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1、,Hepatitis viruses 肝 炎 病 毒,Hong Ling, Ph.D. Microbiol Department, Harbin Medical University,第37章,问题,肝炎病毒有哪些？ 简述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 乙型肝炎病毒的传播方式和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（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）
2、、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 其他病毒如黄热病毒、CMV、EBV、风疹病毒等也可引起肝炎，但不列为肝炎病毒,A,“Infectious”,“Serum”,Viral hepatitis,Enterically transmitted,Parenterally transmitted,F, G, TTV ? other,E,NANB,B,D,C,Viral Hepatitis - Historical Perspectives,Hepatitis A virus,1973年Feinstone应用免疫电镜技术从急性肝炎患者粪便
3、悬液中发现 生物学性状与肠道病毒一致，故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
4、、酸、热（60oC）稳定。高压、紫外、煮沸等可灭活,致病性,传染源为患者和隐性感染者 传播方式是粪口途径。HAV污染食物、水源、海产品等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% 病毒进入机体经过两次病毒血症，到达肝脏，在肝细胞增殖致病,非溶细胞型病毒，不直接杀伤细胞，患者症状高峰是潜伏期末和症状出现初期，与病毒复制高峰时间不相符，说明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 发病后期粪便中可检出sIgA抗体。出现病毒的特异细胞免疫应答 典型的甲肝是自限过程，大约三个月，无慢性病例,Incubation period: Average 30 day
5、sRange 15-50 days Jaundice by 14 yrs, 70%-80% Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae: None,Hepatitis A - Clinical Features,Fecal HAV,Symptoms,0,1,2,3,4,5,6,12,24,Hepatitis A Infection,Total anti-HAV,Titre,ALT,IgM anti-HAV,Months after exposure,T
6、ypical Serological Course,Close personal contact (e.g., household contact, sex contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion),Hepatitis A Virus Transmission,Sources of HAV Infection
7、 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 Dis
8、ease 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,
9、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 waterb
10、orne,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 EIA. Past Infecti
11、on 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，水源保护。但HAV感染以隐性感染和无黄疸型病毒例占多数，故对传染源较难控制 我国已批准将减毒疫苗株H2株和L1株投放市场试用 应急预防可用丙种球蛋白 基因工程疫苗也正在研究之中,Many cases occur in community-wide outbreaks no risk factor identified for most cases highest attack rates in 5-14 year olds child
12、ren serve as reservoir of infection Persons at increased risk of infection travelers homosexual men injecting drug users,Hepatitis A Vaccination Strategies Epidemiologic Considerations,Pre-exposure travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine househol
13、d and other intimate contacts Selected situations institutions (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,
