Introduction

This paper describes a holistic approach to the prevention and control of human food-borne illness from enteric pathogens, based on implementation of the “One Health” paradigm. Antimicrobial resistance (AMR) has been chosen as a particular illustrative theme for this overview to demonstrate the practical utility of a One Health approach.

The rapid emergence, global spread, morbidity, and mortality associated with emerging infections such as severe acute respiratory syndrome and avian and pandemic influenza is stimulating the global community to develop novel approaches for their prevention and control. Ongoing concerns about food-borne pathogens such as Escherichia coli O157:H7, Listeria monocytogenes, and various species of Salmonella, as well as the arrival and impact of new strains of food-borne pathogens such as E. coli O104 as observed during the 2011 outbreak in Germany, add to the need to take into account the complexity of infection from multiple dimensions. These include the following:

1. Burden of illness. The World Health Organization estimates that infectious and parasitic diseases are the second leading cause of death in the world (WHO, 2008). Enteric pathogens are the third leading cause of infectious disease worldwide and account for almost 2 million deaths every year (Girard et al., 2006). As in many other countries, these pathogens also cause a significant disease burden in Canada, where there are an estimated 11 million food-borne enteric illnesses per year with an estimated cost of $3.7 billion dollars (Thomas et al., 2008). Although microbial enteric illness can be caused by bacteria, viruses, parasites, and protozoal organisms, bacteria play a major role in enteric disease (Girard et al., 2006) and are the major focus of enteric surveillance programs. Although most enteric bacterial infections result in subclinical or mild illness, their high rate of incidence in the population can be expected to have economic impact on a country simply through loss of short-term individual productivity. In addition, bacterial infections can cause severe disease, particularly in children, the elderly, and immunosuppressed individuals.
2. Zoonotic and environmental origins. More than 60 percent of new emerging and reemerging pathogens of humans, including those that are transmitted by food and water, arise from animals and the environment (Jones et al., 2008). The rate of emergence appears to be increasing, most likely related to factors such as human population growth, changing patterns of international trade, globalization, mass population migrations, climate change, and environmental degradation. With regard to food safety pathogens, it is anticipated that the increased industrialization of animal production, as is seen worldwide in both developed and developing countries, creates an environment for increased opportunity for entry of pathogens into the food chain.
3. Antimicrobial resistance. The severity of infections and our success in treating the associated clinical diseases are affected by the presence of antimicrobial resistance. Antimicrobial-resistant bacteria are those that are able to replicate in the presence of antimicrobials, here meaning antibiotics and their synthetic derivatives, at levels that normally suppress growth or kill the bacteria. Antimicrobial resistance is a growing concern that threatens animal and human health worldwide, driven mainly by antimicrobial use, both appropriate and inappropriate.

The One Health Paradigm

“One Health” has emerged as a strategic framework for reducing the risks of infectious diseases arising from the animal–human–ecosystems interface. Although a universal definition of One Health has not been achieved, and there are overlaps with integrative approaches used in international research and development, such as “ecosystem approaches to health” (Charron, 2011), there is consensus that One Health is an approach or method of practice that recognizes linkages among human, animal, ecosystem, and economic domains in the context of human health.

The One Health approach focuses on the dynamic interactions at the interfaces between multiple sectors that contribute to the expression of a public health risk. In that interactive context, the approach becomes a tool for disease prevention and control through more informed risk management, encompassing the separate elements of identification, assessment, avoidance, and mitigation of the public health risk. It is worth noting that One Health is bigger than the zoonotic infectious disease issues described below, and incorporates socioeconomic, cultural, and community conditions (the social determinants of health), as well as individual lifestyle and hereditary health factors.

The economic relevance of early and comprehensive intervention is often overlooked, but can be significant. For instance, the direct economic impacts of individual zoonotic disease events that have occurred over the past 15 years can be in the billions (Figure A4-1).

FIGURE A4-1

Economic impact examples. SOURCE: Newcomb et al. (2011).

Canada has been actively engaged in operationalizing the One Health concept through the development of a community of practice by participating and supporting international conferences encompassing the subject. The Public Health Agency of Canada, recognizing the emerging value of the One Health paradigm, hosted an Expert International Consultation on “One World One Health™: from Ideas to Action,” March 16-19, 2009, in Winnipeg, Manitoba (http://www.phac-aspc.gc.ca/publicat/2009/er-rc/index-eng.php). Many other major international meetings have helped define One Health, most recently, in November 2011, the High Level Technical Meeting on Health Risks at the Human–Animal–Ecosystems Interfaces in Mexico City. Upcoming is a meeting scheduled for February 2012 in Davos, Switzerland: Global Risk Forum One Health Summit 2012: One Health–One Planet–One Future.

One Health in relation to food safety has multiple dimensions, including science and research, optimizing animal health and ecosystem health, and food inspection and regulatory activities. In Canada work in this area is conducted by several federal government agencies, such as the Public Health Agency of Canada (surveillance, research, and epidemiology of food-borne illness), the Canadian Food Inspection Agency (animal health and food inspection), Health Canada (food safety regulations and risk assessment), and Agriculture and AgriFood Canada (food animal production). Canada's provincial and territorial jurisdictions have also started to embrace a One Health approach; for instance, Manitoba has a primer on One Health and food safety and has developed an animal health and food safety strategy for the future (“Protecting Animals, Food and People”), and Québec has an animal health and welfare strategy (“One Health, Health for All”). The Canadian academic sector is a critical contributor to the theme, particularly its five veterinary colleges.

Science and research activities include surveillance, detection, and public health risk assessment of nonhuman bacterial isolates, studies on the population and environmental determinants of food-borne zoonoses, systems modeling of the food chain to identify optimal points of intervention, development of intervention strategies such as vaccines and bacteriophage products, and knowledge translation for uptake by food production and processing workers. The activities also include characterization of impacts of particular practices, such as the use of antibiotics in commercial food animal production and its potential in giving rise to antimicrobial resistance in bacteria pathogenic to humans.

Mechanisms of Antimicrobial Resistance

Resistance can be intrinsic, conferred by naturally occurring characteristics of the bacteria, or acquired. Bacteria can acquire resistance through mutations of preexisting genes or through transfer of resistance determinants from other bacteria (horizontal gene transfer). Horizontal transfer occurs much more commonly than de novo development of resistance through mutation (White et al., 2008). It is through horizontal gene transfer that resistance genes, alone or in groups, can spread within bacterial populations and even to other bacterial species.

Resistance genes provide the molecular tools by which bacteria block or oppose the mechanism of action of antimicrobials. Some genes allow bacteria to physically modify their structure to evade drugs, while other genes express enzymes to directly degrade the antimicrobial agent. In addition, resistance mechanisms that are not specific to antimicrobial agents can also be present. For example, cell pumps that allow bacteria to excrete environmental toxins and prevent them from reaching harmful intracellular concentrations can also help bacteria to resist the harmful effects of antimicrobials.

Not all antimicrobial-resistant bacteria are harmful, and resistance genes can be found in nonpathogenic bacteria (Wright, 2007). However, these benign but resistant bacteria may also pose a threat through the transfer of resistance genes to pathogenic bacteria (Figure A4-2).

FIGURE A4-2

Transfer model for antimicrobial resistance genes.

Antimicrobial Usage and Resistance

Antimicrobial use (AMU) in animal and human populations is considered to be the major driver of AMR emergence and persistence. Use of antimicrobials exerts a powerful selective influence on bacteria, encouraging the survival and propagation of resistant strains and influencing how quickly AMR develops. Because different resistance genes are often clustered close together on the bacterial genome, especially on transmissible genetic elements such as plasmids and transposons, selection for resistance against one type of antimicrobial may also co-select for resistance against other unrelated antimicrobials. In addition, use of one antimicrobial can select for resistance to closely related antimicrobials (cross-resistance). For example, in Europe, use of avoparcin, an antimicrobial growth promoter used in food animals, has been linked with resistance to vancomycin, an antimicrobial “of last resort” in human medicine (Kruse et al., 1999).

Genetic mechanisms leading to the development and maintenance of AMR are complex. At one time, is was thought that AMR universally negatively impacted the fitness of microorganisms and that, by removing the selective pressure imposed by antimicrobial usage, resistance genes would be selected against in future bacterial generations. However, Wright (2007) identified several genetic mechanisms that may be exceptions to this rule: resistance genes that increase fitness, resistance genes that do not have a fitness cost, and compensatory mutations that restore bacterial fitness. Finally, environmental factors may play a large role in the persistence of “unused” antimicrobial resistance genes. Selection of genes conferring protection against environmental stressors such as heavy metals and biocides may also co-select for resistance genes (Alonso et al., 2001).

The genetic regulation of AMR is complex and not fully understood. Despite our gaps in knowledge, prudent AMU and adherence to the principles of good antimicrobial stewardship are recommended as key elements in a strategy directed at preserving the efficacy of antimicrobials, particularly those that are very important to human and veterinary medicine.

A Holistic Consideration of AMR and Enteric Disease

Figure A4-3 depicts the complex interactions between enteric organisms, animals, and humans, and the many determinants (socioeconomic, environmental, and geopolitical) that affect these relationships. Antimicrobial-resistant bacteria form the central component of our model. A number of different interactions can be described using this model, some of which require greater insight into their mechanisms and importance. For example, certain bacteria that cause disease in animal hosts may not cause disease in people but may exchange genetic material, including resistance genes, with human pathogens, causing community-acquired and nosocomial infections (Guardabassi et al., 2004).

FIGURE A4-3

The intersection of enteric agents, animals, and humans, and the environmental factors that influence the occurrence of zoonotic bacterial infections and the emergence of AMR.

Enteric infections in people generally occur through fecal–oral transmission, of which several risk factors can be identified: increased contact between humans and animals, extended hospitalization, poor hygiene, consumption of improperly handled and improperly cooked foods including meats, and ingestion of contaminated water. Prior treatment with antimicrobials can also increase an individual's susceptibility to infection by pathogenic bacteria through disruption of the normal bacterial flora and by conferring a competitive advantage to resistant strains of pathogens such as Salmonella (Barza and Travers, 2002).

Previous infections with resistant bacteria can also predispose individuals to future resistant infections and disease. As seen in Figure A4-3, an individual may be infected with a commensal bacterium carrying resistance genes. Maintenance of resistance within the individual may occur through colonization of the gastrointestinal tract with this commensal bacterium or via horizontal transfer to gut flora as shown in the diagram. If this same individual is later infected with a pathogenic bacterium, then resistance may be transferred to this pathogen through horizontal transfer from the gut flora.

Implications on Global Health

A number of provincial and national reports, including the 2002 Walkerton Commission of Inquiry (Government of Ontario) and the 2004 Renewal of Public Health in Canada report (Government of Canada), have advocated for a holistic approach toward understanding enteric disease. This type of approach is especially useful given the complexity of enteric disease and its importance as a global health issue. AMR also has serious implications for global human and animal health.

AMR impairs our ability to treat infectious diseases and endangers the long-term efficacy of antimicrobial drugs available to human and veterinary medicine. Not only are infections caused by resistant bacteria more difficult and more expensive to treat, but also the longer duration of infection may increase disease shedding and spread. AMR thus has important effects on the pathogenicity and epidemiology of zoonotic bacterial agents.

Along with its global health implications, the emergence of resistant bacteria may have broad economic effects. Weakened public confidence over the safety of agricultural commodities, potential inclusion of AMR bacteria as a product adulterant leading to recalls, and changes to consumer buying patterns are major economic concerns to agricultural industries. At the patient level, AMR may reduce the efficacy of certain antimicrobials and thereby increase the cost of infection (e.g., longer hospital stays and changes in AMU for disease treatment and prevention) in people and animals. As discussed by Foster (2009), the economic burden of AMR may be most dramatic in developing nations because of the higher expense of second- or third-line drugs, and the lack of diagnostic capacity to detect resistance early, which may result in treatment failures and complications in antimicrobial selection.

Developing solutions to AMR and enteric disease requires synthesis of knowledge and analysis of data at the local, national, and global scales. Factors such as agricultural land-use patterns, attitudes toward antimicrobial usage, and the nature and extent of interactions between people and animals can have major effects on the development of AMR at the local and national levels. However, these local influences may also have global significance. Global interactions of people, animals, and animal products mean that AMU and the accompanying regulations in one country can affect the efficacy of a particular antimicrobial in another. Similarly, the global epidemiology of enteric pathogens is important in understanding the local burden of enteric disease. For example, it was estimated that 30 percent of all enteric disease cases at a sentinel site in Ontario, Canada, in 2008 were associated with international travel (Government of Canada, 2009).

Application of a Holistic Approach to Zoonotic Bacterial Infections and AMR in Canada

The Public Health Agency of Canada supports two complementary surveillance programs that together provide a holistic approach to AMR and enteric disease (Figure A4-3): (1) the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) and (2) the National Integrated Enteric Pathogen Surveillance Program (C-EnterNet). Both were modeled after similar programs in other countries: NARMS (United States) and DANMAP (Denmark) for CIPARS and FoodNet (United States) and OzFoodNet (Australia) for C-EnterNet. The two Canadian programs generate and collect data that contribute to our understanding of the transmission of zoonotic bacteria, risk factors for infection, and the drivers of AMR and AMU. As surveillance systems, their ongoing and systematic designs allow for the identification of emerging trends and the ability to identify the impacts of prevention and control measures adopted at the national, provincial, and, occasionally, local levels in Canada.

Both programs also provide a research platform that aims to identify and understand how livestock husbandry and production methods, water-borne routes of exposure, wildlife, companion animals, exotic pets, and socioeconomic factors and high-risk human populations are affected by and contribute to zoonotic bacterial infections and AMR.

While CIPARS performs epidemiological surveillance on AMR and AMU through the generation and collection of nationwide data from farms, abattoirs, retail stores, and both human and animal diagnostic health laboratories, C-EnterNet performs epidemiological surveillance on enteric pathogens at intensively sampled local sentinel sites (currently one site in Ontario and one in British Columbia). Like CIPARS, C-EnterNet collects data at the level of the farm, retail store, and human community (via epidemiological and laboratory data on human cases in partnership with the local public health unit). C-EnterNet also performs environmental surveillance by collecting and testing untreated water samples. This parallel testing is critical to understanding the complex system of food and water-borne disease transmission. Results from both programs are publicly accessible through the Public Health Agency of Canada website as well as through annual reports and newsletters.

The epidemiological strength of CIPARS lies in its breadth of surveillance at major points along the farm-to-fork continuum. These data allow for temporal and spatial analyses of provincial and national trends in bacterial recovery and AMR. This is best demonstrated with the recent study of Salmonella Heidelberg and ceftiofur resistance (see the section titled Success Within CIPARS: A Case Example). While CIPARS is most effective at studying trends at broad scales, C-EnterNet's value is in its ability to detect subtle epidemiological effects that may only be captured at the local level. In addition, it is one of the only systems that can delineate endemic versus travel-acquired human infections (see the section titled Success Within C-EnterNet: A Case Example). The sentinel-site surveillance approach provides rich data that would be cost-prohibitive to collect across all of Canada. But, by understanding sentinel populations, the information can be used to determine the predominant sources of enteric pathogens causing infection and the risk factors (including individual behaviours) that contribute to the burden of enteric illness.

It is important to recognize the unique operational aspects of both CIPARS and C-EnterNet and their complementary nature. Having two different but linked surveillance models that encompass different scales is essential in providing a comprehensive look at the specific risk factors associated with AMR and enteric disease. When considered together, both programs provide a holistic picture of the complex relationships between enteric pathogens, the environment, and the health of humans and animals.

Success Within CIPARS: A Case Example

Recent analysis of CIPARS data identified a link between ceftiofur (an antimicrobial of high importance to human medicine) usage in poultry and ceftiofur-resistant Salmonella Heidelberg isolates obtained from people and chicken meat in Québec (Dutil et al., 2010), as shown in Figure A4-4. Because S. Heidelberg is a common serotype that infects and can cause disease in people, this finding had important human health implications.

FIGURE A4-4

Ceftiofur resistance in E. coli from retail chicken and S. Heidelberg from retail chicken and humans, CIPARS 2003-2010. SOURCE: CIPARS (2003, 2004).

Communication of this information led to a voluntary ban on the use of ceftiofur in 2005, and the ongoing collection of surveillance data provided the opportunity to follow trends in human and animal infection and in AMR. The findings from this work have provided strong evidence pointing toward changing patterns in AMU affecting clinical bacterial resistance in human and animal isolates. This study has been used to inform policy on the appropriate use of this antimicrobial and is helping to guide physicians and veterinarians in their selection of appropriate antimicrobials and how these drugs are dispensed.

Conclusions and Key Policy Implications

The global, transdisciplinary, multiscalar, and multijurisdictional nature of AMR and enteric disease highlights the utility of the One Health approach in framing these health issues. One Health principles encourage public health practitioners to engage and collaborate with stakeholders and to consider the numerous socioeconomic, geopolitical, zoonotic, and environmental factors involved in health issues (Figure A4-2). Veterinarians and physicians as well as other human, animal, and ecosystem health professionals have important roles to play in preserving the efficacy of our antimicrobials through leadership roles in disease surveillance, AMU decision making, and health management decisions to prevent disease. Communication and collaboration with farms, industry, veterinarians, physicians, and other public health practitioners must be strengthened and is emphasized as key to the success of the approach to AMR and enteric disease.

C-EnterNet and CIPARS have successfully operated for 7 and 10 years, respectively. A large part of this success and the sustainability of these programs can be attributed to ongoing collaborations with multiple stakeholders and the flexibility of all the partners to adapt to changing needs and conditions. These programs serve as a model for how government agencies can address, in an integrated fashion, urgent problems and issues that cut across multiple departments and jurisdictions.

Acknowledgments

This article is based, in part, on one of 31 case studies included in One Health for One World: A Compendium of Case Studies, edited by David Waltner-Toews, Veterinarians without Borders/Vétérinaires sans Frontières—Canada, April 2010 (accessed on November 22, 2011, at http://www.vwb-vsf.ca/english/documents/OHOWCompendiumCaseStudies_001.pdf). This compendium was commissioned by the Public Health Agency of Canada (PHAC) and presented by PHAC and the United Nations System Influenza Coordinator at an Inter-ministerial Meeting of the International Partnership on Avian and Pandemic Influenza in Hanoi, Vietnam, in April 2010.

References

• Alonso A, Sánchez P, Martínez JL. Environmental selection of antibiotic resistance genes. Environmental Microbiology. 2001;3(1):1–9. [PubMed: 11225718]
• Barza M, Travers K. Excess infections due to antimicrobial resistance: The “Attributable Fraction” Clinical Infectious Diseases. 2002;34(Suppl. 3):S126–S130. [PubMed: 11988883]
• Charron DF, editor. Ecohealth research in practice: Innovative applications of an ecosystem approach to health. New York: Springer/Ottawa, ON: International Development Research Centre; 2011.
• Dutil L, Irwin R, Finley R, Ng LK, Avery B, Boerlin P, Bourgault AM, Cole L, Daignault D, Desruisseau A, Demczuk W, Hoang L, Horsman GB, Ismail J, Jamieson F, Maki A, Pacagnella A, Pillai DR. Ceftiofur resistance in Salmonella enterica serovar Heidelberg from chicken meat and humans, Canada. Emerging Infectious Diseases. 2010;16(1):48–53. [PMC free article: PMC2874360] [PubMed: 20031042]
• Foster SD. The economic burden of resistance in the developing world. In: Sosa A, Byarugaba DK, editors. Antimicrobial resistance in developing countries. New York: Springer Science & Business Media; 2009.
• Girard MP, Steele D, Chaignat CL, Kieny MP. A review of vaccine research and development: Human enteric infections. Vaccine. 2006;24:2732–2750. [PubMed: 16483695]
• Government of Canada. Learning from SARS: Renewal of public health in Canada. Ottawa, ON: Health Canada; 2004.
• Government of Canada. C-EnterNet Short Report 2008. Guelph, ON: Public Health Agency of Canada; 2009.
• Government of Ontario. Report of the Walkerton Inquiry: A strategy for safe drinking water. Toronto: Ontario Ministry of the Attorney General; 2002.
• Guardabassi L, Schwarz S, Lloyd DH. Pet animals as reservoirs of antimicrobial-resistant bacteria. Journal of Antimicrobial Chemotherapy. 2004;54:321–332. [PubMed: 15254022]
• Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P. Global trends in emerging infectious diseases. Nature. 2008;451(7181):990–993. [PMC free article: PMC5960580] [PubMed: 18288193]
• Kruse H, Johansen BK, Rørvik LM, Schaller G. The use of avoparcin as a growth promoter and the occurrence of vancomycin-resistant enterococcus species in Norwegian poultry and swine production. Microbial Drug Resistance. 1999;5(2):135–139. [PubMed: 10432274]
• Newcomb J, Harrington T, Aldrich S. The economic impact of selected infectious disease outbreaks. 2011. (unpublished)
• Ravel A, Nesbitt A, Marshall B, Sittler N, Pollari F. Description and burden of travel-related cases caused by enteropathogens reported in a Canadian community. Journal of Travel Medicine. 2011;18(1):8–19. [PubMed: 21199137]
• Thomas MK, Majowicz SE, Pollari F, Sockett PN. Burden of acute gastrointestinal illness in Canada, 1999-2007: Interim summary of NSAGI activities. Canada Communicable Disease Report. 2008;34(5):8–13. [PubMed: 18800412]
• White JR, Escobar-Paramo P, Mongodin EF, Nelson KE, DiRuggiero J. Extensive genome rearrangements and multiple horizontal gene transfers in a population of Pyrococcus isolates from Vulcano Island, Italy. Applied and Environmental Microbiology. 2008;74(20):6447–6451. [PMC free article: PMC2570278] [PubMed: 18723649]
• WHO (World Health Organization). The global burden of disease: 2004 update. 2008. [June 26, 2012]. http://www​.who.int/healthinfo​/global_burden_disease​/GBD_report_2004update_part2​.pdf.
• Wright G. The antibiotic resistome: The nexus of chemical and genetic diversity. Nature. 2007;5:175–186. [PubMed: 17277795]

5

Laboratory for Foodborne Zoonoses, Public Health Agency of Canada.

6

Department of Population Medicine, University of Guelph.

7

Centre for Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada.

8

Veterinarians without Borders/Vétérinaires sans Frontières, Canada.

9

Public Health Agency of Canada.