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1、,MedicalMicrobiology,DepartmentofMicrobiology,HMU,第37章肝炎病毒Hepatitisviruses,微生物学教研室凌虹,第二篇致病性细菌,教学大纲,掌握内容肝炎病毒的种类乙型肝炎病毒形态结构、致病性、预防原则熟悉内容丁型肝炎病毒结构特征及致病特点戊型肝炎病毒传播途径及致病特点,问题,肝炎病毒有哪些？甲型肝炎病毒的传播方式、致病特点和预防原则简述乙型肝炎病毒的生物学性状、抗原抗体组成及检出的意义、传播方式、致病特点及预防原则丙型肝炎病毒的生物学特点和致病特点丁型肝炎病毒（HDV）的概念简述戊型肝炎病毒传播方式和致病特点,肝炎病毒（Hepatiti
2、svirus）,以侵害肝脏为主引起病毒性肝炎的病毒种类：甲型肝炎病毒（HAV）、乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、丁型肝炎病毒（HDV）、戊型肝炎病毒（HEV）、GBV-C/HGV、TTV其他病毒黄热病毒、CMV、EBV、风疹病毒等,ViralHepatitis-HistoricalPerspectives,HepatitisAvirus,1973年Feinstone应用免疫电镜技术从急性肝炎患者粪便发现生物学性状与肠道病毒一致1982年国际病毒命名委员会将它分类为小核糖核酸病毒科肠道病毒属72型,Anti-HAVPrevalence,High,Intermediate,Low,
3、VeryLow,GeographicDistributionofHAVinfection,生物学性状,HAV为球形颗粒，直径2732nm，无包膜。基因组为线状单正链RNA,由VP14四种多肽组成VP1是主要衣壳蛋白和中和抗原，能中和所有HAV细胞培养：HAV可用猴肾、人胚肾细胞等进行增殖和传代，但不引起CPE易感动物有黑猩猩、南美洲猴、猕猴等接种后可出现急性肝炎抵抗力：较强对乙醚、酸、热（60oC）稳定。高压、紫外、煮沸等可灭活,流行病学,传染源患者和隐性感染者传播方式：粪口途径污染食物、水源、海产品引起暴发或散发流行隐性感染率高成人HAV抗体阳性率高达70%90%,致病性,非溶细胞型病毒，不
4、直接杀伤细胞病毒复制量与症状严重程度不一致，故认为免疫应答参与损伤过程病后期粪便可检出sIgA抗体无慢性病例典型的甲肝是自限过程，大约三个月,甲型肝炎血清学变化过程,SourcesofHAVInfection1983-93,PercentageofCases,Source:CDC,ViralHepatitisSurveillanceProgram,Year,Personalcontact,Daycarecenter,Foreigntravel,Outbreak,Druguse,40,30,20,10,0,1983,1984,1985,1986,1987,1988,1989,1990,1991,
5、1992,1993,ConcentrationofHAVinVariousBodyFluids,Source:ViralHepatitisandLiverDisease1984;9-22JInfectDis1989;160:887-890,Feces,Serum,Saliva,Urine,100,102,104,106,108,1010,InfectiousDosesperml,Age-specificIncidenceofHepatitisA1983-93,Source:CDC,NationalNotifiableDiseasesSurveillanceSystem,Year,Reporte
6、dCases(per100,000),1983,1984,1985,1986,1987,1988,1989,1990,1991,1992,1993,0,5,10,15,20,25,5-14years,15-24years,25-39years,0-4years,40+years,Endemicity,Disease,Rate,PeakAge,ofInfection,TransmissionPatterns,High,Lowto,High,Early,childhood,Persontoperson;,outbreaksuncommon,Moderate,High,Late,childhood/
7、,youngadults,Persontoperson;,foodandwaterborne,outbreaks,Low,Low,Youngadults,Persontoperson;,foodandwaterborne,outbreaks,Verylow,Verylow,Adults,Travelers;outbreaks,uncommon,GlobalPatternsofHepatitisAVirusTransmission,诊断（LaboratoryDiagnosis）,AcuteinfectionisdiagnosedbythedetectionofHAV-IgMinserumbyEI
8、APastInfectioni.e.immunityisdeterminedbythedetectionofHAV-IgGbyEIA,防治原则,加强食品卫生管理，水源减毒疫苗株H2株和L1株已投放市场基因工程疫苗也正在研究之中应急预防可用丙种球蛋白,Manycasesoccurincommunity-wideoutbreaksnoriskfactoridentifiedformostcaseshighestattackratesin5-14yearoldschildrenserveasreservoirofinfectionPersonsatincreasedriskofinfectiontr
9、avelershomosexualmeninjectingdrugusers,HepatitisAVaccinationStrategiesEpidemiologicConsiderations,Pre-exposuretravelerstointermediateandhighHAV-endemicregionsPost-exposure(within14days)RoutinehouseholdandotherintimatecontactsSelectedsituationsinstitutions(e.g.,daycarecenters)commonsourceexposure(e.g
10、.,foodpreparedbyinfectedfoodhandler),HepatitisAPrevention-ImmuneGlobulin,Group,Age,No.,Doses,EL.U.*(ml),Schedule,(months),Childrenand,adolescents,2-18years,3,360(0.5),0,1,6-12,Adults,18years,2,1,440(1.0),0,6-12,Doses,HAVRIX,*ELISAunits,RecommendedDosesHealth-carework;Perinatal,Source:CentersforDisea
11、seControlandPrevention,HCVPrevalencebySelectedGroups,USA,Hemophilia,Injectingdrugusers,Surgeons,PSWs,Hemodialysis,AveragePercentAnti-HCVPositive,Genpopulationadults,Militarypersonnel,STDclients,Pregnantwomen,PrevalenceofHCVInfectionbyAge47(No.RR19),RoutineHCVTestingNotRecommended(UnlessRiskFactorIde
12、ntified),Health-care,emergencymedical,andpublicsafetyworkersPregnantwomenHousehold(non-sexual)contactsofHCV-positivepersons,Screeningofblood,organ,tissuedonorsHigh-riskbehaviormodificationBloodandbodyfluidprecautions,PreventionofHepatitisC,EstimatedIncidenceofAcuteHCVInfection,1960-1999USA,Declinein
13、transfusionrecipients,Declineininjectiondrugusers,Source:Hepatology2000;31:777-82Hepatology1997;26:62S-65S,PosttransfusionHepatitisC,Allvolunteerdonors,HBsAg,DonorScreeningforHIVRiskFactors,Anti-HIV,ALT/Anti-HBc,Anti-HCV,ImprovedHCVTests,AdaptedfromHJAlterandToblerandBusch,ClinChem1997,Treatment,Int
14、erferon-maybeconsideredforpatientswithchronicactivehepatitis.Theresponserateisaround50%but50%ofresponderswillrelapseuponwithdrawaloftreatment.Ribavirin-thereislessexperiencewithribavirinthaninterferon.However,recentstudiessuggestthatacombinationofinterferonandribavirinismoreeffectivethaninterferonal
15、one.,HepatitisDvirus,肝炎病毒（Hepatitisvirus）从HBV感染者中发现的,HDVPrevalence,High,Intermediate,Low,VeryLow,NoData,Taiwan,PacificIslands,GeographicDistributionofHDVInfection,生物学性状,3537nm，球形颗粒环状单股负链RNA和HDAg（即抗原）1.7Kb表面为HBV包膜蛋白（HBsAg）,HBsAg,RNA,dantigen,HDV为缺陷病毒不能独立进行复制，必须在HBV或其它嗜肝DNA病毒辅助才能增殖敏感动物黑猩猩，土拨鼠和北京鸭等,Hep
16、atitisD-ClinicalFeatures,CoinfectionsevereacutediseaselowriskofchronicinfectionSuperinfectionusuallydevelopchronicHDVinfectionhighriskofseverechronicliverdiseasemaypresentasanacutehepatitis,HDVTransmission,PercutanousexposuresinjectingdrugusePermucosalexposuressexcontact,免疫性,抗HDV不能清除病毒，为诊断指标HDVIgM和I
17、gG持续存在，提示为HDV慢性感染,TimeafterExposure,Titer,anti-HBs,Symptoms,ALTElevated,Totalanti-HDV,IgManti-HDV,HDVRNA,HBsAg,SerologicalCourseofAcuteHDVinfection,TimeafterExposure,Titer,Jaundice,Symptoms,ALT,Totalanti-HDV,IgManti-HDV,HDVRNA,HBsAg,SerologicalCourseofHDVsuperinfection,微生物学检查法,血清学方法ELISA检查HDAg或抗HDVH
18、DAg在急性期可阳性，检出率低慢性感染检不到核酸分子杂交法,HBV-HDVCoinfectionPreorpostexposureprophylaxistopreventHBVinfection.HBV-HDVSuperinfectionEducationtoreduceriskbehaviorsamongpersonswithchronicHBVinfection.,HepatitisD-Prevention,HepatitisEvirus，HEV,戊型肝炎病毒经肠道传播的非甲非乙型肝炎病毒疾病：戊型肝炎,GeographicDistributionofHepatitisE,生物学性状,HE
19、V呈球形，直径2738nm核酸为线形（-）ssRNA无包膜，20面体立体对称现分类于杯状病毒只有一个血清型易感动物非洲绿猴、恒河猴、黑猩猩,致病性,粪口途径传播水源污染造成流行，极小生活接触导致感染多感染2040岁成人潜伏期29周，临床表现为急性肝炎，6周即恢复少数重症死亡。无慢性感染病例致病机理不明免疫损伤是主要机制。病后有一定免疫力,WeeksafterExposure,Titer,Symptoms,ALT,IgGanti-HEV,IgManti-HEV,Virusinstool,0,1,2,3,4,5,6,7,8,9,10,11,12,13,SerologicalCourseofHEVi
20、nfection,微生物学检查法,免疫电镜血清学方法，检测抗-HEVHEV核酸检测,PreventionandControlMeasuresforTravelerstoHEV-EndemicRegions,Avoiddrinkingwater(andbeverageswithice)ofunknownpurity,uncookedshellfish,anduncookedfruit/vegetablesnotpeeledorpreparedbytraveler.IGpreparedfromdonorsinWesterncountriesdoesnotpreventinfection.Unkno
21、wnefficacyofIGpreparedfromdonorsinendemicareas.Vaccine?,庚型肝炎病毒,1995年发现属黄病毒科核酸为+ssRNA，9.4KB，编码一个ORF黑猩猩易感感染世界分布,经血或肠道外传播、垂直传播和性传播临床感染急性和慢性过程HGV常与HCV重叠感染诊断血清学方法或PCRHGV是否嗜肝仍不清楚与疾病关系必须将HBV、HDV、HCV感染排除后才可确认,Sourceof,virus,feces,blood/,blood-derived,bodyfluids,blood/,blood-derived,bodyfluids,blood/,blood-d
22、erived,bodyfluids,feces,Routeof,transmission,fecal-oral,percutaneous,permucosal,percutaneous,permucosal,percutaneous,permucosal,fecal-oral,Chronic,infection,no,yes,yes,yes,no,Prevention,pre/post-,exposure,immunization,pre/post-,exposure,immunization,blooddonor,screening;,riskbehavior,modification,pr
23、e/post-,exposure,immunization;,riskbehavior,modification,ensuresafe,drinking,water,Summary:TypeofHepatitis,A,B,C,D,E,Question,CompareHAVandHBVaccordingtothefollowingcriteria:classification,genome,presenceofenvelope,clinicalfeatures,andtransmissions.WhatarethethreeimportantantigensintheHBVparticle?WhyisthedeltaagentfoundonlyinpersonsinfectedwithHBV?,