出血熱病毒課件

HemorrhagicFeverVirus出血熱病毒

HaemorrhagicFeverwithRenalSyndrome(HFRS:laterrenamedhantavirusdisease,HVD)firstrecognizedinHeilongjiang,Chinainthe1930s,andcametotheattentionoftheWestduringtheKoreanwarwhenover3000UNtroopswereafflictedIttranspiredthatthediseasewasnotnewandhadbeendescribedbythe

Chinese1000yearsearlierIn1974,thecausativewasisolatedfromtheKoreanStrippedfieldmiceandwascalledHantaanvirusIn1995,anewdiseaseentitycalledhantaviruspulmonarysyndromewasdescribedinthe“fourcorners”regionoftheU.S.病毒體VirionFormsaseparategenusintheBunyavirusfamily

布尼雅病毒科Unlikeotherbunyaviridae,itstransmissiondoesnot

involvean

arthropodvectorEnveloped-ssRNAvirusVirions

98nmindiameterwithacharacteristicsquaregrid-likestructure.GenomeconsistsofthreeRNAsegments:L,M,andS.基于中和試驗的血清型

SubtypesofHantavirusesBasedNT黑線姬鼠型褐家鼠型歐洲棕背鼠型草原田鼠型巴爾干姬鼠型小家鼠型根據(jù)抗原和基因結(jié)構(gòu)分型（10型）Hantaan（漢灘型）Porrogiaandrelatedviruses-ThisgroupisfoundinChina,EasternUSSR,andsomepartsofS.Europe.Itisresponsibleforthesevereclassicaltypeofhantavirusdisease.Itiscarriedbystrippedfieldmice.(Apodemus

agrarius)

Seoultype（漢城型）associatedwithmoderatehantavirusdisease.Itiscarriedbyratsandhaveaworldwidedistribution.IthasbeenidentifiedinChina,Japan,WesternUSSR,USAandS.America.Puumalatype

mainlyfoundinScandinaviancountries,France,UKandtheWesternUSSR.Itiscarriedbybankvoles(Clethrionomys

glareolus)andcausesmildhantavirusdisease(nephropathia

epidemica).SinNombre（辛諾柏型）foundinmanypartsoftheUS,CanadaandMexico.CarriedbytheDeerMouse(Peromyscus

maniculatus)

andcauseshantaviruspulmonarysyndrome.流行病毒學(xué)EpidemiologyNaturalhost:RodentApodemus

agrarius

(Strippedfieldmice,黑線姬鼠)傳染源：黑線姬鼠、褐家鼠、大林姬鼠Viralcontaminationcomesfromrodenturine,stool,salivarysecretionSeasonalandregionaldistribution(autumnandwinter,Oct.-Jan.)Theinfectionrouteisstilluncertain.Thepossibleentriesarerespiratorytract,mouth,anddirectcontactRodentCarriersofHantavirusesStrippedfieldmouse(Apodemus

agrarius)

Bankvole(Clethrionomysglareolus)

DeerMouse(Peromyscus

maniculatus)

Rat(Rattus)臨床特點ClinicalFeaturesIncubation:2weeks,HFRSPathogenesismechanismisunknown.Immunologicalreactionmayplayrole極低的隱性感染率Verylowsubclinicalinfectionrate(1-4%)

病后穩(wěn)定的免疫力，一般不再發(fā)病Stablehumoralimmunity.norepeatinfection致病性PathogenesisThemultisystempathologyofHVDischaracterizedbydamagetocapillariesandsmallvesselwalls,resultinginvasodilationandcongestionwithhemorrhagesClassically,hantavirusdiseaseconsistsof5distinctphases.ThesephasesmaybeblurredinmoderateormildcasesFebrilephase

發(fā)熱期abruptonsetofasevereflu-likeillnesswithaerythematousrashafteranincubationperiodof2-3daysHypotensivephase

低血壓期beginsatday5ofillnessOliguricphase

少尿期beginsatday9ofillness.Thepatientmaydevelopacuterenalfailureandshock.Haemorrhagesareusuallyconfinedtopetechiae.ThemajorityofdeathsoccurduringthehypotensiveandoliguricphasesDiureticphase

多尿期occursbetweendays12-14Convalescentphase

恢復(fù)期mayrequireupto4monthsComparativeClinicalFeaturesofRecognizedHantavirusDisease(HVD)漢坦病毒肺綜合征

HantavirusPulmonarySyndromeThemajorityofcasesarecausedbytheSinNombrevirus（漢坦病毒屬辛諾柏病毒）Morethan250casesofHPShavebeenreportedthroughoutNorthandSouthAmericawithamortalityrateof50%HPShasasimilarfebrilephase,However,thedamagetothecapillariesoccurpredominantlyinthelungsratherthanthekidney.Shockandcardiaccomplicationsmayleadtodeath

診斷Diagnosis血清學(xué)診斷-avarietyoftestsincludingIF,HAI,SRH,ELISAshavebeendevelopedforthediagnosisofHVDandHPS直接檢測病毒抗原-thisappearstobemoresensitivethanserologytestsintheearlydiagnosisofthedisease.ThevirusantigencanbedemonstratedinthebloodorurineRT-PCR

-foundtoofgreatuseindiagnosinghantaviruspulmonarysyndrome病毒分離Virusisolation-isolationofthevirusfromurineissuccessfulearlyinhantavirusdisease.Isolationofthevirusfromthebloodislessconsistent免疫組化

-usefulindiagnosingHPS治療和預(yù)防TreatmentofHVDandHPSdependsmainlyonsupportivemeasures

支持療法Ribavirin

利巴韋林reportedtobeusefulifgivenearlyinthecourseofhantavirusdiseaseVaccinationaninactivatedvaccineisbeingtriedoutinChina.OthercandidatevaccinesarebeingpreparedRodentControlcontrolmeasuresshouldbeaimedatreducingcontactbetweenhumansandrodents新疆出血熱病毒

XinjiangHemorrhagicFeverVirus于1966年首次從我國新疆塔里木盆地出血熱病人血液、尸體臟器及硬蜱中分離成功而得名該病毒在流行病學(xué)及病毒抗原性等方面與克里米亞-剛果出血熱病毒（Crimean-Congohemorrhagichevervirus，CCHFV）相似，故認(rèn)為XHFV與CCHFV是同一種病毒，屬布尼雅病毒科（Bunyaviridae）內(nèi)羅病毒屬（nairovirus）

生物學(xué)性狀球形或橢圓形，直徑為90nm～120nm，外有包膜，表面有空管樣突起病毒基因組為分節(jié)段的-ssRNA，包括L、M及S節(jié)段，與病毒的核蛋白（C）及少量病毒多聚酶共同組成病毒核衣殼。病毒的核衣殼呈二十面體對稱出生后l～4天的乳鼠對XHFV最為敏感，常用于病毒分離及傳代。用VeroE6等細(xì)胞培養(yǎng)病毒不產(chǎn)生CPE，可用免疫熒光法通過檢測感染細(xì)胞的胞漿內(nèi)可形成嗜堿性包涵體致病性與免疫性新疆出血熱是一種主要發(fā)生于荒漠、牧場的自然疫源性疾病，有嚴(yán)格的地區(qū)性和明顯的季節(jié)性野生動物（嚙齒類動物）和家畜（羊、牛、馬、駱駝、狐貍和兔）是自然宿主和傳染源。羊在維持XHF疫原上起重要作用硬蜱特別是亞洲璃眼蜱（hyalomma

asiaticum）是傳播媒介。病毒在蜱體內(nèi)增殖并經(jīng)卵傳給子代，蜱也是病毒的長期儲存宿主由于蜱在每年的4月～6月期間大量增殖，此時也是人群發(fā)病的高峰。當(dāng)人被帶毒蜱叮咬或與病畜直接接觸（通過破損皮膚）感染病毒侵入體內(nèi)后，經(jīng)5～7天潛伏期發(fā)病，臨床表現(xiàn)以發(fā)熱和出血為主要特征人感染該病毒后可以刺激機體產(chǎn)生中和（NT）抗體、補體結(jié)合（CF）抗體和血凝抑制（HI）抗體。其中NT抗體出現(xiàn)較早，維持較久。病后可獲得持久免疫力微生物學(xué)檢查法確