Hemorrhagic Fever Virus
出血热病毒
Department of Microbiology,HMU
第 34章
Haemorrhagic 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
It transpired that the disease was not new and had
been described by the Chinese 1000 years earlier
In 1974,the causative was isolated from the Korean
Stripped field mice and was called Hantaan virus
In 1995,a new disease entity called hantavirus
pulmonary syndrome was described in the,four
corners” region of the U.S.
病毒体 Virion
Forms a separate genus in
the Bunyavirus family 布尼雅病毒科
Unlike other bunyaviridae,its
transmission does not involve
an arthropod vector
Enveloped -ssRNA virus
Virions 98nm in diameter with
a characteristic square grid-
like structure.
Genome consists of three
RNA segments,L,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
小家鼠型根据抗原和基因结构分型（ 10型）
Hantaan（汉滩型）
Porrogia and related viruses - This group is found in China,Eastern
USSR,and some parts of S,Europe,It is responsible for the severe
classical type of hantavirus disease,It is carried by stripped field mice,
(Apodemus agrarius)
Seoul type（汉城型）
associated with moderate hantavirus disease,It is carried by rats and
have a worldwide distribution,It has been identified in China,Japan,
Western USSR,USA and S.America.
Puumala type
mainly found in Scandinavian countries,France,UK and the Western
USSR,It is carried by bank voles (Clethrionomys glareolus) and causes
mild hantavirus disease (nephropathia epidemica).
Sin Nombre（辛诺柏型）
found in many parts of the US,Canada and Mexico,Carried by the Deer
Mouse (Peromyscus maniculatus) and causes hantavirus pulmonary
syndrome.
流行病毒学 Epidemiology
Natural 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 rodent urine,
stool,salivary secretion
Seasonal and regional distribution (autumn and
winter,Oct.-Jan.)
The infection route is still uncertain,The
possible entries are respiratory tract,mouth,
and direct contact
Rodent Carriers of Hantaviruses
Stripped field mouse (Apodemus agrarius)
Bank vole (Clethrionomys glareolus)
Deer Mouse (Peromyscus maniculatus) Rat (Rattus)
临床特点 Clinical Features
Incubation,2 weeks,HFRS
Pathogenesis 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 Pathogenesis
The multisystem pathology of HVD is
characterized by damage to capillaries and
small vessel walls,resulting in vasodilation and
congestion with hemorrhages
Classically,hantavirus disease consists of 5
distinct phases,These phases may be blurred
in moderate or mild cases
Febrile phase 发热期
abrupt onset of a severe flu-like illness with a
erythematous rash after an incubation period of 2-3
days
Hypotensive phase 低血压期
begins at day 5 of illness
Oliguric phase 少尿期
begins at day 9 of illness,The patient may develop
acute renal failure and shock,Haemorrhages are
usually confined to petechiae,The majority of deaths
occur during the hypotensive and oliguric phases
Diuretic phase 多尿期
occurs between days 12-14
Convalescent phase 恢复期
may require up to 4 months
Nephropathia Far Eastern Rat- bourne Balkan
Epidermica HVD HVD HVD
Virus type Puumala Hantaan Seoul Porogia
Overall Severity 1-2 2-4 1-3 2-4
Multiphasic Disease occasionally Yes Blurred Yes
Renal Abnormalities 1-2 4 1-2 4
Hepatic abnormalities 0 0-1 1-3 0-1
Haemorrhagic phenomenon 0-1 1-4 1-2 1-4
Mortality <1 % 5-10% 1% 5-35%
Score = 0 to 4
Comparative Clinical Features of
Recognized Hantavirus Disease (HVD)
汉坦病毒肺综合征
Hantavirus Pulmonary Syndrome
The 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 throughout North and South
America with a mortality rate of 50%
HPS has a similar febrile phase,However,
the damage to the capillaries occur
predominantly in the lungs rather than the
kidney.
Shock and cardiac complications may lead to
death
诊断 Diagnosis
血清学诊断 - a variety of tests including IF,HAI,SRH,
ELISAs have been developed for the diagnosis of HVD
and HPS
直接检测病毒抗原 - this appears to be more sensitive
than serology tests in the early diagnosis of the disease,
The virus antigen can be demonstrated in the blood or
urine
RT-PCR - found to of great use in diagnosing hantavirus
pulmonary syndrome
病毒分离 Virus isolation - isolation of the virus from
urine is successful early in hantavirus disease,Isolation
of the virus from the blood is less consistent
免疫组化 - useful in diagnosing HPS
治疗和预防
Treatment of HVD and HPS depends mainly
on supportive measures 支持疗法
Ribavirin 利巴韦林
reported to be useful if given early in the course of
hantavirus disease
Vaccination
an inactivated vaccine is being tried out in China,
Other candidate vaccines are being prepared
Rodent Control
control measures should be aimed at reducing
contact between humans and rodents
新疆出血热病毒
Xinjiang Hemorrhagic Fever Virus
于 1966年首次从我国新疆塔里木盆地出血热病人血液、尸体脏器及硬蜱中分离成功而得名
该病毒在流行病学及病毒抗原性等方面与克里米亚 -刚果出血热病毒 （ Crimean-Congo
hemorrhagic hever virus,CCHFV）相似，故认为 XHFV与 CCHFV是同一种病毒，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 90nm～ 120nm，外有 包膜
，表面有空管样突起
病毒基因组为 分节段的 -ssRNA，包括 L,M及 S节段，与病毒的核蛋白（ C）及少量病毒多聚酶共同组成病毒核衣壳。病毒的核衣壳呈 二十面体对称
出生后 l～ 4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
新疆出血热是一种主要发生于荒漠、牧场的自然疫源性疾病，有严格的地区性和明显的季节性
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
由于蜱在每年的 4月～ 6月 期间大量增殖，
此时也是人群发病的高峰。当人被带毒蜱叮咬或与病畜直接接触（通过破损皮肤）
感染
病毒侵入体内后，经 5～ 7天潜伏期发病，
临床表现以 发热和出血 为主要特征
人感染该病毒后可以刺激机体产生中和（
NT）抗体、补体结合（ CF）抗体和血凝抑制（ HI）抗体。其中 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
防治措施主要包括 防蜱咬和灭蜱
严格隔离病人,并对病人血液、分泌物、
排出物等要进行消毒处理
加强医务人员的防护，避免直接接触病人的血液等而被感染
用乳鼠脑组织培养精制的病毒 灭活疫苗 具有一定的预防效果埃博拉病毒
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 virus）感染所致
两种病毒均为 RNA病毒,同属于 丝状病毒科 （
Filoviridae）的 丝状病毒属 （ filovirus），形态结构酷似，但抗原性明显不同致病性
非洲出血热的主要临床特点是 高热、皮肤瘀血
、紫癜、鼻衄、消化道和泌尿生殖道出血、血小板减少以及明显的全身中毒症状,常导致休克和死亡
储存宿主 是 啮齿类动物,经 密切接触 可以传播给人
人与人主要通过 密切接触及体液（尿或粪便）
等的污染而传播
目前尚无特异性防治措施。主要采取维持肾功能和水电解质平衡、积极控制出血和休克等支持疗法进行治疗小结病毒科 病毒 疾病 传播媒介 储存宿主黄病毒科乙脑病毒登革病毒森林脑炎病毒乙脑登革热森林脑炎库蚊伊蚊蜱库蚊伊蚊蜱布尼亚病毒科汉坦病毒 流行性出血热鼠
出血热病毒
Department of Microbiology,HMU
第 34章
Haemorrhagic 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
It transpired that the disease was not new and had
been described by the Chinese 1000 years earlier
In 1974,the causative was isolated from the Korean
Stripped field mice and was called Hantaan virus
In 1995,a new disease entity called hantavirus
pulmonary syndrome was described in the,four
corners” region of the U.S.
病毒体 Virion
Forms a separate genus in
the Bunyavirus family 布尼雅病毒科
Unlike other bunyaviridae,its
transmission does not involve
an arthropod vector
Enveloped -ssRNA virus
Virions 98nm in diameter with
a characteristic square grid-
like structure.
Genome consists of three
RNA segments,L,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
小家鼠型根据抗原和基因结构分型（ 10型）
Hantaan（汉滩型）
Porrogia and related viruses - This group is found in China,Eastern
USSR,and some parts of S,Europe,It is responsible for the severe
classical type of hantavirus disease,It is carried by stripped field mice,
(Apodemus agrarius)
Seoul type（汉城型）
associated with moderate hantavirus disease,It is carried by rats and
have a worldwide distribution,It has been identified in China,Japan,
Western USSR,USA and S.America.
Puumala type
mainly found in Scandinavian countries,France,UK and the Western
USSR,It is carried by bank voles (Clethrionomys glareolus) and causes
mild hantavirus disease (nephropathia epidemica).
Sin Nombre（辛诺柏型）
found in many parts of the US,Canada and Mexico,Carried by the Deer
Mouse (Peromyscus maniculatus) and causes hantavirus pulmonary
syndrome.
流行病毒学 Epidemiology
Natural 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 rodent urine,
stool,salivary secretion
Seasonal and regional distribution (autumn and
winter,Oct.-Jan.)
The infection route is still uncertain,The
possible entries are respiratory tract,mouth,
and direct contact
Rodent Carriers of Hantaviruses
Stripped field mouse (Apodemus agrarius)
Bank vole (Clethrionomys glareolus)
Deer Mouse (Peromyscus maniculatus) Rat (Rattus)
临床特点 Clinical Features
Incubation,2 weeks,HFRS
Pathogenesis 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 Pathogenesis
The multisystem pathology of HVD is
characterized by damage to capillaries and
small vessel walls,resulting in vasodilation and
congestion with hemorrhages
Classically,hantavirus disease consists of 5
distinct phases,These phases may be blurred
in moderate or mild cases
Febrile phase 发热期
abrupt onset of a severe flu-like illness with a
erythematous rash after an incubation period of 2-3
days
Hypotensive phase 低血压期
begins at day 5 of illness
Oliguric phase 少尿期
begins at day 9 of illness,The patient may develop
acute renal failure and shock,Haemorrhages are
usually confined to petechiae,The majority of deaths
occur during the hypotensive and oliguric phases
Diuretic phase 多尿期
occurs between days 12-14
Convalescent phase 恢复期
may require up to 4 months
Nephropathia Far Eastern Rat- bourne Balkan
Epidermica HVD HVD HVD
Virus type Puumala Hantaan Seoul Porogia
Overall Severity 1-2 2-4 1-3 2-4
Multiphasic Disease occasionally Yes Blurred Yes
Renal Abnormalities 1-2 4 1-2 4
Hepatic abnormalities 0 0-1 1-3 0-1
Haemorrhagic phenomenon 0-1 1-4 1-2 1-4
Mortality <1 % 5-10% 1% 5-35%
Score = 0 to 4
Comparative Clinical Features of
Recognized Hantavirus Disease (HVD)
汉坦病毒肺综合征
Hantavirus Pulmonary Syndrome
The 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 throughout North and South
America with a mortality rate of 50%
HPS has a similar febrile phase,However,
the damage to the capillaries occur
predominantly in the lungs rather than the
kidney.
Shock and cardiac complications may lead to
death
诊断 Diagnosis
血清学诊断 - a variety of tests including IF,HAI,SRH,
ELISAs have been developed for the diagnosis of HVD
and HPS
直接检测病毒抗原 - this appears to be more sensitive
than serology tests in the early diagnosis of the disease,
The virus antigen can be demonstrated in the blood or
urine
RT-PCR - found to of great use in diagnosing hantavirus
pulmonary syndrome
病毒分离 Virus isolation - isolation of the virus from
urine is successful early in hantavirus disease,Isolation
of the virus from the blood is less consistent
免疫组化 - useful in diagnosing HPS
治疗和预防
Treatment of HVD and HPS depends mainly
on supportive measures 支持疗法
Ribavirin 利巴韦林
reported to be useful if given early in the course of
hantavirus disease
Vaccination
an inactivated vaccine is being tried out in China,
Other candidate vaccines are being prepared
Rodent Control
control measures should be aimed at reducing
contact between humans and rodents
新疆出血热病毒
Xinjiang Hemorrhagic Fever Virus
于 1966年首次从我国新疆塔里木盆地出血热病人血液、尸体脏器及硬蜱中分离成功而得名
该病毒在流行病学及病毒抗原性等方面与克里米亚 -刚果出血热病毒 （ Crimean-Congo
hemorrhagic hever virus,CCHFV）相似，故认为 XHFV与 CCHFV是同一种病毒，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 90nm～ 120nm，外有 包膜
，表面有空管样突起
病毒基因组为 分节段的 -ssRNA，包括 L,M及 S节段，与病毒的核蛋白（ C）及少量病毒多聚酶共同组成病毒核衣壳。病毒的核衣壳呈 二十面体对称
出生后 l～ 4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
新疆出血热是一种主要发生于荒漠、牧场的自然疫源性疾病，有严格的地区性和明显的季节性
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
由于蜱在每年的 4月～ 6月 期间大量增殖，
此时也是人群发病的高峰。当人被带毒蜱叮咬或与病畜直接接触（通过破损皮肤）
感染
病毒侵入体内后，经 5～ 7天潜伏期发病，
临床表现以 发热和出血 为主要特征
人感染该病毒后可以刺激机体产生中和（
NT）抗体、补体结合（ CF）抗体和血凝抑制（ HI）抗体。其中 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
防治措施主要包括 防蜱咬和灭蜱
严格隔离病人,并对病人血液、分泌物、
排出物等要进行消毒处理
加强医务人员的防护，避免直接接触病人的血液等而被感染
用乳鼠脑组织培养精制的病毒 灭活疫苗 具有一定的预防效果埃博拉病毒
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 virus）感染所致
两种病毒均为 RNA病毒,同属于 丝状病毒科 （
Filoviridae）的 丝状病毒属 （ filovirus），形态结构酷似，但抗原性明显不同致病性
非洲出血热的主要临床特点是 高热、皮肤瘀血
、紫癜、鼻衄、消化道和泌尿生殖道出血、血小板减少以及明显的全身中毒症状,常导致休克和死亡
储存宿主 是 啮齿类动物,经 密切接触 可以传播给人
人与人主要通过 密切接触及体液（尿或粪便）
等的污染而传播
目前尚无特异性防治措施。主要采取维持肾功能和水电解质平衡、积极控制出血和休克等支持疗法进行治疗小结病毒科 病毒 疾病 传播媒介 储存宿主黄病毒科乙脑病毒登革病毒森林脑炎病毒乙脑登革热森林脑炎库蚊伊蚊蜱库蚊伊蚊蜱布尼亚病毒科汉坦病毒 流行性出血热鼠
