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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)
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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
10
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
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
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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
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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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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
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
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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
39
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.
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
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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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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
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
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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)
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)
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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
84CDC
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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
90
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
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
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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
98
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
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
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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