West Nile virus

Douglas J Lanska MD FAAN MS MSPH (

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.

Originally released November 25, 2002; last updated December 18, 2018; expires December 18, 2021

This article includes discussion of West Nile virus and WNV. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


The author explains the clinical presentation, pathophysiology, prevention, diagnostic work-up, and management of West Nile virus infection.

Key points


• Most people who have been bitten by West Nile virus-infected mosquitoes have no symptoms or only mild ones.


• Approximately 20% to 30% of infected individuals develop a mild illness resembling the flu. Mild illness is referred to as West Nile fever. Symptoms of mild illness can include sudden onset of fever with malaise, anorexia, nausea, vomiting, diarrhea, headache, photophobia, neck pain and stiffness, myalgias, maculopapular rash, and lymphadenopathy.


• Only 1 person out of every 150 to 250 infected individuals develops severe disease. Severe neurologic illness may include encephalitis, meningoencephalitis, or poliomyelitis. Symptoms of severe disease can include high fever; nuchal rigidity; confusion, disorientation, obtundation, and memory loss; severe muscle weakness; or paralysis, tremors, and seizures.


• Cases of poliomyelitis in patients with West Nile virus infection have been identified since July 2002. In most cases, limb weakness is associated with signs and symptoms of encephalitis or meningitis. Cases were typically admitted with a 1- to 4-day history of symptoms, including fever, chills, vomiting, headache, fatigue, lethargy, confusion, myalgias, and facial and acute asymmetric painless limb weakness. Physical examination demonstrated asymmetric hyporeflexic or areflexic weakness of various extremities, generally with intact sensation. Several patients developed acute respiratory distress requiring ventilatory support.


• West Nile virus is a flavivirus belonging to the Japanese encephalitis subgroup. This subgroup also includes the serologically closely related St. Louis encephalitis virus. Flaviviruses are small single-stranded RNA viruses, with a spherical envelope between 40 and 50 nm.


• West Nile virus is usually transmitted by Culex mosquitoes from infected birds.


• West Nile virus (as with other arboviruses) is typically inoculated by mosquitoes directly into the bloodstream or subcutaneous tissue. Initial West Nile virus replication occurs in the skin and regional limb nodes, followed by a primary viremia that seeds the reticuloendothelial system, and then a secondary viremia following replication in the reticuloendothelial system. Depending on a number of host factors, including the integrity of the blood-brain barrier, the central nervous system may be seeded during the secondary viremia.


• Penetration of West Nile virus into the central nervous system depends heavily on the degree and persistence of viremia but is also facilitated by altered blood-brain barrier permeability (eg, from hypercarbia, hyperosmotic agents, and mechanical disruption).


• About half of people who develop West Nile virus encephalitis or meningitis have persistent symptoms at 6 months, and only about one third are fully recovered after 12 months.


• Other than mosquito-borne transmission, mechanisms of documented transmission of West Nile virus include blood transfusion, organ transplantation, breast-feeding, transplacental, dialysis-related, and occupational (eg, laboratory workers infected by percutaneous inoculation and possibly through aerosol exposure).


• West Nile virus or another arbovirus (eg, St. Louis encephalitis virus) should be strongly considered in patients with unexplained encephalitis or meningitis in late summer or early fall.


Serologic testing for West Nile virus can be problematic because samples obtained within 8 days of infection may be falsely negative due to crossreactivity between West Nile virus and other flaviviruses and because of persistence of IgM antibodies. Also, West Nile virus IgM antibodies can persist for more than a year after initial infection, potentially producing confusion over whether the antibodies are a marker of current or previous infection.


• Although no specific treatment is approved for West Nile virus infection, intensive supportive care is sometimes needed, including hospitalization and ventilator support.

Historical note and terminology

West Nile virus was first isolated in 1937 in a febrile woman from the West Nile district of Uganda (Hayes 2001; Lanska 2005). The virus was recognized as an arbovirus after it was isolated from mosquitoes, birds, and humans. In the 1950s outbreaks of the disease occurred in the Middle East, with identification of a nonfatal encephalitic form (Lanska 2005). The first major urban outbreaks occurred in Romania in 1996, where there were 17 deaths among 800 cases (Ceausu et al 1997; Cernescu et al 1997; Tsai et al 1998; Han et al 1999; Lanska 2005), and in Russia in 1999, where there were 40 deaths among more than 800 cases (Platonov et al 2001; Lanska 2005).

By the 1990s West Nile virus was recognized in Africa, Europe, the Middle East, and Asia, but it was not identified in the Western Hemisphere until it was identified in the United States in 1999 (Lanska 2005). In 1999 an outbreak was identified in New York City, with 7 deaths among 62 human cases (Centers for Disease Control and Prevention 1999a; Centers for Disease Control and Prevention 1999b; Shieh et al 2000; Fine and Layton 2001; Mostashari et al 2001; Nash et al 2001; Hayes et al 2005a; Lanska 2005). The epidemic coincided with the deaths from West Nile virus of several thousand crows, as well as the deaths of exotic birds at the Bronx and Queens zoos (Eidson et al 2001a; Eidson et al 2001b; Eidson et al 2001c). The viral genome in the 1999 New York City outbreak was almost identical to that of a West Nile virus strain identified in Israel in 1998, suggesting that it originated in the Middle East (Lanciotti et al 1999; Giladi et al 2001). The virus was found to overwinter in mosquitoes (Centers for Disease Control and Prevention 2000b; Kulasekera et al 2001).

Since 1999, the virus spread along the East Coast and then progressively westward to include almost the entire continental United States by the end of 2002 (Craven and Roehrig 2001; Marfin et al 2001; Tyler 2001; Weiss et al 2001; Centers for Disease Control and Prevention 2002a; Johnson 2002a; Petersen et al 2003; Petersen and Hayes 2004; Hayes et al 2005a). The 2002 and 2003 West Nile virus epidemics in the United States were the largest arboviral meningoencephalitis epidemics ever documented in the western hemisphere and the largest West Nile virus meningoencephalitis epidemics ever recorded (O Leary et al 2004; Hayes et al 2005b). In the first 5 years after its introduction in the United States, West Nile virus spread to the 48 contiguous states and caused 667 reported deaths (Hadler et al 2014). Through 2013, there were approximately 39,500 confirmed and probable cases of symptomatic West Nile virus-related disease in the United States reported to the Centers for Disease Control and Prevention, including 17,319 cases (44%) with neuroinvasive disease and 1663 deaths. About 9% of neuroinvasive disease cases are fatal compared to 0.5% of non-neuroinvasive cases (Lindsey et al 2010). It is likely that substantially more than 1 million people have been infected by the West Nile virus in the United States (Busch et al 2006; Davis et al 2006); however, because many infected people do not develop serious symptoms and because surveillance systems are still developing, the true cumulative incidence is unknown. These epidemics have had tremendous economic impact across the country (Zohrabian et al 2004).

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