West Nile virus (or WNV) is a virus of the family Flaviviridae; part of the Japanese encephalitis (JE) antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, 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 a 45–50 nm virion covered with a relatively smooth protein surface. This structure is similar to the dengue fever virus; both belong to the genus Flavivirus within the family Flaviviridae. The genetic material of WNV is a positive-sense, single strand of RNA, which is between 11,000 and 12,000 nucleotides long; these genes encode seven non-structural proteins and three structural proteins. The RNA strand is held within a nucleocapsid formed from 12 kDa protein blocks; the capsid is contained within a host-derived membrane altered by two viral glycoproteins.
W.N.V. has three different effects on humans. The first is an asymptomatic infection; the second is a mild febrile syndrome termed West Nile Fever; the third is a neuroinvasive disease termed West Nile meningitis or encephalitis. In infected individuals the ratio between the three states is roughly 110:30:1.
The second, febrile stage has an incubation period of 2 to 8 days followed by fever, headache, chills, diaphoresis (excessive sweating), weakness, lymphadenopathy (swollen lymph nodes), drowsiness, pain in the joints and symptoms like those of the common cold. Occasionally there is a short-lived truncal rash and some patients experience gastrointestinal symptoms including nausea, vomiting, loss of appetite, or diarrhea. All symptoms are resolved within 7 to 10 days, although fatigue can last for some weeks and lymphadenopathy can take up to two months to resolve.
The more dangerous encephalitis is characterized by similar early symptoms but also a decreased level of consciousness, sometimes approaching near-coma. Deep tendon reflexes are hyperactive at first, later diminished. There are also extrapyramidal disorders. Recovery is marked by a long convalescence with fatigue.
More recent outbreaks have resulted in a deeper study of the disease and other, rarer, outcomes have been identified. The spinal cord may be infected, marked by anterior myelitis with or without encephalitis. WNV-associated Guillain-Barré syndrome has been identified and other rare effects include multifocal chorioretinitis (which has 100% specificity for identifying WNV infection in patients with possible WNV encephalitis), hepatitis, myocarditis, nephritis, pancreatitis, and splenomegaly.
The virus is transmitted through mosquito vectors, which bite and infect birds. The birds are amplifying hosts, developing sufficient viral levels to transmit the infection to other biting mosquitoes which go on to infect other birds (in the Western hemisphere the American robin and the American crow are the most common carriers) and also humans. The infected mosquito species vary according to geographical area; in the US Culex pipiens (Eastern US), Culex tarsalis (Midwest and West), and Culex quinquefasciatus (Southeast) are the main sources.
In mammals the virus does not multiply as readily (i.e. does not develop high viremia during infection), and it is believed that mosquitoes biting infected mammals do not ingest sufficient virus to become infected, making mammals so-called dead-end infections.
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.
The more severe outcomes of WNV infection are clearly associated with advancing age and a patient history of organ transplantation and diabetes. 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 to 4.5% of a sample of West Nile disease sufferers while the incidence of the gene in the general population is only 1%.
Recently, the potential for mosquito saliva to impact the course of WNV disease was demonstrated. Mosquitoes inoculate their saliva into the skin while obtaining blood. Mosquito saliva is a pharmacologic cocktail of secreted molecules, principally proteins, that can affect vascular constriction, blood coagulation, platelet aggregation, inflammation, and immunity. It has become clear that mosquito saliva alters the immune response in a manner that may be advantageous to a virus. Studies have shown that it can specifically modulate the immune response during early virus infection, and mosquito feeding can exacerbate WNV infection leading to higher viremia and more severe forms of disease. It is unknown what benefit, if any, the mosquito receives by assisting the virus in this manner, so it is likely that the virus is simply capitalizing on preexisting qualities of mosquito saliva developed for other purposes.
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. Dogs and cats show few if any signs of infection. There have been no cases of direct canine-human or feline-human transmission; although these pets can become infected, it is unlikely that they are in turn capable of infecting native mosquitoes and thusly continuing the disease cycle.
Avoiding mosquito bites is the most straightforward means to avoid infection—remaining indoors (while preventing mosquitoes from entering) at dawn and dusk, wear light-colored clothing that covers arms and legs as well as trunk, use insect repellents on both skin and clothing (such as DEET, picaradin, or oil of lemon eucalyptus for skin and permethrin for clothes). If one becomes infected, generally, treatment is purely supportive: analgesia for the pain of neurologic diseases; rehydration for nausea, vomiting, or diarrhea; encephalitis may also require airway protection and seizure management.
Reported cases in the U.S. in 2005 exceeded those in 2004 and cases in 2006 exceeded 2005's totals. On August 19, 2006, the LA Times reported that the expected incidence rate of West Nile was dropping as the local population becomes exposed to the virus. "In countries like Egypt and Uganda, where West Nile was first detected, people became fully immune to the virus by the time they reached adulthood", federal health officials said. However, just days later, the CDC said that West Nile cases could reach a three-year high because hot temperatures had allowed a larger brood of mosquitoes.
WNV was first isolated from a feverish adult woman in the West Nile District of Uganda in 1937 during research on yellow fever. A series of serosurveys in 1939 in central Africa found anti-WNV positive results ranging from 1.4% (Congo) to 46.4% (White Nile region, Sudan). It was subsequently identified in Egypt (1942) and India (1953), a 1950 serosurvey in Egypt found 90% of those over 40 years in age had WNV antibodies. The ecology was characterized in 1953 with studies in Egypt and Israel. 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 and found to be widespread in southern Europe, southwest Asia and Australia. Surprisingly the first strain of what is thought to be West Nile can be traced all the way back to the 1600s.
The first appearance of West Nile virus in the Western hemisphere was in 1999 with encephalitis reported in humans, dogs, cats, and horses, and the subsequent spread in the United States may be an important milestone in the evolving history of this virus. The American outbreak began in the New York City area, including New Jersey and Connecticut, and the virus is believed to have entered in an infected bird or mosquito, although there is no clear evidence. The US virus was very closely related to a lineage 1 strain found in Israel in 1998. Since the first North American cases in 1999, the virus has been reported throughout the United States, Canada, Mexico, the Caribbean and Central America. There have been human cases and horse cases, and many birds are infected. Both the US and Israeli strains are marked by high mortality rates in infected avian populations, the presence of dead birds—especially corvidae—can be an early indicator of the arrival of the virus.
A high level of media coverage through 2001/2002 raised public awareness of West Nile virus. This coverage was most likely the result of successive appearances of the virus in new areas, and had the unintended effect of increasing funding for research on this virus and related arthropod-borne viruses. Such research has expanded our understanding of viruses transmitted by mosquitoes.
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).
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.
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 1,494 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 26 cases were reported and two deaths; however, 2005 saw 239 cases and 12 deaths. By October 28, 2006, 127 cases and no deaths had been reported. One case was asymptomatic and only discovered through a blood donation. Currently in 2007, 445 Manitobans have confirmed cases of West Nile and two people have died with a third unconfirmed but suspected. 17 people have either tested positive or are suspected of having the virus in Saskatchewan, and only one person has tested positive in Alberta. Saskatchewan has reported 826 cases of West Nile plus three 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%.
West Nile control is achieved through mosquito control, by elimination of mosquito breeding sites, larviciding active breeding areas and encouraging personal use of mosquito repellents. The public is also encouraged to spend less time outdoors, wear long covering clothing, apply bug repellant that contains DEET and ensure that mosquitoes cannot enter buildings. 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. They also question the effectiveness of insecticide spraying, as they believe 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.
An effective horse vaccine was introduced by Fort Dodge Animal Health (Wyeth).
In 2007 the World Community Grid launched a project where by computer modeling of the West Nile Virus (and related viruses) thousands of small molecules are screened for their potential anti-viral properties in fighting the West Nile Virus. This is a project which by the use of computer simulations potential drugs will be identified which will directly attack the virus once a person is infected. This is a distributed process project similar to SETI@Home where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering West Nile Virus is called "Discovering Dengue Drugs – Together." The software and information about the project can be found at: World Community Grid