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

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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
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ARBOVIRUSES
FAMILY ENVELOPE SYMMETRY GENOME

yes icosahedral ssRNA (+ve)

yes helical ssRNA (-ve)


segmented

no icosahedral dsRNA,
segmented
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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

• ANTIBODY MAY PLAY A ROLE


DURING VIREMIC PHASE

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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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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
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VENEZUELAN EQUINE ENCEPALITIS

• Reservoir: horse, small mammals


• Vector: mosquito
• Mild disease in man

togavirus

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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

– ~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
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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% flavivirus
• ~200 cases/year av. 41
CALIFORNIA SEROGROUP ENCEPHALITIS
(includes La Crosse virus)

• 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

Dengue fever, hemorrhagic fever World wide,


especially tropics

Yellow fever hemorrhagic fever Africa, S. and C. America

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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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

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1

1
1
Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing
1 antibody
Complex formed by neutralizing antibody
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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

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2 2
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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
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Reported Cases
(Thousands)

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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

• Immune enhancement hypothesis


– more mononuclear infected
– infected monocytes release vasoactive
mediators
– increased vascular permeability
– hemorrhagic symptoms
flavivirus

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DENGUE HEMORRHAGIC
FEVER

• children more severe disease

• do not give aspirin

• CFR depends on rapid response


– can be as low as 1% flavivirus

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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 CDC

areas with 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

**Most deaths were among encephalitis patients.

flavivirus 64
http://www.cdc.gov/ncidod/dvbid/westnile/clinicians/epi.ht
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