only 57% of CSF samples and 14% of serum samples were positive with PCR. Patients with WNV may have persistent IgM antibodies for WNV. In a study by Roehrig et al. (2003), seven of 12 patients with serial samples had IgM persistently positive for WNV for 500 or more days.

Prior infection can be detected with measurement of WNV IgG. However, in a survey of 865 deployed front-line troops, 30 had both predeployment and postdeployment IgG antibodies against WNV. There was no evidence of acquisition of infection during deployment: there were no fourfold rises between predeployment and postdeployment samples, and no IgM antibodies were detected. Infection with dengue virus and prior yellow fever virus vaccine may result in detection of cross-reactive antibodies and make interpretation of serologic tests difficult. The above 30 persons’ serum samples were also reactive to St. Louis encephalitis, dengue, and yellow fever viruses. Because of the high cross-reactivity with St. Louis encephalitis virus, dengue and yellow fever viruses, confirmation of a positive WNV IgG requires testing with the plaque-reduction neutralization test, which requires a biosafety level 3 facility (Gea-Banacloche et al. 2004). Prior WNV can be confidently diagnosed if the WNV neutralizing-antibody titers are 4 times higher than all the other flavivirus titers.

Treatment of West Nile Virus Infection

There is no known effective treatment for WNV infection. Ribavirin, a guanosine analogue with broad-spectrum antiviral activity, has been shown to have activity against WNV in vitro (Jordan et al. 2000). Ribavirin also has concentrations in CSF that are 70% of those in serum. Ribavirin has been used successfully to treat related viruses including LaCrosse encephalitis, Hantaan, Lassa fever, and hepatitis C viruses (Jordan et al. 2000). However, in an outbreak in Israel, patients treated with ribavirin had a higher mortality than those who were not treated (Petersen and Roehrig 2001). The poor outcomes could have been due to patient selection, with sicker patients being treated with ribavirin, inasmuch as this was a nonrandomized study. If it is effective, the predicted required dose would be high, around 4 g intravenously every day, similar to that for treatment of Lassa fever. Interferon has also been noted to have in vitro activity against WNV and has been used in individual cases (Kalil et al. 2005).

A chimeric WNV vaccine with a type 4 dengue virus backbone (an attenuated deletion mutant) with an attached WNV envelop glycoprotein has been tested in Rhesus monkeys with development of high levels of neutralizing antibodies which protected them from infection (Platonov 2001). Clinical trials in humans are in progress.

Long-Term Adverse Health Outcomes of Infection with West Nile Virus

The scientific community is just beginning to unveil the long-term adverse health outcomes of WNV infection. Two teams of investigators have conducted long-term followup studies of the self-reported health outcomes of people who suffered acute episodes of W est Nile fever, WNM, WNE, or West Nile meningoencephalitis (Gottfried et al. 2005; Klee et al. 2004). All cases were diagnosed clinically and confirmed with laboratory analysis. A rigorous study by Klee and colleagues reports the health status at 6, 12, and 18 months of 42 New York City residents whose acute illnesses were manifested in 1999 and required hospitalization in all but two cases. A less rigorous study by Gottfried and colleagues reports the health status at 12 months of 24 Tennessee residents whose acute illnesses were diagnosed and reported to the state’s Department of Health in 2002; all but two of those cases had been hospitalized. About



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