Review
West Nile virus

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Summary

West Nile (WN) virus is a mosquito-borne flavivirus and human, equine, and avian neuropathogen. The virus is indigenous to Africa, Asia, Europe, and Australia, and has recently caused large epidemics in Romania, Russia, and Israel. Birds are the natural reservoir (amplifying) hosts, and WN virus is maintained in nature in a mosquito-bird-mosquito transmission cycle primarily involving Culex sp mosquitoes. WN virus was recently introduced to North America, where it was first detected in 1999 during an epidemic of meningoencephalitis in New York City. During 1999–2002, the virus extended its range throughout much of the eastern parts of the USA, and its range within the western hemisphere is expected to continue to expand. During 1999–2001, 142 cases of neuroinvasive WN viral disease of the central nervous system (including 18 fatalities), and seven cases of uncomplicated WN fever were reported in the USA. Most human WN viral infections are subclinical but clinical infections can range in severity from uncomplicated WN fever to fatal meningoencephalitis; the incidence of severe neuroinvasive disease and death increase with age. Serology remains the mainstay of laboratory diagnosis. No WN virus-specific treatment or vaccine is available. Prevention depends on organised, sustained vector mosquito control, and public education.

Section snippets

Causative agent

WN virus is taxonomically placed within the family Flaviviridae, genus Flavivirus. Within the genus Flavivirus, WN virus has been serologically classified within the JE virus antigenic complex, which includes the human pathogens JE, Murray Valley encephalitis, SLE, and Kunjin viruses. The spherical WN virus particle is approximately 50 nm in diameter and consists of a host-derived lipid bilayer membrane surrounding a nucleocapsid core containing a single-stranded positive-sense RNA genome of

Geographical distribution and epidemiology

WN virus sensu lato is indigenous to Africa, Asia, Europe, and Australia,22, 23 and was recently introduced to North America (figure 2), where it was first detected in New York City.1 The likely origin of the introduced strain was the Middle East,24 but the mode of introduction is unknown. During 1999–2002, WN virus extended its range throughout much of the eastern parts of the USA, and has now been detected from Maine to the Florida Keys, and from the Atlantic coast to eastern North Dakota

Transmission cycle and host range

WN virus is maintained in nature in a mosquito-bird-mosquito transmission cycle primarily involving Culex sp mosquitoes (figure 6).22, 39 The virus, however, has been isolated from 29 mosquito species belonging to ten genera in the USA alone (unpublished data).4, 36, 40 The vector status and epidemiological importance of many of these species are unknown. Although Culex pipiens (the northern house mosquito), a highly ornithophilic species that is often abundant in urban areas, was a major

Clinical features

Most WN viral infections are symptomless.7, 27 The incubation period is approximately 2–14 days for symptomatic infections overall, but 2–6 days is typical in WN fever cases.53, 54 The associated clinical syndromes are non-specific and a diagnosis cannot reliably be made on clinical grounds alone.

Uncomplicated WN fever typically begins with sudden onset of fever (usually >39°C), headache, and myalgia, often accompanied by gastrointestinal symptoms. The acute illness usually lasts less than a

Pathogenesis and pathology

The exact mechanisms and sites of WN virus replication following the bite of an infected mosquito are unknown but initial replication is thought to occur in the skin and regional lymph nodes and to produce a primary viraemia that seeds the reticuloendothelial system (RES).20 Depending on the level of secondary viraemia that results from replication in the RES, virus may then seed the CNS. In healthy infected persons, virus can generally be isolated from blood during peak viraemia that occurs

Laboratory diagnosis

Serology continues to have a dominant role in the laboratory diagnosis of WN viral infections (and most other arboviral infections) in human beings.77 The development of WN virus-specific neutralising antibody between the acute and convalescent phases of illness (as shown by a >four-fold rise in titre, typically by plaque-reduction neutralisation assay) remains the most convincing serological evidence of infection, and is associated with long-term immunity. A battery of other flaviviruses

Clinical management

Although the treatment of uncomplicated WN viral infections is symptomatic, all patients with suspected WN meningoencephalitis should be hospitalised for observation and supportive care, and to rule-out treatable CNS infections or conditions (eg, herpesvirus infection, Guillain-Barrè syndrome, and bacterial meningoencephalitis). The most frequent cause of death in WN encephalitis cases is neuronal dysfunction, respiratory failure, and cerebral oedema (following neuronal injury and death). No

Prevention

No human vaccine for WN virus is available, although several laboratories are currently conducting vaccine research. Given the low incidence of WN viral disease in human beings in most areas, however, it is unlikely that such a vaccine would be cost-effective for public health use. Both inactivated and DNA-based vaccines have been developed for use in equines,87 but their efficacy has yet to be demonstrated.

Effective prevention of human WN viral infections depends on the development of locally

Predicting the future

WN virus will almost certainly continue to spread into the contiguous western parts of the USA over the next several years, primarily via the movement of viraemic birds. Similarly, it is likely that this virus will be introduced into Central and South America and the Caribbean, if this has not already occurred. After many years or even decades, WN virus in the western hemisphere will likely achieve an ecological/epidemiological equilibrium resembling that of SLE virus. In the USA, this would

Search strategy and selection criteria

Sources for this review were identified by searches of Medline, and citations from relevant articles and book chapters. Medline search terms were “arthropod-borne virus”, “arbovirus”, “flavivirus”, and “West Nile virus”. English and French language papers were reviewed. Unpublished data from the national arbovirus surveillance system (ArboNET) of the CDC were also used.

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  • Cited by (765)

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    In this review, the term “meningoencephalitis” is used to encompass encephalitis, meningitis, myelitis, and cases with overlapping features of these syndromes. Although some authors use “WN fever” to describe any illness caused by WN viral infection, including neuroinvasive illness, in this review “WN fever” refers only to the uncomplicated febrile illness.

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