1

VIRAL ZOONOSES

• ZOONOTIC VIRUSES– TRANSMISSIBLE FROM ANIMALS

• ARTHROPODS– often via a blood sucking arthropod

• VERTEBRATES– bites, body fluids, inhalation etc

2

VIRAL ZOONOSES

PART I

ARTHROPOD BORNE

3

transmission

• arthropod vectors (blood sucking)

• Many arboviral diseases world wide (hundreds)

4

VIGILANCE

5

• ARBOVIRUSES– FEBRILE DISEASES– ENCEPHALITIS– HEMORRHAGIC FEVERS

6

ARBOVIRUSES

FAMILY ENVELOPE

yes

yes

no

SYMMETRY

icosahedral

helical

icosahedral

GENOME

ssRNA (+ve)

ssRNA (-ve)segmented

dsRNA, segmented

7

BirdsMammalsHumans

8

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

transmission

VERTEBRATE• Migratory activity• Persistence of

viremia• Clinical

consequences• Reservoir ?• Dead end host?

9

PREVENTION

• SURVEILLANCE

• VECTOR CONTROL

• REPELLENTS

• CLOTHING

• TIMING OF ACTIVITY (OR CANCELLATION)

• VACCINE

10

SYLVATIC (JUNGLE) CYCLE

arthropod arthropod

vertebrate human

vertebrate

11

URBAN CYCLE

arthropod arthropod

human

human

human cycle

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

12

OUTBREAKS

• TEND TO BE SUMMER/EARLY FALL

• SPORADIC

• UNPREDICTABLE

13

ARBOVIRAL DISEASE

• MANY DIFFERENT ARBOVIRUSES CAUSE DISEASE

• OFTEN SUB-CLINICAL

14

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

15

RECOVERY

• INTERFERON

• CELL-MEDIATED IMMUNITY

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

16

DIAGNOSIS

– Immunological techniques

– RT-PCR for viral RNA

17

RESISTANCE

• IgG

18

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

19

ARBOVIRUS ENCEPHALITIS

• SPORADIC

• LOW % INFECTIONS -> CLINICAL CASES

• NOT ALL CASES -> MAJOR DISEASE

• PROBABLY UNDERDIAGNOSED

20

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

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

51

2000

52

2001

53

2002

flavivirusWest Nile virus

22flavivirusWest Nile virus

Final 2008 West Nile Virus activity in the United States

23

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

24

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

25

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

26

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

27

WEST NILE VIRUS

flavivirus

transmission:

• Mosquito (vast majority of cases)

• Blood transfusion (blood supply is now screened)

• Organ donation

28

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

29

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

30

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

31

EASTERN EQUINE ENCEPHALITIS

CDC

togavirus

32

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

33

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

35

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

36

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

37

flavivirus

38

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

39

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

patients being treated for Dengue fever in a Paraguayan hospital

flavivirus

40

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

41

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.

44

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

45

DENGUE HEMORRHAGIC FEVER

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

vasoactive mediators– increased vascular permeability– hemorrhagic symptoms

flavivirus

46

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

48

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

49

The end

50

(Time Dec 2007)

51

52

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

53

55

WEST NILE VIRUS

flavivirus

56

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

57

1999

West Nile virus

58

2000

West Nile virus

59

2001

West Nile virus

60

2002

West Nile virus

61

2003

West Nile virus

62

2004

West Nile virus

63

2005

West Nile virus

64

2006

West Nile virus

65

66

67

68

69

VIRAL ZOONOSES

PART I I

VERTEBRATE VECTORS

70

HUMAN RABIES

• >55,000 DEATHS PER YEAR WORLD WIDE

71

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

72

RABIES VIRUS

• Rhabdoviridae family

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

73

NERVE MAN

CDC

74

TRANSMISSION

• BITE - USUAL ROUTE

• CORNEAL AND OTHER TRANSPLANTS

• MUCOSAL MEMBRANES, WOUND

• AEROSOL (RARE)

75Murray et al., Medical Microbiology

Note: no viremia

76

INCUBATION PERIOD

• ~2 weeks to ~18 months

• average about two months

• post-exposure prophylaxis

77

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

78

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)

82

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)

83

South Carolina Department of Health and Environmental Control

~400 people per year treated in SC

~40,000 people per year treated in US

84CDC

85

RABIES AND RODENTS

• Small rodents - rarely infected

• but can occur - especially in woodchucks

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

86

HUMAN RABIES

• IN USA MOST OF RECENT CASES ASSOCIATED WITH BAT RABIES

CDC silver-haired bat

87

HUMAN RABIES

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

88

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

89

PRE-EXPOSURE PROPHYLAXIS

• VETERINARIANS AND STAFF

• WILDLIFE OFFICERS ETC LIKELY TO CONTACT RABID ANIMALS

• TRAVELERS LIKELY TO BE AT RISK

• RABIES RESEARCH WORKERS

90

PRE-EXPOSURE PROPHYLAXIS

• VACCINATE

• REGULAR TESTING AND BOOSTERS

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

91

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

92

RODENT BORNE

FAMILY ENVELOPE

yes

yes

SYMMETRY

helical

helical

GENOME

ssRNA ambi-sensesegmented

ssRNA (-ve)segmentedHantavirus genus

of Bunyaviridae

93

CDC

• rodent urine

• contaminated materials (aerosols)

• respiratory tract

ROUTE OF INFECTION

94

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

95

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

96

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

97

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

98

HANTAVIRUS-ASSOCIATED HEMORRHAGIC FEVERS

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

• other HFRS viral diseases around the world

CDC

Hantavirus genus

99

HANTAVIRUS PULMONARY SYNDROME

CFR ~36% Hantavirus genus

100

HANTAVIRUS PULMONARY SYNDROME

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

2

3

0

48

38 51

1

15

2

5

13

2

25

716

71

3

1

9

2

8

12

30

25

1

1

33

3

1

7

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

102

103

Radiographic Progression of HPS in the Lung

Radiographic Progression of HPS in the Lung

Source: Dr. L. Ketai via CDC

104

VECTOR UNKNOWN

HEMORRHAGIC FEVERS DUE TO EBOLA, MARBURG VIRUSES

105

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)

106

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)

107

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

108

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

109

The end

110

111

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