Editing West Nile fever (section)

===Transmission===
[[File:West Nile virus transmission cycle.jpg|thumb|left|West Nile virus maintains itself in nature by cycling between mosquitoes in the genus ''Culex'' and certain species of birds. A mosquito (the [[Vector (epidemiology)|vector]]) bites an uninfected bird (the [[Host (biology)|host]]), the virus amplifies within the bird, an uninfected mosquito bites the bird and is in turn infected. Other species such as humans and horses are incidental infections, because the virus does not amplify well within these species and they are considered dead-end hosts.]]
The prime method of spread of the West Nile virus (WNV) is the female mosquito. In Europe, cats were identified as [[Feline zoonosis|being hosts]] for [[West Nile virus]].<ref name="RijksCito2016">{{cite journal|last1=Rijks|first1=J.M.|last2=Cito|first2=F.|last3=Cunningham|first3=A.A.|last4=Rantsios|first4=A.T.|last5=Giovannini|first5=A.|title=Disease Risk Assessments Involving Companion Animals: an Overview for 15 Selected Pathogens Taking a European Perspective|journal=Journal of Comparative Pathology|volume=155|issue=1|year=2016|pages=S75–S97|issn=0021-9975|doi=10.1016/j.jcpa.2015.08.003|pmid=26422413|doi-access=free}}</ref>
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.<ref>{{cite journal |vauthors=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=10.3201/eid1108.050289a |pmc=3320478 }}</ref> In Europe, ''Culex pipiens'' is the principal vector.<ref>{{Cite journal |last1=Vogels |first1=Chantal Bf |last2=Göertz |first2=Giel P. |last3=Pijlman |first3=Gorben P. |last4=Koenraadt |first4=Constantianus Jm |date=2017-11-08 |title=Vector competence of European mosquitoes for West Nile virus |journal=Emerging Microbes & Infections |volume=6 |issue=11 |pages=e96 |doi=10.1038/emi.2017.82 |issn=2222-1751 |pmc=5717085 |pmid=29116220}}</ref>

The mosquito species that are most frequently infected with WNV feed primarily on birds.<ref name=Kilpatrick_2011>{{cite journal|last=Kilpatrick |first=A.M. |title= Globalization, land use, and the invasion of West Nile virus |journal=Science |year=2011|volume=334|issue=6054 |pages=323–327|pmid= 22021850 |pmc=3346291 |doi= 10.1126/science.1201010|bibcode=2011Sci...334..323K }}</ref> Different species of mosquitos take a [[hematophagy|blood meal]] from different types of [[vertebrate]] [[Host (biology)|host]]s, 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 (bird)|thrush]] [[Family (biology)|family]]. Among the preferred species within these families are the [[American crow]], a corvid, and the [[American robin]] (''Turdus migratorius'').<ref name="Kilpatrick_2006A">{{cite journal|last=Kilpatrick, AM, P Daszak, MJ Jones, PP Marra, LD Kramer|year=2006|title=Host heterogeneity dominates West Nile virus transmission|journal=Proceedings of the Royal Society B: Biological Sciences|volume=273|issue=1599|pages=2327–2333|doi=10.1098/rspb.2006.3575|pmc=1636093|pmid=16928635}}</ref>

Some species of birds develop sufficient viral levels (>~10<sup>4.2</sup> log PFU/ml;<ref name=Kilpatrick_2007>{{cite journal | last=Kilpatrick, AM, SL LaDeau, PP Marra | title= Ecology of West Nile virus transmission and its impact on birds in the western hemisphere | journal= Auk | volume= 124 | issue= 4 | year=2007 | pages=1121–1136 | doi=10.1642/0004-8038(2007)124[1121:eownvt]2.0.co;2| s2cid= 13796761 | url= https://repository.si.edu/bitstream/handle/10088/35181/NZP_Marra_2007-ECOLOGY_OF_WEST_NILE_VIRUS_TRANSMISSION_AND_ITS_IMPACT_ON_BIRDS_IN_THE_WESTERN_HEMISPHERE.pdf;https://repository.si.edu/bitstream/handle/10088/35181/NZP_Marra_2007-ECOLOGY_OF_WEST_NILE_VIRUS_TRANSMISSION_AND_ITS_IMPACT_ON_BIRDS_IN_THE_WESTERN_HEMISPHERE.pdf | type= Submitted manuscript }}</ref>) 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.<ref name=Komar_2003>{{cite journal | last=Komar, N, S Langevin, S Hinten, N Nemeth, E Edwards, D Hettler, B Davis, R Bowen, M Bunning | title= Experimental infection of North American birds with the New York 1999 strain of West Nile virus | journal= Emerging Infectious Diseases | volume= 9 | issue= 3 | year=2003 | pages=311–322 |pmid= 12643825 | pmc= 2958552 | doi=10.3201/eid0903.020628}}</ref>  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 [[Host (biology)|dead-end hosts]].<ref name=Kilpatrick_2007/>  As a result of the differential infectiousness of hosts, the feeding patterns of mosquitoes play an important role in WNV transmission,<ref name=Kilpatrick_2011/><ref name=Kilpatrick_2006A/> and they are partly genetically controlled, even within a species.<ref>{{Cite journal |last1=Brugman |first1=V. A. |last2=Hernández-Triana |first2=L. M. |last3=England |first3=M. E. |last4=Medlock |first4=J. M. |last5=Mertens |first5=P. P. C. |last6=Logan |first6=J. G. |last7=Wilson |first7=A. J. |last8=Fooks |first8=A. R. |last9=Johnson |first9=N. |last10=Carpenter |first10=S. |date=2017-03-27 |title=Blood-feeding patterns of native mosquitoes and insights into their potential role as pathogen vectors in the Thames estuary region of the United Kingdom |journal=Parasites & Vectors |volume=10 |issue=1 |pages=163 |doi=10.1186/s13071-017-2098-4 |issn=1756-3305 |pmc=5369192 |pmid=28347323 |doi-access=free }}</ref>

Direct human-to-human transmission initially was believed to be caused only by occupational exposure, such as in a laboratory setting,<ref>{{cite journal |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 |author1= Centers for Disease Control and Prevention (CDC)}}</ref> or [[conjunctiva]]l exposure to infected blood.<ref>{{cite journal  |vauthors=Fonseca K, Prince GD, Bratvold J, etal |title=West Nile virus infection and conjunctive exposure |journal=Emerging Infect. Dis. |volume=11|issue=10|pages=1648–9 |year=2005 |pmid=16355512 |doi= 10.3201/eid1110.040212 |pmc=3366727}}</ref> The US outbreak identified additional transmission methods through blood transfusion,<ref>{{cite journal |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 |author1= Centers for Disease Control and Prevention (CDC)}}</ref> organ transplant,<ref>{{cite journal |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 |author1= Centers for Disease Control and Prevention (CDC)}}</ref> intrauterine exposure,<ref>{{cite journal |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 |author1= Centers for Disease Control and Prevention (CDC) }}</ref> and breast feeding.<ref>{{cite journal |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 |author1= Centers for Disease Control and Prevention (CDC) }}</ref> Since 2003, blood banks in the United States routinely screen for the virus among their donors.<ref>{{cite journal |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 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a3.htm |author1=Centers for Disease Control and Prevention (CDC) |url-status=live |archive-url=https://web.archive.org/web/20170625121109/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a3.htm |archive-date=2017-06-25 }}</ref> As a precautionary measure, the UK's [[National Blood Service]] initially ran a test for this disease in donors who donate within 28 days of a visit to the United States, Canada, or the northeastern provinces of Italy, and the [[Scottish National Blood Transfusion Service]]<ref>[https://web.archive.org/web/20080820072151/http://www.scotblood.co.uk/westNile.asp West Nile Virus]. Scottish National Blood Transfusion Service.</ref> asks prospective donors to wait 28 days after returning from North America or the northeastern provinces of Italy before donating. There also have been reports of possible transmission of the virus from mother to child during [[pregnancy]] or [[breastfeeding]] or exposure to the virus in a lab, but these are rare cases and not conclusively confirmed.<ref name="Mayo Clinic">{{cite web|title=West Nile virus|url=https://www.mayoclinic.org/diseases-conditions/west-nile-virus/symptoms-causes/syc-20350320|website=Mayo Clinic|access-date=25 October 2017|url-status=live|archive-url=https://web.archive.org/web/20171026001453/https://www.mayoclinic.org/diseases-conditions/west-nile-virus/symptoms-causes/syc-20350320|archive-date=26 October 2017}}</ref>

Recently, the potential for [[Mosquito#Saliva|mosquito saliva]] to affect the course of WNV disease was demonstrated.<ref name="pmid18000543">{{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|pmc=2048662 |editor1-last=Baylis |editor1-first=Matthew|bibcode=2007PLoSO...2.1171S |doi-access=free }}</ref><ref name="pmid16896145">{{cite journal |vauthors=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=10.4269/ajtmh.2006.75.337 |doi-access=free }}</ref><ref name="pmid16553552">{{cite journal|vauthors=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|s2cid=37464180 }}</ref>  Mosquitoes inoculate their saliva into the skin while obtaining blood. Mosquito saliva is a pharmacological cocktail of secreted molecules, principally proteins, that can affect vascular constriction, [[blood coagulation]], [[platelet aggregation]], [[inflammation]], and [[Immunity (medical)|immunity]]. It clearly alters the [[immune response]] in a manner that may be advantageous to a virus.<ref name="pmid15541033">{{cite journal |vauthors=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|s2cid=32742815}}</ref><ref name="pmid12693849">{{cite journal |vauthors=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=10.1603/0022-2585-40.2.199|s2cid=85624297 |doi-access=free }}</ref><ref name="pmid15189245">{{cite journal |vauthors=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|s2cid=42458052 }}</ref><ref name="pmid10081770">{{cite journal |vauthors=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|s2cid=26774722|url=https://zenodo.org/record/1236522}}</ref> Studies have shown it can specifically modulate the immune response during early virus infection,<ref name="pmid15671753">{{cite journal |vauthors=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}}</ref> and mosquito feeding can exacerbate WNV infection, leading to higher [[viremia]] and more severe forms of disease.<ref name="pmid18000543"/><ref name="pmid16896145"/><ref name="pmid16553552"/>

====Vertical transmission====
[[Vertical transmission]], the transmission of a viral or bacterial disease from the female of the species to her offspring, has been observed in various West Nile virus studies, amongst different species of mosquitoes in both the laboratory and in nature.<ref>{{cite journal | first = LM | last = Bugbee |author2=Forte LR  |date=September 2004 | 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}}</ref> Mosquito progeny infected vertically in autumn may potentially serve as a mechanism for WNV to overwinter and initiate [[enzootic]] [[Horizontal disease transmission|horizontal]] transmission the following spring, although it likely plays little role in transmission in the summer and fall.<ref>{{cite journal |vauthors=Goddard LB, Roth AE, Reisen WK, Scott TW |title=Vertical transmission of West Nile Virus by three California Culex (Diptera: Culicidae) species |journal=J. Med. Entomol. |volume=40 |issue=6 |pages=743–6 |date=November 2003 |pmid=14765647 |doi=10.1603/0022-2585-40.6.743 |doi-access=free }}</ref>