West Nile Virus: Pathogenesis and therapeutic options

West Nile virus, a member of the family Flaviviridae, has spread throughout the United States. With more than 9000 cases and 200 deaths in 2003, West Nile virus has become the most common cause of viral encephalitis in several states. West Nile virus encephalitis is a zoonosis. The life cycle of the virus includes mainly birds as hosts and mosquitoes as vectors. Humans are accidental hosts, insufficient to support the life cycle of the virus because of low-grade, transient viremia. However, human-to-human transmission through blood, organ transplantation, and lactation has been documented. The frequency of severe neurologic disease in the current epidemic suggests a more neurovirulent strain of virus than the one classically associated with West Nile fever. Several neurologic manifestations have been described, but the most characteristic presentation is encephalitis with weakness. Magnetic resonance imaging scans may be normal initially, but a characteristic pattern of involvement of deep gray matter nuclei can be recognized. Although results of polymerase chain reaction may be positive in the cerebrospinal fluid early in the course of the disease, diagnosis is based on serologic tests. Possible cross-reactivity with other members of the genus flavivirus mandates caution when serologic testing results are interpreted. Thus far, no therapeutic intervention has shown consistent clinical efficacy in West Nile virus disease. Several approaches, including interferon-alpha2b and immunoglobulin with high titer against West Nile virus, offer promise based on animal models and limited clinical experience. New drugs with in vitro activity are being investigated, and a vaccine is being developed.