Arthropod-borne viruses Arboviruses Arthropod-borne viruses

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

Classification of arbovirus Togaviridae Bunyaviridae Flaviviridae

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)

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.

Major Clinical manifestations of Arboviral Disease Encephalitis Haemorrhagic Fever Hepatitis Arthritis

Section 1 Epidemic type B encephalitis virus

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1915-1924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。

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

Epidemic type B encephalitis virus

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

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

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

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

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

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

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

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

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

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

breeding grounds

Dengue virus

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

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

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

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)

Aedes albopictus Aedes aegypti

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

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

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

Dengue hemorrhagic fever

Microbiological detection Virus isolation culture Serological detection Virus RNA detection

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.

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

Hemorrhagic fever virus

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,

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

Section Ⅰ Hantavirus Bunyaviridae， Hantavirus

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

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

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

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

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.

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

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.

Natural host Apodemus agrarius Rattus

CDC

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

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

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

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

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%

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

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  

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

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