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Bats as reservoirs of emerging pathogens
Prof. Dr. Steven Van GuchtViral DiseasesWIV-ISPSSID, Brussels, 19/05/2016
WIV-ISP | Rue Juliette Wytsmanstraat 14 | 1050 Brussels | Belgium
T +32 2 642 xx xx | F +32 2 642 xx xx | [email protected] | www.wiv-isp.be
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What are bats?
Megachiroptera:
1 family
old world fruit bats
flying foxes (vleerhonden)
Microchiroptera:
17 families
worldwide
echolocation, hibernation
Hands developed into wings
20% of 5000 species of mammals
Peridomestic
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Old world fruit bat
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The problem with bats
1932: Rabies
1996: Hendra
2000: Nipah
2003: SARS → Chinese horse
shoe bat was
reservoir!
2005: Ebola
2007: Marburg
2007: Reovirus (Meleka, Kampar)
2012: MERS
Next ?
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What is special about bats?
• Good reservoir species
• High virus diversity (cfr rodents):
2007-2013: >248 novel viruses discovered*
Database for bat viruses: www.mgc.ac.cn/DBatVir/
• Pathogens exceptionally lethal for other
mammals, mild or subclinical in bats
• Ancestral host for important mammalian virus
families and genera
*Young CC, Olival KJ. 2016. PLoS One. 2016 Feb 11;11(2):e0149237.
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Bats as ancestral host
Most likely:
Lyssavirus (Rabies)
Alpha-and beta-coronavirus (MERS, SARS, 229E, NL63)
Filovirus (Ebola, Marburg)
Major paramyxoviruses, including Mumps virus and RSV
Possibly also:
Hantavirus (together with shrew and moles)
Hepandavirus, including HBV
Hepacivirus (HCV ancestor)
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Bats live in dense colonies
Bracken cave, Texas: 20 million Mexican-free tailed bats
Congress Avenue bridge Austin: 1 million
= largest colonies of mammals
Mumbai: 1 human/43 m2
Bracken cave: 2222 bats/m2
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Ancient order: 60 million years old
primitive mammalian characteristics, little evolutionConserved ancient cell receptors, enzymes,...Co-evolution virus - bats
From: Gids van de vleermuizen van Europa, Lina, Tirion, Baarn, 2001
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SARS CoV: ACE-2
MERS CoV: DPP4
Conserved mammalian receptors
Hendra and Nipah:
ephrin B2 (arteries,
neurons)
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Metabolism
• Specific traits associated with flight:
High body temperature (41°C): cfr fever
Heigthened DNA repair mechanisms and ROS
scavenging (longevity)
• Low body temperature during hibernation and
torpor (1-2°C): suppression immunity
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Immune system
• Similar immune cells, antibody classes
• Conserved pattern recognition receptors
TLR3, RIG-I, MDA5,…
• IFN system:
Constitutive expression of IFN-alpha
No hyperinflammation
Better control of virus replication?
• Favours persistent infections (?)
Zhou P et al. 2016 PNAS 113(10): 2696–2701
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Genus Lyssavirus: rabies
Movement of bats caused worldwidedissemination
11 out of 12 species circulate in bats
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Bat rabies in Europe
European bat lyssavirus-1 (EBLV-1): Eptesicus serotinus
EBLV-2: Myotis daubentonii
30 rabid bats per year
Spill over infections in sheep, stone marten, cat
4 lethal cases in humans since 1977
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Bat rabies in Belgium
• ± 40 bats examined/year
Pipistrellus (84%)
Eptesicus (6%)
Myotis (3%)
• No local case (yet)
• 2010: 1 positive bat from Spain
• Low sensitivity surveillance
• 10 people/year receive prophylaxis
after bat bite/scratch
Epistat: 2008-2016, 331 bats
examined
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Photographer bitten by rabid bat in
2010
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The vampire bat: what’s in a name?
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Invasion of humans in endemic foci: gold rush, deforestation
Animal husbandry
Disturbance ecosystem = disturbance equilibrium in disease transmission
Vampire bats of the Amazone
Johnson N. et al. Viruses. 2014 Apr 29;6(5):1911-28.
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Fruit bats as reservoirs of Ebola
Leroy et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005 Dec 1;438(7068):575-6.
Picture from Mishra B. Indian J Med Microbiol 2014;32:364-70
6% of hammer-headed bats have ZEBOV antibodies
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Hammer-headed bat (Hipsignathus monstrosus)
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Egyptian fruit bat (rousette)
2007 Uganda: Outbreak Marburg hemorragic fever in miners
5000/100000 bats in 1 cave subclinically infected
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Ebola epidemic 2014-2015
Index case: 1 boy in guinea, sick in dec 2013
Source of infection: bat-infested hollow tree ?
28652 cases, 11325 deaths, 10 countries
Marí Saéz A et al. Investigating the zoonotic origin of the West African Ebola epidemic. EMBO Mol Med. 2014
Dec 30;7(1):17-23.
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FAO warns against bat hunting
and bushmeatHIV-1
HIV-2
HTLV-1
HTLV-2
Ebola
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Hendra virus Australia
Acute respiratory disease and encephalitis
Bats > horses > humans
Since 1994: >11 outbreaks horses, 4 human deaths/7 cases
Fence to keep horses out of the “drip” zone
Since 2012: vaccine for horses
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Nipah virus
Acute respiratory disease and fatal encephalitis
Malayasia 1998: bats > pigs > farmers (109 deaths/283 human cases)
Bangladesh >33 outbreaks: date palm sap
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Origin of SARS CoVHorseshoe bats
High diversity of SARS-like CoV
WIV1 isolate: 95% identity
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Civet cat: little genetic variation of isolatesvery susceptible: high virus titers= amplification host
late epidemic strainearly middle
29 nucleotide deletionin ORF8
Animal market
South-east China
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MERS CoV
• 2012-2016: 642 deaths/1728 cases
• Reservoir is dromedary camel (80% seropositive)
• Bat is ancestral host:
- >20 years ago in East Africa: Bats > camels
- Bats are probably not a direct source for humans
- MERS-like CoV: 80% identity
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Conclusions
• New biomedical insights: virus immunology, longevity, hearing ,….
• In Europe: mainly useful animals (insectivores)
• (Sub)Tropics: deforestation and urbanisation will continue to drive spill-over and outbreaks of forest pathogens
• Metagenomics is rapidly creating insights in wide diversity of viruses in nature
• Major zoonotic events: only 1 or few species, under specific circumstances and in specific regions
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Friend or foe?
Thanks for your attention!