West Nile virus

Taxobox
name = "West Nile virus"


virus_group = iv
familia = "Flaviviridae"
genus = "Flavivirus"
species = "West Nile virus"Infobox_Disease
Name = West Nile Fever
DiseasesDB = 30025
ICD10 = ICD10|A|92|3
MeshID = D014901

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.

ymptoms

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; [cite journal |author=Olejnik E |title=Infectious adenitis transmitted by "Culex molestus |journal=Bull Res Counc Isr |volume=2 |issue= |pages=210–1 |year=1952] the third is a neuroinvasive disease termed West Nile meningitis or encephalitis. [cite journal |author=Smithburn KC, Jacobs HR |title=Neutralization-tests against neurotropic viruses with sera collected in central Africa |journal=Journal of Immunology |volume=44 |issue= |pages=923 |year=1942] In infected individuals the ratio between the three states is roughly 110:30:1. [cite journal |author=Tsai TF, Popovici F, Cernescu C, Campbell GL, Nedelcu NI |title=West Nile encephalitis epidemic in southeastern Romania |journal=Lancet |volume=352 |issue=9130 |pages=767–71 |year=1998 |pmid=9737281 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673698035387]

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. [cite journal |author=Sejvar JJ, Haddad MB, Tierney BC, "et al" |title=Neurologic manifestations and outcome of West Nile virus infection |journal=JAMA |volume=290 |issue=4 |pages=511–5 |year=2003 |pmid=12876094 |doi=10.1001/jama.290.4.511 |url=] WNV-associated Guillain-Barré syndrome has been identified [cite journal |author=Ahmed S, Libman R, Wesson K, Ahmed F, Einberg K |title=Guillain-Barré syndrome: An unusual presentation of West Nile virus infection |journal=Neurology |volume=55 |issue=1 |pages=144–6 |year=2000 |pmid=10891928 |doi= |url=http://www.neurology.org/cgi/pmidlookup?view=long&pmid=10891928] and other rare effects include multifocal chorioretinitis (which has 100% specificity for identifying WNV infection in patients with possible WNV encephalitis), [cite journal |author=Abroug F, Ouanes-Besbes L, Letaief M, "et al" |title=A cluster study of predictors of severe West Nile virus infection |journal=Mayo Clin. Proc. |volume=81 |issue=1 |pages=12–6 |year=2006 |pmid=16438473 |doi= |url=] hepatitis, myocarditis, nephritis, pancreatitis, and splenomegaly. [cite journal |author=Perelman A, Stern J |title=Acute pancreatitis in West Nile Fever |journal=Am. J. Trop. Med. Hyg. |volume=23 |issue=6 |pages=1150–2 |year=1974 |pmid=4429184 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=4429184] [cite journal |author=Omalu BI, Shakir AA, Wang G, Lipkin WI, Wiley CA |title=Fatal fulminant pan-meningo-polioencephalitis due to West Nile virus |journal=Brain Pathol. |volume=13 |issue=4 |pages=465–72 |year=2003 |pmid=14655752 |doi= |url=] [cite journal |author=Mathiot CC, Georges AJ, Deubel V |title=Comparative analysis of West Nile virus strains isolated from human and animal hosts using monoclonal antibodies and cDNA restriction digest profiles |journal=Res. Virol. |volume=141 |issue=5 |pages=533–43 |year=1990 |pmid=1703658 |doi= |url=]

Transmission and susceptibility

Transmission

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. [cite journal |author=Hayes EB, Komar N, Nasci RS, Montgomery SP, O'Leary DR, Campbell GL |title=Epidemiology and transmission dynamics of West Nile virus disease |journal=Emerging Infect. Dis. |volume=11 |issue=8 |pages=1167–73 |year=2005 |pmid=16102302 |doi= |url=http://www.cdc.gov/ncidod/EID/vol11no08/05-0289a.htm]

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, [Taylor R M, Hurlbut H S, Dressler H R, Spangler E W, Thrasher D. "Isolation of West Nile virus from "Culex" mosquitoes." "Journal of the Egyptian Medical Association" 1953; 36: 199–208] 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.

usceptibility

It was initially believed that direct human-to-human transmission was only caused by occupational exposure, [cite journal |author= |title=Laboratory-acquired West Nile virus infections--United States, 2002 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=51 |issue=50 |pages=1133–5 |year=2002 |pmid=12537288 |doi= |url=] or conjunctival exposure to infected blood. [cite journal |author=Fonseca K, Prince GD, Bratvold J, "et al" |title=West Nile virus infection and conjunctival exposure |journal=Emerging Infect. Dis. |volume=11 |issue=10 |pages=1648–9 |year=2005 |pmid=16355512 |doi= |url=] The US outbreak revealed novel transmission methods, through blood transfusion, [cite journal |author= |title=Investigation of blood transfusion recipients with West Nile virus infections |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=51 |issue=36 |pages=823 |year=2002 |pmid=12269472 |doi= |url=] organ transplant, [cite journal |author= |title=West Nile virus infection in organ donor and transplant recipients--Georgia and Florida, 2002 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=51 |issue=35 |pages=790 |year=2002 |pmid=12227442 |doi= |url=] intrauterine exposure, [cite journal |author= |title=Intrauterine West Nile virus infection--New York, 2002 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=51 |issue=50 |pages=1135–6 |year=2002 |pmid=12537289 |doi= |url=] and breast feeding. [cite journal |author= |title=Possible West Nile virus transmission to an infant through breast-feeding--Michigan, 2002 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=51 |issue=39 |pages=877–8 |year=2002 |pmid=12375687 |doi= |url=] Since 2003, blood banks in the US routinely screen for the virus amongst their donors. [cite journal |author= |title=Detection of West Nile virus in blood donations--United States, 2003 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=52 |issue=32 |pages=769–72 |year=2003 |pmid=12917583 |doi= |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a3.htm] As a precautionary measure, the UK's 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.

The more severe outcomes of WNV infection are clearly associated with advancing age [cite journal |author=Panthier R, Hannoun C, Beytout D, Mouchet J |title= [Epidemiology of West Nile virus. Study of a center in Camargue.] |language=French |journal=Ann Inst Pasteur (Paris) |volume=115 |issue=3 |pages=435–45 |year=1968 |pmid=5711530 |doi= |url=] and a patient history of organ transplantation [cite journal |author=Kumar D, Drebot MA, Wong SJ, "et al" |title=A seroprevalence study of west nile virus infection in solid organ transplant recipients |journal=Am. J. Transplant. |volume=4 |issue=11 |pages=1883–8 |year=2004 |pmid=15476490 |doi=10.1111/j.1600-6143.2004.00592.x |url=] 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%. [cite journal | first = WG | last = Glass | coauthors = Lim JK, Cholera R, Pletnev AG, Gao JL, Murphy PM | year = 2005 | month = October 17 | title = Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection | journal = Journal of Experimental Medicine | volume = 202 | issue = 8 | pages = 1087–98 | pmid = 16230476 | doi = 10.1084/jem.20042530] [cite journal | first = WG | last = Glass | coauthors = McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, Pape J, Cheshier RC, Murphy PM | year = 2006 | month = January 23 | title = CCR5 deficiency increases risk of symptomatic West Nile virus infection | journal = Journal of Experimental Medicine | volume = 203 | issue = 1 | pages = 35–40 | pmid = 16418398 | doi = 10.1084/jem.20051970]

Recently, the potential for mosquito saliva to impact the course of WNV disease was demonstrated.cite journal |author=Schneider BS, McGee CE, Jordan JM, Stevenson HL, Soong L, Higgs S |title=Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted west nile virus infection |journal=PLoS ONE |volume=2 |issue=11 |pages=e1171 |year=2007 |pmid=18000543 |doi=10.1371/journal.pone.0001171 |url=http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001171] cite journal |author=Styer LM, Bernard KA, Kramer LD |title=Enhanced early West Nile virus infection in young chickens infected by mosquito bite: effect of viral dose |journal=Am. J. Trop. Med. Hyg. |volume=75 |issue=2 |pages=337–45 |year=2006 |pmid=16896145 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=16896145] cite journal |author=Schneider BS, Soong L, Girard YA, Campbell G, Mason P, Higgs S |title=Potentiation of West Nile encephalitis by mosquito feeding |journal=Viral Immunol. |volume=19 |issue=1 |pages=74–82 |year=2006 |pmid=16553552 |doi=10.1089/vim.2006.19.74] 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.cite journal |author=Wasserman HA, Singh S, Champagne DE |title=Saliva of the Yellow Fever mosquito, Aedes aegypti, modulates murine lymphocyte function |journal=Parasite Immunol. |volume=26 |issue=6–7 |pages=295–306 |year=2004 |pmid=15541033 |doi=10.1111/j.0141-9838.2004.00712.x |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0141-9838&date=2004&volume=26&issue=6-7&spage=295] cite journal |author=Limesand KH, Higgs S, Pearson LD, Beaty BJ |title=Effect of mosquito salivary gland treatment on vesicular stomatitis New Jersey virus replication and interferon alpha/beta expression in vitro |journal=J. Med. Entomol. |volume=40 |issue=2 |pages=199–205 |year=2003 |pmid=12693849 |doi=] cite journal |author=Wanasen N, Nussenzveig RH, Champagne DE, Soong L, Higgs S |title=Differential modulation of murine host immune response by salivary gland extracts from the mosquitoes Aedes aegypti and Culex quinquefasciatus |journal=Med. Vet. Entomol. |volume=18 |issue=2 |pages=191–9 |year=2004 |pmid=15189245 |doi=10.1111/j.1365-2915.2004.00498.x |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0269-283X&date=2004&volume=18&issue=2&spage=191] cite journal |author=Zeidner NS, Higgs S, Happ CM, Beaty BJ, Miller BR |title=Mosquito feeding modulates Th1 and Th2 cytokines in flavivirus susceptible mice: an effect mimicked by injection of sialokinins, but not demonstrated in flavivirus resistant mice |journal=Parasite Immunol. |volume=21 |issue=1 |pages=35–44 |year=1999 |pmid=10081770 | doi = 10.1046/j.1365-3024.1999.00199.x |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0141-9838&date=1999&volume=21&issue=1&spage=35] Studies have shown that it can specifically modulate the immune response during early virus infection,cite journal |author=Schneider BS, Soong L, Zeidner NS, Higgs S |title=Aedes aegypti salivary gland extracts modulate anti-viral and TH1/TH2 cytokine responses to sindbis virus infection |journal=Viral Immunol. |volume=17 |issue=4 |pages=565–73 |year=2004 |pmid=15671753 |doi=10.1089/vim.2004.17.565] and mosquito feeding can exacerbate WNV infection leading to higher viremia and more severe forms of disease.cite journal |author=Schneider BS, McGee CE, Jordan JM, Stevenson HL, Soong L, Higgs S |title=Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted west nile virus infection |journal=PLoS ONE |volume=2 |issue=11 |pages=e1171 |year=2007 |pmid=18000543 |doi=10.1371/journal.pone.0001171 |url=http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001171] cite journal |author=Styer LM, Bernard KA, Kramer LD |title=Enhanced early West Nile virus infection in young chickens infected by mosquito bite: effect of viral dose |journal=Am. J. Trop. Med. Hyg. |volume=75 |issue=2 |pages=337–45 |year=2006 |pmid=16896145 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=16896145] cite journal |author=Schneider BS, Soong L, Girard YA, Campbell G, Mason P, Higgs S |title=Potentiation of West Nile encephalitis by mosquito feeding |journal=Viral Immunol. |volume=19 |issue=1 |pages=74–82 |year=2006 |pmid=16553552 |doi=10.1089/vim.2006.19.74] 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. [ [http://www.cdc.gov/ncidod/dvbid/westnile/birds&mammals.htm CDC] ]

Avoiding mosquito bites is the most straightforward means to avoid infection [cite journal |author=Hayes EB, Gubler DJ |title=West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States |journal=Annu. Rev. Med. |volume=57 |issue= |pages=181–94 |year=2006 |pmid=16409144 |doi=10.1146/annurev.med.57.121304.131418 |url=] —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). [cite journal |author=Fradin MS, Day JF |title=Comparative efficacy of insect repellents against mosquito bites |journal=N. Engl. J. Med. |volume=347 |issue=1 |pages=13–8 |year=2002 |pmid=12097535 |doi=10.1056/NEJMoa011699 |url=] 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. [ [http://www.latimes.com/news/local/la-me-westnile19aug19,0,2186893.story?coll=la-home-local CDC] ] 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. [ [http://news.yahoo.com/s/ap/20060825/ap_on_re_us/west_nile;_ylt=Alqlj1InGYGFq0kRGw4NAoC9SvQA;_ylu=X3oDMTA4dW1uZXIwBHNlYwMyNzQ3 Yahoo] ]

History

Studies of phylogenetic lineages have determined that WNV emerged as a distinct virus around 1000 years ago. [cite journal |author=Galli M, Bernini F, Zehender G |title=Alexander the Great and West Nile virus encephalitis |journal=Emerging Infect. Dis. |volume=10 |issue=7 |pages=1330–2; author reply 1332–3 |year=2004 |month=July |pmid=15338540 |doi= |url=] This initial virus developed into two distinct lineages, Lineage 1 and its multiple profiles is the source of the epidemic transmission in Africa and throughout the world, while Lineage 2 remains as an Africa zoonose.

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 [cite journal |author=Work TH, Hurlbut HS, Taylor RM |title=Isolation of West Nile virus from hooded crow and rock pigeon in the Nile delta |journal=Proc. Soc. Exp. Biol. Med. |volume=84 |issue=3 |pages=719–22 |year=1953 |pmid=13134268 |doi= |url=] and Israel. [cite journal |author=Bernkopf H, Levine S, Nerson R |title=Isolation of West Nile virus in Israel |journal=J. Infect. Dis. |volume=93 |issue=3 |pages=207–18 |year=1953 |pmid=13109233 |doi= |url=] 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. [cite journal |author=Calisher CH |title=West Nile virus in the New World: appearance, persistence, and adaptation to a new econiche--an opportunity taken |journal=Viral Immunol. |volume=13 |issue=4 |pages=411–4 |year=2000 |pmid=11192287 |doi= |url=] 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.

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. [cite journal | first = LM | last = Bugbee | coauthors = Forte LR | year = 2004 | month = Sep | title = The discovery of West Nile virus in overwintering Culex pipiens (Diptera: Culicidae) mosquitoes in Lehigh County, Pennsylvania | journal = Journal of the American Mosquito Control Association | volume = 20 | issue = 3 | pages = 326–7 | pmid = 15532939]

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 West Nile virus infections, 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. 2006 saw another increase, with 4,269 cases and 177 deaths. In 2007, the number of cases reported decreased to 3,623 and the number of deaths dropped to 124.

See also Progress of the West Nile virus in the United States

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. [ [http://www.gov.mb.ca/health/wnv/index.html Province of Manitoba | Manitoba Health | West Nile virus ] ] 17 people have either tested positive or are suspected of having the virus in Saskatchewan, and only one person has tested positive in Alberta. [ [http://www.mytelus.com/ncp_news/article.en.do?pn=regional/alberta&articleID=2734169 Error ] ]
Saskatchewan has reported 826 cases of West Nile plus three deaths. [ [http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070824/west_nile_sask_070824/20070824?hub=Health CTV.ca | Sask. reports 339 cases of West Nile, one death] ]

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%). [cite journal | first = MY | last = Chowers | coauthors = Lang R, Nassar F, Ben-David D, Giladi M, Rubinshtein E, Itzhaki A, Mishal J, Siegman-Igra Y, Kitzes R, Pick N, Landau Z, Wolf D, Bin H, Mendelson E, Pitlik SD, Weinberger M | year = 2001 | month = Jul–Aug | title = Clinical characteristics of the West Nile fever outbreak, Israel, 2000 | journal = Emerging Infectious Diseases | volume = 7 | issue = 4 | pages = 675–8 | pmid = 11585531 | url = http://www.cdc.gov/ncidod/eid/vol7no4/chowers.htm | accessdate = 2006-06-07]

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

urveillance 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 dogs and sentinel monkeys, as well as testing brains of 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) [cite journal | first = M | last = Jozan | coauthors = Evans R, McLean R, Hall R, Tangredi B, Reed L, Scott J | year = 2003 | month = Fall | title = Detection of West Nile virus infection in birds in the United States by blocking ELISA and immunohistochemistry | journal = Vector-borne and Zoonotic Diseases | volume = 3 | issue = 3 | pages = 99–110 | pmid = 14511579 | doi = 10.1089/153036603768395799] or Enzyme-Linked Immunosorbent Assay (ELISA). [cite journal | first = RA | last = Hall | coauthors = Broom AK, Hartnett AC, Howard MJ, Mackenzie JS | year = 1995 | month = Feb | title = Immunodominant epitopes on the NS1 protein of MVE and KUN viruses serve as targets for a blocking ELISA to detect virus-specific antibodies in sentinel animal serum | journal = Journal of Virological Methods | volume = 51 | issue = 2–3 | pages = 201–10 | pmid = 7738140 | doi = 10.1016/0166-0934(94)00105-P]

Dead birds, after necropsy, have their various tissues tested for virus by either 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 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. [cite web
url = http://www.osha.gov/dts/shib/shib082903b.html
title = Workplace Precautions Against West Nile Virus
accessdate = 2007-11-21
work = Safety and Health Information Bulletins (SHIBs)
publisher = U. S. Department of Labor Occupational Safety and Health Administration]
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).

Treatment research

AMD 3100, which had been proposed as an antiretroviral drug for HIV, has shown promise against West Nile encephalitis. Morpholino antisense oligos conjugated to cell penetrating peptides have been shown to partially protect mice from WNV disease. [cite journal | first = Tia S | last = Deas | coauthors = Bennett CJ, Jones SA, Tilgner M, Ren P, Behr MJ, Stein DA, Iversen PL, Kramer LD, Bernard KA, Shi PY | year = 2007 | month = May | title = In vitro resistance selection and in vivo efficacy of morpholino oligomers against West Nile virus | journal = Antimicrob Agents Chemother | pmid = 17485503 | doi = 10.1128/AAC.00069-07 | volume = 51 | pages = 2470] There have also been attempts to treat infections using ribavirin, intravenous immunoglobulin, or alpha interferon. [cite journal |author=Hayes EB, Sejvar JJ, Zaki SR, Lanciotti RS, Bode AV, Campbell GL |title=Virology, pathology, and clinical manifestations of West Nile virus disease |journal=Emerging Infect. Dis. |volume=11 |issue=8 |pages=1174–9 |year=2005 |pmid=16102303 |doi= |url=http://www.cdc.gov/ncidod/EID/vol11no08/05-0289b.htm] GenoMed, a US biotech company, has found that blocking angiotensin II can treat the "cytokine storm" of West Nile virus encephalitis as well as other viruses. [cite journal |author=Moskowitz DW, Johnson FE |title=The central role of angiotensin I-converting enzyme in vertebrate pathophysiology |journal=Curr Top Med Chem |volume=4 |issue=13 |pages=1433–54 |year=2004 |pmid=15379656 |doi= |url=]

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: [http://www.worldcommunitygrid.org/reg/viewRegister.do World Community Grid]

ee also

*CCR5
*Long range RNA cis-elements in WNV

ources

External links

* U.S. Centers for Disease Control and Prevention (CDC) pages
** [http://www.cdc.gov/ncidod/dvbid/westnile/ West Nile virus] topic page
** [http://www.cdc.gov/ncidod/dvbid/westnile/map.htm World map of West Nile and related viruses]
** [http://www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount03.htm 2003 case count]
* U.S. National Institute for Occupational Safety and Health (NIOSH) pages
** [http://www.cdc.gov/niosh/docs/2005-155/ Recommendations for Protecting Outdoor Workers from West Nile Virus Exposure]
** [http://www.cdc.gov/niosh/docs/2006-115/ Recommendations for Protecting Laboratory, Field, and Clinical Workers from West Nile Virus Exposure]
* [http://npic.orst.edu/wnv/ West Nile Virus Resource Guide] —National Pesticide Information Center
* [http://www.vrc.nih.gov Vaccine Research Center (VRC)] —Information concerning WNV vaccine research studies
* [http://www.equinewestnile.com/ equinewestnile.com]
* [http://westnilemaps.usgs.gov/us_human.html US map of West Nile virus]
* [http://www.phac-aspc.gc.ca/wnv-vwn/index.html Canadian Case Surveillance]
* [http://sankey.ws/wnv.html West Nile Virus and Insecticides]
* L. Peterson, M. Marphin. [http://www.cfe.cornell.edu/erap/WNV/WNVEducDocs/Petersen-Marfin2002.pdf "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", [http://www.annalsnyas.org/content/vol951/issue1/ "Annals of the New York Academy of Sciences"] , Vol. 951, 2001.
* [http://www.nature.com/nsu/021014/021014-5.html "Nature" news article on West Nile paralysis]
* [http://www.cbc.ca/news/background/westnile/ CBC News Coverage of West Nile in Canada]
* [http://www.cdc.gov/ncidod/eid/vol5no5/hubalek.htm West Nile Fever in Europe]
* [http://www.encephalitisglobal.com Encephalitis Global, Inc.]
* [http://www.uos.harvard.edu/ehs/pes_wnv.shtml Harvard University fact sheet on West Nile Virus]
* [http://wildlifedisease.nbii.gov/diseasehome.jsp?disease=West%20Nile%20Virus&pagemode=submit West Nile Virus and Wildlife Disease]
* [http://www.latimes.com/news/local/la-me-westnile19aug19,0,2186893.story?coll=la-home-local West Nile Cases Drop as Immunities Emerge, Experts Say]
* Nash D, Mostashari FM, Fine A, et al. N Engl J Med. 2001 June 14;344(24):1807–14 [http://www.ncbi.nlm.nih.gov.arugula.cc.columbia.edu:2048/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11407341&query_hl=1&itool=pubmed_docsum The outbreak of West Nile virus infection in the New York City Area in 1999]
* [http://westnile.ca.gov/news.php?id=64 Low literacy materials in Spanish for WNV prevention]
* [http://www.universityofcalifornia.edu/news/article/17002 Gene mutation turned West Nile virus into killer disease among crows]