Socio-Economic and Behavioural Dimensions of Antimicrobial Use and Resistance in Animals
E. Jane Parmley, Irene Lambraki, Shannon E. Majowicz, and Carolee Carson
WHAT IS ANTIMICROBIAL RESISTANCE AND WHY IS IT IMPORTANT?
Antimicrobial resistance (AMR) (Box 23.1) is a complex and growing health issue that is threatening people and animals around the world through increased morbidity and mortality. Canada (Council of Canadian Academies, 2019), the United States (CDC. 2019), and the United Kingdom (O’Neill. 2016) all report on and predict large direct and indirect economic and social costs associated with resistance, in addition to the health costs. Antimicrobial use (AMU) in humans (O’Neill, 2016), animals (Van Boeckel et al., 2015), crops (Finley et al., 2013), and elsewhere is widely recognized as the main driver of resistance (Pinto Ferreira, 2017).
AMR occurs when bacteria and other microorganisms can replicate in the presence of antimicrobials at levels that normally suppresses their growth or kills them. Resistance can occur due to naturally occurring characteristics of bacteria or can be acquired through genetic mutations or via transfer of genes (Aarestrup
BOX 23.1 ANTIMICROBIALS VERSUS ANTIBIOTICS AND ANTIMICROBIAL RESISTANCE VERSUS ANTIBIOTIC RESISTANCE
Antimicrobials refer to all compounds that kill or inhibit the growth of microorganisms. These microbes include viruses, bacteria, protozoa, fungi, and parasites. The use of any of these compounds can be selected for resistance.
Antibiotics are compounds that kill or inhibit the growth of bacteria.
In general, throughout this chapter, we have used the terms antimicrobial and antimicrobial resistance. However, unless otherwise stated, we are speaking specifically about antibiotics and antibiotic resistance.
et al.. 2008; Boerlin and Reid-Smith, 2008). Not all resistant bacteria are harmful, but non-pathogenic resistant bacteria can serve as reservoirs of resistance genes (Boerlin and Reid-Smith, 2008). While any use of antimicrobials can select for resistance, inappropriate use, such as using antibiotics to treat viral infections or selecting the wrong antimicrobial for the specific pathogen causing the illness, is considered the major driver (Shallcross and Davies, 2014; Castro-Sanchez et ah, 2016; Dar et ah, 2016; Holmes et ah, 2016).
Antimicrobials are one of the most successful medical advances of the 20th century. Diseases that once annually killed thousands of people and animals and made even more sick were dramatically reduced with the introduction of antimicrobials. By reducing death and preventing and controlling bacterial infections, antimicrobials allowed for development and routine implementation of many life-saving medical advances (e.g. cancer chemotherapy) and procedures to improve quality of life (e.g. joint replacements) (Shallcross and Davies, 2014; Laxminarayan et ah, 2013). AMU in agriculture improved feed efficiency in animals and enabled food to be produced more efficiently and profitably (Durso and Cook, 2014; Grace, 2015).
The benefits of widespread AMU come with a cost. As our use of and dependence on antimicrobials increased, bacteria and other microbes evolved to become resistant, and available drugs became ineffective. AMU practices have prioritized short-term individual human and animal health improvements over long-term population, community, and ecosystem health.
HOW DOES AMR AFFECT HUMAN, ANIMAL,
AND ENVIRONMENTAL HEALTH?
AMR has been recognized since the first antimicrobials were identified and used in medicine in the early 1900s. The predicted impacts of unrestricted use on human and animal morbidity and mortality have been described for decades (see
Fleming, 1945), but the full breadth of health and non-health consequences to humans, animals, nature, and society is only now starting to be characterized.
AMR is a global health crisis (Toner et al„ 2015; WHO. 2015a). Its impacts on health and well-being are far-reaching and hard to predict. The impacts already identified include increased duration of disease, increased mortality associated with infections, and increased cost of health care delivery because of the greater severity and duration of illness (Cassini et ah, 2019; Council of Canadian Academies, 2019; CDC, 2019). According to WHO (2015b), over 400,000 people die annually of foodborne diseases and hundreds of millions get sick. If these common bacteria and other microorganisms become resistant, many more will get sick and potentially die (WHO, 2017). O'Neill (2016) predicted that 10 million people will die annually from AMR by 2050. Additional indirect impacts of AMR on humans may include reduced access to life-saving treatments and surgeries which depend on antimicrobials to ward off secondary infections (Shallcross and Davies, 2014).
Farm and companion animal health will be similarly compromised. Although animals are affected in a comparable manner, estimates of the impacts of AMR (e.g. morbidity and mortality) in animal populations are rarely available (Robinson et ah, 2016).
The impacts of rising levels of resistance on food production systems and interventions to reduce AMU threatens global food security (Grace, 2015; FAO, 2016). In Canada, Europe, and the United States, most antimicrobials (by weight) are used in animal agriculture (PHAC, 2018; EFSA, 2017; O’Neill, 2014). It is likely that agricultural AMU exceeds human use globally. The total amount (kg) of antimicrobials used in agriculture is expected to increase over the coming decade, especially in low- and middle-income countries (LMIC) (Schar et ah, 2018; van Boeckel et ah, 2015). Without access to effective antimicrobials to prevent, control, and treat infectious disease, livestock production may no longer be feasible using current large-scale, conventional production methods. Changing agricultural production systems and methods could be costly and could potentially destabilize food prices and agricultural communities. Inability of some producers to continue in business without the same level of access and use of antimicrobials may negatively affect the productivity and profitability of the agricultural sector and have a particularly inequitable effect on rural communities.
Although antimicrobials are rarely used in natural environments, these areas are also affected by AMR. Antimicrobial residues and resistant microbes have been detected in rural and remote natural environments - in soils, water, and wild animals (Aga et ah, 2018; FAO, 2018; Greig et ah, 2015). These residues and resistant microbes may come from run-off/spillage from farms, septic systems, hospital and lab waste discharge sites, and more. Aquaculture also presents a threat to antimicrobial distribution and selection of resistant organisms in the aquatic environments. International trade in livestock and animal products as well as global tourism is also increasing resistant organisms’ geographic distribution.
The health challenges presented by growing levels of AMR will not be distributed equally around the world. In LMIC, the issue of AMR has more to do with access to appropriate diagnostics and drugs. In these regions of the world, physicians and veterinarians have fewer available options, and animal owners have less disposable income to afford effective and appropriate treatments.
WHY IS AMR SUCH A MESSY AND COMPLEX ISSUE?
The decision to use antimicrobials is affected by many different factors. AMU in humans and companion animals is driven by the clinical context, such as treating versus preventing infectious disease. It is also influenced by socio-economic factors, including culture, behaviour and expectations of patients/clients, lack of social infrastructure (e.g. more precarious employment status with no sick days), lack of education about the risks associated with AMR, and how AMR risks are perceived compared to other health threats.
Similar factors influence farmer and veterinarian decisions to use or not to use antimicrobials. Farmer demand for antimicrobials is likely also affected by the type(s) of animals they are raising, the perceived disease threats to those animals, past experience with infectious disease in the herd or the flock, season, cost of production, and market value of the animal product. Current North American agricultural practices rely on antimicrobials to limit disease and maximize growth targets in the animals being farmed. Removal of antimicrobials will require a transformation of how we produce and raise livestock and/or the development of new antimicrobial alternatives (Lhermie et al„ 2019).
The multitude of drivers that influence and are influenced by AMU and AMR makes AMR a very complex health challenge with multiple dependencies throughout the system. This makes it very hard to predict the short-, medium-, and long-term effects of new policies and regulations. Several teams have worked to describe the breadth and complexity of the AMR problem (Majowicz et ah, 2018; Department of Health, 2014), including non-disease factors such as environmental sources, genetics, economics, food security, trade, agriculture sustainability, or other indirect drivers and consequences. Comprehensive views of AMR as an emergent property of a complex adaptive system (Jayasinghe, 2011) can enable researchers to integrate social, biological, and ecological perspectives and provide a framework for development and implementation of effective and sustainable interventions that could reduce the human, animal, and environmental health burden of AMR.
Because of the multitude of drivers of AMU and AMR, the issue has been framed as a wicked problem (Xiang, 2013; Hutchinson, 2017) and even as a superwicked problem (Littmann, 2014). Wicked problems are those that cannot be fully characterized nor eliminated or solved. Intervention effects are difficult to predict; all interventions will have unexpected consequences across the system and no intervention can be reliably transferred to a new setting. A problem becomes super-wicked when time is running out and where there are multiple dependencies across the system. All these characteristics apply to the growing challenge of AMR.
THE NEED FOR NEW PERSPECTIVES: APPLYING HEALTH PROMOTION AND HARM REDUCTION LESSONS TO AMU AND AMR
The World Health Organization’s (WHO) Ottawa Charter for Health Promotion (1986) defines health promotion as "the process of enabling people to increase control over, and to improve, their health” (for more information on health promotion see Chapter 2). It recognizes that health is affected by a w'ide array of determinants and the complex interactions between individual, social, economic, and environmental factors that shape them. Health promotion engages and empowers individuals, groups, communities, and institutions to increase control over the determinants of health and make healthier choices easier choices (WHO, 1997; WHO, 1986). Health promotion has tackled a wide range of issues, such as child and maternal health, mental health, obesity, and tobacco control. In addressing these complex issues, a wide range of activities have been employed. The five key health promotion action areas (Box 23.2) played an important role in driving down population-level tobacco use rates in many countries. Specific examples include preventing tobacco use, protecting people from second-hand smoke exposure, assisting people who smoke to quit, and countering tobacco industry tactics (U.S. Department of Health and Human Services, 2014; Ahluwalia et al„ 2019).
When implemented together at multiple levels, these five action areas represent a comprehensive approach that, over time, alters the environment, changes social norms, and helps build individual and community capacity to empower and improve knowledge and skills to make healthier choices and reduce illness (U.S. Department of Health and Human Services, 2014). These changes are made
BOX 23.2 FIVE KEY HEALTH PROMOTION ACTION AREAS (WHO, 1986)
1. Building healthy public policies
Legislations, regulations, and tax changes coordinated across policy departments, not just health
2. Creating environments that support health
Environments encompass all the places where people (and animals) live, work, and play
3. Strengthening community action to improve health
Forming multisector inter organizational arrangements (e.g. coalitions) to coordinate and drive change
4. Developing personal skills
Equipping people with the knowledge and skills to reduce health risks
5. Reorienting health care services
Moving beyond treating illness and disease towards imbedding health promotion activities into care possible through multisector coordinated actions from local to broader levels (Potvin and Jones, 2011). Coordination is enabled via bringing sectors together to learn from surveillance and monitoring, research, and practice to better understand the complexities of a problem and what works for whom and under what conditions (WHO, 1997). This coordination requires shared vision, leadership, and investment across the human, animal, and environmental health sectors at all levels to support the cause and build trust between individuals and institutions (Seaton et al., 2018).
Strategic priority areas for AMR action focus on surveillance, stewardship. infection prevention and control, and research and innovation (Council of Canadian Academies, 2019; HM Government, 2019; U.S. White House Office, 2015; Government of Canada, 2017; WHO, 2015a). Further health promotion- based efforts need to focus on developing multi-pronged and collaborative approaches that enable all individuals, including physicians, veterinarians, farmers, patients, and others, to make informed decisions about AMU, advocate for health through associated changes in policy, and mediate dialogue between stakeholders with different perspectives (WHO, 1986).
Regardless of the success of current and future interventions, antimicrobials will continue to be used. In recognition of this use, a harm reduction approach offers alternative actions that can be applied to reduce AMR impacts. Historically, harm reduction has been used to minimize the negative health, social and legal impacts associated with illegal drug use, and other chronic health conditions (Hawk et al., 2017) (see Chapter 6 for more on harm reduction), but it could be applied to guide AMU with the fewest negative impacts. This will require research to determine the most appropriate route, dose, and duration of AMU to minimize AMR emergence and spread; exploration of antimicrobial alternatives that will prevent and control infection without contributing to resistance; as well as new innovations to support rapid and reliable diagnostic tests to ensure that the most appropriate antimicrobials are prescribed. This knowledge and availability of tools will help physicians, veterinarians, farmers, and patients make more informed decisions about AMU.
Beyond human and animal patient harm reduction, systemic and economic support is needed to change current health care practices, mainstream food production practices, and on-farm management. Investments in farm infrastructure have been made over decades while antimicrobials have been used, and these will be hard and potentially costly systems to replace. Education to increase awareness of prescribers, users, producers, and consumers about the threats posed by AMR and their contribution to the problem is needed but will not be enough. Further exploration of antimicrobial alternatives and alternative production and management practices are needed to support those industries and sectors that may take longer than others to shift to lower AMU. Like illegal substance use, dependence on AMU is not uniform across the agricultural sector. Lessons from harm reduction can help support industries and individuals that are struggling to change their AMU practices while providing incentives to help shift the industry to a new reality.