出血热病毒-医学微生物学课件

1、Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical UniversityMedical Microbiology医 学 微 生 物 学Department of Microbiology, HMU1第三篇 医学相关病毒第34章出血热病毒Haemorrhagic Fever virus微生物学教研室 宋武琦教学大纲掌握内容汉坦病毒主要生物学性状，包括形态结构、培养特性、抗原分型及抵抗力；流行环节及致病性;微生物学检查法。 新疆出血热病毒致病性及传播媒介 了解

2、内容肾综合征出血热病毒及新疆出血热病毒防治原则；非洲出血热病毒（埃博拉病毒和马堡热病毒）的传播方式及引起疾病 HistoryHaemorrhagic Fever with Renal Syndrome (HFRS: later renamed hantavirus disease, HVD) first recognized in Heilongjiang, China in the 1930s, and came to the attention of the West during the Korean war when over 3000 UN troops were afflicted

3、It transpired that the disease was not new and had been described by the Chinese 1000 years earlierIn 1974, the causative was isolated from the Korean Stripped field mice and was called Hantaan virusIn 1995, a new disease entity called hantavirus pulmonary syndrome was described in the “four corners

4、” region of the U.S.病毒体 VirionForms a separate genus in the Bunyavirus family 布尼雅病毒科Unlike other bunyaviridae, its transmission does not involve an arthropod vectorEnveloped -ssRNA virusVirions 98nm in diameter with a characteristic square grid-like structure.Genome consists of three RNA segments: L

5、, M, and S.基于中和试验的血清型Subtypes of Hantaviruses Based NT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黑线姬田鼠小家鼠根据抗原和基因结构分型（10型）Hantaan（汉滩型）Seoul type（汉城型）Puumala type Sin Nombre（辛诺柏型）流行病毒学 EpidemiologyNatural host: Rodent Apodemus agrarius (Stripped field mice, 黑线姬鼠)传染源：黑线姬鼠、褐家鼠、大林姬鼠Viral contamination comes from rode

6、nt urine, stool, salivary secretionSeasonal and regional distribution (autumn and winter, Oct.-Jan.)The infection route is still uncertain. The possible entries are respiratory tract, mouth, and direct contactRodent Carriers of HantavirusesStripped field mouse (Apodemus agrarius)Bank vole (Clethrion

7、omys glareolus)Deer Mouse (Peromyscus maniculatus) Rat (Rattus)临床特点 Clinical FeaturesIncubation: 2 weeks, HFRSPathogenesis mechanism is unknown. Immunological reaction may play role极低的隐性感染率 Very low subclinical infection rate (1-4%) 病后稳定的免疫力，一般不再发病 Stable humoral immunity. no repeat infection致病性 Pat

8、hogenesisThe multisystem pathology of HVD is characterized by damage to capillaries and small vessel walls, resulting in vasodilation and congestion with hemorrhagesClassically, hantavirus disease consists of 5 distinct phases. These phases may be blurred in moderate or mild casesFebrile phase 发热期 H

9、ypotensive phase 低血压期Oliguric phase 少尿期Diuretic phase 多尿期Convalescent phase 恢复期Comparative Clinical Features of Recognized Hantavirus Disease (HVD)汉坦病毒肺综合征Hantavirus Pulmonary SyndromeThe majority of cases are caused by the Sin Nombre virus（汉坦病毒属辛诺柏病毒）More than 250 cases of HPS have been reported th

10、roughout North and South America with a mortality rate of 50% 诊断 Diagnosis血清学诊断 直接检测病毒抗原RT-PCR病毒分离 Virus isolation免疫组化治疗和预防Treatment of HVD and HPS depends mainly on supportive measures 支持疗法Ribavirin 利巴韦林VaccinationRodent Control新疆出血热病毒Xinjiang Hemorrhagic Fever Virus1966年首次从新疆塔里木盆地出血热病人血液、尸体脏器及硬蜱中分

11、离流行病学及病毒抗原性与克里米亚-刚果出血热病毒（Crimean-Congo hemorrhagic hever virus，CCHFV）相似XHFV与CCHFV同种，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90nm120nm，外有包膜，表面有空管样突起病毒基因组为分节段的-ssRNA出生后l4天的乳鼠对XHFV最为敏感，常用于病毒分离及传代。用Vero E6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

12、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蜱在每年的4月6月大量增殖人群发病的高峰蜱叮咬或与病畜直接接触（破损皮肤）感染57天潜伏期发病，以发热和出血为特征产生中和（NT）抗体、血凝抑制抗体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诊主要依赖于病毒的分离鉴定患者双份血清中特异性抗体的检查防治原则防蜱咬和灭蜱严格隔离病人加强医务人员的防护灭活疫苗埃博拉病毒非洲出血热（Africa hemorrhagic fever）主要包括埃博拉热（Ebola fever）和马堡热（Marburg fever），分别由埃博拉病毒（Ebola virus）和马堡病毒（Marburg