VIRAL ZOONOSES

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VIRAL ZOONOSES

• PART I I
• VERTEBRATE VECTORS

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HUMAN RABIES

• gt55,000 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)

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Note no viremia
Murray et al., Medical Microbiology
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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

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FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY
rabies virus infected
uninfected
CDC
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rabies virus infected
uninfected
CDC
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rabies virus infected - negri body - note dark
blue basophilic granules (Sellers stain)
CDC
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HUMAN RABIES

• SINGLE SEROTYPE
• gt95 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
40,000 people per year treated in US
400 people per year treated in SC
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CDC
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RABIES AND RODENTS

• Small rodents - rarely infected
• but can occur - especially in woodchucks

http//en.wikipedia.org/wiki/FileCloseup_groundho
g.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-sense segmented ssRNA
(-ve) segmented
Hantavirus genus of Bunyaviridae
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ROUTE OF INFECTION

• rodent urine
• contaminated materials (aerosols)
• respiratory tract

CDC
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ARENAVIRUS FAMILY - all have rodent vector
VIRUS Lassa Machupo Sabia Junin Guarnarito White
water Arroyo lymphocytic choriomeningitis virus
(LCMV)
DISEASE Lassa fever (HF) Bolivian HF Brazilian
HF Argentine HF Venezuelan HF Whitewater Arroyo
HF Lymphocytic choriomeningitis (LCM)
OCCURRENCE Africa South America South
America South America South America Western
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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BUNYAVIRIDAE
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
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HANTAVIRUS-ASSOCIATED HEMORRHAGIC FEVERS

• Korean hemorrhagic fever with renal syndrome (CFR
  7)
• other HFRS viral diseases around the world

CDC
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HANTAVIRUS PULMONARY SYNDROME
CFR 36
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HANTAVIRUS PULMONARY SYNDROME

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

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Hantavirus Pulmonary Syndrome Cases by State of
Exposure United States March 26, 2007
Total Cases (N465 in 30 States)
Twenty-seven cases were reported with unknown
state of exposure.
CDC
current CFR35
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(No Transcript)
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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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Ebola virus budding from an infected human cell.
T. Geisbert, USAMRIIDScience 3021141
(2003) (lower magnification than left hand image)
Negative stain image of an isolate of Marburg
virus R. Regnery, CDC. http//www.cdc.gov/ncidod/d
vrd/spb/mnpages/dispages/Fact_Sheets/Filovirus_Fac
t_Sheet.pdf
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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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(No Transcript)
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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/d
on/2008_07_10/en/index.html