Download Approaches to Emerging Diseases

EMERGING INFECTIOUS DISEASES
JOHN BEREZOWSKI DVM PHD
VETERINARY PUBLIC HEALTH INSTITUTE
UNIVERSITY OF BERN
BERN SWITZERLAND
FEB 05 2015
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Learning Objectives
Understand emerging infectious diseases,
what they look like and how we find out about
them
Understand the process and stages of
infectious disease emergence
Learn about some of the determinants for
infectious disease emergence
Learn a little bit about the complex
relationship between infectious disease and
societal values
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WHAT IS AN EMERGING INFECTIOUS
DISEASE?
Definition: emerging and re-emerging infectious diseases
What does an emerging infectious disease look like?
How do we find out about emerging infectious diseases?
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Then…
“We can look forward with
confidence to a considerable
degree of freedom from
infectious diseases at a time
not too far in the future.
Indeed…it seems reasonable
to anticipate that within
some measureable time …all
major infections will have
disappeared”
 T. Aidan Cockburn: 1963
and Now
 15 million (>25%) annual
human deaths worldwide
are caused by infectious
diseases
 61% of human pathogens
are zoonotic
 At least 30 new diseases
of humans have emerged
in the last 20 years
Morens. 2004. Nature, Vol 430, 242-249
 One World, One
Medicine, One Health
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Chikungunya
St Martin Dec 5 2013
RNA Virus A. Aegypti +Albopictus
http://www.healthmap.org/en/
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http://www.healthmap.org/en/
http://www.healthmap.org/en/
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IDs emerge world wide
Source: National Institutes of Health
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IDs also emerge into animal populations!
Pathogen
Porcine Epidemic Diarrhea Virus (PEDv)
Porcine Respiratory Reproductive (PRRS)
Porcine Circovirus (PCV)
Schmallenberg virus:
Bovine Spongiform Encephalopathy
Canine Parvovirus
Influenza viruses
West Nile virus in North America:
Monkey Pox in the USA
Canine Distemper Virus
Chronic wasting disease
Lyme disease
Feline Immunodeficiency Virus
Nipah virus
Hendra virus
Devil facial tumor disease
White Nose Syndrome
Species
Pigs
Pigs
Pigs
Cattle, sheep, goats
Cattle, people
Dogs
Birds, pigs, dogs, equids
Birds, horses, people, others
Prairie dogs, people
Seals, others
Deer, elk
Dogs
Cats
Bats Pigs  people
Bats Horses  people
Tazmanian devils
Bats
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Definitions
 Emerging:
1. PREVIOUSLY UNKNOWN disease that suddenly appears
(emerges) in a population
• Diseases that have never been seen before
• First appear as diagnostic dilemmas
2. KNOWN disease that suddenly appears (emerges) in a
new population
• A different age, production type
• A different part of the world
• Foreign animal diseases (also called transboundary diseases)
 Re-Emerging:
1. KNOWN disease, previously on the decline, that is
becoming more common and will likely continue to do so
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What Does An Emerging Dz Look Like?
Emerging, re-emerging dz are recognized as increases in
the burden of disease
Quantity
• Increased amount (incidence) of new, endemic or transboundary (foreign) dzes
Quality
• Change in the way a pathogen affects the host
• Increased severity of dz: increased morbidity, mortality
• Reduced productivity, reproductive performance
Diagnostic dilemmas
• New previously unrecognized dz..usually as a syndrome
• Changed clinical presentation of endemic dz
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Porcine Epidemic Diarhea
http://www.aphis.usda.gov/
http://www.aphis.usda.gov/
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Known Disease Emergence
2001 Foot And Mouth Disease UK
MS-NBC
BBC
http://www.pbs.org/newshour/bb/health/jan-june01/footmouth_3-30.html#
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Known Dz re-emerging
Monkeypox in Central Africa
Eradication of
Small Pox
Cessation of
Small Pox
Vaccination
Increased
Susceptible
People
Increased
Monkeypox
Disease
http://www.environment.ucla.edu/ctr/news/article.asp?parentid=11358
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How are they recognized?
1. Known Diseases
– We know what to look for
– Well developed structured processes are in place
– Surveillance: mostly based on disease reporting
2. Unknown Diseases (previously unseen)
– Don’t know what to look for
– Not well developed, unstructured, informal
– Surveillance: for what?
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How are they recognized?
Detection
Investigation
Response
Public
Farmer
Health care worker
Veterinarian
Pathologist
Epidemiologist
Academic
Weirdness
Champion
National, Provincial,
International
agencies, industries
Identifies something
abnormal, weird,
unusual
dx dilemma
Promotes
Communicates Dz
Importance
Attracts resources
Implement Dz control,
mangement
eradication, mitigation
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Member of public finds
sick pigeon
Takes to Vet
Vet Sends Pigeon to Dx
Lab
Pathologist IDs new
parasite
Sarcocystitis calchasi
Published in
Journals/Media
http://blogs.scientificamerican.com/guest-blog/2012/01/31/a-wildlife-vet-a-pigeon-a-groundbreaking-discovery/
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PROCESS OF INFECTIOUS DISEASE
EMERGENCE
Chain of infection
How do infectious diseases emerge?
Stages of infectious disease emergence
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“Chain” of Infection
Accesstocontinuingeducation.com
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Reservoir Population
Pathogen
Exposure
Susceptible
Population
 Introduction of a new
agent into a susceptible
population
 Exposure is caused by
movement of infectious
agents
Pathogen
Transmission
Dz +/Epidemic
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Reservoir Population
Pathogen
Exposure
Susceptible
Population
Pathogen
 Adoption, establishment,
and dissemination in the
susceptible population
Transmission
 Requires a pathogen that
can adapt to, and transmit
Dz +/between, these hosts
Epidemic
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Stages of Cross-Species Disease
Emergence
Old Host
1.
2.
3.
4.
5.
Pathogen exclusive to an animal
reservoir
Animal reservoir transmits to
humans/other animals, but no
transmission among them
Animal reservoir transmits to
humans/other animals with a few cycles
of transmission among them
Animal reservoir transmits to
humans/other animals with sustained
transmission among them
Pathogen exclusive to humans/new
animal reservoir
New Host
Reservoir
--
Reservoir
Accidental &
Dead-end
Reservoir
Accidental
(not always
dead-end)
Reservoir
Also a
Reservoir
--
Reservoir
Wolfe ND et al. Nature May 2007 Vol 447: 279-283
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Stage 1: Pathogen exclusive to a single
species
Host that dz
Number of
Pathogens with
Many pathogens
have multiple host
species
occurs in
Pathogens
Multiple Hosts
Humans
1415
61.6%
Livestock
616
77.3%
374
90.9%
1922
62.7%
Overall, only 37.3%
of pathogens have Dogs + Cats
one known host
Total
Are they really one-host pathogens?
Or do we not know the other hosts they infect?
Livestock = cattle sheep, goats, pigs and horses
S. Cleaveland, et al. Phil.Trans.R.Soc.Lond.B (2001) Vol. 356, pp. 991-999
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Stage 2. Animal reservoir transmits to
humans/other animals, but no transmission
among them (dead end hosts)
 Rabies
– Reservoirs are carnivores and chiroptera (bats)
– Cattle and horses and people are dead end hosts
 WNV, EEEV, WEEV
– Reservoir: Birds
– Humans, horses, and dogs are dead end hosts
 Influenza H5N1
– Reservoir: waterfowl and poultry
– Humans are dead end hosts
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1997 – Present
H5N1 Avian Influenza
 First outbreak: 1997, Hong Kong
– A few human respiratory cases
– Acquired directly from chickens
– 1.2 million chickens culled
 Southeast Asia, 2004...
– Widespread outbreak; not controlled, in spite of
massive culling of domestic poultry
– Spread by wild birds? poultry smuggling? use of
poultry vaccine that was partially protective?
 Jan 23, 2015
– Outbreaks continue to occur in chickens
– 718 human cases have been reported since 2003, with
a case fatality rate of 57.5% (413 deaths)
WHO/GIP, data in HQ as of 23 January 2015
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Malignant Catarrhal Fever Viruses
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Stage 3. Animal reservoir transmits to
humans/other animals with a few cycles of
transmission among them
Mycobacterium bovis
– Reservoir: cattle, bison, elk
– Transmitted to people via respiratory route
– Poor human to human transmission
 Nipah Virus
– Reservoir: fruit bats
– Human to human transmission is poor
– Pig to pig transmission is also relatively poor
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1998-1999
Nipah Virus
 Suddenly emerged in Malaysia
– Outbreak Sept 1998 – April 1999
– A fruit bat origin paramyxovirus that had
been “smoldering” in pigs (in retrospect)
since ~1996
 Sick pigs
– Respiratory, rapid spread
– 1.1 million were culled to prevent spread
(out of a national herd of 2.4 million!)
 Sick people (n=265)
– Encephalitis in many cases
– Cases had 40% fatality rate (n=105)
– Survivors often have neurologic sequelae
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Nipah Virus Bangladesh
Risk: Drinking Raw Date Sap
Fruit Bats drink (saliva) urinate,
defecate in collecting jars
No Tx
157 of 208 Infected have died
From 2001 to 2012
http://www.bdnews24.com/details.php?id=217759&cid=2
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Stage 4. Animal reservoir transmits to
humans/other animals with sustained
transmission among them
 SARS: Severe Acute Respiratory Syndrome
– Reservoir: fruit bats
– Efficient transmission in humans
 Schmallenberg virus
– Reservoir species: ?
– Efficient transmission in sheep, goats and cattle
 2009 Influenza H1N1 “Swine Influenza”
– Reservoir: swine
– Very efficient transmission in humans
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2009: Swine Influenza
 H1N1, “swine flu”, “Mexican flu”…
 A recombinant strain
– The segments in the current strain have been
“together”, as a pig virus in North America, since 1998
– Some segments were originally avian, one was via
humans
 First human cases recognized in April, 2009, from
Mexico
– Global spread within a few weeks
– June 11: officially declared pandemic by the WHO
 First swine cases were recognized in Canada in
late April, 2009
– Why not in Mexico?
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Stage 5. Pathogen exclusive to new
reservoir species
Human examples
– HIV/AIDs
Origin: non-human primates
– Measles
Origin: cattle
– Smallpox
Origin: likely camels (camelpox)
– Falciparum malaria Origin: Birds
– Rota virus
Origin: domestic herbivores or
mammals
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WHAT MAKES A DISEASE LIKELY TO
EMERGE?
Determinants of disease emergence:
• Pathogen type, adaptation and change
• Reservoir determinants
• Host population determinants
• Enhancing transmission
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Determinants of emergence
Pathogen
Type of agent
Mutation/Change
Host
Susceptibility
Reservoir
Phylogenetic distance
Transmission
Reservoir size
Pathogen prevalence
Contact frequency
Accesstocontinuingeducation.com
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1.Pathogen: Type of Agent
 Of the >1400 species of
pathogen known to infect
humans, 61% are zoonotic
 75% of emerging diseases of
humans are zoonotic
 Zoonotic pathogens are
twice as likely to be
associated with emerging
diseases
 Which taxonomic groups of
pathogens are most likely to
emerge?
Category
Relative
Risk
Zoonotic
Status
Not zoonotic
0.52
Zoonotic
1.93
Taxonomic
Division
Viruses
4.33
Bacteria
0.71
Fungi
0.33
Protozoa
2.49
Helminths
0.24
Adapted from Table 1, from: Taylor, Latham,
and Woodhouse. 2001. Phil. Trans. R. Soc.
Lond. B. 356:983-989.
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 Increased antibiotic
resistance
 Increased virulence
(E. coli O157:H7)
 Mutations that
enhance
transmissibility
within or between
species
 Evasion of host
immunity
% of Isolates
1. Pathogen: Adaptation and Change
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35
30
25
20
15
10
5
0
Salmonella Resistant to ≥4
Antibiotic Classes
Chicken breast
Ground turkey
Data from NARMS Retail Meat Report, 2010. FDA.
Released 1 March 2012.
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2. Reservoir
Phylogenetic distance between reservoir and
new host
– Best transmission: within a species
– Pathogens are more likely to cross between
closely related species than distant ones
• Close relatives: cattle  sheep
– Pathogens that somehow cross between distantly
related species often cause very different, often
more severe, disease
• Consider Nipah virus, bats  pigs OR people
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3. New Host Species
 New host: susceptibility!!!
– Applies to all diseases, even those that emerge into
new populations of the same species
– Intensive agriculture: a lot of genetically similar hosts,
managed under the same conditions, will have the
same susceptibility
– More people with weakened immune systems:
elderly, HIV/AIDS, cancer patients and survivors, organ
transplant recipients
– Countries that are free of FADs do not vaccinate,
because the lack of disease in susceptible animals
proves they are “disease free”
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Host Susceptibility: How it works
Susceptible + Infected + Recovered
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Host Susceptibility: How it works
Susceptible + Infected + Recovered
Or
Dead
Because the entire
population is susceptible
the consequences can be
catastrophic
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Susceptibles Fuel the Outbreak
Life…Stranger
than
fiction!
Photo Credit: Google Images
Photo Credit : Wikipedia
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Susceptibles Fuel the Outbreak
Photo Credit: OPB.org
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Resistance slows/stops the outbreak
H3N2v
A variant of H3N2
Influenza
with the Matrix (M) Gene
of pH1N1
US Only
Summer and Fall Fairs
2011, 12, 13
Mostly Young Children
Photo Credit: http://www.maniacworld.com/kissing-a-pig.html
http://www.cdc.gov/flu/swineflu/h3n2v-cases.htm
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4. Factors Increasing Transmission
The probability of transmission from a reservoir
to a new host increases with:
Increasing abundance of the reservoir
Increasing pathogen prevalence in the
reservoir
Increasing contact between the reservoir and
the new host
Epidemiologists define “contact” as whatever it
takes to transmit the disease in question
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Increased Transmission:
Livestock Production
Chickens in Maryland
 Increasing Production
– World meat production will
double from 2010 to 2020, mostly in developing countries
– Fewer, larger livestock holdings
– Production/output per animal is increasing
– Results in uniform genetics, production, susceptibility
Rushton,J., Upton, M : Res Vet Sci 2006: 25 (1), 375-388
 Small holdings will be a conduit between intensive
production systems and wildlife
– The 80:20 rule - even in developing countries
– Biosecurity may not be enough! A new disease emerges in
farmed swine every two years, on average
Weiss RA, McMichael AJ 2004 Nature Med Supp;10:S70
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Small Production will not go away
Industrialization: Change from diversity to uniformity
– Genetics, production practices, max productivity, susceptibility
Will Biosecurity be effective?
– John Iverson and the pail of milk
Will new pathogens emerge
– Foodborne?
Weiss RA, McMichael AJ Social and environmental risk factors in the emergence of infectious
disease. 2004 Nature Med Supp;10:S70
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Not Restricted to Developing
Countries
http://www.thebostonchannel.com/health/29481961/detail.ht
ml
Urban Agriculture
Will companion animal general
practitioners need to be able to
service urban livestock
operations?
http://www.amherstma.gov/DocumentView.aspx?DID=4635
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Increased Transmission: Animal Trade
40,000 ships on the
world’s oceans at
any time are
carrying animals or
animal products
Examples:
Live animal markets
Exotic pet “swap meets”
International transport
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Monkey Pox : 2003
762 African Rodents
West Africa
Texas
Gambian giant pouched rat
71 cases
18 hospitalized
No fatalities
Illinois
via
Iowa
Illinois
Indiana
Kansas
Missouri
Wisconsin
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Increased Transmission:
Development & Changing Ecosystems
 Urbanization increases
density of susceptible
human populations
 Changing land use and
climate influence
waterborne and
vectorborne disease
transmission (e.g. dams,
deforestation)
 2006 Outbreak of
Bluetongue in Europe)
Change in Bluetongue vector range
following a 1°C temperature increase
http://europa.eu/rapid/press-release_IP-061113_en.htm?locale=en
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6
 Persons infected with
an exotic disease
anywhere in the world
can be in a major US
city within hours
Days to Circumnavigate (
the Globe
350
)
400
5
300
4
250
200
3
150
2
100
50
1
0
0
1850
1900
Year
1950
2000
 Animal-based tourism
increases contact with
both domestic and
wildlife species
Koh Chang, Thailand
North Georgia State Fair
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World Population in billions (
)
Increased Transmission:
Travel and Tourism
2004 to 2006
11 million pounds
of bush meat
entered the US
http://news.discovery.com/animals/bushmeat-diseases-entering-new-york.html
http://www.google.com/imgres?hl=en&sa=X&biw=1707&bih=1171&tbm=isch&
prmd=imvns&tbnid=EOkMEirmOFMPTM:&imgrefurl=http://www.ensnewswire.com/ens/may2001/2001-05-2206.asp&docid=k4nAKsv7qwoyUM&imgurl=http://www.ensnewswire.com/ens/pics12/bushmeat1.jpg&w=287&h=258&ei=CncxT7CcMsjf0Q
H0nKDbBw&zoom=1&iact=hc&vpx=1429&vpy=451&dur=1394&hovh=206&hovw
=229&tx=187&ty=104&sig=111577599839487095308&page=2&tbnh=132&tbnw
=144&start=67&ndsp=67&ved=1t:429,r:25,s:67
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Last but not Least:
Transmission from Intentional Release
Surprisingly
Few Examples
Siege of Kaffa 1347
French Indian War
Salmonella in a salad bar
in Oregon 1984
Anthrax In Mail in US 2001
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Social
Disobedience
New Zealand
Rabbit Calicivirus
Fiasco
1997
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DZ AND SOCIETAL VALUES
Some examples
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Change in economic
conditions
Everyone must exit the population
India
Largest cattle population in the
world 287 Million
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Cows Vs Badgers
Badgers are a
reservoir for bovine
tuberculosis
26,000 cattle culled
last year
40,000 badgers to be
culled in the next 4
years
Badger Trust
VS
Farmers Union
http://www.thisiscornwall.co.uk/Badger-cull-aheadsoon-possible/story-16880569-detail/story.html
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Cows Vs Badgers
UK Gov’t
Postponed Cull
For One Year
http://blogs.nature.com/news/2012/10/badger-cull-update.html
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Squirrel Wars
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Chytridiomycosis
Policy Development
Batrachochytrium dendrobatidis
• Devastated amphibian
populations around the world
• Bullfrogs are non-clinical carriers
Issues: Commerce, Culture, Risk
• Commerce in bullfrogs: food,
pets, dissection
• Asian culture
• Risk to California amphibians
Societal values are not unified
• Culture and Commerce
Vs
• Environmental groups
Policy: Ban import of bullfrogs
• Fish and Game Commission
Voted to ban imports
• Dept. of Fish and Game
Chose not to implement ban
http://www.latimes.com/news/local/la-me-frog-legs-20111121,0,7997537.story
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Range Wars
Sheep Have an MCF Virus
Bison are very susceptible
Who’s fault is it?
Are sheep producers responsible
if their sheep kill the neighbor’s
bison?
Bison producers exit the industry
Municipal governments have
been petitioned
 Ban sheep production
 Ban new sheep producers
 Require a buffer zone
between sheep and bison
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http://www.telegraph.co.uk/news/worldnews/ebola/11363433/Ebola-has-killed-athird-of-the-worlds-chimpanzees-and-gorillas.html
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http://conservationmagazine.org/2014/05/ebola-vaccine-trial-in-chimps-could-savewild-apes/
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Questions
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