Anti-Microbial-Resistance: Impact on One Health, Sustainable Development Goals, Microbiome & Policy

The discovery of antibiotics was the inflection point in human existence since it contributed enormously to the extension of the human lifespan. However, this excitement was tempered by the detection of antimicrobial resistance (AMR) prior to the launch of the first antibiotic (Penicillin), which continues to be a major deterrent leading to significant mortality and morbidity. This phenomenon has consistently evolved, as evidenced by several reports such as: GLASS (2021),¹ 2020 AMR Benchmark (WEF),² the DRIVE-AB (2018),³ and the Scoping Report on AMR in India (2017).4 The economic burden due to AMR related mortality is estimated to exponentially rise to above 10 million deaths per year by 2050 costing an estimated $100 trillion.⁵

AMR by itself is a complex and interdisciplinary publichealth challenge driven by multiple factors, especially the (ab)use of antimicrobials in all the areas of the World Health Organization’s One Health coverage – human, animal, agriculture, as well as environment. In many countries, especially the developing, self-medication with antibiotics without a physician’s consultation is a major problem of balancing the Access to Medicines (antibiotics) versus misuse of antibiotics. Compounding this are the increasing prevalence of infectious diseases, incomplete coverage of vaccination, poor access to water, sanitation, and hygiene infrastructure. The continued evolution of AMR has also impeded United Nation’s Sustainable Development Goals set to serve as a global blueprint for a better, more equitable, more sustainable life on our planet. Further, the swelling body of information in the last decade on the gut microbiome has demonstrated that it is the reservoir of antibiotic resistance genes (ARG) which potentially transfer horizontally among microbes and contribute to the emergence of drug-resistant bacteria. This is a cause for concern since the microbiome can also alter physiology quite dramatically. Similarly, animal and plant microbiomes which are diverse and stable are also affected by AMR. It is imperative to understand the persistence and spread of ARG in food production systems such as agriculture, aquaculture etc. It is essential to have pragmatic policies, two of which focus on – health systems organisation and management, and health system governance and accountability. Hence, developing and implementing a reliable and verifiable surveillance platform that consistently gathers AMR data in real-time is essential in quantifying the burden of AMR.

AMR

Antimicrobial Resistance must be understood as a response to an indiscriminate exposure of microbes to antibiotics rather than a microbial attack on human health. The very fact that we are using antibiotics in various sectors such as poultry, cattle, agriculture, food industry, human health, in addition to release into the environment is a clear indication that we are exploiting them, irrationally. Unfortunately, this alarming exploitation has not been paralleled by the development of novel antimicrobials. Literature shows the trend of increasing AMR, resulting in our inability to treat highly resistant microbes including WHO’s Global priority critical list of Multidrug-Resistant (MDR) microbes.⁶ Developing countries are among those with the highest bacterial disease burden in the world, and the devastating consequences of AMR are further compounded by using unapproved antibiotic formulations that are estimated to be >50% of all antibiotics sold.⁷ As COVID-19 surged, the overuse or widespread misuse of antibiotics also increased with a risk of new drug-resistant strains emerging. Thus, AMR that was already widespread, has now got an impetus during the COVID-19 pandemic. Concerted global efforts are needed to urgently address this crucial evidence.⁸ AMR was one of the three major outcomes of the World Health Assembly (WHA74) held in May this year, the other two being the pandemic and vaccines.

AMR & One Health

One Health is an approach to design and implement programs, policies, legislation, and research in which all sectors of life (human, animal, agriculture & environment) communicate and work together to achieve better public health outcomes.⁹ It encompasses the same microbes dwelling among the plants, animals and humans sharing the eco-systems, hence seamlessly expediting the spread of ARGs among these areas. It needs professionals with a range of expertise who are active in different sectors to effectively detect, respond to, and prevent outbreaks, document & share epidemiological data and laboratory information across sectors. There are two immediate issues in AMR in One Health that need attention: overuse of anti-microbials in humans, and in that of non-human (food-animals, agriculture etc).

AMR & SDGs

The continued evolution of AMR is likely to limit achieving United Nations’ SDGs by 2030 since AMR impacts many of the SDGs related to changes in society and healthcare. AMR significantly increases cost of treatment thus causing financial burden pushing the poor further into poverty affecting SDG-1 (No Poverty). Further, AMR threatens long-term security of food production and the livelihood of farmers affecting SDG2 (Zero Hunger) and SDG-8 (Decent work and economic growth). The common infections among the vulnerable population (children, women etc) will increasingly be associated with severe complications and increased risk of death impeding achieving the SDG-3 (Good health & well-being). AMR risks increasing inequalities within societies, especially the extra vulnerable such as migrants and refugees thus affecting SDG-10 (Reduced inequity). Many infections may be transmitted by contaminated water and thus increasing the spread of MDR strains into the environment impeding SDG-6 (Clean water and sanitation). Work on AMR therefore needs to have a greater systems perspective and requires coordination across different sectors through the One Health approach. The core missions of universal health coverage and the SDGs respectively are to gain ‘Health for All’ and to ‘Leave No-one Behind’.

AMR & Microbiome

The microbiome is the genome of all the microbes (symbiotic and/or pathogenic) living in and on several forms of life including the vertebrates. Intimate relationships between the host immune system and the human microbiome are shaped by their interactions. Even essential use of antimicrobials will tend to leave their mark not only on the microbiome and the pathogen, but also the host immunity. Strategies to enhance immune responses to vaccines and manipulation of the microbiome to alter resistant organisms could be valuable approaches in tackling AMR. We need to realize that the microbiome is now recognized as the largest invisible “organ” of our existence, ensuring it being protected from exposure to the AMR genes is very critical in controlling AMR in all sectors comprising the One Health approach.

AMR & Policy

It is important to generate policy guidelines to provide technical support requiring access to tools necessary to address AMR, even though these policies are also hindered by the paucity of relevant data on antibiotic use, AMR, and the health and economic burden. Few potential policy decisions to manage AMR within universal health coverage strategies include (a) achieving one universal health coverage, (b) build political commitment to invest in measures to address AMR that reduces the impact on economic burden, (c) identify points through which AMR can be addressed in national universal health coverage strategies and how resources can be harmonized, (d) advocate for inclusion of AMR in broader health and development programs at global, regional, national, & local level, and (e) build pragmatic one health collaborations across its sectors to ensure greater coordination between the universal health coverage and AMR combating strategies.

Mitigation: Antimicrobial Stewardship

The way forward is by antimicrobial stewardship and by strengthening global governing agencies’ agenda such as (a) National Action Plan on AMR, (b) National Programme on Containment of AMR, (c) industry thrust on alternate therapies, (d) addressing antibiotic policy & triggering better antibiotic control, (e) strengthening inter-disciplinary research. Twenty-four leading scientists from Academia & Industry funded by Wellcome Trust & Dept. Health (England) deliberated and proposed the 19 approaches to either target bacteria or, target the host to treat bacterial infection.¹⁰ One of those is the importance to develop the non-antibiotic approaches such as antibodies, probiotics, engineered bacteriophages, vaccines etc, for managing infectious diseases.¹⁰

Conclusion

Antimicrobial resistance has reached its tipping point and is the quiet before the storm. The threat of AMR is paramount, and we need to address its complex causation such as disappearing geographical boundaries with “migrating” humans, food-animals, agriculture, and all-too-easy access to antimicrobials esp. in unregulated countries. Combating AMR requires concerted global cooperation since implementing good control practices only in one country or in one population will not deter the spread of resistant strains. We need to implement harmonizing surveillance between nations in order to measure the extent of the AMR and combat it effectively and have to include not only human samples but also that of food-animals, agriculture and environmental sources. Instead of only using antibiotics for treating infections, we should start considering alternatives to antibiotics (probiotic, herbal etc), and examine the intended goal such as to stimulate and promote body’s own healthy immune response, directly battle with bacteria, or both. When we contain AMR by roping in stakeholders from all sectors of One Health such as humans, animals, environment, agriculture, we can strengthen the microbiome, and facilitate achieving the UN’s SDG. It is clear that we must act, and act now in the spirit of a true One & Universal Health.

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Conflicts of interest

The authors declare no conflict of Interest, financial or otherwise