West Nile Virus

West Nile virus (WNV) is a single-stranded RNA virus that belongs to the family Flaviviridae, genus Flavivirus. This family includes several important human arthropod-borne pathogens, such as dengue (DENV), Zika (ZIKV), tick-borne encephalitis (TBEV), yellow fever (YFV) or Japanese encephalitis (JEV) virus. Structurally, it is an enveloped, spherical virus about 40-50 nm in diameter with a lipid bilayer membrane surrounding a capsid core. The genome codes for seven nonstructural proteins and three structural proteins: the envelope, membrane, and capsid proteins. Following a bite from WNV-infected mosquitoes, the virus reaches cells through the blood. It then multiplies in tissues and produces a low-level viremia, which decreases with the appearance of anti-WNV IgM antibodies. It subsequently infects organs (such as spleen, liver, kidney and CNS) and has also been detected in the urine of a patient 8 days after the onset of symptoms.

The virus has animals as its reservoir, particularly wild birds and mosquitoes, which also serve as the main means of transmission to humans. Most frequently responsible are mosquitoes of the genus Culex in particular (although the virus has been found in 65 other mosquito species and 326 bird species). In North America, although the WNV genome has been found in more than 58 mosquito species, Culex pipiens (the northern house mosquito), Culex quinquefasciatus (the southern house mosquito) and Culex tarsalis are the most important vectors; it has also been isolated from ticks in the Eastern Hemisphere, but their role in the transmission cycle is unclear. Almost all human WNV infections are due to bites from infected mosquitoes; however, other modes of transmission in humans have been noted. Transfusion-associated transmission of WNV was first identified in 2002, when 23 people in the United States were infected after receiving platelets, red blood cells, or plasma from 16 viremic blood donors.A similar case occurred in 2005, when the virus infected three of four organ recipients from a common donor with WNV infection. This donor was seropositive for WNV IgM antibodies but negative for WNV nucleic acid, suggesting that transmission may be possible in the absence of detectable serum viremia.Since that time, many other cases or clusters of WNV infection acquired through solid organ transplantation have been reported in the United States and Europe.Other rare circumstances of transmission have been identified. Intrauterine transmission has been documented in a case of a mother who was infected with WNV at about 27 weeks' gestation and subsequently delivered a baby with severe chorioretinitis and lissencephaly.

West Nile virus is globally distributed and retained by a complex transmission cycle involving multiple mosquito and bird species; with a wide distribution in Africa, the Middle East, parts of Europe and the former Soviet Union, South Asia, Australia, and, since 1999, North, Central and South America and the Caribbean. The first outbreak of WNV occurred in Israel in 1951, followed by outbreaks in 1952, 1953, 1957 with the first recorded case of severe neurological disease from WNV. Since its emergence in the Americas in 1999, the virus has caused more than 48,000 reports, 24,000 neuroinvasive cases, more than 2,300 deaths, and an estimated 7 million total human infections in the continental United States. The 2002 and 2003 seasons were the largest WNV neurological disease outbreaks recorded to date; the 2003 season represents the largest WNV outbreak to date. At present, WNV is considered one of the most important zoonotic diseases of concern to people in the United States and beyond. WNV remains a significant threat to humans in many parts of the world. Its potential to cause epidemics in endemic areas is alarming. Its ability to acquire mutations that lead to increased virulence, paired with its flexibility in using various mosquito species as vectors and birds as amplifying hosts make epidemics extremely unpredictable. Finally, global warming and the ever-increasing trafficking of humans, animals, and goods are additional factors favoring the further spread of WNV.

The incubation period from the time of the infected mosquito bite ranges from 2 to 14 days.
The disease is generally mild. Only 20 percent of infected patients may experience nonspecific symptoms such as fever, general malaise, cough, headache, eye pain, nausea, vomiting, and enlarged lymph nodes, but more severe cases with neurological complications such as encephalitis or meningitis are also possible, affecting mainly elderly or immunocompromised individuals.

Diagnosis from WNV infection is made through laboratory tests. This is sometimes challenging because of the continuous mutation of the virus from season to season, the low viral load at the onset of the disease, and the reactivity of the tests to other flaviviruses as well.
If the virus involves the CNS (Central Nervous System), diagnostic tests are performed on cerebrospinal fluid, taken by lumbar puncture.

Currently there is no definitive treatment for WNV infection. Supportive therapy is applied to treat symptoms and pain while monitoring some vital parameters. Patients with uncomplicated WNF generally do not require specific intervention, although headache control and rehydration may sometimes be necessary.
However, infected persons in whom other risk factors are also present, including advanced age and immunosuppression, should be observed to control progression to more severe neuroinvasive disease.
The antiviral agent ribavirin has demonstrated activity in vitro against WNV infection, but efficacy has not yet been demonstrated in animal models or in humans.

Given the absence of a definitive treatment for WNV infection, prevention remains the focus of human WNV management from a public health perspective. Prevention can take the form of community-based programs and personal protection. Public mosquito control programs to reduce vector populations are employed to varying degrees in various communities across North America and may involve removal of mosquito breeding sites, use of larvicide, and spraying for adult mosquitoes. Personal protective measures include limiting outdoor activities at dawn and dusk when mosquito activity is high, covering exposed skin with long sleeves and pants, and using insect repellents. The most effective repellents for use on the skin are products that contain diethyltoluamide (DEET), picaridin (KBR 3023), IR3535, or eucalyptus lemon oil. In general, higher concentrations of active ingredient provide a longer duration of protection, regardless of the active ingredient.Permethrin is an effective insecticide and repellent approved for use on clothing or textiles but not on skin.Although several candidate WNV vaccines are being evaluated, none is licensed or available for use in humans. It is unclear whether vaccination with related flavivirus vaccines (e.g., Japanese encephalitis or yellow fever) provides significant protection against WNV disease. Although it is likely that an effective WNV vaccine could be developed for humans, the cost-effectiveness and commercial feasibility of such a vaccine remain uncertain.