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!