Animals As Sentinels of Human
Environmental Health Hazards:
Linking Animal and Human Health
Peter Rabinowitz MD MPH
Yale University School of Medicine
Occupational & Environmental Medicine Program
Colorado State University
February 3, 2006
What is Occupational and
Environmental Medicine?
• Medical specialty concerned with the prevention and
treatment of illness caused by hazardous exposures in
the workplace or environment
– Chemical Hazards
• Asbestos, lead, etc.
– Physical Hazards
• Noise, heat, radiation, etc.
– Biological Hazards
• TB, West Nile, Lyme, SARS etc.
Should Human Health
Professionals Use Animal Disease
Data in Assessing Human
Environmental Health Risks?
Overview
• Environmental health and animals as
sentinels
• The explosion of animal sentinel data
• An evidence-based approach to animal
sentinels
• The Canary Database
• The need for better “Sentinel Science”
Definition of “Animal Sentinel”
• Refers directly to human health
• “Organisms in which changes in known
characteristics can be measured to assess the
extent of environmental contamination and its
implication for human health and to provide
early warning of those implications” (O’Brien
1993)
Examples of Animal Sentinelstoxic hazards
• Canaries in coal minesintentional use of birds for
surveillance
– Greater susceptibility to CO
effects
• Dancing cats in
Minamata- naturally
occurring event
– Higher exposure to
methylmercury from fish
The Sentinel Canary- A Relic?
Tokyo Sarin Attack
Potential Advantages of Animal
Sentinels
• Animals may be more susceptible than
humans
• Animals are often exposed at higher level
than humans to environmental hazards
• Shorter lifespan, intergenerational period to
see effects of chronic exposures
Animal Populations: Potential
Sentinels
• Wildlife
– Ongoing environmental exposures
– Species diversity
• Domestic
– Ongoing surveillance, food safety etc.
– Sentinel flocks
• Companion
– Shared exposures with humans
Animal Sentinels for Human Health
Hazards?
• Amphibian limb deformities
• Endocrine disruption in wildlife populations
• Pets with cancer
• But is there a definite…
Linkage to Human Health?
• How to assess the evidence provided by
animal sentinel data
Example: Amphibian Malformation
• What is the causative
agent? Infectious?
Toxic?
• Is agent also a hazard
to humans?
• Is there shared
exposure with
humans?
• What is the human
corollary of amphibian
malformation?
Animals as Sentinels of Human
Infectious Disease Threats
• Many emerging infectious diseases are zoonotic in origin
• Can animal populations provide early warning?
– Greater exposure
– Greater susceptibility
• Intentional surveillance (ex. Sentinel chickens) vs.
naturally occurring disease events (wild bird mortality)
• Surveillance of asymptomatic reservoirs- value to
humans
Traditional Use of Animal Data re:
Infectious Hazards
• Rabies surveillance and control
• Herd health
• Flavivirus monitoring in vectors and
sentinel flocks
West Nile Virus
• US epidemic began with observation of
event in wildlife population (dead birds)
• Organized avian surveillance
• Enhanced vector surveillance
• Sentinel flocks
CDC Guidelines for WNV
Surveillance
• Avian
– Avian morbidity/mortality surveillance
• “most sensitive early detection system for WNV
activity”
• Utility seems to fluctuate
– Live bird surveillance
• Captive sentinel surveillance
• Free-ranging bird surveillance
• Sensitivity variable
CDC Guidelines for WNV
Surveillance
• Equine
– Important in some regions
– In some areas cases do not precede humans
• Mosquito
– “Remains the primary tool for quantifying the
intensity of virus transmission in an area”
– Labor intensive
WNV Questions
• Why does the predictive ability of avian
surveillance for human risk fluctuate?
• Is mosquito surveillance better?
• What other species should be routinely
included in surveillance systems?
– Pets, wild mammals, etc.?
• What are temporal/spatial relationships
between environmental risk factors for
animal sentinel events and also human
health risk?
Environmental
Factors
Vector/Reservoir
Abundance
L and cover/
land use
V egetation
index
M osquito
S pecies
A bundance
W etlands
C lim ate
P opulation
density
B ird
A bundance
Animal
Sentinel
Events
Human
Health
W NV
P ositive
M osquito
P ool
W NV
P ositive
B irds and
H orses
H um an
P op.
D ensity
H um an
W NV
C ase
WNV-Strength of Evidence that:
• Can animal data provide meaningful early
warning for humans?
– Sensitivity
– Specificity
– Time lag for ‘early warning’
– Over what geographic area?
Avian Influenza
• Development of HPAI strain heralded by
mortality in wild birds
• “Spillback” into domestic birds
• “Spillover” into wild bird populations, some
migratory
• Can wild birds serve as sentinels for AI
risk?
Proposed AI Early Detection
System for HPAI in Wild Migratory
Birds
• Investigation of wild bird
mortality/morbidity events
• Surveillance in live wild birds
• Surveillance in hunter-killed birds
• Captive sentinel species
AI Sentinel Questions
•
•
•
•
Where to test
What species to track?
Environmental Risk factors
What other pathogens to test for in
asymptomatic reservoirs?
• Relationship between animal sentinel
event and human health risk
Explosion of ‘Animal Sentinel’ Data
•
•
•
•
Veterinary surveillance at local, state, and national levels
Arbonet
Avian Influenza National Surveillance System
USDA/CEAH
– National Surveillance Unit
• WHO OIE
• Outbreaks: SARS, Monkeypox, AI, Nipah
• Comparative genomics
Growing Awareness of AnimalHuman Health Linkages
• “One Medicine” initiative
• Consortium for Conservation Medicine
• One World One Health
Need for Rapid Development of
“Sentinel Science”
• Reduce data gaps for linkages between animal and
human health disease risk
– Animal/human exposure pathways and relationships
– Interspecies susceptibility differences, genomic
overlap
– Environmental risk factors for sentinel events
• Evidence-based analysis of linkages between animal
and human epidemiology
• Practical analysis of surveillance systems
• Remote sensing, information visualization, time series
analysis, and other methods to improve analytic
capability
Evidence-Based Medicine (EBM)
• Movement to replace empiric dogma of
clinical medicine with explicit, evidence
based approaches.
• For a particular clinical question, assemble
relevant studies to answer
• Systematic reviews of the medical
literature
• Grading the level of evidence
Animal Sentinel Studies from EBM
Point of View
• What is the evidence that animals:
– Are experiencing disease related to environmental risk factors?
• Causation
– Are providing reliable early warning of human health risk?
• Sensitivity
• Specificity
• Time lag
– Share exposure with humans?
– Are more susceptible than humans to the hazard?
– Experience health effects that can be linked to human outcomes?
• How good are the studies?
• Is there consistency across studies?
Challenges to Assembling the
Evidence for Animal Sentinels
• Difficult to locate “animal sentinel studies” in medical
databases (Medline)
– Lack of search terms (nothing for ‘animal sentinel’)
– Limited species capture (gambian rat, dunlin)
– Journal limitations (Jl of Animal Ecology, Intl Jl Poultry Sci, etc.)
• Lack of communication between animal and human
health professionals
• Differences in study techniques between animal and
human health researchers
• Funding for animal sentinel research-cracks
The Sentinel Studies Project at
Yale
• Canary Database Project
• Animal Sentinel Research
The Canary Database
(canarydatabase.org)
National Library of Medicine:
Communication Systems Grant
Goals:
• Assemble evidence for human
health relevance of animal
sentinel data
• Facilitate evidence-based reviews
• Make scientific literature on
sentinels more accessible
• Promote interdisciplinary
communication
– Epidemiology as common
language
What Data are in the Canary
Database?
• Peer-reviewed studies of non-traditional
animal species with exposures and/or
outcomes relevant to human health:
– biological, chemical, physical hazards
• Searches of Medline, CAB, Agricola, etc
• Curation of studies by trained curators
according to protocol
Identifying Relevant Animal Sentinel
Studies and Linkages to Human Health
Study of Animal Sentinel Event
Species
Hazard(s)
Health Effect(s)
Study
Methodology
Relevant to Humans?
Comparative
susceptibilities
between species
leading to animalhuman comparison?
Shared exposure
pathway with
humans?
Includes both
human and animal
exposure and/or
outcome data?
Relevance to Human Health
Evidence for
causation?
Curation Protocol
• Developed by national advisory board with
expertise in:
–
–
–
–
–
–
–
–
Epidemiology/human health
Animal health
Environmental health
Infectious disease ecology
Toxicology
Medical informatics
Ecology
Zoology
Canary Database Advisory Board
• Anne Fairbrother DVM, EPA
• Peter Daszak PhD, Consortium for Conservation
Medicine
• Henry Gardner DrPh: Colorado State U.
• Joanna Burger PhD, Rutgers
• Durland Fish PhD, Yale
• Mark Cullen MD, Yale
• Judy Zelikoff PhD, NYU
• Constance Rinaldo MS, Harvard
• Mark Pokras DVM, Tufts School of Vet Med
• Perry Miller MD, Yale
Database Project Team
– Peter Rabinowitz, MD, MPH ( PI)
– Joshua Dein VMD, USGS National Wildlife
Health Ctr. (Co-I)
– Prakash Nadkarni MD (Co-I)
– Zimra Gordon DVM, MPH
– Lynda Odofin DVM, MPH
– Dan Chudnov MS, Informatics
– Matt Wilcox MS, Library Science
Curation of Studies in Database
• Linkages to human health:
– Does study present evidence about:
•
•
•
•
•
Cause and effect in animals?
Shared exposure with humans?
Interspecies susceptibility?
Animal and human outcome data?
Inclusion of genomic data?
Curation of Studies (cont.)
•
•
•
•
•
•
Hazard (s) studied
Health Outcome(s)
Species (NCBI, ITIS, MeSH taxonomies)
Environmental and Host Factors
Geographic location (gazetteer)
Epidemiological Study Methodology(ies)
Study Methodology Classification
Canary Database User
Community
•
•
•
•
•
•
•
•
Public health professionals
Clinicians
Toxicologists
Veterinary professionals/librarians
Ecologists
Medical librarians
Infectious Disease Biologists
Zoologists
Current Status of Canary
Database
• Website and database construction
complete
• Curation: >1500 studies to date
• Public release of site: April 2005
• Approximately 10,000 website hits/month
On Line Demonstration
• Search “anthrax” in Canary Database
Current Projects: EvidenceBased Reviews
• Example: Animals as Sentinels of
Bioterrorism Agents
Evidence: BT Agents
S tu d y o f B io te rro ris m a g e n t in
a n im a ls
E v id e n c e fo r s h o rte r
in c u b a tio n p e rio d o r g re a te r
s u s c e p tib ility in a n im a ls v s .
h u m a n s O R re p o rts o f
a n im a ls s ic k b e fo re
hum ans?
E v id e n c e fo r d e te c ta b le
in fe c tio n in a n im a ls d u e to
o n g o in g e n v iro n m e n ta l
e x p o s u re ?
E v id e n c e fo r a n im a l-to a n im a l o r a n im a l-to -h u m a n
tra n s m is s io n ?
E v id e n c e fo r a n im a ls a s e a rly
w a rn in g o f B T th re a t
E v id e n c e fo r a n im a ls a s m o n ito rs o f
o n g o in g e n v iro n m e n ta l e x p o s u re to
B T a g e n ts
E v id e n c e o f p o te n tia l fo r
a n im a ls to p ro p a g a te
o u tb re a k o f B T a g e n t
Levels of Evidence (based on
CEBM/SORT Taxonomeis)
• LEVEL 1:
– Experimental studies
– Cohort Studies
• LEVEL 2:
– Cross sectional, ecologic, case-control studies
• LEVEL 3:
– Case reports/series, expert opinion/consensus
Agent
Evidence for animals
providing early warning
of an acute biote rroris m
attack
Evidence that animals
could serve as
marke rs for ongoing
exposure risk
Evidence for animals being
able to significantly
propagate/maintain
epide mic
Yes: sheep, cattle (Level 3 evidence (11))
No: dogs and pigs (Level 1 evidence(31))
Yes: sheep, cattle (Level 3
evidence (11, 18))
-
CATEGORY A
Anthrax
Tulare mia
No (level 3 evidence(12))
Botulism
Filovirus
No (Level 3 evidence (38))
Yes: dogs, cats (Level 1 evidence
(19)), multiple species (Level 2
evidence (32, 33))
Yes: rodents (Level 2 evidence
(20))
No: horses, cows (Level 2 evidence
(12))
No (Level 3 evidence (38))
-
-
Yes: wildlife (level 3 evidence (16))
No: sheep (Level 1 evidence (39))
Plague
Yes: cats (Level 1 evidence (19))
Yes: cats, camels, goats (Level 3 evidence
(34, 35))
Yes: T icks, rodents, prairie dogs (Level 2
evidence ((36, 37))
No (Level 3 evidence (38))
CATEGORY B
Brucellosis
No (level 3 evidence (5))
Yes: wild hogs, goats (Level 2
evidence (40, 41))
Yes: Cattle (Level 2 (45))
Food borne
illness
Yes: cattle ( level 3 evidence (13))
-
Yes: cats, sheep, goat, cattle (Level 3
evidence (42, 43, 44))
Yes: wildlife, cattle, dogs (Level 3
evidence(15))
-
-
Yes: horses (Level 2 evidence(46))
Yes: horses (Level 3 evidence (47))
Yes: horses (Level 3 evidence(15, 48))
Yes: birds (Level 1evidence (23))
Yes: Wild birds (Level 2 evidence (23))
Yes: cattle, sheep (Level 3 evidence(15))
Yes: Sheep (Level 1 evidence,
Yes: Mosquitoes-rodents (Level 1 evidence
Q Fever
Salmonella
Shigella
Cryptosporidium
etc.
Glanders
Alpha viruses
(VEE/EEE)
Rift valley
Conclusion
• Some animals can provide early warning
• Many species can warn of ongoing
exposure risk
• For certain diseases, risk of propagation in
animal populations
• Many data gaps: species susceptibility,
exposures, study limitations
Current sentinel research work
• Use of information visualization and spatial
analysis of remote sensing data and
sentinel events to determine
environmental risk factors for WNV
emergence
– (in cooperation with Durland Fish PhD, Yale
Center for Ecoepidemiology, and Pacific
Northwest Laboratories)
Use of Remote Sensing Data
¯
K i lo m e te rs
10
5
0
G A P L an d co ver
B irch d o m in a n t
Co n if e r
M a p le /O a k / Co n if e r co - d o m in a n t
V ecto r sp ec ies
N. Ha rd wo o d s (S u g a r M ap le d o m in a n t)
No n f o re s t c o ve r
O a k d o m in a n t
Co q u ill e tid i a p e rtu r b a n s
Cu le x p i p ie n s
O a k/ M a p le / B irch c o -d o m i n a n t
P a lu st rin e W e tla n d s
Re d M a p le d o m in a n t
Urb a n
Starlight Information Visualization of CT WNV
Mosquito Data
Links to all B eacon P oint
T rap S ite
Network display showing relationship between
virus types and locations, color coded by positive
or negative test results
Other Sentinel Research/Projects
• Spatial/temporal analysis of animals as
sentinels of AI (Using Promed Reports)
• Animals as sentinels of chemical terrorism
agents
• Integration of Canary Database with
Comparative Genomics databases
• Cross-training of veterinary and medical
students in sentinel issues
Summary
• Animal sentinel data can provide data for
environmental health decision making
• But: evidence gaps must be addressed
• Need for greater communication between animal
and human health professionals
• Canary Database can be resource for evidencebased decision-making
• Need for interdisciplinary development of
“Sentinel Science”
Thank You!
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