VIRAL ZOONOSES
• ZOONOTIC VIRUSES
– TRANSMISSIBLE FROM ANIMALS
• ARTHROPODS
– often via a blood sucking arthropod
• VERTEBRATES
– bites, body fluids, inhalation etc
1
VIRAL ZOONOSES
PART I
ARTHROPOD BORNE
2
transmission
• arthropod vectors (blood sucking)
• Many arboviral diseases world wide
(hundreds)
3
VIGILANCE
4
• ARBOVIRUSES
– FEBRILE DISEASES
– ENCEPHALITIS
– HEMORRHAGIC FEVERS
5
ARBOVIRUSES
FAMILY
ENVELOPE
SYMMETRY
GENOME
yes
icosahedral
ssRNA (+ve)
yes
helical
ssRNA (-ve)
segmented
no
icosahedral
dsRNA,
segmented
6
Birds
Mammals
Humans
7
ARTHROPOD
• Habitat
• Diurnal activity
• Preferred host
• Annual activity
• Overwintering ability
• Transovarial
transmission
VERTEBRATE
• Migratory activity
• Persistence of
viremia
• Clinical
consequences
• Reservoir ?
• Dead end host?
8
PREVENTION
•
•
•
•
•
SURVEILLANCE
VECTOR CONTROL
REPELLENTS
CLOTHING
TIMING OF ACTIVITY (OR
CANCELLATION)
• VACCINE
9
SYLVATIC (JUNGLE) CYCLE
vertebrate
arthropod
arthropod
vertebrate
human
10
URBAN CYCLE
human
arthropod
arthropod
human
human cycle
note: viruses which have a human cycle may also have a
sylvatic/jungle cycle
11
OUTBREAKS
• TEND TO BE SUMMER/EARLY FALL
• SPORADIC
• UNPREDICTABLE
12
ARBOVIRAL DISEASE
• MANY DIFFERENT ARBOVIRUSES
CAUSE DISEASE
• OFTEN SUB-CLINICAL
13
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
14
RECOVERY
• INTERFERON
• CELL-MEDIATED IMMUNITY
• ANTIBODY MAY PLAY A ROLE IN
PREVENTING SPREAD DURING
VIREMIC PHASE
15
DIAGNOSIS
– Immunological techniques
– RT-PCR for viral RNA
16
RESISTANCE
• IgG
17
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
18
ARBOVIRUS ENCEPHALITIS
• SPORADIC
• LOW % INFECTIONS -> CLINICAL
CASES
• NOT ALL CASES -> MAJOR DISEASE
• PROBABLY UNDERDIAGNOSED
19
WEST NILE VIRUS
• Reservoir: birds
• Vector: mosquito
• human, horse
– dead end hosts
flavivirus
20
http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm
3
50
1999
2000
2003
52
1999
2
2000
2003
54
2000 1999
2001
2003
50
2000
2002 200
2001
1999
51
2002
20
2003
51
2003
54
2000
50
53
2003
52
52
2000
West Nile virus
2003
flavivirus
2
21
Final 2008 West Nile Virus activity in the United States
West Nile virus
flavivirus
22
WEST NILE VIRUS
• Symptoms:
– Fever
– Meningitis
– Encephalitis
More rarely:
– Acute flaccid paralysis
• West Nile polio-like paralysis
– poliomyelitis - inflammation spinal cord
flavivirus
23
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. 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
24
WEST NILE VIRUS
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
flavivirus
25
26
http://www.cdc.gov/ncidod/dvbid/westnile/resources/wnv_transplant%20brochure6_12_07.pdf
WEST NILE VIRUS
transmission:
• Mosquito (vast majority of cases)
• Blood transfusion (blood supply is now screened)
• Organ donation
flavivirus
27
flavivirus
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%
28
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
29
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
30
EASTERN EQUINE ENCEPHALITIS
CDC
togavirus
31
WESTERN EQUINE ENCEPALITIS
• Reservoir: birds
• Vector: mosquito
• Sentinels
– horse,quail, turkey
• Children at higher
risk
• CFR 3-5%
• humans and horses
dead end hosts
USA: last confirmed human case 1999
togavirus
32
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
33
bunyavirus
2000 - 2 cases in SC, Charleston area
La Crosse life cycle
34
ARBOVIRUSES – FEVER AND
HEMORRHAGIC FEVER
FAMILY
MAIN DISEASES
DISTRIBUTION
Dengue
fever, hemorrhagic fever
World wide,
especially tropics
Yellow fever
hemorrhagic fever
Africa, S. and C. America
REOVIRIDAE
Colorado tick fever
fever
North America
FLAVIVIRIDAE
35
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
36
flavivirus
37
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
38
flavivirus
http://news.bbc.co.uk/2/hi/americas/6422319.stm
patients being treated for Dengue fever in a Paraguayan hospital
39
flavivirus
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
flavivirus
• more rarely encephalitis
40
DENGUE HEMORRHAGIC
FEVER/DENGUE SHOCK
SYNDROME
•
•
•
•
•
•
hemorrhages
plasma leakage
hemoconcentration
hypotension
circulatory failure
shock
flavivirus
41
CDC
DHF - petechiae
42
flavivirus
Dengue hemorrhagic fever - pleural effusion
Vaughn DW et al. J Infect Dis 1997; 176:322-30.
CDC
43
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
44
DENGUE HEMORRHAGIC
FEVER
• Immune enhancement hypothesis
– more mononuclear cells infected
– infected monocytes release vasoactive
mediators
– increased vascular permeability
– hemorrhagic symptoms
flavivirus
45
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
46
47
flavivirus
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
last yellow fever epidemic in US - 1905
CDC
48
flavivirus
The end
49
(Time Dec 2007)
50
51
Aedes albopictus is a species of
mosquito which is a good vector
for Dengue
52
53
WEST NILE VIRUS
flavivirus
55
WEST NILE VIRUS
SC
Case fatality ratio:
• Higher in elderly
• The 1 fatality in SC in
2005 was over 65
years old
SC - 2005
• Peaks about Aug-Sept
flavivirus
56
http://westnilemaps.usgs.gov/sc_human.html
1999
West Nile virus
57
2000
West Nile virus
58
2001
West Nile virus
59
2002
West Nile virus
60
2003
West Nile virus
61
2004
West Nile virus
62
2005
West Nile virus
63
2006
West Nile virus
64
65
66
67
68
VIRAL ZOONOSES
PART I I
VERTEBRATE VECTORS
69
HUMAN RABIES
• >55,000 DEATHS PER YEAR WORLD WIDE
70
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 rabiesinfected 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.
71
Edited (abbreviated) from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm53d709.htm
RABIES VIRUS
RHABDOVIRUSES
• Rhabdoviridae
family
• Lyssavirus genus
• helical, enveloped
• ss RNA, -VE sense
G glycoprotein
SPIKES
M protein
lipid bilayer membrane
helical nucleocapsid (RNA plus
N protein)
polymerase complex
26
72
NERVE MAN
CDC
73
TRANSMISSION
• BITE - USUAL ROUTE
• CORNEAL AND OTHER TRANSPLANTS
• MUCOSAL MEMBRANES, WOUND
• AEROSOL (RARE)
74
Note: no viremia
Murray et al., Medical Microbiology
75
INCUBATION PERIOD
• ~2 weeks to ~18 months
• average about two months
• post-exposure prophylaxis
76
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
77
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
78
FLUORESCENT ANTI-RABIES NUCLEOPROTEIN
ANTIBODY
rabies virus infected
uninfected
CDC
79
rabies virus infected
uninfected
CDC
80
rabies virus infected - negri body - note dark blue basophilic
granules (Sellers stain)
CDC
81
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)
82
South Carolina Department of
Health and Environmental Control
~40,000 people per
year treated in US
~400 people
per year
treated in SC
83
84
CDC
RABIES AND RODENTS
• Small rodents rarely infected
• but can occur especially in
woodchucks
http://en.wikipedia.org/wiki/File:Closeup_groundhog.jpg
85
HUMAN RABIES
• IN USA MOST OF
RECENT CASES
ASSOCIATED WITH
BAT RABIES
86
CDC silver-haired bat
HUMAN RABIES
• HUMAN-TO-HUMAN
– surgically - via transplants
– no direct human-to-human ever documented
87
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
88
IM
PRE-EXPOSURE
PROPHYLAXIS
• VETERINARIANS AND STAFF
• WILDLIFE OFFICERS ETC LIKELY TO
CONTACT RABID ANIMALS
• TRAVELERS LIKELY TO BE AT RISK
• RABIES RESEARCH WORKERS
89
PRE-EXPOSURE
PROPHYLAXIS
• VACCINATE
• REGULAR TESTING AND BOOSTERS
• STILL NEED POST-EXPOSURE
PROPHYLAXIS
– REDUCED COURSE OF VACCINATIONS
– HRIG NOT NECESSARY
90
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
91
RODENT BORNE
FAMILY
Hantavirus genus
of Bunyaviridae
ENVELOPE
SYMMETRY
GENOME
yes
helical
ssRNA
ambi-sense
segmented
yes
helical
ssRNA (-ve)
segmented
92
ROUTE OF INFECTION
• rodent urine
• contaminated materials (aerosols)
• respiratory tract
CDC
93
ARENAVIRUS FAMILY - all have rodent vector
VIRUS
DISEASE
OCCURRENCE
Lassa
Lassa fever (HF)
Africa
Machupo
Sabia
Junin
Guarnarito
Whitewater Arroyo
Bolivian HF
Brazilian HF
Argentine HF
Venezuelan HF
Whitewater Arroyo HF
South America
South America
South America
South America
Western US
lymphocytic
choriomeningitis
virus (LCMV)
Lymphocytic
Widespread
choriomeningitis (LCM)
94
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%
95
CDC
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
96
BUNYAVIRIDAE
HANTAVIRUSES - all have rodent vector
NAME
TYPE OF DISEASE
OCCURRENCE
Korean HFRS
hemorrhagic fever with
renal syndrome (HFRS)
S.E.Asia
HFRS
hemorrhagic fever with
renal syndrome
Europe, Asia
Hantavirus
pulmonary
syndrome (HPS)
hantavirus pulmonary
syndrome
North and South
America
Rodent vector - limited number species per virus
97
HANTAVIRUS-ASSOCIATED
HEMORRHAGIC FEVERS
• Korean hemorrhagic fever with renal
syndrome (CFR ~7%)
• other HFRS viral diseases around the
world
CDC
Hantavirus genus
98
HANTAVIRUS PULMONARY
SYNDROME
CFR ~36%
Hantavirus genus
99
HANTAVIRUS PULMONARY
SYNDROME
• Can be caused by various members of
the hantavirus family
– Including Sin Nombre virus
100
Hantavirus Pulmonary Syndrome Cases
by State of Exposure United States – March 26, 2007
33
Total Cases (N=465 in 30 States)
9
25
8
15
2
16
2
51
38
3
5
7
25
3
1
12
7
1
2
3
1
13
1
2
48
71
30
2
1
0 Cases
1-4 Cases
5-9 Cases
>=10 Cases
Twenty-seven cases were reported with unknown state of exposure.
current CFR=35%
CDC
102
Radiographic Progression of
HPS in the Lung
Source: Dr. L. Ketai via CDC
103
VECTOR UNKNOWN
HEMORRHAGIC FEVERS DUE TO EBOLA,
MARBURG VIRUSES
104
VECTOR UNKNOWN
FAMILY
ENVELOPE
SYMMETRY
GENOME
yes
helical
ssRNA (-ve)
Filoviruses may be up to ~14,000 nm long (rhabdoviruses
105
have similar diameter but are only ~180 nm long)
Negative stain image of an isolate of Marburg virus
R. Regnery, CDC.
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fa
ct_Sheets/Filovirus_Fact_Sheet.pdf
Ebola virus budding from an infected human cell.
T. Geisbert, USAMRIID
Science 302:1141 (2003)
(lower magnification than left hand image)
106
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
107
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
108
http://www.cdc.gov/ncidod/EID/13/1/6.htm
The end
109
110
Case of Marburg Haemorrhagic Fever imported into the Netherlands from Uganda
10 July 2008
WHO 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 Organization
http://www.who.int/csr/don/2008_07_10/en/index.html
111