1. One Health with Special Reference to Antimicrobial Resistance Antimicrobial Resistance and Global Health Canadian Coalition for Global Health Research and McMaster University April 9th, 2014 Mohamed A. Karmali, MB ChB, FRCP (C) Public Health Agency of Canada

2. Emerging Pathogens and Zoonoses (Woolhouse and Gowtage-Sequerias, EID 11:1842-1846, 2005) Of 1,407 known human pathogenic species 816 (58%) are zoonotic Of 177 emerging or re-emerging pathogens 130 (73%) are zoonotic

3. Emerging and Re-emerging Pathogens Ebola SARS West Nile Virus HPAI Nipah Mers CoV STEC/VTEC Borellia burgdorferi Etc.

4. The Concept of the Interdependence of Human Health, Animal Health and Environmental Health is Ancient (Wikepedia – One Health) Hippocrates (c 460 BC to c 370) – “On Airs, Waters, and Places” Lancisi, 17 th C, Italy – integrated study of human and animal health Villerme and Parent-Duchâtelet, early 19 th C – French Public Health movement (LaBerge, 1992) Virchow coined the term zoonosis (19 th C, Germany) Sir William Osler(19 th C) held joint Faculty positions in Medicine at McGill University and Veterinary Medicine (U of Montréal) Calvin Schwabe, 19 th C – “One Medicine” James Steele, 1947 established field of Veterinary Public Health at CDC W. Karesh 2004, Wildlife Conservation Society, “One World-One Health TM ” American Veterinary Medical Association, 2008, “One Health” 4

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6. JOINT STRATEGIC FRAMEWORK ON “One World, One Health” (Sharm el-Sheikh, Oct. 2008)

7. 7 Objectives of the Framework (2008) ● Develop surveillance capacity (national, regional, global) ● Strengthen public and animal health capacity to prevent, detect and respond to disease outbreaks at national, regional and international levels ● Strengthen national emergency response capability, including a global rapid response support capacity ● Promote inter-agency and cross-sectoral collaboration and partnership ● Control HPAI and other existing/re-emerging infectious diseases ● Conduct strategic research to aid in mitigating EIDs

8. Pressures for current and future Emergence/Re-emergence of Zoonoses Exponential growth in human and livestock populations Overcrowding International travel Rapid urbanization Close contact between humans and animals Environmental degradation Closer integration between livestock and wildlife Rapidly changing farming systems Forest encroachment and habitat disruption Climate and ecosystem change Globalization of trade in animals and animal products Conflict, mass population migration, poverty

9. Climate Change’s Impact on Infectious Diseases –Vector-borne diseases –Water-borne diseases –Agriculture Production –Migration of Animals –Changing ecosystems for wildlife and animals –Built environment –Human-Animal Interface –Ecologies and a new research portfolio –Evidence-based public health impact

10. Pathogen circulation in the animal host Transmission from animal to human (Emergence) Infection and Clinical impact in human population Manage infection and outbreaks in human populations Shifting the paradigm upstream Prevent transmission and Predict emergence Control in animal population where feasible Heyman, D: Policies and Strategies to Meet the Challenge of Emerging Disease Threat through Prevention, Preparedness and Response. 2 nd International One Health Congress Conference, Bangkok 2013

11. Riots, Rage and Resistance: A Brief History of How Antibiotics Arrived on the Farm Maureen Ogle, Scientific American, September 2013 (Guest Blog) Early 20 th Century saw food shortages in the US 1910, millions of Americans joined a national meat boycott to protest prices US government pours money into research to stimulate production of affordable meat In the 1940s, with of antibiotics, a discovery was made serendipitously that sub-therapeutic doses of antibiotics greatly stimulated animal growth This led to a veritable food revolution which saw the production of affordable meat in the US 11

12. Changes in Intestinal Flora of Farm Personnel after Introduction of Tetracycline- supplemented Feed on a Farm S.B. Levy NEJM 295:583-588, 1976 Within 5 months after chickens on a farm were fed Tet- supplemented feed, 31.3% of weekly fecal samples from farm dwellers contained > 80% Tet R bacteria In contrast only 6.8% samples from 24 neighbours contained Tet R bacteria (p<0.001) The resistant bacteria contained transferable plasmids that encoded for multiple antibiotic resistance

13. Isolated from a variety of animals: dogs, cats, rabbits, horses, cattle, pigs, poultry, and exotic species (e.g., elk, cheetah, monkey, polar bears) Ubiquitous in the environment Food animals Disease causing in some e.g., suckling pigs, horses Ribotype 027/ NAP 1 (occurs in dogs, cattle, pigs but relatively uncommon) Ribotype 078 more common in animals but the role of animals in dissemination remains unclear Food Recovered from pork, beef, chicken, fish, raw veg Importance? Role in dissemination? Clostridium difficile in Animals

14. Isolated from a variety of animals: dogs, cats, rabbits, horses, cattle, pigs, poultry, and exotic species including whales, alpacas, rats. Companion animals reflect prevalence of local community-acquired MRSA; can be household reservoirs esp. dogs. Horses – some strains of CMRSA-5 are well adapted to horses. Food animals – some community-acquired strains but main issue is “livestock associated” MRSA - ST398 Common in pigs in Europe, US, Canada, etc. Also occurs less frequent in cattle (dairy, beef, veal); few reports for poultry High proportion of human community cases in parts of Europe (Netherlands, Denmark etc.) but very rare among human cases in Canada Food – pork (~5-10%), beef (~5%), chicken (<1%) Importance? Role in dissemination? Occupational risk – vets (~10-15% colonization), farmers (~20%), slaughterplant workers etc. MRSA in Animals JS Weese. MRSA in Animals. ILA J 2010

15. Emerging Infectious Dis. 16: 587-594, 2010

16. Use of cephalosporins and beta-lactams in food animals in Canada in ovo use of ceftiofur in broiler hatching eggs (extra-label use to be voluntarily stopped by Canadian poultry industry May 2014) Bla (cmy-2) relatively common in the food chain in Canada, US, Europe; especially in poultry Salmonella and E. coli – linked to ceftiofur use in hatching eggs ESBLs (TEM, SHV etc.) rare in Canada in the foodchain Pouget et al. AEM 2013 Jun;79(12):3864-6. Characterization of bla(SHV) genes on plasmids from scherichia coli and Salmonella enterica isolates from Canadian food animals (2006-2007). CTX-M – the most significant cause of resistance to beta-lactam antibiotics in E. coli, reported worldwide Movement into the food chain also a worldwide issue; some reports in North America but so far uncommon 2012. Wittum et al. Detection of Salmonella enterica isolates producing CTX-M Cephalosporinase in U.S. livestock populations. AEM 2012;78(20):7487-91. ESBLs (and ESCs) in Animals

17. PLoS One, 7: 1-6, May 2012; e37152

18. Appl. Environ. Microbiol. 78:7487-91, 2012

19. Annual number of human Salmonella enterica serotype Kentucky isolates per country (France, England and Wales, and Denmark), 2000–2008, and the proportion of isolates resistant to ciprofloxacin. Le Hello S et al. J Infect Dis. 2011;204:675-684 © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com Poultry identified as a major reservoir

20. Figure 1. Sources and distribution of pharmaceuticals in the environment1 (STP: sewage treatment plant). Kümmerer K J. Antimicrob. Chemother. 2003;52:5-7 ©2003 by Oxford University Press

21. Acknowledgements Richard Reid-Smith Nick Previsich and Linda Williams