosquito population. Chikungunya virus is a mosquito-borne virus that caused an outbreak in Italy in 2007 and now has the potential to enter and spread in the United States via mosquitoes native to certain areas. The Aedes albopictus mosquito, also known as the Asian tiger mosquito, was the primary carrier of the virus in the recent outbreak in Italy and is commonly found in southern and eastern regions of the United States. Another Aedes mosquito, A aegypti, is responsible for outbreaks in Asia and Africa, and is found in the United States, primarily in southern states.

References

(1.) Mostashari F, Bunning ML, Kitsutani PT, et al. Epidemic West Nile Encephalitis, New York, 1999: Results of a household-based seroepidemiologycal survey. Lancet. 2001;358:261-264.

(2.) General reference: CDC Division of Vector-Borne Diseases Available at http://www.cdc.gov/ncidod/dvbid/Arbor/arbdet.htm. Accessed March 3, 2009. Available at http://www.cdc.gov/ncidod/dvbid/westnile/surv&control Case Courtn08_detailed.htm. Accessed March 3, 2009. Available at http://www.cdc.gov/ncidod/dvbid/ westnile/resources/wnv-guidelines-aug-2003.pdf. Accessed March 3,2009.

(3.) Vaccines: Available at http://www3.niaid.nih.gov/topics/westNile/research/prevention.htm. Accessed March 3, 2009. Available at http://www.nih.gov/news/pr/apr2005/niaid-18.htm. Accessed March 3,2009.

(4.) Hogrefe WR, R Moore, M Lape-Nixon, M Wagner, HE Prince. Performance of Immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays using a West Nile virus recombinant antigen (preM/E) for detection of West Nile virus - and other flavivirus-specific antibodies. J Clin Microbiol. 2004;42:4641-4648.

(5.) Available at http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_2009.htm. Accessed March 3,2009.

Chris Gardner, BS, is Technical Services manager at Focus Diagnostics Inc. (www.focusdx.com) in Cypress, CA, which currently has available commercial PCR and serological testing for Chikungunya virus.

By Chris Gardner, BS