消化道传播的病原微生物HAV

,第10章 肠道传播的病原微生物,Medical Microbiology医 学 微 生 物 学,Department of Microbiology, GMC,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,教学大纲,掌握内容肝炎病毒的种类 甲型肝炎病毒形态结构、致病性、预防原则熟悉内容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戊型肝炎病毒传播方式和致病特点,肝炎病毒（Hepatitis virus）,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,Viral Hepatitis - Historical Perspectives,一、Hepatitis A virus,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-HAV Prevalence,High,Intermediate,Low,Very Low,Geographic Distribution of HAV infection,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,Sources of HAV Infection 1983-93,Percentage of Cases,Source: CDC, Viral Hepatitis Surveillance Program,Year,Personal contact,Day care center,Foreign travel,Outbreak,Drug use,40,30,20,10,0,1983,1984,1985,1986,1987,1988,1989,1990,1991,1992,1993,Concentration of HAV in Various Body Fluids,Source:Viral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890,Feces,Serum,Saliva,Urine,100,102,104,106,108,1010,Infectious Doses per ml,Age-specific Incidence of Hepatitis A 1983-93,Source: CDC, National Notifiable Diseases Surveillance System,Year,Reported Cases (per 100,000),1983,1984,1985,1986,1987,1988,1989,1990,1991,1992,1993,0,5,10,15,20,25,5-14 years,15-24 years,25-39 years,0-4 years,40+ years,Endemicity,Disease,Rate,Peak Age,of Infection,Transmission Patterns,High,Low to,High,Early,childhood,Person to person;,outbreaks uncommon,Moderate,High,Late,childhood/,young adults,Person to person;,food and waterborne,outbreaks,Low,Low,Young adults,Person to person;,food and waterborne,outbreaks,Very low,Very low,Adults,Travelers; outbreaks,uncommon,Global Patterns of Hepatitis A Virus Transmission,诊断（Laboratory Diagnosis）,Acute infection is diagnosed by the detection of HAV-IgM in serum by EIAPast Infection i.e. immunity is determined by the detection of HAV-IgG by EIA,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,Many cases occur in community-wide outbreaksno risk factor identified for most caseshighest attack rates in 5-14 year oldschildren serve as reservoir of infectionPersons at increased risk of infectiontravelershomosexual meninjecting drug users,Hepatitis A Vaccination StrategiesEpidemiologic Considerations,Pre-exposuretravelers to intermediate and high HAV-endemic regionsPost-exposure (within 14 days)Routinehousehold and other intimate contactsSelected situationsinstitutions (e.g., day care centers)common source exposure (e.g., food prepared by infected food handler),Hepatitis A Prevention - Immune Globulin,Group,Age,No.,Doses,EL.U.* (ml),Schedule,(months),Children and,adolescents,2-18 years,3,360 (0.5),0, 1, 6-12,Adults,18 years,2,1,440 (1.0),0, 6-12,Doses,HAVRIX,*ELISA units,Recommended Doses & Schedules of HAV Vaccination,二、Hepatitis E virus，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,Geographic Distribution of Hepatitis E,生物学性状,HEV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,Weeks after Exposure,Titer,Symptoms,ALT,IgG anti-HEV,IgM anti-HEV,Virus in stool,0,1,2,3,4,5,6,7,8,9,10,11,12,13,Serological Course of HEV infection,微生物学检查法,免疫电镜血清学方法，检测抗-HEVHEV核酸检测,Prevention and Control Measures for Travelers to HEV-Endemic Regions,Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooke