Arbo Viruses

VIRAL ZOONOSES • ZOONOTIC VIRUSES – TRANSMISSIBLE FROM ANIMALS • ARTHROPODS – often via a blood sucking arthropod

• VERTEBRATES – bites, body fluids, inhalation etc

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VIRAL ZOONOSES ARTHROPOD BORNE ARBO VIRUSES

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Arthropod-borne Viruses “Viruses maintained in nature principally, or to an important extent, through biological transmission between susceptible vertebrate hosts by haematophagus arthropods or through transovarian and possibly venereal transmission in arthropods.”

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Transmission • Arthropod vectors (blood sucking)

• Many Arboviral diseases world wide (hundreds) 5

Arbovirus • Viruses from various families which are transmitted via arthropods from one vertebrates to another. • Diseases caused by arboviruses – Encephalitis – Febrile diseases – Hemorrhagic fevers 6

VIGILANCE

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• ARBOVIRUSES – ENCEPHALITIS – FEBRILE DISEASES – HEMORRHAGIC FEVERS

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Arthropod Vectors

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Examples of Arthropod Vectors

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Animal Reservoirs

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Diseases Caused

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Diagnosis

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Prevention

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PREVENTION • • • • •

SURVEILLANCE VECTOR CONTROL REPELLENTS CLOTHING TIMING OF ACTIVITY (OR CANCELLATION) • VACCINE 15

ARBOVIRUSES FAMILY

ENVELOPE

SYMMETRY

GENOME

yes

icosahedral

ssRNA (+ve)

yes

helical

ssRNA (-ve) segmented

no

icosahedral

dsRNA, segmented 16

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ARTHROPOD • Habitat • Diurnal activity • Preferred host • Annual activity • Overwintering ability (The method that an organism uses for surviving a winter.)

• Transovarial transmission

VERTEBRATE • Migratory activity • Persistence of viremia • Clinical consequences • Reservoir ? • Dead end host? 18

SYLVATIC (JUNGLE) CYCLE vertebrate

arthropod

arthropod vertebrate

man

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URBAN CYCLE man

arthropod

arthropod man

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ARBOVIRAL DISEASE • MANY DIFFERENT ARBOVIRUSES CAUSE DISEASE • OFTEN SUB-CLINICAL • INITIAL VIRAL REPLICATION – ENDOTHELIAL CELLS – MACROPHAGES/MONOCYTE LINEAGE

• INTERFERON (RNA VIRUSES) • VIREMIA

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RECOVERY • INTERFERON • CELL-MEDIATED IMMUNITY • ANTIBODY MAY PLAY A ROLE DURING VIREMIC PHASE 22

Protective • IgG

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ARBOVIRUSES – ENCEPHALITIS

FAMILY

DISTRIBUTION

TOGAVIRIDAE Eastern equine encephalitis Western equine encephalitis Venezuelan equine encephalitis

East US, Canada West US, Canada, Mexico, Brazil Central and S America, Texas, Florida

FLAVIVIRIDAE West Nile virus encephalitis St Louis encephalitis

North America, parts of Europe, parts of Africa North America

BUNYAVIRIDAE California serogroup (La Crosse etc)

North America 24

ARBOVIRUS ENCEPHALITIS • SPORADIC • LOW % INFECTIONS -> CLINICAL CASES • NOT ALL CASES -> MAJOR DISEASE • PROBABLY UNDERDIAGNOSED

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Encephalitis B virus • Japanese encephalitis virus • Epidemic encephalitis B

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Biological Properties • • • • • •

30-40nm +ssRNA envelope icosahedral only one serotype E protein 27

Epidemiology • Source – Mosquito and livestocks

• Vector – mainly Culex tritaeniorhynchus

• epidemic region – sub-tropic and tropic of Asia

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30

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Pathogenicity • Pathogenesis – Two viremia

• Clinical findings – Subclinical infections – Acute encephalitis

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Prevent and Treatment • Prevention – Vector control • Avoid being bitten by mosquito • Eliminating all Culex breeding places

– Vaccination • man • Animal resovior

• Treatment – No 33

EASTERN EQUINE ENCEPALITIS • Reservoir: birds • Vector: mosquito • Sentinels – horse,quail, turkey

• <15, >50yrs at higher risk • CFR ~35% • ~5 cases/year av.

CDC

togavirus 34

EASTERN EQUINE ENCEPALITIS

CDC

togavirus

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WESTERN EQUINE ENCEPALITIS • Reservoir: birds • Vector: mosquito • Sentinels – horse,quail, turkey

• Children at higher risk • CFR 3-5% • No human cases recently

togavirus 36

VENEZUELAN EQUINE ENCEPALITIS • Reservoir: horse, small mammals • Vector: mosquito • Mild disease in man

togavirus 37

WEST NILE VIRUS

• Reservoir: birds

• Vector: mosquito

flavivirus

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http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm

WEST NILE VIRUS • Symptoms: – Fever – Meningitis – Encephalitis More rarely: – Acute flaccid paralysis • poliomyelitis -inflammation spinal cord

flavivirus

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http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm

West Nile Virus For every ~150 people infected – ~30 mild symptoms • mild fever headache, body ache, maybe rash – may never see physician, even if do, may not be diagnosed

– ~1 severe illness • e.g. encepalitis, meningitis, high fever, stiff neck, stupor, disorientation, coma, tremors, convulsions, muscle weakness – frequency of flaccid paralysis unknown, but less than frequency of encephalitis 40

ST. LOUIS ENCEPHALITIS • Second commonest mosquito borne disease in US • Reservoir: birds – Man usually dead end host

• • • • •

Vector: mosquito <1% infections clinical Elderly at higher risk CFR 3-25% ~200 cases/year av.

flavivirus 41

CALIFORNIA SEROGROUP ENCEPHALITIS (includes La Crosse virus) • Recently commoner in eastern US • Reservoir: small mammals • Vector: mosquitos • Children at higher risk • Low CFR • ~70 cases/year av.

bunyavirus 42

ARBOVIRUSES – FEVER AND HEMORRHAGIC FEVER FAMILY

MAIN DISEASES

DISTRIBUTION

Dengue

fever, hemorrhagic fever

World wide, especially tropics

Yellow fever

hemorrhagic fever

Africa, S. and C. America

REOVIRIDAE Colorado tick fever

fever

North America

FLAVIVIRIDAE

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COLORADO TICK FEVER Vector: tick • Mild disease in man • Fever, rash, arthralgia • RMSF important consideration in differential diagnosis • Probably common, rarely reported

Reovirus family 44

World Distribution of Dengue 1999

Aedes aegypti Aedes aegypti

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flavivirus

Dengue Virus • Flaviviridae • Flavivirus • Four virus serotypes

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Pathogenicity • Source – Human and primate

• Vector – Mosquito

• Occurrence – world wide---tropic or subtropic areas

• Transmission – Two viremia 47

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Aedes aegypti

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Pathogenicity • Clinical Findings – dengue fever (DF) – dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) – Hypothesis on Pathogenesis of DHF • Antibody-dependent enhancement (ADE)

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Homologous Antibodies Form Non-infectious Complexes 1

1

1

1

Dengue 1 virus Neutralizing antibody to Dengue 1 virus

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Non-neutralizing antibody Complex formed by neutralizing antibody and virus

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Heterologous Antibodies Form Infectious Complexes 2 2

2

2

2

2

Dengue 2 virus Non-neutralizing antibody to Dengue 1 virus Complex formed by non-neutralizing antibody and virus

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Heterologous Complexes Enter More Monocytes, Where Virus Replicates 2 2

2 2

2 2 2

2

2

2 2

Dengue 2 virus Non-neutralizing antibody

2

Complex formed by nonneutralizing antibody and Dengue 2 virus

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DENGUE FEVER • • • •

Jungle cycle (monkeys-mosquitos) Urban cycle (man-mosquitos) Rapidly increasing disease in tropics Approx. 100-200 cases/yr in US due to import – Occasional indigenous transmission

• 50-100 million cases per year worldwide 54

flavivirus

Reported Cases of DHF in the Americas, 1970 - 1999 Reported Cases (Thousands)

60 50 40 30 20 10 0

1970s

1980s

1990s*

* Provisional data through 1999 2001 - 609000 dengue cases in Americas alone (15,000 DHF)

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Dengue virus Mosquito feeds / acquires virus

Viremia 0

5

8

12

ILLNESS Human #1

CDC

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DENGUE FEVER • • • • • • • •

Fever Headache Retro-orbital pain Myalgia, arthralgia Bone-ache ‘breakbone fever’ Sometimes rash May look like flu, measles, rubella More rarely encephalitis

flavivirus 57

DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROME • • • • • •

hemorrhages plasma leakage hemoconcentration hypotension circulatory failure shock flavivirus

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DHF - petechiae

CDC

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Dengue hemorrhagic fever - pleural effusion ughn DW et al. J Infect Dis 1997; 176:322-30. CDC

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DENGUE HEMORRHAGIC FEVER • Immune enhancement hypothesis – more mononuclear infected – infected monocytes release vasoactive mediators – increased vascular permeability – hemorrhagic symptoms

flavivirus 61

DENGUE HEMORRHAGIC FEVER • children more severe disease • do not give aspirin • CFR depends on rapid response – can be as low as 1%

flavivirus 62

YELLOW FEVER • •

• • • •

Jungle and urban cycles Vector- Aedes mosquitoes, including A. aegypti, A. africanus, A. simpsoni, A. furcifer, A. luteocephalus, and A. albopictus (Asian tiger mosquito). Hemorrhages Degeneration liver, kidney, heart CFR 50% Vaccine – Important to consider in travel to areas with yellow fever

CDC

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flavivirus

WEST NILE VIRUS Table. Median age (in years) of development of West Nile illness following infection Year*

Fever

Meningitis

Encephalitis Death** (with or without associated meningitis)

2002

49

46

64

78

2003

45

46

62

80

**Most deaths were among encephalitis patients.

flavivirus

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http://www.cdc.gov/ncidod/dvbid/westnile/clinicians/epi.ht

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