West Nile fever

West Nile fever is an infection by the West Nile virus, which is typically spread by mosquitoes.^[1] In about 80% of infections people have few or no symptoms.^[2] About 20% of people develop a fever, headache, vomiting, or a rash.^[1] In less than 1% of people, encephalitis or meningitis occurs, with associated neck stiffness, confusion, or seizures.^[1] Recovery may take weeks to months.^[1] The risk of death among those in whom the nervous system is affected is about 10 percent.^[1]

West Nile virus (WNV) is usually spread by mosquitoes that become infected when they feed on infected birds, which

The virus was discovered in Uganda in 1937, and was first detected in North America in 1999.^[1][3] WNV has occurred in Europe, Africa, Asia, Australia, and North America.^[1] In the United States thousands of cases are reported a year, with most occurring in August and September.^[4] It can occur in outbreaks of disease.^[3] Severe disease may also occur in horses, for which a vaccine is available.^[3] A surveillance system in birds is useful for early detection of a potential human outbreak.^[3]

Signs and symptoms

About 80% of those infected with

• West Nile fever (WNF), which occurs in 20 percent of cases, is a
  vomiting, loss of appetite, and diarrhea. Fewer than one-third of patients develop a rash
  .
• West Nile
  poliomyelitis-like syndrome.^[9] Many patients with WNND have normal neuroimaging studies, although abnormalities may be present in various cerebral areas including the basal ganglia, thalamus, cerebellum, and brainstem.^[9]
• West Nile virus encephalitis (WNE) is the most common neuroinvasive manifestation of WNND. WNE presents with similar symptoms to other viral encephalitis with fever, headaches, and altered mental status. A prominent finding in WNE is
  sensory abnormalities.^[10][11]
• West Nile meningitis (WNM) usually involves fever, headache, stiff neck and pleocytosis, an increase of white blood cells in cerebrospinal fluid. Changes in consciousness are not usually seen and are mild when present.
• West Nile meningoencephalitis is inflammation of both the brain (encephalitis) and meninges (meningitis).
• West Nile poliomyelitis (WNP), an
  acute flaccid paralysis
  syndrome associated with WNV infection, is less common than WNM or WNE. This syndrome is generally characterized by the acute onset of asymmetric limb weakness or paralysis in the absence of sensory loss. Pain sometimes precedes the paralysis. The paralysis can occur in the absence of fever, headache, or other common symptoms associated with WNV infection. Involvement of respiratory muscles, leading to acute respiratory failure, sometimes occurs.
• West-Nile reversible paralysis, Like WNP, the weakness or paralysis is asymmetric.^[12] Reported cases have been noted to have an initial preservation of deep tendon reflexes, which is not expected for a pure anterior horn involvement.^[12] Disconnect of upper motor neuron influences on the anterior horn cells possibly by myelitis or glutamate excitotoxicity have been suggested as mechanisms.^[12] The prognosis for recovery is excellent.
• Nonneurologic complications of WNV infection that may rarely occur include fulminant
  hemorrhagic fever with coagulopathy.^[17] Chorioretinitis may also be more common than previously thought.^[18]
• Skin manifestations, specifically rashes, are common; however, there are few detailed descriptions in case reports, and few images are available. Punctate erythematous, macular, and papular eruptions, most pronounced on the extremities have been observed in WNV cases and in some cases histopathologic findings have shown a sparse superficial perivascular lymphocytic infiltrate, a manifestation commonly seen in viral exanthems. A literature review provides support that this punctate rash is a common cutaneous presentation of WNV infection.^[19]

Cause

Virology

WNV is one of the Japanese encephalitis antigenic serocomplex of viruses.^[20] Image reconstructions and

West Nile virus has been seen to replicate faster and spread more easily to birds at higher temperatures; one of several ways climate change could affect the epidemiology of this disease.[22]

Transmission

The prime method of spread of the West Nile virus (WNV) is the female mosquito. In Europe, cats were identified as being hosts for West Nile virus.^[23] The important mosquito vectors vary according to area; in the United States, Culex pipiens (Eastern United States, and urban and residential areas of the United States north of 36–39°N), Culex tarsalis (Midwest and West), and Culex quinquefasciatus (Southeast) are the main vector species.^[24]

The mosquito species that are most frequently infected with WNV feed primarily on birds.^[25] Different species of mosquitos take a blood meal from different types of vertebrate hosts, Mosquitoes show further selectivity, exhibiting preference for different species of birds. In the United States, WNV mosquito vectors feed preferentially on members of the Corvidae and thrush family. Among the preferred species within these families are the American crow, a corvid, and the American robin (Turdus migratorius).^[26]

Some species of birds develop sufficient viral levels (>~10^4.2 log PFU/ml;^[27]) after being infected to transmit the infection to biting mosquitoes that in turn go on to infect other birds. In birds that die from WNV, death usually occurs after 4 to 6 days.^[28] In mammals and several species of birds, the virus does not multiply as readily and so does not develop high viremia during infection. Mosquitoes biting such hosts are not believed to ingest sufficient virus to become infected, making them so-called dead-end hosts.^[27] As a result of the differential infectiousness of hosts, the feeding patterns of mosquitoes play an important role in WNV transmission,^[25][26] and they are partly genetically controlled, even within a species.^[29]

Direct human-to-human transmission initially was believed to be caused only by occupational exposure, such as in a laboratory setting,

A genetic factor also appears to increase susceptibility to West Nile disease. A mutation of the gene CCR5 gives some protection against HIV but leads to more serious complications of WNV infection. Carriers of two mutated copies of CCR5 made up 4.0 to 4.5% of a sample of people with West Nile disease, while the incidence of the gene in the general population is only 1.0%.^[52][53]

The most at risk occupations in the U.S. are outdoor workers, for example farmers, loggers, landscapers/groundskeepers, construction workers, painters, summer camp workers and pavers.^[54] Two reports of accidental exposure by laboratory personnel working with infected fluids or tissues have been received. While this appears to be a rare occurrence, it highlights the need for proper handling of infected materials. The World Health Organization states that there are no known cases of health care workers acquiring the virus from infected patients when the appropriate infection control precautions are observed.^[55]

Diagnosis

Definitive diagnosis of WNV is obtained through detection of virus-specific antibody IgM and neutralizing antibodies. Cases of West Nile virus meningitis and encephalitis that have been serologically confirmed produce similar degrees of CSF pleocytosis and are often associated with substantial CSF neutrophilia.^[58] Specimens collected within eight days following onset of illness may not test positive for West Nile IgM, and testing should be repeated. A positive test for West Nile IgG in the absence of a positive West Nile IgM is indicative of a previous flavivirus infection and is not by itself evidence of an acute West Nile virus infection.^[59]

If cases of suspected West Nile virus infection, sera should be collected on both the acute and convalescent phases of the illness. Convalescent specimens should be collected 2–3 weeks after acute specimens.

It is common in serologic testing for cross-reactions to occur among flaviviruses such as dengue virus (DENV) and tick-borne encephalitis virus; this necessitates caution when evaluating serologic results of flaviviral infections.^[60]

Four FDA-cleared WNV IgM ELISA kits are commercially available from different manufacturers in the U.S., each of these kits is indicated for use on serum to aid in the presumptive laboratory diagnosis of WNV infection in patients with clinical symptoms of meningitis or encephalitis. Positive WNV test results obtained via use of these kits should be confirmed by additional testing at a state health department laboratory or CDC.^[61]

In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of autopsy tissues can also be useful. Only a few state laboratories or other specialized laboratories, including those at CDC, are capable of doing this specialized testing.^[62]

Differential diagnosis

A number of various diseases may present with symptoms similar to those caused by a clinical West Nile virus infection. Those causing neuroinvasive disease symptoms include the

Many of the guidelines for preventing occupational West Nile virus exposure are common to all mosquito-borne diseases.^[63]

Public health measures include taking steps to reduce mosquito populations. Personal recommendations are to reduce the likelihood of being bitten. General measures to avoid bites include:

• Using insect repellent on exposed skin to repel mosquitoes. Repellents include products containing
  mosquito netting
  with an elastic edge for a tight fit.
• When using sunscreen, apply sunscreen first and then repellent. Repellent should be washed off at the end of the day before going to bed.^[66]
• Wear long-sleeve shirts, which should be tucked in, long trousers, socks, and hats to cover exposed skin (although most fabrics do not totally protect against bites). Insect repellents should be applied over top of protective clothing for greater protection. Do not apply insect repellents underneath clothing.^[67]
• Repellents containing permethrin (e.g., Permanone) or other insect repellents may be applied to clothing, shoes, tents, mosquito nets, and other gear. (Permethrin is not suitable for use directly on skin.) Most repellent is generally removed from clothing and gear by a single washing, but permethrin-treated clothing is effective for up to five washings.^[57]
• Most mosquitoes that transmit disease are most active at dawn and in the evening dusk. A notable exception is the
  Asian tiger mosquito, which is a daytime feeder and is more apt to be found in, or on the periphery of, shaded areas with heavy vegetation. They are now widespread in the United States, and in Florida they have been found in all 67 counties.^[68]
• In an at-risk area, staying in air-conditioned or well-screened room, or sleeping under an insecticide-treated bed net is recommended. Bed nets should be tucked under mattresses, and can be sprayed with a repellent if not already treated with an insecticide.^[63]

Monitoring and control

West Nile virus can be sampled from the environment by the pooling of trapped mosquitoes via

• 
  A carbon dioxide-baited CDC light trap at NPSmonitoring site: The highest individual light trap total for 2010 was from a trap located in a salt marsh in the Fire Island National Seashore: around 25,142 mosquitoes were collected during a 16-hour period on August 31.^[73]
• 
  being laid.^[74]
• 
  Used

  stagnant water and are a breeding ground for many species of mosquitoes. Some species such as the Asian tiger mosquito prefer manmade containers, such as tires, in which to lay their eggs. The rapid spread of this aggressive daytime feeding species beyond their native range has been attributed to the used tire trade.^[68][75]

WNV was first isolated from a feverish 37-year-old woman at Omogo in the

Outbreaks of West Nile virus encephalitis in humans have occurred in Algeria (1994), Romania (1996 to 1997), the Czech Republic (1997), Congo (1998), Russia (1999), the United States (1999 to 2009), Canada (1999–2007), Israel (2000) and Greece (2010).^[90]

Epizootics of disease in horses occurred in Morocco (1996), Italy (1998), the United States (1999 to 2001), and France (2000), Mexico (2003) and Sardinia (2011).^{[citation needed]}

Outdoor workers (including biological fieldworkers, construction workers, farmers, landscapers, and painters), healthcare personnel, and laboratory personnel who perform necropsies on animals are at risk of contracting WNV.^[91]

In 2012, the US experienced one of its worst epidemics in which 286 people died, with the state of Texas being hard hit by this virus.^[92][93]

Weather

Drought has been associated with a higher number of West Nile virus cases in the following year.^[94] As drought can decrease fish and other populations that eat mosquito eggs, higher numbers of mosquitoes can result.^[94] Higher temperatures are linked to decreased time for replication and increased viral load in birds and mosquitoes.^[22]

Research

A vaccine for horses (

As of 2019, six vaccines had progressed to human trials but none had been licensed in the United States. Only the two live attenuated vaccines produced strong immunity after a single dose.[99]

References

External links

Wikimedia Commons has media related to West Nile virus.

• De Filette M, Ulbert S, Diamond M, Sanders NN (2012). "Recent progress in West Nile virus diagnosis and vaccination". Vet. Res. 43 (1): 16.
  PMID 22380523
  .
• "West Nile Virus". Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention (CDC). 2018-10-30.
• CDC—West Nile Virus—NIOSH Workplace Safety and Health Topic
• West Nile Virus Resource Guide—National Pesticide Information Center
• Virus Pathogen Database and Analysis Resource (ViPR): Flaviviridae
• Species Profile – West Nile Virus (Flavivirus), National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for West Nile Virus.