West Nile virus

West Nile virus is a virus of the family Flaviviridae, found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. The main route of human infection is through the bite of an infected mosquito.

Image reconstructions and cryoelectron microscopy reveal 50-nm virions covered with a relatively smooth protein surface. This structure is remarkably similar to the dengue fever virus. Both belong to the genus flavivirus within the family Flaviviridae.

Symptoms and Treatments

In most people (80%), infection causes no symptoms. In others, the virus causes mild flu-like symptoms known as West Nile fever. The virus is able to pass the blood-brain barrier, and the most serious effects (in 0.7% of the infected) are encephalitis (inflammation of the brain) and meningitis (inflammation of the lining of the brain and spinal cord), both of which can be fatal. Persons over 50 years of age are at higher risk of developing severe disease, the symptoms of which include fever, nausea, and changes in mental status. In rare cases (first reported October 2002), patients may develop temporary blindness which can last from one to four weeks. This will begin as partial blindness but the person's vision will rapidly deteriorate to total blindness. Very rarely meningismus (stiff neck) is reported.

Symptoms develop 3–15 days after infection. No effective treatment is known. The disease can be diagnosed by employing an ELISA test detecting IgM antibodies against the virus. Several related viruses also cause encephalitis and result in similar antibodies, but a final diagnosis can be made by further tests.

Transmission and susceptibility

The virus is mostly maintained in birds (in the Western hemisphere, particularly the American Robin and the American Crow). Female mosquitoes, mainly of the species Culex pipiens, Culex restuan, and Culex quinquefasciatus, bite infected birds, carry the virus in their salivary glands, and infect other birds when they bite again. Culex pipiens is thought to be the main mosquito species which transmits the virus from birds to mammals. In mammals the virus does not multiply as readily, and it is believed that mosquitoes biting infected mammals do not further transmit the virus. A 2004 paper in Science found that Culex pipiens mosquitoes existed in two populations in Europe, one which bites birds and one which bites humans. In North America 40% of Culex pipiens were found to be hybrids of the two types which bite both birds and humans, providing a vector for West Nile virus. This is thought to provide an explanation of why the West Nile disease has spread more quickly in North America than Europe.

It was initially believed that direct human-to-human transmission was impossible, but in 2002 the Centers for Disease Control and Prevention (CDC) discovered the transmission of West Nile virus through blood transfusion and organ transplants as well as through breast milk, prenatal infection, and occupational exposure. Blood banks in the US now routinely screen for the virus amongst their donors during the epidemic season. In Britain, as a precautionary measure, the National Blood Service runs a test for this disease in donors who donate within 28 days of a visit to the United States or Canada.

There is no vaccine for humans. A vaccine for horses based on killed viruses exists; some zoos have given this vaccine to their birds, although its effectiveness there is unknown.

A genetic factor appears to increase susceptibility to West Nile disease. A mutation of the gene CCR5 gives protection against the HIV virus but leads to more serious complications of WNV infection. Carriers of two mutated copies of CCR5 made up 4 to 4.5% of a sample of West Nile disease sufferers while the incidence of the gene in the general population is only 1%.

History

West Nile virus was first isolated from a feverish adult woman in the West Nile District of Uganda in 1937. The ecology was characterized in Egypt in the 1950s. The virus became recognized as a cause of severe human meningoencephalitis in elderly patients during an outbreak in Israel in 1957. The disease was first noted in horses in Egypt and France in the early 1960s.

The first appearance of West Nile virus in North America in 1999 with encephalitis reported in humans and horses, and the subsequent spread in the United States may be an important milestone in the evolving history of this virus. The US outbreak began in the New York City area, and the virus is believed to have entered in an infected bird or mosquito. Since the first North American cases in 1999, the virus has been reported throughout the United States, Canada and Mexico. There have been human cases and horse cases, and many birds — especially crows and other corvids — are infected. Corvids die of the disease more often than other species of birds so the presence of dead crows is an early indicator of the arrival of the virus.

A very high level of media coverage through 2001/2002 raised public fears of West Nile virus, even though common diseases such as influenza take far more lives each year. This disproportionate coverage is most likely the result of the novelty of the disease and the successive announcements of the disease's initial appearance in new areas.

Environmentalists have condemned attempts to control the transmitting mosquitoes by spraying pesticide, saying that the detrimental health effects of spraying outweigh the relatively few lives which may be saved, and that there are more environmentally friendly ways of controlling mosquitoes. There are also questions about the effectiveness of insecticide spraying because mosquitoes that are resting or flying above the level of spraying will not be killed; the most common vector in the northeastern U.S., Culex pipiens, is a canopy feeder.

Overwintering Mechanism

Vertical transmission of West Nile Virus from female Culex pipiens mosquitoes to their progeny has been demonstrated in the laboratory. It has been suggested that vertically infected Culex could survive the winter to initiate a WNV amplification cycle the following spring. Culex mosquitoes spend the winter hibernating in protected structures such as root cellars, bank barns, caves, abandoned tunnels and other subterranean locations. The first overwintering adult mosquitoes to test positive for WNV were collected in New York, 2000. Since then positive samples have been identified in New Jersey, 2003 and in Pennsylvania, 2003, 2004 and 2005.

Geographic distribution

West Nile virus has been described in Africa, Europe, the Middle East, west and central Asia, Oceania (subtype Kunjin), and most recently, North America.

Recent 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 2003), Canada (1999–2003), and Israel (2000).

Epizootics of disease in horses occurred in Morocco (1996), Italy (1998), the United States (1999 to 2001), and France (2000). In 2003, West Nile virus spread among horses in Mexico.

In the US in 2002, West Nile virus was documented in animals in 44 states and the District of Columbia with Illinois, Louisiana, Michigan, and Ohio reporting the most deaths. By 2003, 45 states and D.C. had reported human cases.

Recent outbreaks

United States: From 1999 through 2001, the CDC confirmed 149 cases of human West Nile virus infection, including 18 deaths. In 2002, a total of 4,156 cases were reported, including 284 fatalities. 13 cases in 2002 were contracted through blood transfusion. The cost of West Nile-related health care in 2002 was estimated at $200 million. The first human West Nile disease in 2003 occurred in June and one West Nile-infected blood transfusion was also identified that month. In the 2003 outbreak, 9,862 cases and 264 deaths were reported by the CDC. At least 30% of those cases were considered severe involving meningitis or encephalitis. In 2004, there were only 2,539 reported cases and 100 deaths. In 2005, there was a slight increase in the number of cases, with 3,000 cases and 119 deaths reported.

Canada: One human death occurred in 1999. In 2002, ten human deaths out of 416 confirmed and probable cases were reported by Canadian health officials. In 2003, 14 deaths and 1,388 confirmed and probable cases were reported. Cases were reported in 2003 in Nova Scotia, Quebec, Ontario, Manitoba, Saskatchewan, Alberta, British Columbia, and the Yukon. In 2004, only 25 cases were reported and two deaths; however, 2005 saw 239 cases and 12 deaths.

Israel: In 2000, the CDC found that there were 417 confirmed cases with 326 hospitalizations. 33 of these people died. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%).

Romania: In 1996-1997 about 500 cases occurred in Romania with a fatality rate of nearly 10%.

Surveillance methods

West Nile virus can be sampled from the environment by the pooling of trapped mosquitoes, testing avian blood samples drawn from wild birds and sentinel chickens, as well as testing dead birds found by various animal control agencies and the public. Testing of the mosquito samples requires the use of RT-PCR to directly amplify and show the presence of virus in the submitted samples. When using the blood sera of wild bird and sentinel chickens, samples must be tested for the presence of West Nile virus antibodies by use of immunohistochemistry (IHC) or Enzyme-Linked Immunosorbent Assay (ELISA).

Dead birds, after necropsy, have their various tissues tested for virus by neither RT-PCR or immunohistochemistry, where virus shows up as brown stained tissue because of a substrate-enzyme reaction.

Control

West Nile control is achieved through mosquito control, by elimination of mosquito breeding sites, larviciding active breeding areas and encouraging personal use of mosquito repellants. The public is also encouraged to spend less time outdoors, wear long covering clothing and ensure that mosquitos cannot enter buildings.

Experimental treatment

Morpholino antisense oligos have shown activity against West Nile virus in experimental systems and are currently (2005) in US clinical trials as a WNV treatment.

References

External links

CDC pages
US map of West Nile virus
Canadian Case Surveillance
L. Peterson, M. Marphin. "West Nile virus: A Primer for the Clinician", Annals of Internal Medicine, Vol. 137 No. 3, August 2002.
D. J. White, D. L. Morse (eds.). "West Nile virus: Detection, Surveillance, and Control", Annals of the New York Academy of Sciences, Vol. 951, 2001.
Nature news article on West Nile paralysis
CBC News Coverage of West Nile in Canada
West Nile Fever in Europe
Encephalitis Global, Inc.
Harvard University fact sheet on West Nile Virus

Flaviviruses | Infectious diseases | Zoonoses | Tropical disease | Eponymous diseases

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