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1、Department of Microbiology,Guangzhou Medical College第10章 肠道传播的病原微生物Medical Microbiology医 学 微 生 物 学Department of Microbiology,GMCDepartment of Microbiology,GMCDepartment of Microbiology,Guangzhou Medical College第6节 甲型肝炎病毒Hepatitis A viruses第10章 肠道传播的病原微生物Department of Microbiology,Guangzhou Medical C
2、ollege 教学大纲n n掌握内容n n肝炎病毒的种类肝炎病毒的种类 n n甲型肝炎病毒形态结构、致病性、预防原则甲型肝炎病毒形态结构、致病性、预防原则n n熟悉内容n n戊型肝炎病毒传播途径及致病特点戊型肝炎病毒传播途径及致病特点Department of Microbiology,Guangzhou Medical College问题n n肝炎病毒有哪些？n n甲型肝炎病毒的传播方式、致病特点和预防原则n n简述戊型肝炎病毒传播方式和致病特点Department of Microbiology,Guangzhou Medical College肝炎病毒（Hepatitis virus）n
3、 n以侵害肝脏为主引起病毒性肝炎的病毒以侵害肝脏为主引起病毒性肝炎的病毒n n种类：种类：n n甲型肝炎病毒（甲型肝炎病毒（HAVHAV）、乙型肝炎病毒（）、乙型肝炎病毒（HBVHBV）、）、丙型肝炎病毒（丙型肝炎病毒（HCVHCV）、丁型肝炎病毒（）、丁型肝炎病毒（HDVHDV）、）、戊型肝炎病毒（戊型肝炎病毒（HEVHEV）、）、GBV-C/HGVGBV-C/HGV、TTVTTVn n其他病毒其他病毒n n黄热病毒、黄热病毒、CMVCMV、EBVEBV、风疹病毒等、风疹病毒等 Viral Hepatitis-Historical PerspectivesA“Infectious”“Seru
4、m”Viral hepatitisEntericallytransmittedParenterallytransmittedF,G,TTV?otherENANBNANBB DCDepartment of Microbiology,Guangzhou Medical College一、Hepatitis A virusn n1973年Feinstonen n应用免疫电镜技术从急性肝炎患者粪便发现应用免疫电镜技术从急性肝炎患者粪便发现n n生物学性状与肠道病毒一致n n19821982年国际病毒命名委员会将它分类为小核糖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核酸病毒科肠道病毒属7
5、272型型Department of Microbiology,Guangzhou Medical CollegeAnti-HAV PrevalenceAnti-HAV PrevalenceHighIntermediateLowVery LowGeographic Distribution of HAV infectionDepartment of Microbiology,Guangzhou Medical College生物学性状生物学性状n nHAV为球形颗粒，直径2732nm，无包膜。基因组为线状单正链RNADepartment of Microbiology,Guangzhou Me
6、dical Collegen n由由VP1VP14 4四种多肽组成四种多肽组成n nVP1VP1是主要衣壳蛋白和中和抗原，能中和所有是主要衣壳蛋白和中和抗原，能中和所有HAVHAVn n细胞培养：细胞培养：HAVHAV可用猴肾、人胚肾细胞等进行增可用猴肾、人胚肾细胞等进行增殖和传代，但不引起殖和传代，但不引起CPECPEn n易感动物有黑猩猩、南美洲猴、猕猴等易感动物有黑猩猩、南美洲猴、猕猴等n n接种后可出现急性肝炎接种后可出现急性肝炎n n抵抗力：较强抵抗力：较强n n对乙醚、酸、热（对乙醚、酸、热（6060o oC C）稳定。高压、紫外、煮沸等）稳定。高压、紫外、煮沸等可灭活可灭活Dep
7、artment of Microbiology,Guangzhou Medical College流行病学n n传染源n n患者和隐性感染者患者和隐性感染者n n传播方式：粪口途径n n污染食物、水源、海产品引起暴发或散发流行污染食物、水源、海产品引起暴发或散发流行 n n隐性感染率高n n成人成人HAVHAV抗体阳性率高达抗体阳性率高达70%90%70%90%Department of Microbiology,Guangzhou Medical College致病性n n非溶细胞型病毒，不直接杀伤细胞n n病毒复制量与症状严重程度不一致，故认为免病毒复制量与症状严重程度不一致，故认为免疫应
8、答参与损伤过程疫应答参与损伤过程n n病后期粪便可检出sIgA抗体n n无慢性病例n n典型的甲肝是自限过程，大约三个月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Department of Microbiology,Guangzhou Medical CollegeSources of HAV Infection Sources of HAV Infection 1983-931983-93Percentage of CasesPercentage of CasesPercentage of CasesSource:CDC,Viral Hepatitis Surveillance
9、 ProgramYearYearYearPersonal Personal Personal contactcontactcontactDay care centerDay care centerDay care centerForeign travelForeign travelForeign travelOutbreakOutbreakOutbreakDrug useDrug useDrug use40302010019831984198519861987198819891990199119921993Department of Microbiology,Guangzhou Medical
10、 CollegeConcentration of HAV in Various Body Fluids Source:Viral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890FecesFecesSerumSerumSalivaSalivaUrineUrine1001021041061081010Infectious Doses per mlInfectious Doses per mlDepartment of Microbiology,Guangzhou Medical CollegeAge-specif
11、ic Incidence of Age-specific Incidence of Hepatitis A 1983-93Hepatitis A 1983-93Source:CDC,National Notifiable Diseases Surveillance SystemYearYearYearReported Cases(per 100,000)Reported Cases(per 100,000)Reported Cases(per 100,000)198319841985198619871988198919901991199219930510152025 5-14 years5-1
12、4 years5-14 years 15-24 years15-24 years15-24 years 25-39 years25-39 years25-39 years 0-4 years0-4 years0-4 years 40+years 40+years 40+years Department of Microbiology,Guangzhou Medical CollegeEndemicityDiseaseRatePeak Ageof InfectionTransmission PatternsHighLow to HighEarly childhoodPerson to perso
13、n;outbreaks uncommonModerateHighLate childhood/young adultsPerson to person;food and waterborne outbreaksLowLowYoung adultsPerson to person;food and waterborne outbreaksVery lowVery lowAdultsTravelers;outbreaks uncommonGlobal Patterns of Hepatitis A Virus TransmissionDepartment of Microbiology,Guang
14、zhou Medical College诊断（Laboratory Diagnosis）n nAcute infection is diagnosed by the detection of HAV-IgM in serum by EIAn nPast Infection i.e.immunity is determined by the detection of HAV-IgG by EIA Department of Microbiology,Guangzhou Medical College防治原则防治原则n n加强食品卫生管理，水源n n减毒疫苗株H2株和L1株已投放市场n n基因工程
15、疫苗也正在研究之中基因工程疫苗也正在研究之中n n应急预防可用丙种球蛋白Department of Microbiology,Guangzhou Medical Collegen nMany cases occur in community-wide outbreaksMany cases occur in community-wide outbreaksn nno risk factor identified for most casesno risk factor identified for most casesn nhighest attack rates in 5-14 year o
16、ldshighest attack rates in 5-14 year oldsn nchildren serve as reservoir of infectionchildren serve as reservoir of infectionn nPersons at increased risk of infectionPersons at increased risk of infectionn ntravelerstravelersn nhomosexual menhomosexual menn ninjecting drug usersinjecting drug users H
17、epatitis A Vaccination StrategiesEpidemiologic ConsiderationsDepartment of Microbiology,Guangzhou Medical Collegen nPre-exposurePre-exposuren ntravelers to intermediate and high HAV-endemic regionstravelers to intermediate and high HAV-endemic regionsn nPost-exposure(within 14 days)Post-exposure(wit
18、hin 14 days)RoutineRoutinen nhousehold and other intimate contactshousehold and other intimate contactsSelected situationsSelected situationsn ninstitutions(e.g.,day care centers)institutions(e.g.,day care centers)n ncommon source exposure(e.g.,food prepared by infected food common source exposure(e
19、.g.,food prepared by infected food handler)handler)Hepatitis A Prevention-Immune GlobulinDepartment of Microbiology,Guangzhou Medical CollegeGroupAgeNo.DosesEL.U.*(ml)Schedule(months)Children and adolescents2-18 years3360(0.5)0,1,6-12Adults18 years21,440(1.0)0,6-12DosesHAVRIX*ELISA unitsRecommended
20、Doses&Schedules of HAV VaccinationDepartment of Microbiology,Guangzhou Medical College二、Hepatitis E virus，HEVn n戊型肝炎病毒n n经肠道传播的非甲非乙型肝炎病毒经肠道传播的非甲非乙型肝炎病毒n n疾病：戊型肝炎Department of Microbiology,Guangzhou Medical CollegeGeographic Distribution of Hepatitis EDepartment of Microbiology,Guangzhou Medical Coll
21、ege生物学性状生物学性状Department of Microbiology,Guangzhou Medical Collegen nHEV呈球形，直径2738nmn n核酸为线形（核酸为线形（-）ssRNAssRNAn n无包膜，无包膜，2020面体立体对称面体立体对称n n现分类于杯状病毒现分类于杯状病毒n n只有一个血清型只有一个血清型n n易感动物n n非洲绿猴、恒河猴、黑猩猩非洲绿猴、恒河猴、黑猩猩Department of Microbiology,Guangzhou Medical College致病性致病性n n粪口途径传播n n水源污染造成流行，极小生活接触导致感染水源污染
22、造成流行，极小生活接触导致感染n n多感染2040岁成人n n潜伏期潜伏期2929周，临床表现为急性肝炎，周，临床表现为急性肝炎，6 6周周即恢复即恢复n n少数重症死亡。无慢性感染病例少数重症死亡。无慢性感染病例n n致病机理不明n n免疫损伤是主要机制。病后有一定免疫力免疫损伤是主要机制。病后有一定免疫力Department of Microbiology,Guangzhou Medical CollegeWeeks after Weeks after ExposureExposureTiterTiterSymptomsALTIgG anti-HEVIgM anti-HEVVirus in
23、 stool012345678910111213Serological Course of HEV infectionDepartment of Microbiology,Guangzhou Medical College微生物学检查法微生物学检查法n n免疫电镜n n血清学方法，检测抗-HEVn nHEV核酸检测Department of Microbiology,Guangzhou Medical College Prevention and Control Measures for Travelers to HEV-Endemic Regionsn nAvoid drinking wat
24、er(and beverages with ice)of Avoid drinking water(and beverages with ice)of unknown purity,uncooked shellfish,and unknown purity,uncooked shellfish,and uncooked fruit/vegetables not peeled or uncooked fruit/vegetables not peeled or prepared by traveler.prepared by traveler.n nIG prepared from donors in Western countries IG prepared from donors in Western countries does not prevent infection.does not prevent infection.n nUnknown efficacy of IG prepared from donors in Unknown efficacy of IG prepared from donors in endemic areas.endemic areas.n nVaccine?Vaccine?