• 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
2
Arthropod-borne Viruses
3
4
Transmission
• Arthropod vectors (blood sucking)
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VIGILANCE
7
• 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
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ARBOVIRUSES
FAMILY ENVELOPE SYMMETRY GENOME
no icosahedral dsRNA,
segmented
16
17
ARTHROPOD VERTEBRATE
• Habitat • Migratory activity
• Diurnal activity • Persistence of
• Preferred host viremia
• Annual activity • Clinical
• Overwintering ability consequences
(The method that an organism uses for surviving a winter.)
• Reservoir ?
• Transovarial • Dead end host?
transmission
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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 21
RECOVERY
• INTERFERON
• CELL-MEDIATED IMMUNITY
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Protective
• IgG
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ARBOVIRUSES – ENCEPHALITIS
FAMILY DISTRIBUTION
TOGAVIRIDAE
Eastern equine encephalitis East US, Canada
Western equine encephalitis West US, Canada, Mexico, Brazil
Venezuelan equine encephalitis Central and S America, Texas, Florida
FLAVIVIRIDAE
West Nile virus encephalitis North America, parts of Europe, parts of
Africa
St Louis encephalitis North America
BUNYAVIRIDAE
California serogroup (La Crosse etc) North America
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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
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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
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EASTERN EQUINE ENCEPALITIS
• Reservoir: birds
• Vector: mosquito
• Sentinels
– horse,quail, turkey
CDC
• <15, >50yrs at higher
risk
• CFR ~35%
• ~5 cases/year av. togavirus
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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 togavirus
recently 36
VENEZUELAN EQUINE ENCEPALITIS
togavirus
37
WEST NILE VIRUS
• Reservoir: birds
• Vector: mosquito
flavivirus 38
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 39
http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm
West Nile Virus
For every ~150 people infected
• Recently commoner
in eastern US
• Reservoir: small
mammals
• Vector: mosquitos
• Children at higher
risk
• Low CFR bunyavirus
• ~70 cases/year av. 42
ARBOVIRUSES – FEVER AND
HEMORRHAGIC FEVER
FAMILY MAIN DISEASES DISTRIBUTION
FLAVIVIRIDAE
REOVIRIDAE
Colorado tick fever fever North America
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COLORADO TICK FEVER
Vector: tick
• Mild disease in man
• Fever, rash,
arthralgia
• RMSF important
consideration in
differential diagnosis
• Probably common, Reovirus family
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rarely reported
World Distribution of Dengue
1999
Aedes aegypti
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Aedes aegypti 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
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48
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
Non-neutralizing
1 antibody
Complex formed by neutralizing antibody
51
and virus
Heterologous Antibodies Form
Infectious Complexes
2 2
2
2
Dengue 2 virus
Non-neutralizing antibody to Dengue 1
2 virus
Complex formed by non-neutralizing
antibody and virus 52
Heterologous Complexes Enter More
Monocytes, Where Virus Replicates
2
2
2
2
2
2 2
2
2
2 Dengue 2 virus
Non-neutralizing antibody
2 Complex formed by non-
neutralizing antibody and 53
Dengue 2 virus
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
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flavivirus
Reported Cases of DHF
in the Americas, 1970 - 1999
60
50
Reported Cases
(Thousands)
40
30
20
10
0
1970s 1980s 1990s*
* Provisional data through 1999 55
2001 - 609000 dengue cases in Americas alone (15,000 DHF)
Dengue virus
Mosquito feeds /
acquires virus
Viremia
0 5 8 12
ILLNESS
Human #1 CDC 56
DENGUE FEVER
• Fever
• Headache
• Retro-orbital pain
• Myalgia, arthralgia
• Bone-ache ‘breakbone fever’
• Sometimes rash
• May look like flu, measles, rubella
flavivirus
• More rarely encephalitis
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DENGUE HEMORRHAGIC
FEVER/DENGUE SHOCK
SYNDROME
• hemorrhages
• plasma leakage
• hemoconcentration
• hypotension
• circulatory failure
• shock
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flavivirus
DHF - petechiae
CDC 59
Dengue hemorrhagic fever - pleural effusion 60
ughn DW et al. J Infect Dis 1997; 176:322-30.
CDC
DENGUE HEMORRHAGIC
FEVER
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DENGUE HEMORRHAGIC
FEVER
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YELLOW FEVER
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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
flavivirus 64
http://www.cdc.gov/ncidod/dvbid/westnile/clinicians/epi.ht
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