Navigating the Interconnected Web of Health: A Comprehensive Review of the One Health Paradigm and Its Implications for Disease Management
Traditionally, the investigation and treatment of diseases have predominantly fallen within the purview of medical science, confined to a narrow framework. However, a growing body of scientific evidence now points to the intricate web of ecosystem-mediated diseases, exemplified by the escalating threats posed by zoonoses and antimicrobial resistance (AMR). This burgeoning awareness emphasizes the need for multifaceted approaches to address complex challenges. In response, the “One Health” paradigm has emerged as a pivotal strategy to confront intricate problems. Central to this concept is the recognition of the interconnectedness among humans, animals, and the environment, a perspective gaining prominence due to the heightened risks and challenges presented by the increased frequency and severity of disease outbreaks. “One Health” is defined by the World Health Organization (WHO) as an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems. Specific examples of the impact of animals on human health include COVID-19, rabies, avian influenza, and vector-borne diseases, such as malaria and Lyme disease. Conversely, human behaviors, such as habitat destruction, overuse of antibiotics in livestock, and the human-mediated spread of invasive species, have adversely affected animal health. Potential adverse impacts of each component are presented in . This review seeks to establish a foundational understanding of the One Health concept by elucidating the current knowledge and insights surrounding it. Specifically, we spotlight zoonoses and AMR as prime examples of the One Health concept. Additionally, we explore how climate change and agricultural malpractice can disrupt the entire system, ultimately impacting human health. Finally, we provide recommendations and outline future research directions in this critical area. 

In recent decades, the One Health approach has garnered substantial recognition and endorsement. The intrinsic relationship between public health and the environment has been acknowledged since ancient times; Hippocrates, in Ancient Greece, contended that geographical conditions and climate could influence health outcomes and diseases. In the 19th century, Rudolf Virchow introduced the term “zoonosis” and emphasized the similarity in health outcomes between animals and humans, highlighting the pivotal role of environmental factors in human health. Sir William Osler, Virchow's student and an epidemiologist, coined the term “one medicine” to closely associate veterinary sciences with human health outcomes. The term “One Health” gained widespread usage during the outbreak of severe acute respiratory disease in 2003, and it was further emphasized during the highly pathogenic avian influenza H5N1 outbreak in 2004, leading to the formulation of the “Manhattan Principles” at a Wildlife Conservation Society meeting. These principles underscored the crucial acknowledgment of the interconnected health of humans, animals, and the environment. In 2010, the WHO, the Food and Agriculture Organization, and the Organization for Animal Health (OIE) formed the “Tripartite Alliance” to recognize their shared responsibility in addressing health risks at the human-animal-environment interface. In March 2022, the partnership evolved into the “Quadripartite” with the inclusion of the United Nations Environment Programme, establishing a Global One Health Joint Plan of Action for 2022–2026. The One Health concept encompasses various disciplines, with the recognition that the overlap between the health of humans, animals, and the environment is constantly expanding, making it an ever-evolving dynamic concept. The Quadripartite's One Health Joint Plan of Action is structured around six interdependent action tracks aimed at preventing, detecting, and responding to health threats while enhancing the health of humans, animals, plants, and the environment. Six action tracks proposed in the One Health Joint Plan of Action are as follows: the first is enhancing One Health capacities to strengthen health systems by establishing foundational mechanisms, tools, and capacities, and creating an enabling environment for effective implementation. The second action track is reducing the risks from emerging and re-emerging zoonotic epidemics and pandemics. This is to reduce the risk of local and global impacts of zoonotic pathogens by understanding drivers, identifying upstream interventions, and strengthening surveillance systems. The third one is controlling and eliminating endemic zoonotic, neglected tropical and vector-borne diseases. The main target of this action is community-centric risk-based solutions. The fourth action track is strengthening the assessment, management, and communication of food safety risks. This is about the nexus of the human-animal-plant-environmental interface through food production and consumption. The fifth one is curbing the silent pandemic of AMR, which is to limit the emergence and spread of resistant pathogens. The final action track is integrating the environment into One Health. This is based on the acknowledgement that the health of humans, domestic and wild animals, and the environment are closely linked and interdependent. In 2020, the multidisciplinary One Health High-Level Expert Panel was established to enhance cross-sectoral collaboration, attracting around 17000 learners globally within 2 years through open-access training courses. Global initiatives to address public health emergencies at the human-animal-environment interface include the International Health Regulations by the WHO, the Performance of Veterinary Services Pathway by the OIE, and the incorporation of One Health principles into the United Nations' 2030 Agenda for Sustainable Development Goals. Through One Health, the Quadripartite aims to enhance each country's ability to respond to escalating health threats and to surveil and prevent disease outbreaks by integrating human health and environmental data. Many countries, both developed and developing, have implemented policy programs to address One Health-related issues ( ). Some of these programs tackle global challenges, while others focus on local endemic problems specific to certain regions. 

Infectious diseases represent some of the most formidable health and security challenges confronting the world, a trend anticipated to persist for decades. The WHO reports that over 60% of emerging infectious diseases are of zoonotic or animal origin, with approximately 70% originating in wildlife. In 2018, the WHO Research and Development Blueprint recognized the emergence of an enigmatic threat referred to as “Disease X,” identified as the foremost health risk. In 2020, Disease X materialized as the COVID-19 outbreak. The ominous term “Disease X” underscores the potential emergence of currently unknown pathogens from unidentified spillover events, resulting in outbreaks hat pose global threats to human health. Notably, the pandemic underscored the lack of an effective mechanism for early detection of emergent pathogen spillover from environmental sources such as wildlife and highlighted the vulnerability to the rapid spread of disease through international air travel and other transport systems. Zoonotic diseases, shared between animals and humans, pose significant risks to both animal and human health, profoundly impacting economies and livelihoods. These diseases spread through contact between humans and animals and with their environment, manifesting as foodborne, waterborne, vector-borne, or transmitted through direct or indirect contact and environmental contamination. The One Health concept advocates for collaboration across sectors to enhance the surveillance, detection, and control of diseases. From an economic standpoint, controlling zoonotic disease outbreaks and implementing early prevention measures benefit governments globally. The World Bank estimates economic losses from six major outbreaks of highly fatal zoonoses during 1997–2009 at US$80 billion, emphasizing that preventive measures could have reduced the cost to approximately US$6.7 billion. Zoonotic diseases can be transmitted to humans through various contact-dependent and contact-independent scenarios. One significant cause of zoonotic disease outbreaks is when animals from livestock production serve as intermediate hosts, facilitating the adaptation of pathogens acquired from wildlife and the environment. For instance, domestic pigs may act as intermediate vessels, enabling genetic recombination of influenza A viruses from wild birds, resulting in new influenza strains transmitted to human populations. The majority of newly identified human viral infections in the last decade have had a zoonotic origin, emphasizing the influence of animals on human disease. As such, developing technology for early diagnosis and control of zoonotic disease outbreaks is of paramount importance. An illustrative case is the outbreak of hemorrhagic fever in Uganda during 2007 and 2008, caused by the Marburg virus, a close relative of Ebola, known for high transmissibility and human mortality rates. The outbreak affected gold miners at the Kitaka mine and tourists visiting the Python Cave, both habitats of Egyptian fruit bats, the natural reservoirs of the virus. An initial response focused solely on exterminating bat colonies, disrupting the ecosystem. However, a subsequent study, following the recovery of bat populations, revealed higher levels of the virus and infection potential than before. This intervention, concentrating on the human health outcome without considering the broader One Health aspects, worsened the situation in the long term. 

Anthropogenic interference with ecosystems heightens the risk of zoonotic spillovers, while climate change-induced extreme weather events exacerbate the impact of these spillovers on human health. Factors such as elevated temperatures, rising sea levels, flooding, increased precipitation, and droughts directly contribute to disease outbreaks by amplifying the transmission of vector-borne and waterborne diseases. Simultaneously, they disrupt healthcare systems and sanitation protocols, intensifying health disparities. The disruption of ecosystems by extreme weather events significantly impacts biodiversity, a crucial factor in preventing infectious disease outbreaks and pandemics. Climate change facilitates the geographical expansion of infectious disease pathogens, enabling them to find new habitats and extend their range into previously unaffected regions. Notably, vector-borne diseases such as Zika and Dengue, typically confined to tropical climates due to temperature requirements, are now encroaching into temperate climates due to rising temperatures. Instances of cholera in Europe imported from regions experiencing heightened epidemic activity due to climate change underscore the role of human migration in disease transmission. The shifting geographic range of vectors and the shortened pathogen incubation period are key mechanisms through which climate change influences disease transmission. An illustrative case is the emergence of the phocine distemper virus, known for causing mortality in Atlantic seals, in sea otters in the North Pacific Ocean. Reduced sea ice, attributed to global warming, is identified as a potential driver, as it increases contact between Arctic and sub-Arctic mammals, fostering the spread of this unprecedented disease. The rapid melting of permafrost and deepening of the active layer raise concerns about exposing pathogenic viruses and bacteria, potentially leading to the resurgence of previously eradicated diseases. Bacillus anthracis , the causative agent of anthrax, stands out as a notable bacterial pathogen present in permafrost. This organism has a global distribution and poses potential risks to human health. A notable outbreak of anthrax in Siberia in 2016, linked to the exposure to infected animal carcasses previously preserved in permafrost, resulted in the death of 2000 reindeer and one human case. While human viral pathogens have been detected in permafrost, the risk of infection from these sources is considered negligible. Viruses are susceptible to environmental pressures, particularly during thawing, which significantly reduces their viability. Consequently, as of the current date, there are no documented instances of viral infections in humans attributed to pathogens released from thawed permafrost. 

AMR is acknowledged as a primary cause of global mortality, exerting the most significant impact on low-income countries and resource-limited settings. This pervasive and escalating threat is propelled by the overuse and misuse of antimicrobials across the human, animal, and plant sectors. AMR presents a multifaceted and intricate challenge, affecting humans, animals, plants, and the environment. The extensive use of antimicrobial agents in the livestock industry establishes favorable conditions for the selection of microorganisms resistant to multiple drugs, fostering the emergence of new pathogenic strains and amplifying the risk of spillover events. A report commissioned by the U.K. government in 2016 estimated that without intervention, AMR could cause up to 10 million annual deaths globally by 2050, with a potential reduction in gross domestic product by 2%–3%. The role of drug resistance in the genesis of outbreaks and epidemics is expected to garner increased attention in the coming decades, alongside anthropogenic pressures on the environment and animal species. For over six decades, antibiotics have been instrumental in treating diseases in humans and livestock, with their use in animals for disease treatment and growth promotion surpassing that in human medicine. The livestock industry's reliance on antibiotics, particularly tetracyclines, has led to significant environmental concerns. Due to the low biodegradation rates within livestock, a substantial portion of administered antibiotics, ranging from 30% to 90%, is excreted in manure, which is then used as fertilizer, introducing large quantities of antibiotics into agricultural lands. This cycle contributes to the pervasive presence of antimicrobial substances in the soil, affecting human health and natural ecosystems. The stability of these compounds in the environment increases their residual presence during crop growth periods, posing a potential risk to food safety and public health. Environmental exposure to antibiotics is a significant issue, as it leads to an increase in antibiotic-resistant bacteria and the expression of resistance genes, warranting extensive research. Despite the recognized need, research on the toxicity of antibiotics on crops remains relatively limited, underscoring the importance of studying the impact of various antibiotics and their concentrations on crop growth. Among these, tetracycline, chlortetracycline, and oxytetracycline are of particular concern due to their prevalent use and relatively high residue levels in agricultural soils (0.003–100 mg kg -1 ), highlighting an urgent need for further investigation and the development of strategies to mitigate the spread of AMR in the agriculture field. The overuse of antimicrobials in aquaculture has also resulted in antibiotic resistance in the surrounding water, sediments, and fish-associated bacterial strains. Proximity to fish farming sites has revealed high incidences of antibiotic-resistant bacterial populations, particularly resistant to quinolones, tetracyclines, and penicillins. Antibiotic resistance can readily disseminate within aquatic microbial communities, reaching human pathogenic bacteria and triggering spillover events with repercussions for human health outcomes. The well-documented use of antibiotics in aquaculture contributes to the dispersion of antibiotic residues in the marine environment, escalating the rates of antibiotic resistance in aquatic bacteria, and critically facilitating the transfer of resistance to human pathogens. The presence of AMR in estuaries has been noted on a continental scale, underscoring the imperative for multiscale approaches that incorporate ecosystem considerations. Identifying antimicrobial-resistant contaminants in fresh produce through cross-sectional studies worldwide underscores the intricate ways AMR can affect human health. This situation highlights the influence of dietary choices on the gastrointestinal carriage and colonization of antimicrobial-resistant organisms, as seen in studies linking the consumption of contaminated fruits and vegetables to increased diversity of resistant microflora in vegetarians. Furthermore, experimental research with animal models, such as studies showing a higher prevalence of streptomycin-resistant and multi-drug-resistant E. coli in sheep grazing on antibiotic-treated pastures, illustrates the environmental vectors of AMR transmission. These findings emphasize the critical need for implementing sustainable practices in agriculture and aqua-culture, promoting responsible antibiotic use, and curbing the ecological spread of antibiotics and resistance. Such strategies are vital for addressing the AMR challenge, ensuring the safety and sustainability of food production systems for future generations, and aligning with global efforts to protect public health. 

To counter the escalating frequency of spillover events leading to health crises, One Health offers preventive measures to mitigate zoonosis and AMR. Livestock vaccination against brucellosis and leptospirosis has demonstrated effectiveness in reducing disease burdens. An effective strategy to curb zoonotic disease outbreaks and AMR is the mass vaccination of animal populations, offering a cost-effective and feasible alternative to the overuse of antimicrobials. Successful cases underscore the efficacy of One Health approaches in addressing disease threats. In the United States in 2014, an outbreak of Highly Pathogenic Avian Influenza Virus (HPAI) introduced by migratory birds triggered the largest recorded animal disease emergency. A collaborative effort, the Interagency Steering Committee for Avian Influenza Surveillance in Wild Migratory Birds, established a complex surveillance system, enabling early identification of HPAI viruses in wild birds. This system, facilitated by interagency collaboration, served as an early warning mechanism, preventing the transmission of the virus to poultry and mitigating the threat of a zoonotic spillover event. This successful collaboration emphasized the importance of the One Health approach in achieving ecosystem conservation, disease prevention, and the health of wildlife, food-animals, and humans. The Quadripartite currently advocates a multi-sectoral One Health approach to address the “silent pandemic” of AMR. The term “silent pandemic” underscores the information disparity globally, with high-resource countries providing data on AMR while low-resource countries face under-detection, leading to increased deaths due to ineffective antibiotic treatments. Under the Global Action Plan on AMR, the Global Early Warning System for health threats and emerging risks at the human-animal-ecosystem interface (GLEWS+) was established for early warning, detection, and risk assessment. While these systems aim for global unification of data, there are examples of countries successfully addressing AMR through the One Health perspective. In 1995, Denmark implemented the Danish Antimicrobial Resistance Monitoring Programme (DANMAP) to mitigate zoonotic threats and AMR. With a national action plan under the One Health perspective, DANMAP monitored antibiotic residues, bacterial resistance, reduced antimicrobial use in livestock, and surveilled disease spread. The success of this action plan contributed to increased scientific knowledge on AMR, with Denmark significantly reducing AMR in agricultural settings and improving clinical health outcomes. The European Union's “farm to fork” action plan, initiated in 2010, further advanced food safety and sustainability based on DANMAP's surveillance. New Zealand, as an isolated “closed system,” serves as a case study for the successful application of One Health through governance and scientific collaboration. The “One Health Aotearoa (OHA)” alliance in New Zealand focuses on mitigating AMR, improving water quality, and curbing the effects of zoonotic disease spillover. The success of OHA was exemplified during a gastroenteritis outbreak in Havelock North in 2016, classified as one of the world's largest reported waterborne outbreaks. OHA researchers, employing a One Health surveillance system, traced the outbreak to sheep feces contaminating drinking water bores, successfully containing the outbreak. The OHA system integrates collaboration between the national veterinary laboratory, the New Zealand microbiology network, and a centralized surveillance system for notifiable diseases called EpiSurv, illustrating the importance of cross-disciplinary responses under One Health surveillance in effectively managing new outbreaks. Several scientific investigations employing the One Health concept have been successfully conducted, as outlined in . 

To successfully incorporate One Health through multi-sectoral collaboration, it is imperative to provide proper training to individuals working in distinct sectors. This training is vital for raising awareness regarding the interconnectedness of humans, animals, and the environment. Incorporating One Health professional training programs into the curriculum for veterinary, human, and environmental scientists can bridge educational gaps, fostering collaboration across multiple disciplines. Evaluating the operationalization of One Health within the International Health Regulations, including a distinct category, can enhance the implementation of national action plans and serve as guidelines for countries. Crucially, integrating One Health into the curricula of medical and veterinary schools can profoundly influence students to approach new challenges in a multi-sectoral manner. A study conducted at Georgetown University demonstrated that the inclusion of One Health-related subjects and activities in the curriculum can be achieved efficiently and cost-effectively. The incorporation of a One Health elective for third-year medical students covered topics such as emerging infectious diseases, zoonoses, vector-borne diseases, epidemiology, disease preparedness, the human-animal-environment interface, and the impact of climate change on public health. The survey conducted before and after the course revealed that students recognized the vital importance of a holistic approach to healthcare, where the human-animal-environment interface is considered. They emphasized the increasing importance of interdepartmental and interdisciplinary collaboration in the face of emerging challenges. This study underscores the achievability of successfully integrating One Health preparedness at a low cost, emphasizing the importance of closing educational gaps through increased knowledge of One Health strategies as a cornerstone of education. A more effective One Health approach to reduce spillover events of the virus could have involved prohibiting human access during high-risk times, such as birthing seasons, along with enhanced personal protective equipment and health screening when access was allowed. Instead of disrupting the ecosystem, the One Health approach provides an opportunity to collaboratively work with the ecosystem to minimize the risk of spillover events. The environment, often neglected in One Health triad responses, assumes critical importance due to its role in exacerbating antibiotic resistance and zoonoses under climate change. Despite its dynamic nature, the environment remains the least explored and integrated aspect of One Health systems. Addressing climate change, habitat fragmentation, pollution, and environmental degradation is essential to safeguard ecosystem function and human health The success of One Health integration in New Zealand highlights the potential for a multi-sectoral approach to address issues beyond infectious diseases, such as climate change. Integrating environmental surveillance into One Health systems will gain importance as climate change amplifies the frequency and incidence of disease outbreaks. AMR is a growing concern in food-animal and livestock production, acknowledging the interconnectedness of animal and human health. However, AMR is increasingly problematic in aquaculture settings due to a lack of regulations and rising temperatures linked to climate change. The One Health approach proposes characterizing and surveilling resistant bacterial strains, enhancing aquaculture sector hygiene, minimizing antimicrobial usage, and including environmental surveillance in sediments and surrounding water to address AMR. Success in curbing AMR through surveillance in other sectors necessitates extending these approaches to aquaculture. We propose several research directions to further advance the One Health concept. First, emerging technologies, including machine learning (ML) models, advanced molecular biology tools, and remote sensing techniques, should be integrated to address multi-scale medical challenges on a global scale. This integration is particularly critical as ML algorithms are capable of analyzing highly complex systems with diverse input features, which frequently encompass high-throughput sequencing data and spatially explicit information collected at regional or continental scales. Second, fostering transdisciplinary research and education is imperative to strengthen the One Health framework. This need is underscored by a recent survey indicating that only 56% of medical schools in the United States incorporate One Health-related topics into their curricula. Addressing this gap requires collaborative research efforts across diverse academic disciplines, publication of findings in journals with broad readerships, development of novel syllabi and courses in medical schools, and organization of interdisciplinary conferences. For instance, numerous academic societies focused on microbial ecology predominantly emphasize either natural ecosystems or medical perspectives, thereby limiting interdisciplinary dissemination of knowledge. Third, the effective implementation and benefits of the One Health concept heavily rely on public health efficiency and cost-effectiveness. Nevertheless, reliable metrics for evaluating One Health outcomes remain insufficient. Current assessments predominantly depend on modeled projections rather than empirical data derived from implemented interventions. Consequently, establishing a standardized framework for evaluation metrics is urgently required to facilitate widespread adoption and support of the One Health approach among stakeholders. Finally, sub-disciplines that serve as intermediaries among diverse fields, including medicine, environmental science, and ecology, should receive increased support to enhance One Health research and its practical implementation. Disciplines such as epidemiology, ecosystem ecology, and environmental toxicology represent promising candidates for fulfilling this role. 

