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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

PART I

ARTHROPOD BORNE

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transmission

• arthropod vectors (blood sucking)

• Many arboviral diseases world wide (hundreds)

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VIGILANCE

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• ARBOVIRUSES– FEBRILE DISEASES– ENCEPHALITIS– HEMORRHAGIC FEVERS

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ARBOVIRUSES

FAMILY ENVELOPE

yes

yes

no

SYMMETRY

icosahedral

helical

icosahedral

GENOME

ssRNA (+ve)

ssRNA (-ve)segmented

dsRNA, segmented

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BirdsMammalsHumans

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ARTHROPOD• Habitat• Diurnal activity• Preferred host• Annual activity• Overwintering ability• Transovarial

transmission

VERTEBRATE• Migratory activity• Persistence of

viremia• Clinical

consequences• Reservoir ?• Dead end host?

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PREVENTION

• SURVEILLANCE

• VECTOR CONTROL

• REPELLENTS

• CLOTHING

• TIMING OF ACTIVITY (OR CANCELLATION)

• VACCINE

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SYLVATIC (JUNGLE) CYCLE

arthropod arthropod

vertebrate human

vertebrate

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URBAN CYCLE

arthropod arthropod

human

human

human cycle

note: viruses which have a human cycle may also have a sylvatic/jungle cycle

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OUTBREAKS

• TEND TO BE SUMMER/EARLY FALL

• SPORADIC

• UNPREDICTABLE

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ARBOVIRAL DISEASE

• MANY DIFFERENT ARBOVIRUSES CAUSE DISEASE

• OFTEN SUB-CLINICAL

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ARBOVIRAL DISEASE

• INITIAL VIRAL REPLICATION– endothelial cells– macrophages/monocyte lineage

• INTERFERON (RNA VIRUSES)– headache, fever, myalgia

• VIREMIA– spread to target tissues, depending on

tropism of virus

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RECOVERY

• INTERFERON

• CELL-MEDIATED IMMUNITY

• ANTIBODY MAY PLAY A ROLE IN PREVENTING SPREAD DURING VIREMIC PHASE

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DIAGNOSIS

– Immunological techniques

– RT-PCR for viral RNA

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RESISTANCE

• IgG

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ARBOVIRUSES – ENCEPHALITIS

FAMILY DISTRIBUTION

FLAVIVIRIDAE  

West Nile virus encephalitis North America, parts of Europe, parts of Africa

St Louis encephalitis North America

TOGAVIRIDAE  

Eastern equine encephalitis East US, Canada

Western equine encephalitis West US, Canada, Mexico, Brazil

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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WEST NILE VIRUS

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

• Reservoir: birds

• Vector: mosquito

• human, horse– dead end hosts

flavivirus

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2000

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2001

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2002

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2001

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2002

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1999

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2001

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2002

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2003

1999

2000

2001

2002

2003

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1999

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2001

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2002

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2003

1999

2000

2001

2002

2003

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2000

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2001

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2002

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2000

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2001

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2002

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2001

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2001

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2002

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2000

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2001

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2002

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2001

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2002

flavivirusWest Nile virus

22flavivirusWest Nile virus

Final 2008 West Nile Virus activity in the United States

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WEST NILE VIRUS

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

• Symptoms:– Fever– Meningitis– Encephalitis

More rarely:– Acute flaccid paralysis

• West Nile polio-like paralysis– poliomyelitis - inflammation spinal cord

flavivirus

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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. encephalitis, meningitis, high fever, stiff neck,

stupor, disorientation, coma, tremors, convulsions, muscle weakness

– frequency of flaccid paralysis unknown, but much less than frequency of encephalitis

flavivirus

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Case fatality ratio:

• Seen in all age groups but higher in the elderly– the majority of cases of neuroinvasive

diseases and fatalities are over 50 yrs age

• Transplant recipients may be at higher risk– increased incidence of clinical disease– increased risk of severe disease

WEST NILE VIRUS

flavivirus

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http://www.cdc.gov/ncidod/dvbid/westnile/resources/wnv_transplant%20brochure6_12_07.pdf

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WEST NILE VIRUS

flavivirus

transmission:

• Mosquito (vast majority of cases)

• Blood transfusion (blood supply is now screened)

• Organ donation

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Reported Human WNV Disease Cases, US

1999 62

2000 21

2001 66

2002 4156

2003 9862

2004 2539

2005 3000

2006 4269

2007 3630

2008 1338

2009 515 (as of 10-20-09)

2008 Case Fatality Rate = 44/1356 = 3.2%

flavivirus

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ST. LOUIS ENCEPHALITIS

• Second commonest mosquito borne disease in US

• Reservoir: birds– Man is usually a dead end

host

• Vector: mosquito• <1% infections clinical• Elderly at higher risk• CFR 3-25%• ~100 cases/year av.

flavivirus

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EASTERN EQUINE ENCEPHALITIS

• Reservoir: birds• Vector: mosquito• Sentinels

– horse,quail, turkey

• Under 15yrs, over 50yrs at higher risk

• CFR ~35%• ~5 cases/year av.• horses and humans

dead end hosts

CDC

togavirus

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EASTERN EQUINE ENCEPHALITIS

CDC

togavirus

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WESTERN EQUINE ENCEPALITIS

• Reservoir: birds• Vector: mosquito• Sentinels

– horse,quail, turkey

• Children at higher risk

• CFR 3-5%• humans and horses

dead end hoststogavirus

USA: last confirmed human case 1999

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CALIFORNIA SEROGROUP ENCEPHALITIS(includes La Crosse virus)

• Recently commoner in eastern US

• Reservoir: small mammals

• Vector: mosquitos• Children at higher risk• Low CFR• ~80 cases/year av.

bunyavirus

34La Crosse life cycle

2000 - 2 cases in SC, Charleston area

bunyavirus

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ARBOVIRUSES – FEVER AND HEMORRHAGIC FEVER

FAMILY

FLAVIVIRIDAE

Dengue

Yellow fever

REOVIRIDAEColorado tick fever

DISTRIBUTION

World wide, especially tropics

Africa, S. and C. America

North America

MAIN DISEASES

fever, hemorrhagic fever

hemorrhagic fever

fever

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COLORADO TICK FEVER- coltivirus

Vector: tick

• Mild disease in man

• Fever, rash, arthralgia

• RMSF important consideration in differential diagnosis

• Probably common, rarely reported Reovirus family

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flavivirus

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DENGUE FEVER

• jungle cycle (monkeys-mosquitoes)• urban cycle (man-mosquitoes)• 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– ~900,000 cases in Central and S. America in 2007

flavivirus

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http://news.bbc.co.uk/2/hi/americas/6422319.stm

patients being treated for Dengue fever in a Paraguayan hospital

flavivirus

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DENGUE FEVER

• Fever (overlaps with viremic phase)• headache• retro-orbital pain• myalgia, arthralgia• severe joint and muscle pain

‘breakbone fever’• sometimes rash• may look like flu, measles, rubella• more rarely encephalitis

flavivirus

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DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK

SYNDROME • hemorrhages

• plasma leakage

• hemoconcentration

• hypotension

• circulatory failure

• shock

flavivirus

42DHF - petechiae

CDC

flavivirus

43Dengue hemorrhagic fever - pleural effusion

CDCVaughn DW et al. J Infect Dis 1997; 176:322-30.

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DENGUE HEMORRHAGIC FEVER

• immunopathological

• 4 serotypes (1, 2, 3, 4)– increase in areas in which all 4 circulate has led to more

cases DHF fever in South and Central America– Entomologic, serologic and virologic conditions are now

such that locally acquired DHF can occur in South Texas

• maternal antibody flavivirus

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DENGUE HEMORRHAGIC FEVER

• Immune enhancement hypothesis– more mononuclear cells infected– infected monocytes release

vasoactive mediators– increased vascular permeability– hemorrhagic symptoms

flavivirus

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DENGUE HEMORRHAGIC FEVER

• do not give aspirin, ibuprofen – because of anticoagulant affects– (acetaminophen OK)

• children more severe disease

• CFR depends on rapid response– can be as low as 1%

flavivirus

47flavivirus

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CDC

YELLOW FEVER

• jungle and urban cycles• hemorrhages• degeneration liver, kidney,

heart• CFR 50%• Vaccine (live attenuated)

– important to consider in travel to areas with yellow fever

– egg grown– contraindicated in immune

suppression

flaviviruslast yellow fever epidemic in US - 1905

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The end

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(Time Dec 2007)

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Aedes albopictus is a species of mosquito which is a good vector for Dengue

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WEST NILE VIRUS

flavivirus

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WEST NILE VIRUS

flavivirus

Case fatality ratio:

• Higher in elderly• The 1 fatality in SC in

2005 was over 65 years old

• Peaks about Aug-Sept

SC

SC - 2005

http://westnilemaps.usgs.gov/sc_human.html

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1999

West Nile virus

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2000

West Nile virus

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2001

West Nile virus

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2002

West Nile virus

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2003

West Nile virus

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2004

West Nile virus

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2005

West Nile virus

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2006

West Nile virus

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