1. Arthropod-borne viruses
Arboviruses
Arthropod-borne viruses

2. Arthropod-borne viruses (arboviruses) are
viruses  that are transmitted through blood
sucking arthropods between susceptible
vertebrate  hosts.
Arthropod-borne viruses cause zoonotic diseases
or natural focus infection disease.
Marked geographical and seasonal distribution.
haematophagus食血的
transovarial transmission【医学】经卵巢传播，经卵巢传递

3. Classification of arbovirus
Togaviridae
Bunyaviridae
Flaviviridae

4. Prevalence in China
Epidemic type B encephalitis virus (Epidemic type B encephalitis )
Dengue virus (Dengue fever)
Forest encephalitis virus (Forest encephalitis )
Crimean-Congo hemorrhagic fever virus(Crimean-Congo hemorrhagic fever)

5. Arthropod Vectors Mosquitoes Ticks Sandflies
Japanese encephalitis, dengue, yellow fever, St. Louis encephalitis, etc.
Ticks
Crimean-Congo haemorrhagic fever, forest encephalitis etc.
Sandflies
Sicilian sandfly fever, Rift valley fever.

6. Major Clinical manifestations of Arboviral Disease
Encephalitis
Haemorrhagic Fever
Hepatitis
Arthritis

7. Section 1 Epidemic type B encephalitis virus

8. Epidemic type B encephalitis virus
Virus first discovered and originally restricted to Japan (1934), also called Japanese encephalitis virus(JEV).
Epidemic type B encephalitis: acute inflammation of cerebral parenchyma
In order to distinguish it from von Economo’s (type A) encephalitis, it was named Japanese encephalitis B or epidemic encephalitis B.
为区别于流行性甲型脑炎病毒而命名。甲型脑炎又称为昏睡型脑炎encephalitis lethargica ，流行于 年，病因可能是病毒，但未分离出来，传播途径不清。1917年4月康斯坦丁·冯·艾克诺默(Constantin von Economo)医生在维也纳精神病学会上发表了他对这种疾病的临床和病理的发现，并提出为一种独立的疾病，故又称Von Economo脑炎。

9. Biological properties
Flaviviridae, Flavivirus
Spherical, 35-50nm
Icosahedral ，enveloped virus
+ssRNA genome

10. Epidemic type B encephalitis virus

11. Adsorption to host cell
Envelope protein
hemagglutinin that can agglutinate RBCs of chicken, goose and pigeon
Neutralizing antigen that can produce
hemagglutination inhibition antibody
Adsorption to host cell
C protein, M protein– virus assembly
NS3,NS5 protein — virus replication

12. Cell culture: virus can multiply in shrewmouse kidney, chicken embryo, C6/36, obvious CPE
Animal model: Sucking mouse. Intracerebral inoculation of sucking or weaned mice will induce fatal encephalitis.
Only one serotype
Resistance : weak. Sensitive to acid,liposoluble agent,heat,and chemical disinfectant

13. Epidemiology
Infection source: infected animals, e.g. young pigs are main infection source.
Transmission route: via the bite of infected Culex mosquitoes ,esp. Culex tritaeniorhynchus.
Viruses are preserved in the body and egg of mosquitoes, therefore, mosquitoes are not only transmission vector,also long-term reservoir
Susceptible people：<10 years old
动物感染病毒无明显症状体征，但有病毒血症，可作为传染源
病毒在蚊-动物-蚊中传播，期间如带毒蚊子叮咬人，引起人类感染
儿童接种疫苗，成年人发病人数相对增加

14. Animal-Arthropod-Man Cycle
The viruses are maintained in nature in a transmission cycle involving mosquitoes and pigs. Men become infected incidentally.

15. Epidemiological characteristics
Now large scale epidemics occur in China, Japan,korea,India and Southeast Asia.
Rural area>urban area
Sporadic
Summer time(July-september)

17. pathogenicity Encephalitis Virus entry via mosquito bite
Subclinical infection
Multiplication in endothelia cell
Invade into blood
First viremia
Multiplication in Mφ in lymph tissue(liver,spleen)
Invade into blood
Mild infection
Second viremia
0.1%
Invade brain barrier
Encephalitis
Inflammation of cerebral parenchyma and meninges

18. Clincal manifestations
Incubation period:10 days (two viremia)
Most of infected persons are subclinical infection. Few cases(0.1%) develop encephalitis.
Encephalitis : High fever、headache、vomiting、convulsion、coma、meningeal irritation sign.
Central respiratory failure, cerebral hernia
Death rate:10%—40%
Sequela （5-20%） : dementia、paralysis, aphasia

19. Immunity Humoral immunity play a more important role.
Long lasting protective immunity, that is the case for inapparant infection.

20. Microbiological detection
Isolation
Virus antigen detection
Serological test: IgM detection
Virus RNA detection:RT-PCR

21. Prevention Control and kill of mosquitoes Prevent animal infection
Pesticides, elimination of breeding grounds, insect repellants
Prevent animal infection
Vaccination of pigs before the epidemic season
Vaccination
Children under 10-year-old, one month before the epidemic season
Inactivated vaccine
double subcutaneous injections in duration of one week, repeat vaccination one year later

22. breeding grounds

23. Dengue virus

24. Biology Characteristics
Flaviviridae,flavivirus
Spherical (17--25nm）,enveloped virus
Virus structure is similar to JEV
Virus cultivation and animal model : sucking mouse
4 Serotype, cross antigenicity

25. Epidemiology
Dengue  is the biggest arbovirus problem in the world today  with over 2 million cases per year
Dengue is found in Southeast Asia, Africa ,the Caribbean and South America
Rapidly increasing disease in tropics area

26. World Distribution of Dengue
flavivirus
Areas infested with Aedes aegypti
Areas with Aedes aegypti and recent epidemic dengue

27. Epidemiology Natural reservoir：human and monkeys
Infection source：patients and subclinical infection
Transmission vecter : Aedes aegypti ,Aedes albopictus
Human infections arise from a human-mosquito-human
occur in both an urban cycle(man-mosquitos) and jungle cycle(monkeys-mosquitos)

28. Aedes albopictus
Aedes aegypti

29. Pathogenicity and immunity
Virus entry via infected mosquito bite
Multiplication in endothilia cell and Mo/Mφ
Viremia
DF DHF/DSS

30. Clinical features Inapparant infection are common dengue fever fever
headache
rash
myalgia, arthralgia
bone-ache ‘breakbone fever’
may look like flu, measles, rubella

31. Dengue haemorrhagic fever
Dengue shock syndrome
Early symptoms are similar to DF.
Hemorrhages
circulatory failure
Hypotension, shock
Death rate:5%-10%

32. Dengue hemorrhagic fever

33. Microbiological detection
Virus isolation culture
Serological detection
Virus RNA detection

34. Prevention No specific antiviral therapy is available.
Prevention of dengue in endemic areas depends on mosquito eradication. Remove all containers which may serve as vessels for egg deposition.
Vaccines are under trial.

35. Forest encephalitis virus
Flaviviridae,flavivirus
Biological properties are similar to JEV
Northeast and southeast of China
Wild animals are infection source
Ticks are transmission vector and reservior
Forest encephalitis: mortality 30%
Long lasting immunity after infection
Inactivated vaccine for forest workers

36. Hemorrhagic fever virus

37. Outline
Hemorrhagic fever refer to a group of diseases characterized by hyperpyrexia、hemorrhage and hypotension shock with organ damage.(“3 H”)
5 virus families:Togaviridae，Flaviviridae , Bunyavirudae ,Arenaviridae and Filoviridae
Hantavirus are common in China,

38. Human hemorrhagic fever virus
Family
virus
vetor
disease
distribution
Togaviridae
Chikungunya virus
mosquito
chikungunya fever
Asia、Africa
Flaviviridae
Yellow fever virus
Yellow fever
Africa、America
Dengue virus
dengue
Asia、 Caribbean
Kyasanur virus
tick
Kyasanur forest fever
India
Omsk virus
Omsk fever
Russia
Bunyaviridae
Hanta virus
rodents
HFRS
All over the world
Rift valley virus
Rift valley fever
Africa
Crimean-congo hemorrhagic fever virus （Xing Jiang Hemorrhogic Fever Virus）
Crimean-congo hemorrhagic fever （Xing Jiang Hemorrhogic Fever)
Africa、niddle Asia、China
Arenaviridiae
Junin virus
Argentina fever
Argentina
Machupo virus
Bolivia fever
Bolivia
Lassa virus
Lassa fever
Filoviridae
Marburg virus ?
Maburg disease
Africa、Germany
Ebola virus ？
Ebola fever

39. Section Ⅰ Hantavirus Bunyaviridae， Hantavirus

40. Hanta virus cause 2 diseases
hemorrahagic fever with renal syndrome, HFRS
hantavirus pulmonary syndrome, HPS

41. Morphology Spherical or polymorphism, 75-210nm
Envelope: 2 glycoprotein spikes, G1 and G2(neutralizing Ag and agglutinate goose RBC)
Capsid : N protein(NP)
-ssRNA，3 Segments

42. L：RNA polymerase Virus replication M：envelop spikes G1、G2 S：NP
Neutralizing epitopes and agglutinate goose RBC
S：NP
Strong immunogenicity

43. Cultivation: VeroE6、A549、shrewmouse kidney
No CPE，IFA
Susceptible animals: Apodemus agrarius

44. Serological typing:
14 serotypes
6 serotypes are pathogenic to human.
I and II in China
Resistance:
weak. sensitive to acid, heat and liposoluble
agents, and UV.

45. Epidemiology
Marked distribution: Hemorrhagic fever with renal failure syndrome (HFRS) occurs mainly in Europe and Asia. HPS occurs in America.
Marked season: Oct-Dec

47. Epidemiology Natural host : rodents Transmission route:
rodent excreta spread (respiratory air droplets,
gastrointestinal, direct contact)
vertical tranmission
Mite bite transmission??
Susceptible people: most are subclinical infection
Adult male are commonly infected.

48. Natural host
Apodemus agrarius
Rattus

49. CDC

50. Transmission of Hantaviruses
Chronically infected rodent
Horizontal transmission of infection by intraspecific aggressive behavior
Virus also present in throat swab and feces
Virus is present in aerosolized excreta, particularly urine
4. Transmission of Hantaviruses: The virus is horizontally transmitted between rodents through intraspecific aggressive behaviors, such as biting. The virus is transmitted to humans from aerosolized rodent excreta, particularly urine. Transmission to humans also can occur from inhalation of secondary aerosols, and from rodent bites or other direct contact of infectious material with mucous membranes or broken skin.
Secondary aerosols, mucous membrane contact, and skin breaches are also sources of infection

51. Pathogenicity Virus damage cell directly
Virus damage endothelium cells -vessels permeability increase -plasma leakage - hypotension shock
Immunopathological damage
type Ⅰand type Ⅲ hypersensitivity

52. Clinical manifestations
Incubation period: 2 weeks
Acute onset, quick development
Typical case have three features: fever, bleeding ,kidney damage

53. Clinical process:
5 phases
fever phase
hypotension phase
oliguric phase
polyuria phase
convalescent phase

54. Preliminary symptoms are flu-like (fever, chills, headaches, frontal or retroorbital headaches, backaches) accompanied by loss of appetite (anorexia) and vomiting.
Flushing of the face, neck, and chest
Hemorrhagic spots may occur in the axilla , soft palate and chest
convalescence can take several months but recovery is often complete.
The fatality rate is about 7%

55. significant feature of the disease: systemic damage to the vascular endothelium, capillary dilatation, and leakage.
Immune mechanisms play an important role.

57. Immunity
long lasting protective immunity after
infection. No reinfection
Laboratory diagnosis
Specimen: acute patient blood, autopsy tissue from infected animals
Cultivation: Vero-E6 cell ,A549 cell, sucking mice
Serological diagnosis: IgM/IgG
indirect immunofluorescent assay
ELISA  

58. collecting specimens from trapped rodents
rodent [‘rəudənt] n. 【脊椎动物】啮齿目(Rodentia)动物 adj. 1. 咬的，啮的 2. 啮齿类动物的 3. 侵蚀性的
relatively small gnawing animals having a single pair of constantly growing incisor teeth specialized for gnawing

59. Control and treatment Inactivated vaccines are available in China.
Supportive care