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Denguefever
FromWikipedia,thefreeencyclopedia

Denguefeverisamosquitobornetropicaldiseasecausedbythedenguevirus.[1]Symptomstypicallybegin
threetofourteendaysafterinfection.[2]Thismayincludeahighfever,headache,vomiting,muscleandjoint
pains,andacharacteristicskinrash.[1][2]Recoverygenerallytakestwotosevendays.[1]Inasmallproportionof
cases,thediseasedevelopsintothelifethreateningdenguehemorrhagicfever,resultinginbleeding,low
levelsofbloodplateletsandbloodplasmaleakage,orintodengueshocksyndrome,wheredangerouslylow
bloodpressureoccurs.[2]

Denguefever
dengue,breakbonefever

DengueisspreadbyseveralspeciesofmosquitooftheAedestype,principallyA.aegypti.[1]Thevirushasfive
differenttypes[3]infectionwithonetypeusuallygiveslifelongimmunitytothattype,butonlyshortterm
immunitytotheothers.Subsequentinfectionwithadifferenttypeincreasestheriskofseverecomplications.[1]
Anumberoftestsareavailabletoconfirmthediagnosisincludingdetectingantibodiestothevirusorits
RNA.[2]
Anovelvaccinefordenguefeverhasbeenapprovedinthreecountries,butitisnotyetcommercially
available.[4]Preventionisbyreducingmosquitohabitatandlimitingexposuretobites.Thismaybedoneby
gettingridoforcoveringstandingwaterandwearingclothingthatcoversmuchofthebody.[1]Treatmentof
acutedengueissupportiveandincludesgivingfluideitherbymouthorintravenouslyformildormoderate
disease.Formoreseverecasesbloodtransfusionmayberequired.[2]Abouthalfamillionpeoplerequire
admissiontohospitalayear.[1]Nonsteroidalantiinflammatorydrug(NSAIDs)suchasibuprofenshouldnotbe
used.[2]
DenguehasbecomeaglobalproblemsincetheSecondWorldWarandiscommoninmorethan
110countries.[5][6]Eachyearbetween50and528millionpeopleareinfectedandapproximately10,000to
20,000die.[7][8][9][10]Theearliestdescriptionsofanoutbreakdatefrom1779.[6]Itsviralcauseandspreadwere
understoodbytheearly20thcentury.[11]Apartfromeliminatingthemosquitoes,workisongoingfor
medicationtargeteddirectlyatthevirus.[12]

Contents

https://en.wikipedia.org/wiki/Dengue_fever

Thetypicalrashseenindenguefever
Classificationandexternalresources
Pronunciation UK/de/or US/di/
Specialty

Infectiousdisease

ICD10

A90(http://apps.who.int/classificati
ons/icd10/browse/2016/en#/A90)

ICD9CM

061(http://www.icd9data.com/getIC
D9Code.ashx?icd9=061)
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Contents
1 Signsandsymptoms
1.1 Clinicalcourse
1.2 Associatedproblems
2 Cause
2.1 Virology
2.2 Transmission
2.3 Predisposition
3 Mechanism
3.1 Viralreplication
3.2 Severedisease
4 Diagnosis
4.1 Classification
4.2 Laboratorytests
5 Prevention
5.1 Vaccine
5.2 Antidengueday
6 Management
7 Epidemiology
8 History
8.1 Etymology
9 Research
9.1 Vector
9.2 Wolbachia
9.3 Treatment
10 References
11 Externallinks

OMIM

614371(http://omim.org/entry/6143
71)

DiseasesDB

3564(http://www.diseasesdatabase.c
om/ddb3564.htm)

MedlinePlus

001374(http://www.nlm.nih.gov/m
edlineplus/ency/article/001374.htm)

eMedicine

med/528(http://www.emedicine.co
m/med/topic528.htm)

PatientUK

Denguefever(http://patient.info/doc
tor/denguefeverpro)

MeSH

C02.782.417.214(https://www.nlm.
nih.gov/cgi/mesh/2016/MB_cgi?mod
e=&term=Dengue&field=entry#Tre
eC02.782.417.214)

Signsandsymptoms
Typically,peopleinfectedwithdenguevirusareasymptomatic(80%)orhaveonlymildsymptomssuchasanuncomplicatedfever.[7][13][14]Othershavemore
severeillness(5%),andinasmallproportionitislifethreatening.[7][14]Theincubationperiod(timebetweenexposureandonsetofsymptoms)rangesfrom3to
14days,butmostoftenitis4to7days.[15]Therefore,travelersreturningfromendemicareasareunlikelytohavedengueiffeverorothersymptomsstartmore

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than14daysafterarrivinghome.[5]Childrenoftenexperiencesymptomssimilartothoseofthecommon
coldandgastroenteritis(vomitinganddiarrhea)[16]andhaveagreaterriskofseverecomplications,[5][17]
thoughinitialsymptomsaregenerallymildbutincludehighfever.[17]

Clinicalcourse
Thecharacteristicsymptomsofdenguearesudden
onsetfever,headache(typicallylocatedbehindthe
eyes),muscleandjointpains,andarash.The
alternativenamefordengue,"breakbonefever",
comesfromtheassociatedmuscleandjoint
pains.[7][19]Thecourseofinfectionisdividedinto
threephases:febrile,critical,andrecovery.[18]
Thefebrilephaseinvolveshighfever,potentially
over40C(104F),andisassociatedwith
Schematicdepictionofthesymptomsofdenguefever
generalizedpainandaheadachethisusuallylasts
twotosevendays.[18][19]Nauseaandvomitingmay
alsooccur.[17]Arashoccursin5080%ofthosewithsymptoms[19][20]inthefirstorseconddayofsymptoms
Clinicalcourseofdenguefever[18]
asflushedskin,orlaterinthecourseofillness(days47),asameasleslikerash.[20][21]Arashdescribedas
"islandsofwhiteinaseaofred"hasalsobeenobserved.[22]Somepetechiae(smallredspotsthatdonot
disappearwhentheskinispressed,whicharecausedbybrokencapillaries)canappearatthispoint,[18]asmaysomemildbleedingfromthemucousmembranesof
themouthandnose.[5][19]Thefeveritselfisclassicallybiphasicorsaddlebackinnature,breakingandthenreturningforoneortwodays.[21][22]
Insomepeople,thediseaseproceedstoacriticalphaseasfeverresolves.[17]Duringthisperiod,thereisleakageofplasmafromthebloodvessels,typicallylasting
onetotwodays.[18]Thismayresultinfluidaccumulationinthechestandabdominalcavityaswellasdepletionoffluidfromthecirculationanddecreasedblood
supplytovitalorgans.[18]Theremayalsobeorgandysfunctionandseverebleeding,typicallyfromthegastrointestinaltract.[5][18]Shock(dengueshocksyndrome)
andhemorrhage(denguehemorrhagicfever)occurinlessthan5%ofallcasesofdengue,[5]howeverthosewhohavepreviouslybeeninfectedwithotherserotypes
ofdenguevirus("secondaryinfection")areatanincreasedrisk.[5][23]Thiscriticalphase,whilerare,occursrelativelymorecommonlyinchildrenandyoung
adults.[17]

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Therecoveryphaseoccursnext,withresorptionofthe
leakedfluidintothebloodstream.[18]Thisusuallylasts
twotothreedays.[5]Theimprovementisoftenstriking,
andcanbeaccompaniedwithsevereitchingandaslow
heartrate.[5][18]Anotherrashmayoccurwitheithera
maculopapularoravasculiticappearance,whichis
followedbypeelingoftheskin.[17]Duringthisstage,a
fluidoverloadstatemayoccurifitaffectsthebrain,it
maycauseareducedlevelofconsciousnessor
seizures.[5]Afeelingoffatiguemaylastforweeksin
adults.[17]
Therashthatcommonlyformsduringtherecovery
fromdenguefeverwithitsclassicislandsofwhitein
aseaofred.

Associatedproblems

Denguecanoccasionallyaffectseveralotherbody
systems,[18]eitherinisolationoralongwiththeclassic
denguesymptoms.[16]Adecreasedlevelofconsciousnessoccursin0.56%ofseverecases,whichis
attributableeithertoinflammationofthebrainbythevirusorindirectlyasaresultofimpairmentofvital
organs,forexample,theliver.[16][22][24]

Therashofdenguefeverintheacutestageofthe
infectionblancheswhenpressed

Otherneurologicaldisordershavebeenreportedinthecontextofdengue,suchastransversemyelitisandGuillainBarrsyndrome.[16][24]Infectionoftheheart
andacuteliverfailureareamongtherarercomplications.[5][18]
Apregnantwomanwhodevelopsdenguemaybeatahigherriskofmiscarriageaswellaslowbirthweightandprematurebirth.[25]

Cause
Virology
Denguefevervirus(DENV)isanRNAvirusofthefamilyFlaviviridaegenusFlavivirus.Othermembersofthesamegenusincludeyellowfevervirus,WestNile
virus,St.Louisencephalitisvirus,Japaneseencephalitisvirus,tickborneencephalitisvirus,Kyasanurforestdiseasevirus,andOmskhemorrhagicfevervirus.[22]
Mostaretransmittedbyarthropods(mosquitoesorticks),andarethereforealsoreferredtoasarboviruses(arthropodborneviruses).[22]

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Thedenguevirusgenome(geneticmaterial)containsabout11,000nucleotidebases,whichcodeforthethree
differenttypesofproteinmolecules(C,prMandE)thatformthevirusparticleandsevenothertypesofprotein
molecules(NS1,NS2a,NS2b,NS3,NS4a,NS4b,NS5)thatarefoundininfectedhostcellsonlyandare
requiredforreplicationofthevirus.[23][26]Therearefive[3]strainsofthevirus,calledserotypes,ofwhichthe
firstfourarereferredtoasDENV1,DENV2,DENV3andDENV4.[13]Thefifthtypewasannouncedin
2013.[3]Thedistinctionsbetweentheserotypesarebasedontheirantigenicity.[27]

Transmission

ThemosquitoAedesaegyptifeedingonahumanhost

DenguevirusisprimarilytransmittedbyAedes
mosquitoes,particularlyA.aegypti.[13]Thesemosquitoes
usuallylivebetweenthelatitudesof35Northand
35Southbelowanelevationof1,000metres(3,300ft).[13]
Theytypicallybiteduringtheearlymorningandinthe
evening,[28][29]buttheymaybiteandthusspreadinfection
ATEMmicrographshowingdenguevirusvirions
atanytimeofday.[30]OtherAedesspeciesthattransmitthe
(theclusterofdarkdotsnearthecenter)
diseaseincludeA.albopictus,A.polynesiensisandA.
scutellaris.[13]Humansaretheprimaryhostofthe
virus,[13][22]butitalsocirculatesinnonhumanprimates.[31]Aninfectioncanbeacquiredviaasinglebite.[32]
Afemalemosquitothattakesabloodmealfromapersoninfectedwithdenguefever,duringtheinitial2to
10dayfebrileperiod,becomesitselfinfectedwiththevirusinthecellsliningitsgut.[33]About810days
later,thevirusspreadstoothertissuesincludingthemosquito'ssalivaryglandsandissubsequentlyreleased
intoitssaliva.Thevirusseemstohavenodetrimentaleffectonthemosquito,whichremainsinfectedfor
life.[15]Aedesaegyptiisparticularlyinvolved,asitpreferstolayitseggsinartificialwatercontainers,tolive
incloseproximitytohumans,andtofeedonpeopleratherthanothervertebrates.[15]

Denguecanalsobetransmittedviainfectedbloodproductsandthroughorgandonation.[34][35]IncountriessuchasSingapore,wheredengueisendemic,theriskis
estimatedtobebetween1.6and6per10,000transfusions.[36]Verticaltransmission(frommothertochild)duringpregnancyoratbirthhasbeenreported.[37]Other
persontopersonmodesoftransmissionhavealsobeenreported,butareveryunusual.[19]Thegeneticvariationindenguevirusesisregionspecific,suggestive
thatestablishmentintonewterritoriesisrelativelyinfrequent,despitedengueemerginginnewregionsinrecentdecades.[17]

Predisposition

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Severediseaseismorecommoninbabiesandyoungchildren,andincontrasttomanyotherinfections,itismorecommoninchildrenwhoarerelativelywell
nourished.[5]Otherriskfactorsforseverediseaseincludefemalesex,highbodymassindex,[17]andviralload.[38]Whileeachserotypecancausethefullspectrum
ofdisease,[23]virusstrainisariskfactor.[17]Infectionwithoneserotypeisthoughttoproducelifelongimmunitytothattype,butonlyshorttermprotectionagainst
theotherthree.[13][19]TheriskofseverediseasefromsecondaryinfectionincreasesifsomeonepreviouslyexposedtoserotypeDENV1contractsserotypeDENV
2orDENV3,orifsomeonepreviouslyexposedtoDENV3acquiresDENV2.[26]Denguecanbelifethreateninginpeoplewithchronicdiseasessuchasdiabetes
andasthma.[26]
Polymorphisms(normalvariations)inparticulargeneshavebeenlinkedwithanincreasedriskofseveredenguecomplications.Examplesincludethegenescoding
fortheproteinsknownasTNF,mannanbindinglectin,[7]CTLA4,TGF,[23]DCSIGN,PLCE1,andparticularformsofhumanleukocyteantigenfromgene
variationsofHLAB.[17][26]Acommongeneticabnormality,especiallyinAfricans,knownasglucose6phosphatedehydrogenasedeficiency,appearstoincrease
therisk.[38]PolymorphismsinthegenesforthevitaminDreceptorandFcRseemtoofferprotectionagainstseverediseaseinsecondarydengueinfection.[26]

Mechanism
Whenamosquitocarryingdenguevirusbitesaperson,thevirusenterstheskintogetherwiththemosquito'ssaliva.Itbindstoandenterswhitebloodcells,and
reproducesinsidethecellswhiletheymovethroughoutthebody.Thewhitebloodcellsrespondbyproducinganumberofsignalingproteins,suchascytokines
andinterferons,whichareresponsibleformanyofthesymptoms,suchasthefever,theflulikesymptoms,andtheseverepains.Insevereinfection,thevirus
productioninsidethebodyisgreatlyincreased,andmanymoreorgans(suchastheliverandthebonemarrow)canbeaffected.Fluidfromthebloodstreamleaks
throughthewallofsmallbloodvesselsintobodycavitiesduetocapillarypermeability.Asaresult,lessbloodcirculatesinthebloodvessels,andtheblood
pressurebecomessolowthatitcannotsupplysufficientbloodtovitalorgans.Furthermore,dysfunctionofthebonemarrowduetoinfectionofthestromalcells
leadstoreducednumbersofplatelets,whicharenecessaryforeffectivebloodclottingthisincreasestheriskofbleeding,theothermajorcomplicationofdengue
fever.[38]

Viralreplication
Onceinsidetheskin,denguevirusbindstoLangerhanscells(apopulationofdendriticcellsintheskinthatidentifiespathogens).[38]Thevirusentersthecells
throughbindingbetweenviralproteinsandmembraneproteinsontheLangerhanscell,specificallytheCtypelectinscalledDCSIGN,mannosereceptorand
CLEC5A.[23]DCSIGN,anonspecificreceptorforforeignmaterialondendriticcells,seemstobethemainpointofentry.[26]Thedendriticcellmovestothe
nearestlymphnode.Meanwhile,thevirusgenomeistranslatedinmembraneboundvesiclesonthecell'sendoplasmicreticulum,wherethecell'sproteinsynthesis
apparatusproducesnewviralproteinsthatreplicatetheviralRNAandbegintoformviralparticles.ImmaturevirusparticlesaretransportedtotheGolgi
apparatus,thepartofthecellwheresomeoftheproteinsreceivenecessarysugarchains(glycoproteins).Thenowmaturenewvirusesarereleasedbyexocytosis.
Theyarethenabletoenterotherwhitebloodcells,suchasmonocytesandmacrophages.[23]

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Theinitialreactionofinfectedcellsistoproduceinterferon,acytokinethatraisesanumberofdefensesagainstviralinfectionthroughtheinnateimmunesystem
byaugmentingtheproductionofalargegroupofproteinsmediatedbytheJAKSTATpathway.Someserotypesofdenguevirusappeartohavemechanismsto
slowdownthisprocess.Interferonalsoactivatestheadaptiveimmunesystem,whichleadstothegenerationofantibodiesagainstthevirusaswellasTcellsthat
directlyattackanycellinfectedwiththevirus.[23]Variousantibodiesaregeneratedsomebindcloselytotheviralproteinsandtargetthemforphagocytosis
(ingestionbyspecializedcellsanddestruction),butsomebindtheviruslesswellandappearinsteadtodeliverthevirusintoapartofthephagocyteswhereitisnot
destroyedbutisabletoreplicatefurther.[23]

Severedisease
Itisnotentirelyclearwhysecondaryinfectionwithadifferentstrainofdenguevirusplacespeopleatriskofdenguehemorrhagicfeveranddengueshock
syndrome.Themostwidelyacceptedhypothesisisthatofantibodydependentenhancement(ADE).TheexactmechanismbehindADEisunclear.Itmaybe
causedbypoorbindingofnonneutralizingantibodiesanddeliveryintothewrongcompartmentofwhitebloodcellsthathaveingestedthevirusfor
destruction.[23][26]ThereisasuspicionthatADEisnottheonlymechanismunderlyingseveredenguerelatedcomplications,[7][24]andvariouslinesofresearch
haveimpliedaroleforTcellsandsolublefactorssuchascytokinesandthecomplementsystem.[38]
Severediseaseismarkedbytheproblemsofcapillarypermeability(anallowanceoffluidandproteinnormallycontainedwithinbloodtopass)anddisordered
bloodclotting.[16][17]Thesechangesappearassociatedwithadisorderedstateoftheendothelialglycocalyx,whichactsasamolecularfilterofblood
components.[17]Leakycapillaries(andthecriticalphase)arethoughttobecausedbyanimmunesystemresponse.[17]Otherprocessesofinterestincludeinfected
cellsthatbecomenecroticwhichaffectbothcoagulationandfibrinolysis(theopposingsystemsofbloodclottingandclotdegradation)andlowplateletsinthe
blood,alsoafactorinnormalclotting.[38]

Diagnosis
Thediagnosisofdengueistypicallymadeclinically,onthebasisofreportedsymptomsandphysicalexaminationthis
appliesespeciallyinendemicareas.[7]However,earlydiseasecanbedifficulttodifferentiatefromotherviralinfections.[5]A
probablediagnosisisbasedonthefindingsoffeverplustwoofthefollowing:nauseaandvomiting,rash,generalizedpains,
lowwhitebloodcellcount,positivetourniquettest,oranywarningsign(seetable)insomeonewholivesinanendemic
area.[39]Warningsignstypicallyoccurbeforetheonsetofseveredengue.[18]Thetourniquettest,whichisparticularlyuseful
insettingswherenolaboratoryinvestigationsarereadilyavailable,involvestheapplicationofabloodpressurecuffat
betweenthediastolicandsystolicpressureforfiveminutes,followedbythecountingofanypetechialhemorrhagesa
highernumbermakesadiagnosisofdenguemorelikelywiththecutoffbeingmorethan10to20per1inch2
(6.25cm2).[18][40]

Warningsigns[17][39]
Worseningabdominalpain
Ongoingvomiting
Liverenlargement
Mucosalbleeding
Highhematocritwithlowplatelets
Lethargyorrestlessness
Serosaleffusions

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Thediagnosisshouldbeconsideredinanyonewhodevelopsafeverwithintwoweeksofbeinginthetropicsorsubtropics.[17]Itcanbedifficulttodistinguish
denguefeverandchikungunya,asimilarviralinfectionthatsharesmanysymptomsandoccursinsimilarpartsoftheworldtodengue.[19]Often,investigationsare
performedtoexcludeotherconditionsthatcausesimilarsymptoms,suchasmalaria,leptospirosis,viralhemorrhagicfever,typhoidfever,meningococcaldisease,
measles,andinfluenza.[5][41]Zikafeveralsohassimilarsymptomsasdengue.[42]
Theearliestchangedetectableonlaboratoryinvestigationsisalowwhitebloodcellcount,whichmaythenbefollowedbylowplateletsandmetabolicacidosis.[5]
Amoderatelyelevatedlevelofaminotransferase(ASTandALT)fromtheliveriscommonlyassociatedwithlowplateletsandwhitebloodcells.[17]Insevere
disease,plasmaleakageresultsinhemoconcentration(asindicatedbyarisinghematocrit)andhypoalbuminemia.[5]Pleuraleffusionsorascitescanbedetectedby
physicalexaminationwhenlarge,[5]butthedemonstrationoffluidonultrasoundmayassistintheearlyidentificationofdengueshocksyndrome.[5][7]Theuseof
ultrasoundislimitedbylackofavailabilityinmanysettings.[7]Dengueshocksyndromeispresentifpulsepressuredropsto20mmHgalongwithperipheral
vascularcollapse.[17]Peripheralvascularcollapseisdeterminedinchildrenviadelayedcapillaryrefill,rapidheartrate,orcoldextremities.[18]Whilewarning
signsareanimportantaspectforearlydetectionofpotentialseriousdisease,theevidenceforanyspecificclinicalorlaboratorymarkerisweak.[43]

Classification
TheWorldHealthOrganization's2009classificationdividesdenguefeverintotwogroups:uncomplicatedandsevere.[7][39]Thisreplacesthe1997WHO
classification,whichneededtobesimplifiedasithadbeenfoundtobetoorestrictive,thoughtheolderclassificationisstillwidelyused[39]includingbytheWorld
HealthOrganization'sRegionalOfficeforSouthEastAsiaasof2011.[44]Severedengueisdefinedasthatassociatedwithseverebleeding,severeorgan
dysfunction,orsevereplasmaleakagewhileallothercasesareuncomplicated.[39]The1997classificationdivideddengueintoundifferentiatedfever,denguefever,
anddenguehemorrhagicfever.[5][45]DenguehemorrhagicfeverwassubdividedfurtherintogradesIIV.GradeIisthepresenceonlyofeasybruisingorapositive
tourniquettestinsomeonewithfever,gradeIIisthepresenceofspontaneousbleedingintotheskinandelsewhere,gradeIIIistheclinicalevidenceofshock,and
gradeIVisshocksoseverethatbloodpressureandpulsecannotbedetected.[45]GradesIIIandIVarereferredtoas"dengueshocksyndrome".[39][45]

Laboratorytests
Thediagnosisofdenguefevermaybeconfirmedbymicrobiologicallaboratorytesting.[39][46]Thiscanbedonebyvirusisolationincellcultures,nucleicacid
detectionbyPCR,viralantigendetection(suchasforNS1)orspecificantibodies(serology).[26][41]Virusisolationandnucleicaciddetectionaremoreaccurate
thanantigendetection,butthesetestsarenotwidelyavailableduetotheirgreatercost.[41]DetectionofNS1duringthefebrilephaseofaprimaryinfectionmaybe
greaterthan90%sensitivehoweverisonly6080%insubsequentinfections.[17]Alltestsmaybenegativeintheearlystagesofthedisease.[5][26]PCRandviral
antigendetectionaremoreaccurateinthefirstsevendays.[17]In2012aPCRtestwasintroducedthatcanrunonequipmentusedtodiagnoseinfluenzathisis
likelytoimproveaccesstoPCRbaseddiagnosis.[47]

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Theselaboratorytestsareonlyofdiagnosticvalueduringtheacutephaseoftheillnesswiththeexceptionof
serology.Testsfordenguevirusspecificantibodies,typesIgGandIgM,canbeusefulinconfirminga
diagnosisinthelaterstagesoftheinfection.BothIgGandIgMareproducedafter57days.Thehighest
levels(titres)ofIgMaredetectedfollowingaprimaryinfection,butIgMisalsoproducedinreinfection.IgM
becomesundetectable3090daysafteraprimaryinfection,butearlierfollowingreinfections.IgG,by
contrast,remainsdetectableforover60yearsand,intheabsenceofsymptoms,isausefulindicatorofpast
infection.Afteraprimaryinfection,IgGreachespeaklevelsinthebloodafter1421days.Insubsequentre
infections,levelspeakearlierandthetitresareusuallyhigher.BothIgGandIgMprovideprotective
immunitytotheinfectingserotypeofthevirus.[15][19][26]IntestingforIgGandIgMantibodiestheremaybe
crossreactivitywithotherflaviviruseswhichmayresultinafalsepositiveafterrecentinfectionsor
vaccinationswithyellowfevervirusorJapaneseencephalitis.[17]ThedetectionofIgGaloneisnot
considereddiagnosticunlessbloodsamplesarecollected14daysapartandagreaterthanfourfoldincreasein
levelsofspecificIgGisdetected.Inapersonwithsymptoms,thedetectionofIgMisconsidered
diagnostic.[15]

Prevention

Graphofwhenlaboratorytestsfordenguefever
becomepositive.Dayzeroreferstothestartof
symptoms,1streferstointhosewithaprimary
infection,and2ndreferstointhosewithasecondary
infection. [17]

Preventiondependsoncontrolofandprotectionfromthebitesofthemosquitothattransmitsit.[28][48]The
WorldHealthOrganizationrecommendsanIntegratedVectorControlprogramconsistingoffive
elements:[28]
1.Advocacy,socialmobilizationandlegislationtoensurethatpublichealthbodiesandcommunitiesare
strengthened
2.Collaborationbetweenthehealthandothersectors(publicandprivate)
3.Anintegratedapproachtodiseasecontroltomaximizeuseofresources
4.Evidencebaseddecisionmakingtoensureanyinterventionsaretargetedappropriatelyand
5.Capacitybuildingtoensureanadequateresponsetothelocalsituation.
TheprimarymethodofcontrollingA.aegyptiisbyeliminatingitshabitats.[28]Thisisdonebygettingridof
opensourcesofwater,orifthisisnotpossible,byaddinginsecticidesorbiologicalcontrolagentstothese
areas.[28]Generalizedsprayingwithorganophosphateorpyrethroidinsecticides,whilesometimesdone,isnot
thoughttobeeffective.[14]Reducingopencollectionsofwaterthroughenvironmentalmodificationisthe
preferredmethodofcontrol,giventheconcernsofnegativehealtheffectsfrominsecticidesandgreater
logisticaldifficultieswithcontrolagents.[28]Peoplecanpreventmosquitobitesbywearingclothingthatfully

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coverstheskin,usingmosquitonettingwhileresting,and/ortheapplicationofinsectrepellent(DEETbeingthemosteffective).[32]However,thesemethods
appearnottobesufficientlyeffective,asthefrequencyofoutbreaksappearstobeincreasinginsomeareas,probablyduetourbanizationincreasingthehabitatof
A.aegypti.Therangeofthediseaseappearstobeexpandingpossiblyduetoclimatechange.[3]

Vaccine
In2016apartiallyeffectivevaccinefordenguefeverbecamecommerciallyavailableinthePhilippinesandIndonesia.[49][50]Ithasalsobeenapprovedforusby
Mexico,Brazil,ElSalvador,CostaRica,andParaguay.[50]InIndonesiaitcostsaboutUS$207fortherecommendedthreedoses.[50]
ThevaccineisproducedbySanofiandgoesbythebrandnameDengvaxia.[51]Itisbasedonaweakenedcombinationoftheyellowfevervirusandeachofthe
fourdengueserotypes.[29][52]Twostudiesofavaccinefounditwas60%effectiveandpreventedmorethan80to90%ofseverecases.[53][54]Thisislessthan
wishedforbysome.[55]
Thereareongoingprogramsworkingonadenguevaccinetocoverallfourserotypes.[48]Nowthatthereisafifthserotypethiswillneedtobefactoredin.[3]One
oftheconcernsisthatavaccinecouldincreasetheriskofseverediseasethroughantibodydependentenhancement(ADE).[56]Theidealvaccineissafe,effective
afteroneortwoinjections,coversallserotypes,doesnotcontributetoADE,iseasilytransportedandstored,andisbothaffordableandcosteffective.[56]

Antidengueday
InternationalAntiDengueDayisobservedeveryyearonJune15.[57]Theideawasfirstagreeduponin2010
withthefirsteventheldinJakarta,Indonesiain2011.[57]Furthereventswereheldin2012inYangon,Myanmar
andin2013inVietnam.[57]Goalsaretoincreasepublicawarenessaboutdengue,mobilizeresourcesforits
preventionandcontroland,todemonstratetheAsianregion'scommitmentintacklingthedisease.[58]

Management
Therearenospecificantiviraldrugsfordengue,howevermaintainingproperfluidbalanceisimportant.[17]
Treatmentdependsonthesymptoms.[59]Thosewhoareabletodrink,arepassingurine,haveno"warningsigns"
andareotherwisehealthycanbemanagedathomewithdailyfollowupandoralrehydrationtherapy.[59]Those
whohaveotherhealthproblems,have"warningsigns",orwhocannotmanageregularfollowupshouldbe
caredforinhospital.[5][59]Inthosewithseveredenguecareshouldbeprovidedinanareawherethereisaccess
toanintensivecareunit.[59]
https://en.wikipedia.org/wiki/Dengue_fever

Aposternotifyingpeoplethatthereare10or
morecasesofdengueintheneighbourhood.

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Intravenoushydration,ifrequired,istypicallyonlyneededforoneortwodays.[59]Inchildrenwithshockduetodenguearapiddoseof20mL/kgisreasonable.[60]
Therateoffluidadministrationisthantitratedtoaurinaryoutputof0.51mL/kg/h,stablevitalsignsandnormalizationofhematocrit.[5]Thesmallestamountof
fluidrequiredtoachievethisisrecommended.[59]
Invasivemedicalproceduressuchasnasogastricintubation,intramuscularinjectionsandarterialpuncturesareavoided,inviewofthebleedingrisk.[5]
Paracetamol(acetaminophen)isusedforfeveranddiscomfortwhileNSAIDssuchasibuprofenandaspirinareavoidedastheymightaggravatetheriskof
bleeding.[59]Bloodtransfusionisinitiatedearlyinpeoplepresentingwithunstablevitalsignsinthefaceofadecreasinghematocrit,ratherthanwaitingforthe
hemoglobinconcentrationtodecreasetosomepredetermined"transfusiontrigger"level.[61]Packedredbloodcellsorwholebloodarerecommended,while
plateletsandfreshfrozenplasmaareusuallynot.[61]Thereisnotenoughevidencetodetermineifcorticosteroidshaveapositiveornegativeeffectindengue
fever.[62]
Duringtherecoveryphaseintravenousfluidsarediscontinuedtopreventastateoffluidoverload.[5]Iffluidoverloadoccursandvitalsignsarestable,stopping
furtherfluidmaybeallthatisneeded.[61]Ifapersonisoutsideofthecriticalphase,aloopdiureticsuchasfurosemidemaybeusedtoeliminateexcessfluidfrom
thecirculation.[61]

Epidemiology
Mostpeoplewithdenguerecoverwithoutanyongoingproblems.[39]Thefatalityrateis15%,[5]andless
than1%withadequatetreatment[39]howeverthosewhodevelopsignificantlylowbloodpressuremayhave
afatalityrateofupto26%.[5]Dengueiscommoninmorethan110countries.[5]Itinfects50to528million
peopleworldwideayear,leadingtohalfamillionhospitalizations,[7][8]andapproximately20,000deaths.[9]
Forthedecadeofthe2000s,12countriesinSoutheastAsiawereestimatedtohaveabout3millioninfections
and6,000deathsannually.[63]Itisreportedinatleast22countriesinAfricabutislikelypresentinallof
themwith20%ofthepopulationatrisk.[64]Thismakesitoneofthemostcommonvectorbornediseases
worldwide.[43]
Infectionsaremostcommonlyacquiredintheurbanenvironment.[15]Inrecentdecades,theexpansionof
villages,townsandcitiesintheareasinwhichitiscommon,andtheincreasedmobilityofpeoplehas
increasedthenumberofepidemicsandcirculatingviruses.Denguefever,whichwasonceconfinedto
SoutheastAsia,hasnowspreadtoSouthernChina,countriesinthePacificOceanandAmerica,[15]andmight
poseathreattoEurope.[14]

https://en.wikipedia.org/wiki/Dengue_fever

A.aegyptiandDenguedistributionin2006
A.aegyptidistributionwithhistoryofepidemic
dengue
A.aegyptidistributionwithouthistoryof
epidemicdengue

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Ratesofdengueincreased30foldbetween1960and2010.[65]Thisincreaseisbelievedtobeduetoa
combinationofurbanization,populationgrowth,increasedinternationaltravel,andglobalwarming.[7]The
geographicaldistributionisaroundtheequator.Ofthe2.5billionpeoplelivinginareaswhereitiscommon
70%arefromAsiaandthePacific.[65]Aninfectionwithdengueissecondonlytomalariaasadiagnosed
causeoffeveramongtravelersreturningfromthedevelopingworld.[19]Itisthemostcommonviraldisease
transmittedbyarthropods,[23]andhasadiseaseburdenestimatedat1,600disabilityadjustedlifeyearsper
millionpopulation.[26]TheWorldHealthOrganizationcountsdengueasoneofseventeenneglectedtropical
diseases.[66]

Denguefeverdeathspermillionpersonsin2012
00

22

48

Likemostarboviruses,denguevirusismaintainedinnatureincyclesthatinvolvepreferredbloodsucking
11
33
9561
[15]
vectorsandvertebratehosts. ThevirusesaremaintainedintheforestsofSoutheastAsiaandAfricaby
transmissionfromfemaleAedesmosquitoesofspeciesotherthanA.aegyptitotheiroffspringandto
lowerprimates.[15]Intownsandcities,thevirusisprimarilytransmittedbythehighlydomesticatedA.aegypti.Inruralsettingsthevirusistransmittedtohumans
byA.aegyptiandotherspeciesofAedessuchasA.albopictus.[15]Boththesespecieshadexpandingrangesinthesecondhalfofthe20thcentury.[17]Inallsettings
theinfectedlowerprimatesorhumansgreatlyincreasethenumberofcirculatingdengueviruses,inaprocesscalledamplification.[15]

History
ThefirstrecordofacaseofprobabledenguefeverisinaChinesemedicalencyclopediafromtheJinDynasty(265420AD)whichreferredtoa"waterpoison"
associatedwithflyinginsects.[6][67]Theprimaryvector,A.aegypti,spreadoutofAfricainthe15thto19thcenturiesdueinparttoincreasedglobalization
secondarytotheslavetrade.[17]Therehavebeendescriptionsofepidemicsinthe17thcentury,butthemostplausibleearlyreportsofdengueepidemicsarefrom
1779and1780,whenanepidemicsweptacrossAsia,AfricaandNorthAmerica.[6]Fromthattimeuntil1940,epidemicswereinfrequent.[6]
In1906,transmissionbytheAedesmosquitoeswasconfirmed,andin1907denguewastheseconddisease(afteryellowfever)thatwasshowntobecausedbya
virus.[11]FurtherinvestigationsbyJohnBurtonClelandandJosephFranklinSilercompletedthebasicunderstandingofdenguetransmission.[11]
ThemarkedspreadofdengueduringandaftertheSecondWorldWarhasbeenattributedtoecologicdisruption.Thesametrendsalsoledtothespreadofdifferent
serotypesofthediseasetonewareas,andtotheemergenceofdenguehemorrhagicfever.ThissevereformofthediseasewasfirstreportedinthePhilippinesin
1953bythe1970s,ithadbecomeamajorcauseofchildmortalityandhademergedinthePacificandtheAmericas.[6]Denguehemorrhagicfeveranddengue
shocksyndromewerefirstnotedinCentralandSouthAmericain1981,asDENV2wascontractedbypeoplewhohadpreviouslybeeninfectedwithDENV1
severalyearsearlier.[22]

Etymology
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TheoriginsoftheSpanishworddenguearenotcertain,butitispossiblyderivedfromdingaintheSwahiliphraseKadingapepo,whichdescribesthediseaseas
beingcausedbyanevilspirit.[67]SlavesintheWestIndieshavingcontracteddengueweresaidtohavethepostureandgaitofadandy,andthediseasewasknown
as"dandyfever".[68][69]
Theterm"breakbonefever"wasappliedbyphysicianandUnitedStatesFoundingFatherBenjaminRush,ina1789reportofthe1780epidemicinPhiladelphia.
Inthereporttitleheusesthemoreformalterm"biliousremittingfever".[70]Thetermdenguefevercameintogeneraluseonlyafter1828.[69]Otherhistoricalterms
include"breakheartfever"and"ladengue".[69]Termsforseverediseaseinclude"infectiousthrombocytopenicpurpura"and"Philippine","Thai",or"Singapore
hemorrhagicfever".[69]

Research
Researcheffortstopreventandtreatdengueincludevariousmeansofvectorcontrol,[71]vaccine
development,andantiviraldrugs.[48]

Vector
Withregardstovectorcontrol,anumberofnovelmethodshavebeenusedtoreducemosquitonumberswith
somesuccessincludingtheplacementoftheguppy(Poeciliareticulata)orcopepodsinstandingwatertoeat
themosquitolarvae.[71]TherearealsotrialswithgeneticallymodifiedmaleA.aegyptithatafterreleaseinto
thewildmatewithfemales,andrendertheiroffspringunabletofly.[72]

Wolbachia
AttemptsareongoingtoinfectthemosquitopopulationwithbacteriaoftheWolbachiagenus,whichmakes
themosquitoespartiallyresistanttodenguevirus.[17][73]WhileartificiallyinducedinfectionswithWolbachia
iseffective,itisunclearifnaturallyacquiredinfectionsareprotective.[74]Workingisstillongoingasof2015
todeterminethebesttypeofWolbachiatouse.[75]

PublichealthofficersreleasingP.reticulatafryinto
anartificiallakeintheLagoNortedistrictof
Braslia,Brazil,aspartofavectorcontroleffort

Treatment
ApartfromattemptstocontrolthespreadoftheAedesmosquitothereareongoingeffortstodevelopantiviraldrugsthatwouldbeusedtotreatattacksofdengue
feverandpreventseverecomplications.[12][76]Discoveryofthestructureoftheviralproteinsmayaidthedevelopmentofeffectivedrugs.[12]Thereareseveral
plausibletargets.ThefirstapproachisinhibitionoftheviralRNAdependentRNApolymerase(codedbyNS5),whichcopiestheviralgeneticmaterial,with
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nucleosideanalogs.Secondly,itmaybepossibletodevelopspecificinhibitorsoftheviralprotease(codedbyNS3),whichsplicesviralproteins.[77]Finally,itmay
bepossibletodevelopentryinhibitors,whichstopthevirusenteringcells,orinhibitorsofthe5cappingprocess,whichisrequiredforviralreplication.[76]

References
The2014versionofthisarticlehaspassedacademicpeerreviewandbeenpublishedinthejournalOpen
Medicine[i]
Thepublishedversioncanbereadandcitedhere(http://www.ncbi.nlm.nih.gov/pubmed/25426178) andthe
peerreviewhere(https://en.wikipedia.org/wiki/Talk:Dengue_fever/Archive_1#Formal_peer_review_by_Ope
n_Medicine).
Publishedversion
i.HeilmanJM,DeWolffJ,BeardsGM,BasdenBJ(2014)."Denguefever:aWikipediaclinicalreview".OpenMedicine.pp.105115.PMC4242787 .PMID25426178.

References
1."DengueandseveredengueFactsheetN117".WHO.May2015.Retrieved
3February2016.
2.Kularatne,SA(15September2015)."Denguefever.".BMJ(Clinicalresearch
ed.).351:h4661.PMID26374064.
3.NormileD(2013)."Surprisingnewdenguevirusthrowsaspannerindisease
controlefforts".Science.342(6157):415.doi:10.1126/science.342.6157.415.
PMID24159024.
4.Maron,Dina(December30,2015)."FirstDengueFeverVaccineGetsGreenLight
in3Countries".ScientificAmerican.Retrieved3February2016.
5.RanjitS,KissoonN(January2011)."Denguehemorrhagicfeverandshock
syndromes".Pediatr.Crit.CareMed.12(1):90100.
doi:10.1097/PCC.0b013e3181e911a7.PMID20639791.
6.GublerDJ(July1998)."Dengueanddenguehemorrhagicfever".Clin.Microbiol.
Rev.11(3):48096.PMC88892 .PMID9665979.
7.WhitehornJ,FarrarJ(2010)."Dengue".Br.Med.Bull.95:16173.
doi:10.1093/bmb/ldq019.PMID20616106.
8.BhattS,GethingPW,BradyOJ,etal.(April2013)."Theglobaldistributionand
burdenofdengue".Nature.496(7446):5047.doi:10.1038/nature12060.
PMC3651993 .PMID23563266.

https://en.wikipedia.org/wiki/Dengue_fever

9.Carabali,MHernandez,LMArauz,MJVillar,LARidde,V(30July2015).
"Whyarepeoplewithdenguedying?Ascopingreviewofdeterminantsfordengue
mortality.".BMCinfectiousdiseases.15:301.doi:10.1186/s128790151058x.
PMC4520151 .PMID26223700.
10.Stanaway,JDShepard,DSUndurraga,EAHalasa,YACoffeng,LEBrady,OJ
Hay,SIBedi,NBensenor,IMCastaedaOrjuela,CAChuang,TWGibney,
KBMemish,ZARafay,AUkwaja,KNYonemoto,NMurray,CJ(10February
2016)."Theglobalburdenofdengue:ananalysisfromtheGlobalBurdenof
DiseaseStudy2013.".TheLancet.Infectiousdiseases.doi:10.1016/S1473
3099(16)000268.PMID26874619.
11.HenchalEA,PutnakJR(October1990)."Thedengueviruses".Clin.Microbiol.
Rev.3(4):37696.doi:10.1128/CMR.3.4.376.PMC358169 .PMID2224837.
12.NobleCG,ChenYL,DongH,etal.(March2010)."Strategiesfordevelopmentof
Denguevirusinhibitors".AntiviralRes.85(3):45062.
doi:10.1016/j.antiviral.2009.12.011.PMID20060421.
13.WHO(2009),pp.1416.
14.ReiterP(11March2010)."Yellowfeveranddengue:athreattoEurope?".Euro
Surveill.15(10):19509.PMID20403310.
15.GublerDJ(2010)."Dengueviruses".InMahyBWJVanRegenmortelMHV.
DeskEncyclopediaofHumanandMedicalVirology.Boston:AcademicPress.
pp.37282.ISBN0123751470.
14/17

11/6/2016

DenguefeverWikipedia

16.VaratharajA(2010)."Encephalitisintheclinicalspectrumofdengueinfection".
Neurol.India.58(4):58591.doi:10.4103/00283886.68655.PMID20739797.
17.SimmonsCPFarrarJJNguyenvVWillsB(April2012)."Dengue".NEnglJ
Med.366(15):142332.doi:10.1056/NEJMra1110265.PMID22494122.
18.WHO(2009),pp.2527.
19.ChenLH,WilsonME(October2010)."Dengueandchikungunyainfectionsin
travelers".CurrentOpinioninInfectiousDiseases.23(5):43844.
doi:10.1097/QCO.0b013e32833c1d16.PMID20581669.
20.WolffKJohnsonRA,eds.(2009)."Viralinfectionsofskinandmucosa".
Fitzpatrick'scoloratlasandsynopsisofclinicaldermatology(6thed.).NewYork:
McGrawHillMedical.pp.8102.ISBN9780071599757.
21.KnoopKJ,StackLB,StorrowA,ThurmanRJ,eds.(2010)."Tropicalmedicine".
Atlasofemergencymedicine(3rded.).NewYork:McGrawHillProfessional.
pp.6589.ISBN0071496181.
22.GouldEA,SolomonT(February2008)."Pathogenicflaviviruses".TheLancet.
371(9611):5009.doi:10.1016/S01406736(08)60238X.PMID18262042.
23.RodenhuisZybertIA,WilschutJ,SmitJM(August2010)."Dengueviruslife
cycle:viralandhostfactorsmodulatinginfectivity".Cell.Mol.LifeSci.67(16):
277386.doi:10.1007/s000180100357z.PMID20372965.
24.CarodArtalFJ,WichmannO,FarrarJ,GascnJ(September2013).
"Neurologicalcomplicationsofdenguevirusinfection".LancetNeurol.12(9):
90619.doi:10.1016/S14744422(13)701509.PMID23948177.
25.Paixo,ESTeixeira,MGCosta,MDRodrigues,LC(July2016)."Dengue
duringpregnancyandadversefetaloutcomes:asystematicreviewandmeta
analysis".TheLancetInfectiousDiseases.16(7):857865.doi:10.1016/S1473
3099(16)000888.PMID26949028.
26.GuzmanMG,HalsteadSB,ArtsobH,etal.(December2010)."Dengue:a
continuingglobalthreat".NatureReviewsMicrobiology.8(12Suppl):S7S16.
doi:10.1038/nrmicro2460.PMID21079655.
27.Solomonides,Tony(2010).Healthgridapplicationsandcoretechnologies:
proceedingsofHealthGrid2010([OnlineAusg.].ed.).Amsterdam:IOSPress.
p.235.ISBN9781607505822.
28.WHO(2009),pp.5964.
29.GlobalStrategyForDenguePreventionAndControl(PDF).WorldHealth
Organization.2012.pp.1617.ISBN9789241504034.
30."Travelers'HealthOutbreakNotice".CentersforDiseaseControlandPrevention.
2June2010.Archivedfromtheoriginalon26August2010.Retrieved27August
2010.
31."Vectorborneviralinfections".WorldHealthOrganization.Retrieved17January
2011.

https://en.wikipedia.org/wiki/Dengue_fever

32.CenterforDiseaseControlandPrevention."Chapter5denguefever(DF)and
denguehemorrhagicfever(DHF)".2010YellowBook.Retrieved23December
2010.
33.St.Georgiev,Vassil(2009).NationalInstituteofAllergyandInfectiousDiseases,
NIH.(1ed.).Totowa,N.J.:Humana.p.268.ISBN9781603272971.
34.WilderSmithA,ChenLH,MassadE,WilsonME(January2009)."Threatof
denguetobloodsafetyindengueendemiccountries".Emerg.Infect.Dis.15(1):
811.doi:10.3201/eid1501.071097.PMC2660677 .PMID19116042.
35.StramerSL,HollingerFB,KatzLM,etal.(August2009)."Emerginginfectious
diseaseagentsandtheirpotentialthreattotransfusionsafety".Transfusion.49
Suppl2:1S29S.doi:10.1111/j.15372995.2009.02279.x.PMID19686562.
36.TeoD,NgLC,LamS(April2009)."Isdengueathreattothebloodsupply?".
TransfusMed.19(2):6677.doi:10.1111/j.13653148.2009.00916.x.
PMC2713854 .PMID19392949.
37.WiwanitkitV(January2010)."Unusualmodeoftransmissionofdengue".Journal
ofInfectioninDevelopingCountries.4(1):514.doi:10.3855/jidc.145.
PMID20130380.
38.MartinaBE,KorakaP,OsterhausAD(October2009)."Denguevirus
pathogenesis:anintegratedview".Clin.Microbiol.Rev.22(4):56481.
doi:10.1128/CMR.0003509.PMC2772360 .PMID19822889.
39.WHO(2009),pp.1011.
40.Halstead,ScottB.(2008).Dengue.London:ImperialCollegePress.p.180&429.
ISBN9781848162280.
41.WHO(2009),pp.9095.
42.Musso,D.Nilles,E.J.CaoLormeau,V.M.(2014)."Rapidspreadofemerging
ZikavirusinthePacificarea".ClinicalMicrobiologyandInfection.20(10):
O595O596.doi:10.1111/14690691.12707.PMID24909208.
43.Yacoub,SophieWills,Bridget(2014)."Predictingoutcomefromdengue".BMC
Medicine.12(1):147.doi:10.1186/s1291601401479.PMC4154521 .
PMID25259615.
44.Comprehensiveguidelinesforpreventionandcontrolofdengueanddengue
haemorrhagicfever.(PDF)(Rev.andexpanded.ed.).NewDelhi,India:World
HealthOrganizationRegionalOfficeforSouthEastAsia.2011.p.17.ISBN978
9290223870.
45.WHO(1997)."Chapter2:clinicaldiagnosis".Denguehaemorrhagicfever:
diagnosis,treatment,preventionandcontrol(PDF)(2nded.).Geneva:World
HealthOrganization.pp.1223.ISBN9241545003.
46.Wiwanitkit,V(July2010)."Denguefever:diagnosisandtreatment".Expert
reviewofantiinfectivetherapy.8(7):8415.doi:10.1586/eri.10.53.
PMID20586568.
47."NewCDCtestfordengueapproved".CentersforDiseaseControland
Prevention.20June2012.
15/17

11/6/2016

DenguefeverWikipedia

48.WHO(2009)p.137146.
49.East,Susie(6April2016)."World'sfirstdenguefevervaccinelaunchedinthe
Philippines".CNN.Retrieved17October2016.
50."DengueFeverVaccineAvailableinIndonesia".October17,2016.
51."Dengvaxia,World'sFirstDengueVaccine,ApprovedinMexico".
www.sanofipasteur.com.Retrieved20151210.
52.GuyB,BarrereB,MalinowskiC,SavilleM,TeyssouR,LangJ(September
2011)."FromresearchtophaseIII:preclinical,industrialandclinicaldevelopment
oftheSanofiPasteurtetravalentdenguevaccine".Vaccine.29(42):722941.
doi:10.1016/j.vaccine.2011.06.094.PMID21745521.
53.Villar,LuisDayan,GustavoHoracioArredondoGarca,JosLuisRivera,Doris
MaribelCunha,RivaldoDeseda,CarmenReynales,HumbertoCosta,Maria
SelmaMoralesRamrez,JavierOsvaldoCarrasquilla,GabrielRey,LuisCarlos
Dietze,ReynaldoLuz,KleberRivas,EnriqueMontoya,MariaConsuelo
MirandaSupelano,MargaritaCortsZambrano,BetzanaLangevin,EdithBoaz,
MarkTornieporth,NadiaSaville,MelanieNoriega,Fernando(3November
2014)."EfficacyofaTetravalentDengueVaccineinChildreninLatinAmerica".
NewEnglandJournalofMedicine.372(2):113123.
doi:10.1056/NEJMoa1411037.PMID25365753.
54.Villar,LDayan,GHArredondoGarca,JLRivera,DMCunha,RDeseda,C
Reynales,HCosta,MSMoralesRamrez,JOCarrasquilla,GRey,LCDietze,
RLuz,KRivas,EMirandaMontoya,MCCortsSupelano,MZambrano,B
Langevin,EBoaz,MTornieporth,NSaville,MNoriega,FCYD15Study,
Group(8January2015)."Efficacyofatetravalentdenguevaccineinchildrenin
LatinAmerica.".TheNewEnglandJournalofMedicine.372(2):11323.
doi:10.1056/nejmoa1411037.PMID25365753.
55.Pollack,Andrew(20151209)."FirstDengueFeverVaccineApprovedby
Mexico".TheNewYorkTimes.ISSN03624331.Retrieved20151210.
56.WebsterDP,FarrarJ,RowlandJonesS(November2009)."Progresstowardsa
denguevaccine".LancetInfectDis.9(11):67887.doi:10.1016/S1473
3099(09)702543.PMID19850226.
57."MarkingASEANDengueDay".Retrieved16June2015.
58.ACTIONAGAINSTDENGUEDengueDayCampaignsAcrossAsia.World
HealthOrganization.2011.ISBN9789290615392.
59.WHO(2009),pp.3237.
60.deCaen,ARBerg,MDChameides,LGooden,CKHickey,RWScott,HF
Sutton,RMTijssen,JATopjian,AvanderJagt,WSchexnayder,SM
Samson,RA(3November2015)."Part12:PediatricAdvancedLifeSupport:2015
AmericanHeartAssociationGuidelinesUpdateforCardiopulmonaryResuscitation
andEmergencyCardiovascularCare.".Circulation.132(18Suppl2):S52642.
doi:10.1161/CIR.0000000000000266.PMID26473000.
https://en.wikipedia.org/wiki/Dengue_fever

61.WHO(2009),pp.4043.
62.Zhang,FKramer,CV(1July2014)."Corticosteroidsfordengueinfection".The
Cochranedatabaseofsystematicreviews.7(7):CD003488.
doi:10.1002/14651858.CD003488.pub3.PMID24984082.
63.ShepardDS,UndurragaEA,HalasaYA(2013).GublerDJ,ed."Economicand
diseaseburdenofdengueinSoutheastAsia".PLoSNeglTropDis.7(2):e2055.
doi:10.1371/journal.pntd.0002055.PMC3578748 .PMID23437406.
64.Amarasinghe,AKuritsk,JNLetson,GWMargolis,HS(August2011)."Dengue
virusinfectioninAfrica.".EmergingInfectiousDiseases.17(8):134954.
doi:10.3201/eid1708.101515.PMC3381573 .PMID21801609.
65.WHO(2009),p.3.
66.NeglectedTropicalDiseases."The17neglectedtropicaldiseases".WorldHealth
Organization.Retrieved10April2013.
67.Anonymous(2006)."Etymologia:dengue"(PDF).Emerg.Infec.Dis.12(6):893.
doi:10.3201/eid1206.ET1206.
68.Anonymous(15June1998)."DefinitionofDandyfever".MedicineNet.com.
Retrieved25December2010.
69.HalsteadSB(2008).Dengue(TropicalMedicine:ScienceandPractice).River
Edge,N.J:ImperialCollegePress.pp.110.ISBN1848162286.
70.BarrettAD,StanberryLR(2009).Vaccinesforbiodefenseandemergingand
neglecteddiseases.SanDiego:Academic.pp.287323.ISBN0123694086.
71.WHO(2009),p.71.
72.Fong,I(2013).ChallengesinInfectiousDiseases.Springer.p.219.ISBN9781
461444961.
73." 'Bug'couldcombatdenguefever".BBCNEWS.BritishBroadcasting
Corporation.2January2009.
74.Johnson,KN(4November2015)."TheImpactofWolbachiaonVirusInfectionin
Mosquitoes.".Viruses.7(11):570517.doi:10.3390/v7112903.PMC4664976 .
PMID26556361.
75.Lambrechts,LFerguson,NMHarris,EHolmes,ECMcGraw,EAO'Neill,
SLOoi,EERitchie,SARyan,PAScott,TWSimmons,CPWeaver,SC(July
2015)."Assessingtheepidemiologicaleffectofwolbachiafordenguecontrol.".
TheLancet.Infectiousdiseases.15(7):8626.doi:10.1016/S1473
3099(15)000912.PMID26051887.
76.SampathA,PadmanabhanR(January2009)."Moleculartargetsforflavivirus
drugdiscovery".AntiviralRes.81(1):615.doi:10.1016/j.antiviral.2008.08.004.
PMC2647018 .PMID18796313.
77.TomlinsonSM,MalmstromRD,WatowichSJ(June2009)."Newapproachesto
structurebaseddiscoveryofdengueproteaseinhibitors".InfectiousDisorders
DrugTargets.9(3):32743.doi:10.2174/1871526510909030327.
PMID19519486.
16/17

11/6/2016

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WHO(2009).DengueGuidelinesforDiagnosis,Treatment,PreventionandControl(PDF).Geneva:WorldHealthOrganization.ISBN9241547871.

Externallinks
Denguefever(https://www.dmoz.org/Health/Conditions_and_Diseases/Infectious_Diseases/Viral/Hemorrhagic_Fevers/Dengue_Fever/)atDMOZ
"Dengue".WHO.Retrieved27June2011.
"Dengue".U.S.CentersforDiseaseControlandPrevention.Retrieved27June2011.
"Denguefever".UKHealthProtectionAgency.Retrieved27June2011.
"DengueMap".U.S.CentersforDiseaseControlandPrevention/HealthMap.Retrieved27June2011.
Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Dengue_fever&oldid=745336685"
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