1 VIRAL ZOONOSES ZOONOTIC VIRUSES –TRANSMISSIBLE FROM ANIMALS ARTHROPODS –often via a blood...

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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

21

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

50

1999

51

2000

52

2001

53

2002

54

2003

1999

2000

2001

2002

2003

50

1999

51

2000

52

2001

53

2002

54

2003

1999

2000

2001

2002

2003

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2000

52

2001

53

2002

51

2000

52

2001

53

2002

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2000

52

2001

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2002

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2000

52

2001

53

2002

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2000

52

2001

53

2002

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2000

52

2001

53

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

vasoactive mediators– increased vascular permeability– hemorrhagic symptoms

flavivirus

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• 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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VIRAL ZOONOSES

PART I I

VERTEBRATE VECTORS

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HUMAN RABIES

• >55,000 DEATHS PER YEAR WORLD WIDE

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On July 1, 2004, CDC reported rabies as the cause of encephalitis in an organ donor from Arkansas and three organ recipients at BUMC. The donor's death was attributed to a brain hemorrhage. It was later found that he had reported being bitten by a bat.

An additional organ transplant patient at BUMC died of encephalopathy of unknown origin. On July 7, pathologists identified intracytoplasmic inclusions, suggestive of rabies, in neurons in multiple areas of the brain. Specimens were sent to CDC and …. preliminary characterization of the agent was consistent with a rabies virus variant associated with insectivorous bats.

A segment of iliac artery from the Arkansas donor subsequently determined to have rabies was used in the transplantation of the liver in the most recently identified rabies-infected recipient. The artery segment from the rabies-infected donor likely is the source of the latest rabies infection.

Identification of contacts of this liver recipient is under way, and initiation of PEP (post-exposure prophylaxis) is in progress.

Edited (abbreviated) from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm53d709.htm

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RABIES VIRUS

• Rhabdoviridae family

• Lyssavirus genus• helical, enveloped• ss RNA, -VE sense

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NERVE MAN

CDC

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TRANSMISSION

• BITE - USUAL ROUTE

• CORNEAL AND OTHER TRANSPLANTS

• MUCOSAL MEMBRANES, WOUND

• AEROSOL (RARE)

75Murray et al., Medical Microbiology

Note: no viremia

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INCUBATION PERIOD

• ~2 weeks to ~18 months

• average about two months

• post-exposure prophylaxis

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SYMPTOMS

• Variable, often misdiagnosed

• Tingling, paresthesia at bite site

• Fever, headache, malaise, anorexia

• Nausea, vomiting, myalgia, hydrophobia

• Confusion, hallucinations, seizures, paralysis

• Coma, respiratory failure, death

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DIAGNOSIS

• neutralizing antibodies in serum or CSF• direct fluorescence antibody

– nuchal biopsy (nape of neck), brain biopsy

• RT-PCR saliva• post-mortem staining of brain slice

– Negri bodies (not always seen)• may be important in detection of unsuspected

cases

79CDC

rabies virus infected

uninfected

FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY

80CDC

rabies virus infected

uninfected

81CDC

rabies virus infected - negri body - note dark blue basophilic granules (Sellers stain)

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HUMAN RABIES

• SINGLE SEROTYPE

• >95% WORLDWIDE DEATHS ASSOCIATED WITH CANINE RABIES– CANINE RABIES PREVALENT IN LATIN AMERICA, ASIA,

AFRICA

• USA 1990-2006 ~75% BAT-ASSOCIATED– 52 cases– 39 cases bat-associated strain– 1 case raccoon-associated strain– 12 cases dog/coyote (11 acquired outside US)

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South Carolina Department of Health and Environmental Control

~400 people per year treated in SC

~40,000 people per year treated in US

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RABIES AND RODENTS

• Small rodents - rarely infected

• but can occur - especially in woodchucks

http://en.wikipedia.org/wiki/File:Closeup_groundhog.jpg

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HUMAN RABIES

• IN USA MOST OF RECENT CASES ASSOCIATED WITH BAT RABIES

CDC silver-haired bat

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HUMAN RABIES

• HUMAN-TO-HUMAN– surgically - via transplants– no direct human-to-human ever documented

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POST-EXPOSURE PROPHYLAXIS

• CLEAN WOUND– soap and water; if available, a virucidal agent such as povidine-

iodine solution should be used to irrigate the wounds. • STATE HEALTH DEPARTMENT

– determine risk, examine animal (if available)

• VACCINATION– Human Diploid Cell Vaccine– Purified Chicken Embryo Cell vaccine

• HUMAN RABIES IMMUNE GLOBULIN– HRIG– infiltrate as much as possible around wound, if any left IM

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PRE-EXPOSURE PROPHYLAXIS

• VETERINARIANS AND STAFF

• WILDLIFE OFFICERS ETC LIKELY TO CONTACT RABID ANIMALS

• TRAVELERS LIKELY TO BE AT RISK

• RABIES RESEARCH WORKERS

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PRE-EXPOSURE PROPHYLAXIS

• VACCINATE

• REGULAR TESTING AND BOOSTERS

• STILL NEED POST-EXPOSURE PROPHYLAXIS– REDUCED COURSE OF VACCINATIONS– HRIG NOT NECESSARY

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TREATMENT

• ONCE SYMPTOMS DEVELOP, TREATMENT VIRTUALLY ALWAYS UNSUCCESSFUL

• INTENSIVE SUPPORTIVE CARE

• ONLY 6 CASES OF DOCUMENTED RECOVERY – 5 of these received some type of prophylaxis

before onset of symptoms

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RODENT BORNE

FAMILY ENVELOPE

yes

yes

SYMMETRY

helical

helical

GENOME

ssRNA ambi-sensesegmented

ssRNA (-ve)segmentedHantavirus genus

of Bunyaviridae

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CDC

• rodent urine

• contaminated materials (aerosols)

• respiratory tract

ROUTE OF INFECTION

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ARENAVIRUS FAMILY - all have rodent vector

VIRUS

Lassa

MachupoSabiaJuninGuarnaritoWhitewater Arroyo

lymphocytic choriomeningitis virus (LCMV)

DISEASE

Lassa fever (HF)

Bolivian HFBrazilian HFArgentine HFVenezuelan HFWhitewater Arroyo HF

Lymphocytic choriomeningitis (LCM)

OCCURRENCE

Africa

South AmericaSouth AmericaSouth AmericaSouth AmericaWestern US

Widespread

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ARENAVIRUS-ASSOCIATED HEMORRHAGIC FEVERS

• Lassa fever, Bolivian, Argentine, Venezuelan, Brazilian hemorrhagic fever

• A few recent cases in California of deaths thought to be associated with an arenavirus (Whitewater Arroyo Virus)

• dehydration, hemoconcentration, hemorrhage, shock, cardiovascular collapse

• CFR 5-35%

CDC

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LYMPHOCYTIC CHORIOMENINGITIS VIRUS

• Arenavirus– 5% wild mice infected, without obvious disease– can also get from pet rodents such as hamsters

• often sub-clinical

• clinical cases:– flu like symptoms, plus nausea, vomiting– may get meningitis, and/or encepalitis and/or myelitis– usually recover, may be sequelae– problems for fetus (1st- 2nd trimester)– has been associated with deaths in transplant recipients

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HANTAVIRUSES - all have rodent vector

NAME

Korean HFRS

HFRS

Hantavirus pulmonary syndrome (HPS)

TYPE OF DISEASE

hemorrhagic fever with renal syndrome (HFRS)

hemorrhagic fever with renal syndrome

hantavirus pulmonary syndrome

OCCURRENCE

S.E.Asia

Europe, Asia

North and South America

Rodent vector - limited number species per virus

BUNYAVIRIDAE

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HANTAVIRUS-ASSOCIATED HEMORRHAGIC FEVERS

• Korean hemorrhagic fever with renal syndrome (CFR ~7%)

• other HFRS viral diseases around the world

CDC

Hantavirus genus

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HANTAVIRUS PULMONARY SYNDROME

CFR ~36% Hantavirus genus

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HANTAVIRUS PULMONARY SYNDROME

• Can be caused by various members of the hantavirus family– Including Sin Nombre virus

2

3

0

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38 51

1

15

2

5

13

2

25

716

71

3

1

9

2

8

12

30

25

1

1

33

3

1

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Hantavirus Pulmonary Syndrome Casesby State of Exposure United States – March 26, 2007

Total Cases (N=465 in 30 States)

0 Cases

>=10 Cases5-9 Cases1-4 Cases

Twenty-seven cases were reported with unknown state of exposure.

current CFR=35% CDC

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Radiographic Progression of HPS in the Lung

Radiographic Progression of HPS in the Lung

Source: Dr. L. Ketai via CDC

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VECTOR UNKNOWN

HEMORRHAGIC FEVERS DUE TO EBOLA, MARBURG VIRUSES

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VECTOR UNKNOWN

FAMILY ENVELOPE

yes

SYMMETRY

helical

GENOME

ssRNA (-ve)

Filoviruses may be up to ~14,000 nm long (rhabdoviruses have similar diameter but are only ~180 nm long)

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Negative stain image of an isolate of Marburg virusR. Regnery, CDC. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Filovirus_Fact_Sheet.pdf

Ebola virus budding from an infected human cell. T. Geisbert, USAMRIIDScience 302:1141 (2003)(lower magnification than left hand image)

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EBOLA AND MARBURG VIRUSES

• hemorrhagic fevers• case fatality rate can be as high as 60-90%

for certain strains• occur in Africa, natural reservoir and vector

unknown– infections seen in laboratory monkeys, but these

do not seem to be natural host– bats may be a natural host

• high viremia - stringent barrier nursing

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Wildlife, Exotic Pets, and Emerging Zoonoses

• human population expansion and encroachment on wildlife habitat

• changes in agricultural practices • wildlife trade and translocation • bushmeat, live animal markets, exotic

foods• increased travel, ecotourism • petting zoos and exotic pets

http://www.cdc.gov/ncidod/EID/13/1/6.htm

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The end

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Case of Marburg Haemorrhagic Fever imported into the Netherlands from Uganda10 July 2008WHO has been notified by the Government of the Netherlands of a case of Marburg haemorrhagic fever (MHF) in a Dutch tourist who visited Uganda. Marburg virus infection has been demonstrated by laboratory tests performed by the Bernhard Nocht Institute in Hamburg, Germany. The 40-year-old woman travelled in Uganda from 5-28 June, 2008, and entered caves on two occasions. The first cave was visited on 16 June at Fort Portal. No bats were seen in this cave. She was reportedly exposed to fruit bats during a visit to the “python cave” in the Maramagambo Forest between Queen Elisabeth Park and Kabale on 19 June. This cave is thought to harbour bat species that have been found to carry filoviruses in other locations in sub-Saharan Africa. Filoviruses cause two types of viral haemorrhagic fever: Marburg and Ebola. A large bat population was seen in the cave and the woman is reported to have had direct contact with one bat.The woman returned to the Netherlands on 28 June in good health. The first symptoms (fever, chills) occurred on 2 July and she was admitted to hospital on 5 July. Rapid clinical deterioration with liver failure and severe haemorrhaging occurred on 7 July. The patient remains in a critical clinical condition.Contact tracing and temperature monitoring have been initiated for unprotected contacts with a history of possible exposure to the case after 2 July. Although further epidemiological investigation is needed to exclude other possible sites of exposure to MHF virus, as a precaution Dutch authorities have alerted the tour operator to avoid visits to the caves until further information is available.

World Health Organizationhttp://www.who.int/csr/don/2008_07_10/en/index.html

1 VIRAL ZOONOSES ZOONOTIC VIRUSES –TRANSMISSIBLE FROM ANIMALS ARTHROPODS –often via a blood...

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