In the 20 years since West Nile virus (WNV) first emerged in the United States, more than 51,000 clinical cases have been reported, including ...ArticleAuthorsMetricsCommentsMediaCoverageReaderComments(0)FiguresFiguresAbstractAftertheunexpectedarrivalofWestNilevirus(WNV)intheUnitedStatesin1999,themosquito-bornevirusquicklyspreadthroughoutNorthAmerica.Overthepast20years,WNVhasbecomeendemic,withsporadicepizootics.Concernsabouttheeconomicimpactofinfectioninhorsesleadtothelicensureofanequinevaccineasearlyas2005,butfewadvancesregardinghumanvaccinesortreatmentshavesincebeenmade.Thereisahighlevelofvirustransmissioninhot/humid,subtropicalclimates,andhighmorbiditythatmaydisproportionatelyaffectvulnerablepopulationsincludingthehomeless,elderly,andthosewithunderlyinghealthconditions.AlthoughWNVcontinuestocausesignificantmorbidityandmortalityatgreatcost,fundingandresearchhavedeclinedinrecentyears.Thesefactors,combinedwithneglectbypolicymakersandamenabilityofcontrolmeasures,indicatethatWNVhasbecomeaneglectedtropicaldisease.Citation:RoncaSE,RuffJC,MurrayKO(2021)A20-yearhistoricalreviewofWestNilevirussinceitsinitialemergenceinNorthAmerica:HasWestNilevirusbecomeaneglectedtropicaldisease?PLoSNeglTropDis15(5):e0009190.https://doi.org/10.1371/journal.pntd.0009190Editor:PedroF.C.Vasconcelos,InstitutoEvandroChagas,BRAZILPublished:May6,2021Copyright:©2021Roncaetal.ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Funding:TheauthorswerefundedinpartbyNIH/NIAID(U19AI089992-06)(K.O.M.),theChaoFoundation(K.O.M.),andtheBrockmanFoundation(https://brockmanfoundation.org)(K.O.M).Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.Competinginterests:Theauthorshavedeclaredthatnocompetinginterestsexist.IntroductionandhistoryofWestNilevirusinNorthAmericaWestNilevirus(WNV)wasfirstdiscoveredinUgandai