West Nile Virus: A Review.

Importance: West Nile virus (WNV), a neurotropic flavivirus spread by Culex species mosquitoes, is the leading cause of mosquito-borne disease in the contiguous US. From 2014 to 2023, a mean of 1298 WNV neuroinvasive disease cases and 129 deaths were reported annually in the US.

Observations: Almost all WNV infection occurs via mosquito bites, but transmission can rarely occur via blood transfusion, organ transplantation, and transplacental, perinatal, breastmilk, percutaneous, and conjunctival exposure. Since 2018, large WNV outbreaks have been reported in Europe, Tunisia, Israel, and the US. In 2021, the largest county-level US outbreak occurred in Arizona, with 1487 disease cases and 101 deaths reported. Based on seroprevalence surveys, approximately 80% of human WNV infections are asymptomatic, 20% cause a febrile illness (West Nile fever), and less than 1% cause neuroinvasive disease (eg, meningitis, encephalitis, acute flaccid myelitis). Mortality of patients with neuroinvasive disease is approximately 10% overall but is 20% in individuals 70 years or older and 30% to 40% in patients with hematologic malignancies, solid organ transplants, and those receiving B-cell-depleting monoclonal antibodies. Among patients hospitalized for WNV disease, 30% to 40% are discharged to long-term care facilities, and more than 50% have long-term sequelae such as fatigue, weakness, myalgia, memory loss, and depression. WNV transmission during solid organ transplantation was identified in 14 clusters in the US and Italy from 2002 to 2023. Since WNV screening of the US blood supply began in 2003, 14 cases of WNV transmission through blood transfusion have been reported. For patients with fever or neurologic symptoms during summer and fall months, WNV should be considered; IgM testing of serum and/or cerebrospinal fluid is recommended, followed by confirmatory neutralizing antibody testing in cases of possible exposure to cross-reacting flaviviruses, atypical presentation or death, or suspected unusual transmission modes such as organ transplantation. Reverse transcription-polymerase chain reaction testing is often more sensitive than IgM testing in patients with severe immunocompromise. There are no evidence-based therapies or human vaccines for WNV disease. Preventive methods include personal protective behaviors, such as using Environmental Protection Agency-registered mosquito repellents, wearing protective clothing, and limiting outdoor exposure from dusk to dawn, and community mosquito control measures.

Conclusions and relevance: WNV causes more than 1200 neuroinvasive disease cases and 120 deaths annually in the US. People who are older or immunocompromised are at higher risk of severe disease and death. Since there are no therapies or human vaccines, prevention relies on personal protective measures, WNV surveillance, and mosquito control interventions.