Animals As Sentinels of Human Animals As Sentinels of Human Environmental Health Hazards: Environmental Health Hazards:

Linking Animal and Human HealthLinking Animal and Human Health

Peter Rabinowitz MD MPHYale University School of Medicine

Occupational & Environmental Medicine Program

Colorado State University February 3, 2006

What is Occupational and What is Occupational and Environmental Medicine?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 Should Human Health Professionals Use Animal Disease Professionals Use Animal Disease

Data in Assessing Human Data in Assessing Human Environmental Health Risks? Environmental Health Risks?

OverviewOverview

• 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”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 Sentinels- Examples of Animal Sentinels- toxic hazardstoxic hazards

• Canaries in coal mines- intentional 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?The Sentinel Canary- A Relic?

Tokyo Sarin AttackTokyo Sarin Attack

Potential Advantages of Animal Potential Advantages of Animal Sentinels 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 Animal Populations: Potential SentinelsSentinels

• Wildlife– Ongoing environmental exposures– Species diversity

• Domestic– Ongoing surveillance, food safety etc.– Sentinel flocks

• Companion– Shared exposures with humans

Animal Sentinels for Human Health Animal Sentinels for Human Health Hazards?Hazards?

• Amphibian limb deformities

• Endocrine disruption in wildlife populations

• Pets with cancer

• But is there a definite…

Linkage to Human Health?Linkage to Human Health?

• How to assess the evidence provided by animal sentinel data

Example: Amphibian MalformationExample: 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 Animals as Sentinels of Human Infectious Disease ThreatsInfectious 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: Traditional Use of Animal Data re: Infectious HazardsInfectious Hazards

• Rabies surveillance and control

• Herd health

• Flavivirus monitoring in vectors and sentinel flocks

West Nile VirusWest 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 CDC Guidelines for WNV SurveillanceSurveillance

• 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 CDC Guidelines for WNV SurveillanceSurveillance

• 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 QuestionsWNV 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?

Land cover/ land use

Vegetation index

Wetlands

Climate

Mosquito Species Abundance

WNV Positive Mosquito Pool

WNV Positive Birds and Horses

Human WNV Case

Population density

Human Pop. Density

Bird Abundance

Environmental Factors Vector/Reservoir

Abundance

Animal Sentinel Events

Human Health

WNV-Strength of Evidence that: 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 InfluenzaAvian 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 Proposed AI Early Detection System for HPAI in Wild Migratory System for HPAI in Wild Migratory

BirdsBirds

• Investigation of wild bird mortality/morbidity events

• Surveillance in live wild birds

• Surveillance in hunter-killed birds

• Captive sentinel species

AI Sentinel QuestionsAI 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’ DataExplosion 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 Animal-Growing Awareness of Animal-Human Health LinkagesHuman Health Linkages

• “One Medicine” initiative

• Consortium for Conservation Medicine

• One World One Health

Need for Rapid Development of Need for Rapid Development of “Sentinel Science”“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)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 Animal Sentinel Studies from EBM Point of ViewPoint 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 Challenges to Assembling the Evidence for Animal SentinelsEvidence 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 The Sentinel Studies Project at YaleYale

• Canary Database Project

• Animal Sentinel Research

The Canary Database The Canary Database (canarydatabase.org)(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 What Data are in the Canary Database?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 Identifying Relevant Animal Sentinel

Studies and Linkages to Human HealthStudies and Linkages to Human Health

Hazard(s) Health Effect(s) StudyMethodology

Species

Relevant to Humans?

Comparativesusceptibilities

between speciesleading to animal-

human comparison?

Shared exposurepathway with

humans?

Includes bothhuman and animalexposure and/oroutcome data?

Evidence forcausation?

Study of Animal Sentinel Event

Relevance to Human Health

Curation Protocol 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 BoardCanary 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 TeamDatabase 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 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.) 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 ClassificationStudy Methodology Classification

Canary Database User Canary Database User CommunityCommunity

• Public health professionals• Clinicians• Toxicologists• Veterinary professionals/librarians• Ecologists• Medical librarians• Infectious Disease Biologists• Zoologists

Current Status of Canary Current Status of Canary DatabaseDatabase

• Website and database construction complete

• Curation: >1500 studies to date

• Public release of site: April 2005

• Approximately 10,000 website hits/month

On Line DemonstrationOn Line Demonstration

• Search “anthrax” in Canary Database

Current Projects: Evidence-Current Projects: Evidence-Based ReviewsBased Reviews

• Example: Animals as Sentinels of Bioterrorism Agents

Evidence: BT AgentsEvidence: BT Agents

Study of Bioterrorism agent in animals

Evidence for shorter incubation period or greater susceptibility in animals vs. humans OR reports of animals sick before humans?

Evidence for detectable infection in animals due to ongoing environmental exposure?

Evidence for animals as monitors of ongoing environmental exposure to BT agents

Evidence for animals as early warning of BT threat

Evidence of potential for animals to propagate outbreak of BT agent

Evidence for animal-to-animal or animal-to-human transmission?

Levels of Evidence (based on Levels of Evidence (based on CEBM/SORT Taxonomeis)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 bioterrorism attack

Evidence that animals could serve as markers for ongoing exposure risk

Evidence for animals being able to significantly propagate/maintain epidemic

CATEGORY A

Anthrax Yes: sheep, cattle (Level 3 evidence (11)) No: dogs and pigs (Level 1 evidence(31))

Yes: sheep, cattle (Level 3 evidence (11, 18))

-

Plague Yes: cats (Level 1 evidence (19))

Yes: dogs, cats (Level 1 evidence (19)), multiple species (Level 2 evidence (32, 33))

Yes: cats, camels, goats (Level 3 evidence (34, 35))

Tularemia No (level 3 evidence(12)) Yes: rodents (Level 2 evidence (20)) No: horses, cows (Level 2 evidence (12))

Yes: T icks, rodents, prairie dogs (Level 2 evidence ((36, 37))

Botulism No (Level 3 evidence (38)) No (Level 3 evidence (38)) No (Level 3 evidence (38))

Filovirus - - Yes: wildlife (level 3 evidence (16))

CATEGORY B

Q Fever No: sheep (Level 1 evidence (39)) Yes: wild hogs, goats (Level 2 evidence (40, 41))

Yes: cats, sheep, goat, cattle (Level 3 evidence (42, 43, 44))

Brucellosis No (level 3 evidence (5)) Yes: Cattle (Level 2 (45)) Yes: wildlife, cattle, dogs (Level 3 evidence(15))

Food borne illness

Salmonella Shigella

Cryptosporidium etc.

Yes: cattle ( level 3 evidence (13)) - -

Glanders - Yes: horses (Level 2 evidence(46)) Yes: horses (Level 3 evidence (47))

Alpha viruses (VEE/EEE)

Yes: horses (Level 3 evidence(15, 48)) Yes: birds (Level 1evidence (23)) Yes: Wild birds (Level 2 evidence (23))

Rift valley fever

Yes: cattle, sheep (Level 3 evidence(15)) Yes: Sheep (Level 1 evidence, (49))

Yes: Mosquitoes-rodents (Level 1 evidence (21))

Ricin Toxin - - -

Epsilon Toxin

- - -

CATEGORY C

(Emerging diseases)

Nipah virus - Yes: Multiple species (Level 3 evidence(50))

Yes: pigs (level 1 evidence (51))

Hantavirus No (Level 2 evidence(52))

Yes: multiple species (level 2 evidence (52))

Yes: rodents (Level 2 evidence (53))

Flavivirus: (WNV, JE)

Yes: wild birds (Level 3 evidence(54)) Yes: mosquitoes, birds (Level 2 evidence(55))

Yes: birds, reptiles (Level 1 evidence (24, 25))

Level 1ev idence: experimental or cohort study or randomized clinical trial. Level 2 ev idence: case-control or cross-sectional study. Level 3 ev idence: case reports or case series, expert opinion.”-“: Insufficient evidence found

ConclusionConclusion

• 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 workCurrent 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 DataUse of Remote Sensing Data

¯10 05Kilometers

Vector species

Coquilletidia perturbans

Culex pipiens

GAP Landcover

Birch dominant

Conifer

Maple/Oak/Conifer co-dominant

N.Hardwoods (Sugar Maple dominant)

Nonforest cover

Oak dominant

Oak/Maple/Birch co-dominant

Palustrine Wetlands

Red Maple dominant

Urban

Water

Starlight Information Visualization of CT WNV Starlight Information Visualization of CT WNV Mosquito DataMosquito Data

Links to all Beacon PointTrap Site

Network display showing relationship betweenvirus types and locations, color coded by positiveor negative test results

Other Sentinel Research/ProjectsOther 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

SummarySummary• 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 evidence-

based decision-making• Need for interdisciplinary development of

“Sentinel Science”

Thank You!Thank You!