West Nile

The West Nile virus outbreak illustrates several important points. First, it illustrates the difficulty in identifying a virus, especially one that had never been seen before in the U.S. Second, it shows that even with an initial misidentifi-cation, state and federal agencies were still able to act effectively, knowing how similar viruses could be controlled. And last, this case illustrates that virus distribution can be tracked by monitoring those infected as well as its vector.

In late August 1999, eight concurrent cases of patients having encephalitis and/or profound muscle weakness surfaced in Queens, New York. Geographically, the reported cases were traced to a two by two-mile area of a residential neighborhood, immediately sparking exposure concerns. By the end of the year, 59 patients were hospitalized in New York City, and seven deaths were reported.33 Cases presented with a mild 3-6-day symptomatic period, including sudden onset of malaise, nausea, vomiting, headache, rash, cough, and sore throat. Less than 1% of those infected developed neurologic disease (i.e., encephalitis);34 reported deaths were among the young, elderly, or immunocompromised. Also during this initial period it was noticed that several birds throughout the New York area were dying. The birds seemed to be dying from a neurological condition. Samples were sent to the CDC for identification.

Shortly after initial cases were reported, the CDC believed that the infectious agent was likely to be the endemic St. Louis encephalitis (SLE) virus. The CDC based their conclusion on serologic (IgM-capture ELISA) findings, which tested for the presence of patient antibodies to SLE antigens. The laboratory findings of SLE as the infectious agent were consistent with the symptoms of those infected, as well as the fact that SLE was responsible for 4,478 confirmed cases in the U.S. from 1964-1998.35 SLE is an arbovirus, or a virus transmitted to human via arthropods, such as mosquitoes. Steps were quickly taken to monitor and control mosquito populations.

However, shortly after their initial assessment, the CDC changed their conclusion, and stated that the infectious agent was West Nile virus (WNV), not SLE. They based this on the more discriminating method of sequencing viral RNA isolates via RT-PCR, as well as results from specific monoclonal antibody detection of WNV-specific antigens (envelope glycoproteins). The controversy continued as other independent researchers believed the virus to be Kunjin virus, another closely related arbovirus.36 It was later confirmed that the agent was indeed WNV through independent genetic testing by the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID).33

The cause for confusion was due to the close relationship between WNV and SLE. Both flavivirieses share significant similarity in their envelope proteins and some antibodies cross-react. Another compounding factor was that WNV had never been seen before in the U.S., although it was responsible for outbreaks in other geographic locations, including Africa, Europe, and the Middle East.

The diagnosis of WNV infection is made by both clinical findings and sero-logic tests, which detect patient IgM antibodies present in CSF or serum.34,37 Direct virus isolation has been used, but due to limited sensitivities, is not a primary diagnostic procedure. RT-PCR methods for detecting WNV-specific RNA have been used extensively for detection in tissues and CSF Blood banks now use RT-PCR to screen the blood supplies, due to the high incidence of asymptomatic WNV-infected donors: 23 persons have been reported to have been infected with WNV after receiving transfusions from 16 WNV-infected blood donors.38,39

West Nile virus was also identified as the agent responsible for the deaths of birds observed throughout the New York area. This has become a very important observation, for geographical mapping of the dead birds is valuable for tracking WNV infection as it continues to spread to other states and countries. The CDC stated: "dead-bird-based surveillance has proven to be the most sensitive method for detecting WNV presence in an area.'' However the CDC goes on to state "mosquito-based surveillance remains the primary tool for quantifying the intensity of virus transmission in an area, and should remain the mainstay in most surveillance programs for WNV and other arboviruses.''

figure 4.5 Spread of West Nile virus. From the initial outbreak in New York in 1999, the maps chart the rapid westward spread of WNV by showing the geographic distribution of human cases in years 2002-2004. Courtesy of the CDC. (See color insert.)
Microbial Forensics


figure 4.5 (Continued)


□ Positive Test Results — No Dala figure 4.5 (Continued)

In addition to mosquito and dead-bird surveillance, the CDC as well as state organizations tracked live birds, equine WNV infections, and obvious human infections. These data showed that the virus was continuing to spread westward (Figure 4.5). Computer-assisted tracking services like Arbonet and the U.S. Department of the Interior website,40 provide up-to-date tracking information. Such data allow for efficient knowledge acquisition regarding geographic distribution and changes in virus intensity, which gives the public the ability to take necessary precautions.

WNV continues to be a problem with over 4,000 cases reported in the U.S. in 2002. Accurate up-to-date tracking of infected humans, animals, and mosquito populations will continue to provide extremely valuable information about virus spread, locations at risk, and the efficiency of controlling arboviruses through mosquito control. Surveillance efforts must be supported to allow effective action against WNV and against future arbovirus epidemics as they occur.

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