出血热病毒课件

HemorrhagicFeverVirus出血热病毒

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

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

布尼雅病毒科Unlikeotherbunyaviridae,itstransmissiondoesnot

involvean

arthropodvectorEnveloped-ssRNAvirusVirions

98nmindiameterwithacharacteristicsquaregrid-likestructure.GenomeconsistsofthreeRNAsegments:L,M,andS.基于中和试验的血清型

SubtypesofHantavirusesBasedNT黑线姬鼠型褐家鼠型欧洲棕背鼠型草原田鼠型巴尔干姬鼠型小家鼠型根据抗原和基因结构分型（10型）Hantaan（汉滩型）Porrogiaandrelatedviruses-ThisgroupisfoundinChina,EasternUSSR,andsomepartsofS.Europe.Itisresponsibleforthesevereclassicaltypeofhantavirusdisease.Itiscarriedbystrippedfieldmice.(Apodemus

agrarius)

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

mainlyfoundinScandinaviancountries,France,UKandtheWesternUSSR.Itiscarriedbybankvoles(Clethrionomys

glareolus)andcausesmildhantavirusdisease(nephropathia

epidemica).SinNombre（辛诺柏型）foundinmanypartsoftheUS,CanadaandMexico.CarriedbytheDeerMouse(Peromyscus

maniculatus)

andcauseshantaviruspulmonarysyndrome.流行病毒学EpidemiologyNaturalhost:RodentApodemus

agrarius

(Strippedfieldmice,黑线姬鼠)传染源：黑线姬鼠、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)临床特点ClinicalFeaturesIncubation:2weeks,HFRSPathogenesismechanismisunknown.Immunologicalreactionmayplayrole极低的隐性感染率Verylowsubclinicalinfectionrate(1-4%)

病后稳定的免疫力，一般不再发病Stablehumoralimmunity.norepeatinfection致病性PathogenesisThemultisystempathologyofHVDischaracterizedbydamagetocapillariesandsmallvesselwalls,resultinginvasodilationandcongestionwithhemorrhagesClassically,hantavirusdiseaseconsistsof5distinctphases.ThesephasesmaybeblurredinmoderateormildcasesFebrilephase

发热期abruptonsetofasevereflu-likeillnesswithaerythematousrashafteranincubationperiodof2-3daysHypotensivephase

低血压期beginsatday5ofillnessOliguricphase

少尿期beginsatday9ofillness.Thepatientmaydevelopacuterenalfailureandshock.Haemorrhagesareusuallyconfinedtopetechiae.ThemajorityofdeathsoccurduringthehypotensiveandoliguricphasesDiureticphase

多尿期occursbetweendays12-14Convalescentphase

恢复期mayrequireupto4monthsComparativeClinicalFeaturesofRecognizedHantavirusDisease(HVD)汉坦病毒肺综合征

HantavirusPulmonarySyndromeThemajorityofcasesarecausedbytheSinNombrevirus（汉坦病毒属辛诺柏病毒）Morethan250casesofHPShavebeenreportedthroughoutNorthandSouthAmericawithamortalityrateof50%HPShasasimilarfebrilephase,However,thedamagetothecapillariesoccurpredominantlyinthelungsratherthanthekidney.Shockandcardiaccomplicationsmayleadtodeath

诊断Diagnosis血清学诊断-avarietyoftestsincludingIF,HAI,SRH,ELISAshavebeendevelopedforthediagnosisofHVDandHPS直接检测病毒抗原-thisappearstobemoresensitivethanserologytestsintheearlydiagnosisofthedisease.ThevirusantigencanbedemonstratedinthebloodorurineRT-PCR

-foundtoofgreatuseindiagnosinghantaviruspulmonarysyndrome病毒分离Virusisolation-isolationofthevirusfromurineissuccessfulearlyinhantavirusdisease.Isolationofthevirusfromthebloodislessconsistent免疫组化

-usefulindiagnosingHPS治疗和预防TreatmentofHVDandHPSdependsmainlyonsupportivemeasures

支持疗法Ribavirin

利巴韦林reportedtobeusefulifgivenearlyinthecourseofhantavirusdiseaseVaccinationaninactivatedvaccineisbeingtriedoutinChina.OthercandidatevaccinesarebeingpreparedRodentControlcontrolmeasuresshouldbeaimedatreducingcontactbetweenhumansandrodents新疆出血热病毒

XinjiangHemorrhagicFeverVirus于1966年首次从我国新疆塔里木盆地出血热病人血液、尸体脏器及硬蜱中分离成功而得名该病毒在流行病学及病毒抗原性等方面与克里米亚-刚果出血热病毒（Crimean-Congohemorrhagichevervirus，CCHFV）相似，故认为XHFV与CCHFV是同一种病毒，属布尼雅病毒科（Bunyaviridae）内罗病毒属（nairovirus）

生物学性状球形或椭圆形，直径为90nm～120nm，外有包膜，表面有空管样突起病毒基因组为分节段的-ssRNA，包括L、M及S节段，与病毒的核蛋白（C）及少量病毒多聚酶共同组成病毒核衣壳。病毒的核衣壳呈二十面体对称出生后l～4天的乳鼠对XHFV最为敏感，常用于病毒分离及传代。用VeroE6等细胞培养病毒不产生CPE，可用免疫荧光法通过检测感染细胞的胞浆内可形成嗜碱性包涵体致病性与免疫性新疆出血热是一种主要发生于荒漠、牧场的自然疫源性疾病，有严格的地区性和明显的季节性野生动物（啮齿类动物）和家畜（羊、牛、马、骆驼、狐狸和兔）是自然宿主和传染源。羊在维持XHF疫原上起重要作用硬蜱特别是亚洲璃眼蜱（hyalomma

asiaticum）是传播媒介。病毒在蜱体内增殖并经卵传给子代，蜱也是病毒的长期储存宿主由于蜱在每年的4月～6月期间大量增殖，此时也是人群发病的高峰。当人被带毒蜱叮咬或与病畜直接接触（通过破损皮肤）感染病毒侵入体内后，经5～7天潜伏期发病，临床表现以发热和出血为主要特征人感染该病毒后可以刺激机体产生中和（NT）抗体、补体结合（CF）抗体和血凝抑制（HI）抗体。其中NT抗体出现较早，维持较久。病后可获得持久免疫力微生物学检查法确