Virology, pathology, and clinical manifestations of West Nile Virus disease

Emerging Infectious Diseases, August, 2005 by Edward B. Hayes, James J. Sejvar, Sherif R. Zaki, Robert S. Lanciotti, Amy V. Bode, Grant L. Campbell

The diagnosis of WNV encephalitis can be supported histopathologically, and there is no pathognomonic lesion. Differential diagnoses include arboviral and other viral encephalitides, rickettsial infections, and various noninfectious diseases. When serum samples and frozen tissues are not available, IHC testing of formalin-fixed tissues with specific monoclonal and polyclonal antibodies is particularly useful.

Prognosis

The clinical course of WNF ranges from a mild febrile illness of several days' duration to debilitating fatigue, aching, and weakness that may last for weeks or months (16,29,41). Although cases of meningitis without alteration of the patient's mental status or other focal neurologic features have a favorable prognosis, persistent headaches and fatigue may be reported (29). Patients with WNV encephalitis or focal neurologic manifestations often have persistent neurologic deficits for months or years (28,29). Of 35 patients hospitalized with WNV disease in New York, only 13 (37%) reported full recovery in physical, cognitive, and functional abilities 12 months after illness onset (41). Many patients with WNV-associated poliomyelitislike syndrome do not recover, but some improvement in limb strength may occur over time (42,43). The overall case-fatality rate for neuroinvasive WNV disease is [approximately equal to] 9% (26).

Clinical Management

Management of severe WNV illness remains supportive. Patients with severe meningeal symptoms often require pain control for headaches and antiemetic therapy and rehydration for associated nausea and vomiting. Patients with severe encephalitis should be observed for development of elevated intracranial pressure and seizures, and patients with encephalitis or paralysis must be monitored for inability to protect the airway. Acute neuromuscular respiratory failure may develop rapidly, particularly in patients with prominent bulbar signs; prolonged ventilatory support may be required (22,30,34).

Ribavirin, interferon-[alpha], WNV-specific immunoglobulin, and antisense gene-targeted compounds have all been considered as specific treatments for WNV disease, but no rigorously conducted clinical trials have been completed. Nonspecific immunoglobulin and plasmapheresis should be considered for patients with Guillain-Barre syndrome but are not indicated for patients with paralysis due to damage of anterior horn cells (30).

Vaccine Development

Two vaccines are available for vaccinating equines: an inactivated WNV vaccine and a recombinant vaccine that uses canarypox virus to express WNV antigens (44,45). An inactivated vaccine is also being studied for use in humans (46). A chimeric live virus vaccine incorporating the genetic sequences for E and prM antigens into a 17-D yellow fever virus backbone has been shown to be efficacious in hamsters and is undergoing initial clinical trials in humans (46). Another chimeric vaccine incorporating WNV genetic sequences into a backbone of attenuated serotype-4 dengue virus induced protective immunity in monkeys (44). A DNA vaccine that elicits expression of WNV E and prM antigens has been used in mice, horses, and birds (44). Vaccination of crows with Kunjin virus, a subtype of WNV, protected against WNV, and a DNA vector, which elicited expression of attenuated Kunjin virus, provided protective immunity against WNV in mice (46).