1 EBOLA AND MARBURG VIRUSES HUMAN ANIMAL HUMAN-ANIMAL INTERFACES Douanier Rousseau C.Goldsmith/S.Zaki Second FAO-OIE-WHO consultation: Influenza and other Emerging Zoonotic Diseases Verona April 2010 Mononegavirales, Filoviridae, Filoviruses : 5 distinct Ebola strains : Sudan, Zaire, Reston, Côte Ebola and Marburg Haemorrhagic Fevers d'Ivoire, Bundibugyo 2 lineages for Marburg : POP, RAVN Reservoir: bats are strongly suspected BSL 4 Incubation 2-21 days Case Fatality Ratio 24-89% Case Fatality Ratio 24 89% Treatment : no specific treatment available, careful rehydration, supportive, intensive care, Vaccines in development
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EBOLA AND MARBURG VIRUSES HUMAN-ANIMAL · PDF file1 EBOLA AND MARBURG VIRUSES HUMAN-ANIMAL INTERFACES Douanier Rousseau C.Goldsmith/S.Zaki Second FAO-OIE-WHO consultation: Influenza
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d'Ivoire, Bundibugyo2 lineages for Marburg : POP, RAVN
Reservoir: bats are strongly suspectedBSL 4 Incubation 2-21 daysCase Fatality Ratio 24-89%Case Fatality Ratio 24 89%Treatment : no specific treatment available,
careful rehydration, supportive, intensive care,
Vaccines in development
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09 DRC 1999
07 DRC 1999
05 DRC 1999
Ravn Kenya 1987
1 1
1
1
Complete genome analysis:Filoviruses
Marburg 21% nt
Popp Uganda 1967
Zaire 1976
Ozolins Zimbabwe 1975
Musoka Kenya 1980
Zaire 1995
1379c Angola 2005
1
1
1
1
800 yrs
Reston 1989
Cote d’Ivoire 1994
Bundibugyo 2007
Zaire 1976
Sudan 2000
1
1
1
1
Ebola
32% nt
39% nt
Towner et al., PLoS Pathogens, 21 Nov 2008
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Yambuku‘76
Nzara‘76
Zaire’79 80
Zaire‘95
I. Coast’96 97
CentralAfrican Republic
‘99 T t l
Summary of tropical African animals tested for evidence of Ebola Zaire, 1976-1999
1976 cases; 1st 6 cases were cotton factory employees who worked in a room where bats roosted
Cote d’Ivoire ebolavirus1994; chimpanzees which developed EHF had been feeding in a fig tree together with fruit bats for two weeks before developing the disease
Reston ebolavirus1989-96; all outbreaks in primate facilities link back to a single primate export facility in the Philippines which was a former fruit orchard and animals potentially exposed to fruit bats
Marburg virus1967 imported monkeys from Ugandan locations where fruit bats prevalent1975 tourists slept in rooms where insectivorous bats were present Zimbabwe1980 and 1987; two patients in Kenya both visited a cave inhabited by batsshortly before becoming ill1998-2000; Durba DRC outbreak linked to gold mine with infected bats2007; Kitaka Uganda, two cases link to mine with infected fruit bats2008; Python cave Uganda, two cases linked to cave with infected fruit bats
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Bats Bats –– the likely reservoir for the the likely reservoir for the Marburg and Ebola virusesMarburg and Ebola viruses
Direct lab dataDirect lab dataZaire ebolavirus
Detection of virus-specific antibody and genome RNA in 3 speciesDetection of virus specific antibody and genome RNA in 3 species of bats in Gabon
1996; Experimentally infected fruit bats shown to replicate ebolavirus without developing overt disease
Marburg virusDetection of virus-specific antibody, and genome RNA predominantly in Egyptian fruit bats (Rousettus aegyptiacus) inpredominantly in Egyptian fruit bats (Rousettus aegyptiacus) in Gabon, Durba DRC, Kitaka Uganda and Python Cave, Uganda
Multiple virus isolates from Kitaka and Python caves
Multiple diverse virus genetic lineages co-existing in R. aegyptiacus colonies; no correlation between genetic and geographic distances – likely reflecting mobility and large meta-population of host
Filovirus infection of batsFilovirus infection of bats
Marburg virus in R. aegyptiacus• virus infection (PCR) 1.6 – 5.1 %• past infection (IgG) 2.3 – 20.5 %
Zaire ebolavirus in 3 species of bats• virus infection (PCR) 2.8 – 19%• past infection (IgG) 6.8 – 23%
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Proposed mechanisms of Ebola virustransmission to wildlife, domestic animals
(or humans) from bats
•Competition for fruit between chiropterans and non-human primates leads to spatiotemporal clustering of frugivorousprimates leads to spatiotemporal clustering of frugivorous animals leading to an increased likelihood of spillover
•Infectious virus in:• saliva
-Nipah virus (Chua et al., 2002; Reynes et al., 2005)-Hendra virus (in horse saliva-Williamson et al., 1998)
• feces (guano) or urine(g )-Nipah virus (Chua et al., 2002)-Hendra virus (Williamson et al., 1998)-Ebola virus (experimentally infected bats Swanepoel et al., 1996)-Menangle virus (Hooper et al., 2000)
• birthing fluids (blood, placental tissues etc)-Hendra virus (Young et al., 1997; Halpin et al., 2000)
Suspected modes of transmission to humans
• Contact with reservoir (bats): hunters, miners, ecologists, tourists
• Contact with secondary hosts (pigs, primates): hunters, farmers slaughter house workersfarmers, slaughter house workers
• Contact with human (patients): family, nosocomial infections, burial practices
Geographic distribution of Rousettus aegyptiacus in Africa
•Geographic distribution encompassesthe location of all known Marburgthe location of all known Marburgoutbreaks
•Reproduces twice a year-(~75-80% of adult females pregnant)
•Reproductive capacity combined withthe large colony sizes (>100,000) predicts large meta-populations
•Can have long life span up toCan have long life span, up to25 years in captivity
•Up to nine subspecies withinAfrica and Asia
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Pathogenesis in different species and ability to transmit diseases
Bats: unknownNon human primates:
laboratory: death in 5 to 7 days, very few survivorswild: death, some survivors (Gabon 2004 13% chimps IgG)
Excretion…
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Animal model of disease and vaccine model prediction
Rapid systemic spread with high viremiaInfection and necrosis of macrophages and dendritic
cellsRelease of proinflammatory mediators, leading to
increased vascular permeability and shockMassive lymphocyte apoptosis.
These changes are seen in non-human primates, guinea pigs and mice… BUT
12 No. of deathsOther source
Suspected Ebola hemorrhagic fever by source of infection,
Zaire, 1995
0
2
4
6
8
10Ot e sou ceMW 29yo MNA 45yo F
0
9-Apr
13-Apr
17-Apr
21-Apr
25-Apr
29-Apr
3-May7-M
ay
11-M
ay
15-M
ay
19-M
ay
23-M
ay
27-M
ay
31-M
ay4-J
un8-J
un12
-Jun
16-Ju
n
20-Ju
n
24-Ju
n
Date of death (1995)
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2008 Disease activity in pigs in 2008 Disease activity in pigs in PhilippinesPhilippines
• Porcine Respiratory and Reproductive Syndrome (PRRS) virus has caused respiratory failure in neonates or abortions in sows during sporadic PRRS outbreaks worldwide (also known as Blue Ear pig disease)
•• PRRSV is RNA virus, contains a ss positive-sense RNA genome (15kb); genus
arterivirus (same genus as SHFV !)
• Since 2006 large outbreaks of more virulent atypical PRRS swept through large areas of China and Vietnam – major economic impact
• Disease outbreaks in pigs in Bulacan, Philippines May 2007 through mid-2008. Increase in morbidity/mortality consistent with atypical PRRS, similar to Vietnam and China
• PRRS or swine influenza suspected
• Samples from 4 farms sent to USDA Plum Island facility Oct 2008 for testing• PRRS identified, but also Circo 2 virus. PRRSV does not grow on Vero cells
• One pig tissue yields a virus isolate growing on Vero cells.
• Panviral microarray developed in-house at Plum Island provides evidence of Reston ebolavirus
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Pig disease symptomsPig disease symptoms• High fever 41C• Labored breathing• Labored breathing• thumping• Coughing, nasal discharge• Loss of appetite, Diarrhea• Skin hemorrhage/reddish discoloration
S f d i b t iti• Some found in recumbent position
• High nursery house and growing house mortalities• Sows previously affected by high fever and
abortions
Ebola Reston virus: Hypothesis of transmission
Ebola Reston virus: Hypothesis of transmission
Fruit bats Secondary
Transmission
Human
Food Chain
Pigs: Amplification
Healthcare workers
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QuestionsQuestionsSource of virus infecting the pigs ?How common and widespread is the problem ?
Does Reston ebolavirus cause disease in pigs(alone or in combination with PRRSV) ?
Is there pig to pig transmission ? – Geelong
To what extent are humans getting infected down the Farm to Table chain ?to Table chain ?
Any evidence of human disease associated with Reston ebolavirus infection?
One World, One Health
•CDC – SPB, IDPB
•Uganda Virus Research Institute (UVRI)
Serena Reeder
Brian Amman
Jon Towner
•NICD – South Africa
•WHOAlan Kemp
Stuart Nichol
Tom KsiazekPierre Rollin
Bob Swanepoel
Eileen Farnon Andy Comer Pierre Formenty Tara Sealy