Setting the One Health Agenda and the Human-Companion Animal Bond

“One Health”, also called “One Medicine”, began as an initiative advocating greater integration of human and animal medicine, in the 1800s. This concept has recently come to prominence, driven by the recognition that 75% of the newly emerging infectious diseases will arise from animal reservoirs, and that successful control and prevention will require a coordinated human medical and veterinary approach. Consequently, many One Health discussions have centered on the surveillance of animals in order to anticipate the potential emergence of new zoonotic diseases. An area that has been given only cursory mention, are the many ways that small companion animals benefit individual, community and possibly world health. The goal of this paper is to briefly review some of the evidenced-based data concerning the benefits of having companion animals in our lives, focusing on four major areas; cancer, heart disease, autism spectrum disorder (ASD), and the potential positive economic effects of the human-companion animal bond on One Health. Heart disease and cancer are the two leading causes of morbidity and mortality in the world, while ASD is a growing concern, not only for its individual effects, but also for its effect on family units, educational institutions, and its social implications for the community. In addition, these diseases can greatly affect the national and global cost of healthcare, as well as the economic output of a nation. It is therefore important to include and build on the concept of the Human-Animal Bond (HAB) as it relates to healthcare in these areas.


Human and Companion Animals: A Historical Perspective
The Human-Animal Bond (HAB) has been defined as "the dynamic relationship between people and animals such that each influences the psychological and physiological state of the other" [10]. In the case of small companion animals, this relationship likely goes back to the time of domestication of the dog some 35,000 years ago. Throughout history, there are numerous examples of the important role of dogs and cats in society, religion, art and science and early recognition of the benefits of interaction with these companion animals. Formal recognition of the benefits to human health of keeping small companion animals goes back to the 18th century [8]. In the 19th century, animals were commonly found in mental health institutions and the social reformist and nurse Florence Nightingale advocated that the chronically ill should keep "a small pet" for an increased sense of well-being [11,12]. In the past 25 years there have been major advances in the formal scientific documentation of such benefits and there is much contemporary research into the Human-Companion Animal Bond.

Methodology
A journal review using PubMed, HABRI Central, Pet Partners library collection, as well as the 2013 IAHAIO (International Association of Human-Animal Interactions Organization) conference proceedings, was conducted from January 2012 through August 2014. Articles were selected based on research primarily pertaining to four major areas; that of cardiology, cancer, autism and economic and public health benefits of the HAB These areas were chosen primarily for their significant global effect on the human population in morbidity and mortality (cancer and heart disease) and by the (in the author's opinion) growing amount of research involving the HAB in these particular fields. Economics was included as this appears as a topic world-wide as it relates to the effects, politics and delivery of healthcare.
Key words used in these searches were: Human-Animal Bond; One Health; Pets; Animal-Assisted Therapy; Dogs; Heart Disease; Cancer; Autism; Public Health.

Heart Disease and the Human-Companion Animal Bond
Heart-related disease is the leading cause of human death in the world, accounting for approximately 17 million deaths yearly [13]. Since the 1980s when research documented an association between pet ownership and a significant decrease in mortality one year following a coronary event [14], the therapeutic value of animals has been increasingly studied. A current review of the research, while not always consistent [15,16], suggests that pet ownership and/or positive interactions with an animal can reduce or affect the risk factors (i.e. physical inactivity, obesity, hypertension, hyperlipidemia, stress and depression) associated with cardiovascular disease [15,16].
In a review of the research on positive interactions with animals and human cardiovascular disease, the American Heart Association published this statement in May 2013: "Pet ownership, particularly dog ownership, may be reasonable for reduction in cardiovascular disease risk (CVD)" [17]. A summary of the American Heart Association findings is given below:  Pet ownership is correlated with lower systolic and often diastolic blood pressures. Just one of many examples, in one randomized study, ambulatory blood pressures decreased significantly (p < 0.001) in a patient group that adopted pet dogs. In a later follow-up study, all participants (including the "pet-deferred" group) had adopted dogs with similar reduction in systolic blood pressure [18].  In three cited studies [19][20][21], the largest containing 5741 participants and the smallest with 32, all reported lower cholesterol and/or triglyceride levels linked to pet ownership. One study also linked non-dog ownership with increased diabetes and tobacco use [21].  Dog ownership was associated with increased physical activity in studies performed in such culturally dissimilar regions such as Canada, Australia and Japan [22][23][24].  Due to the increased physical activity of many dog owners, the level of obesity appears to be reduced in most studies. One mechanism whereby dog ownership may assist in weight management programs is the role they play in social support, which is a powerful predictor of adoption and maintenance of behavior change (e.g., a weight loss program). Besides providing encouragement and motivation to walk, concerns about safety while out walking may be reduced [23,25,26].  Pet ownership may be an independent modulator of cardiac autonomic imbalances. The mechanisms responsible for this interaction are complex, but the current hypothesis links improved mood and emotional state to decreased central and regional autonomic activity, improved endothelial function and thereby more appropriate blood pressure and reduced cardiac arrhythmias, with pets conferring more significant positive effects than drugs [27][28][29].  Cardioprotective effects may be conferred on pet-owners versus those without pets. Independent of the severity of cardiovascular disease, dog ownership in one study decreased the mortality of cardiovascular re-occurrence by ~ fourfold [30].
Additionally, in a canine assisted ambulation (CAA) study, relative to CVD, a decreased refusal of the patients to early ambulation was documented, with resulting shorter hospital stays and improved outcomes [31].

Cancer and the Human-Companion Animal Bond
Cancer is another leading cause of human death and morbidity in the world, with approximately 8.2 million deaths and 14.2 million cases diagnosed in 2012 [32]. Positive interactions with animals may be beneficial for many going through cancer therapy, with patients reporting improved perceived health and decreased depression [33,34]. Additionally, improved arterial oxygen saturation levels and positive influences on the psychosocial well-being of patients have been reported [35].
In pediatric cancer studies, it was reported that interactions with therapy animals were beneficial in a number of ways:  Normalizing the hospital experience: children demonstrated an improved acceptance of the hospital experience, that it was "more like home", and that they felt "less ill", and even happier, when interacting with the animal therapy team [36][37][38][39].  Improved motivation to participate in the treatment protocol, to maintain their motivation over time, and to want to "get better" or stay optimistic [39,40].
 Distracted or lessened worry, anxiety, unhappiness and pain, which in turn improved comfort level and provided some degree of joy [39,41].
In an investigational epidemiological study involving 1591 Non-Hodgkin Lymphoma cases and 2515 controls in the San Francisco area, pet ownership was associated with a reduced risk for Non-Hodgkin's lymphoma and diffuse large-cell lymphoma [42]. Possible explanations may be the association between pet ownership and altered immune function and desensitization to allergens, given that immune-competence and immune-related activity and the association with Non-Hodgkin's Lymphoma are well accepted. In addition to providing comfort, relief and potential cancer risk reduction; some animals appear to have the ability to identify people suffering from bladder, ovarian, lung, prostate and breast cancers through olfactory signals; providing a potential valuable (and less invasive) addition to human cancer diagnosis [43,44]. As in many diseases, early detection can provide for a more efficient and rapid intervention and management of this disease.

Autism and the Human-Companion Animal Bond
Autism spectrum disorder (ASD) is a socially debilitating neurodevelopmental disorder that is estimated to affect 1 in 88 children in the USA [45]. ASD involves impairment of social development, associated communication deficits, depressed interest and repetitive behaviors, and as such is a highly disruptive and deeply felt event for families of such individuals. Ever since the seminal presentation by Boris Levinson in 1961, where he proposed that interactions with dogs might improve social communication of ASD children, and later, the publication of his book, Pet-Oriented Child Psychotherapy, where he again advocated for what is now called Animal Assisted Therapy (AAT) [46], there has been gradual, and now, widespread incorporation of AAT into ASD therapy. Reported benefits include improved prosocial behaviors, self-efficacy, motivation to engage and improved emotional connections to other family members [47].
Research into the dynamics of the processes that appear to effect these changes in ASD and other conditions related to human health is ongoing. A few examples of recent research findings may illuminate how positive interactions with animals may effect these changes:  A South African study demonstrated increases in β-endorphins, oxytocin, prolactin, β-phenylethylamine and dopamine after positive interactions with dogs [48]. These hormones have been associated with blood pressure regulation, analgesia, stress relief, joy, pleasure and bonding behavior.  Elevated levels of oxytocin have been particularly associated with positive interactions with animals and oxytocin is seen to be a potentially key neuropeptide in ASD. Increased oxytocin levels are associated with improved bonding and interactions with others, more appropriate trusting, less repetitive behaviors, reduced aggression, more empathy and improved learning [49].

Economic Benefits of the Human-Companion Animal Bond
In 1997-2009, the global economic impact of zoonotic infectious diseases was estimated at US $80 billion [50]. Economic losses from diseases that could benefit from AAT or pet companionship are equally significant. In the USA alone, cardiac disease accounted for an estimated $444 billion in direct cost and lost productivity in 2010 [51]. Human health savings of $3.86 billion over 10 years have been linked to pet ownership as related to a decrease in doctor visits in studies in Australia and Germany [52], and in a separate study, savings of 175 million annually was estimated if Australian dog owners would all walk their dogs for 30 min each day [53]. The potential positive effects of pets on cardiac disease (as described above) and cancer alone could be extremely significant, but in addition, animals are reported to have positive effects on a wide spectrum of health and social issues including wound healing and immune health through the effects of the neurotransmitter oxytocin [49,[54][55][56], pediatric respiratory diseases [57], child development [58], elder care [59][60][61] and pain reduction or distraction [39]. Pets are potential influencers of community health, with some evidence they can provide a "sense of community" and improve the "social capital" of a community [62]. Pets have even been implicated to improve the motivation of people to give up smoking or lose weight [19,63].

Conclusions
The payback for recognizing and nurturing this connection between animals and humans has potential implications for the community and for individual stability and health, improved economic outputs and healthcare cost savings. Already, AAT is being put into practice by organizations such as 35+ year old Pet Partners (formerly Delta Society) [64], whose 11,000 therapy animal teams visit over 1 million patients throughout the USA and 14 other countries. The positive effects that companion animals can possibly have on our lives and communities, reinforces the need for a more prominent standing of the HAB among global One Health initiatives, research and discussions.

Acknowledgments
We are grateful to the many organizations funding research in this newly emerging area of human health care. Special thanks to Pet Partners for donating research time and to the many colleagues who alerted us to specific articles pertaining to the human-animal bond.
This manuscript is an outcome of discussions of the World Small Animal Veterinary Association (WSAVA) One Health Committee and the two authors represent the full membership of the committee. The work of the WSAVA One Health Committee is supported by a consortium of sponsors, including: the WSAVA Foundation, Bayer Animal Health, Elanco, Hills Pet Nutrition, MSD Animal Health, Merial, Nestle Purina and Zoetis.

Author Contributions
Gregg Takashima researched and provided the primary content. Michael Day provided review and editing of the manuscript.