Environmental aspects of antimicrobial resistance in India: Current progress & way forward

The health, technological and economic implications of antimicrobial resistance (AMR) have been recognized globally. The data generated or projected at various levels has provided irrefutable evidence that the cost of inaction to contain AMR shall be enormous with potentially catastrophic consequences1,2. The impact of AMR on human health has now become evident. A recent study3 showed 1.27 million deaths due to resistant pathogens and 4.75 million deaths attributable to diseases due to resistant pathogens. In India, almost 30 per cent of the deaths caused by bacterial sepsis in neonates are due to multiresistant pathogens4.

The UN General Assembly and several other global and regional political leadership and intercountry agencies comprising quadripartite arrangement, namely, the World Health Organization (WHO), the Food and Agricultural Organization of the United Nations (FAO), the United Nations Environment Programme (UNEP) and the World Organization for Animal Health (WOAH), have joined hands in calling upon a worldwide coordinated, efficient, multisectoral, sustained efforts under the true spirit of One Health to contain AMR5. The outcome document of the Health Ministers’ meeting during the G20 summit in 2023 has highlighted the urgency for concerted action on AMR6. The overall objective is to prolong and sustain the efficacy of affordable antimicrobial agents and prevent the world from sliding into the ‘post-antibiotic era’.

Framework for combating antimicrobial resistance (AMR)

In 2015, the WHO through a global consultative process developed a Global Action Plan (GAP) on AMR and recommended all countries to develop their respective National Action Plan on AMR (NAP-AMR) in alignment with the GAP. Till May 2023, 170 countries had drafted their NAPs, and 108 implementations have commenced7. India released its NAP-AMR in 2017 for the period 2017-2021. It was based on a One Health approach and articulated activities pertaining to three major sectors, namely, human health, animal health and environmental sector8.

In several countries including India, the COVID-19 pandemic became a major barrier in the implementation of AMR containment activities. The COVID-19 pandemic, however, also demonstrated extensive misuse of antimicrobial agents, contrary to the fundamental concept of managing AMR9. Nevertheless, despite the pandemic, the NAP succeeded in augmenting advocacy and awareness on this public health challenge, establishing surveillance networks and identifying issues in executing coordinated and joint activities mainly by human health, and animal health sectors while the environment sector lagged behind10. However, the focus in most of these activities has been on interventions in the human health and veterinary sector, with the environment component suboptimally supported and implemented. The environment has multiple and extensive dimensions that substantially influence the development and spread of resistance in bacteria. However, there is a need for augmenting awareness and knowledge on the basis of available evidence to facilitate policy formulation, programme development and integrating environment component in the One Health approach to contain AMR.

Importance of environment in antimicrobial resistance

The emergence of resistance in any bacterium is a natural unstoppable genetic modification. Antimicrobials select out the resistant subpopulations which, in a conducive environment, become a dominating population. The emergence of resistance occurs at any site where there is an interaction between antimicrobials and pathogens. Apart from within the human and animal body or the high-pressure milieu of hospitals or animal care settings, these frequently take place in external environments, mainly water and soil. Humans, animals, agriculture and the environment are intertwined, and accordingly, the resistant pathogens or the genes that confer resistance freely move between various sectors that comprise One Health11. Environmental health, particularly water, sanitation and hygiene (WASH), food hygiene and safety and waste management are key components of One Health. These are needed to prevent the spread of microorganisms which are anti-microbial resistant particularly in developing countries in the broader interest of the global public health12.

Multiple pathways of spread of resistance in the environment are well known13,14. Studies from India have supported global knowledge on these pathways, wherein pharmaceutical industry effluents and sewage from various other agricultural, domestic and health facilities frequently contaminate the environment15,16.

The environment receives antimicrobial residues and pathogens, acts as a source for the same and provides an excellent milieu for antimicrobials and bacteria to interact to facilitate emergence and both horizontal and vertical transmission of genes conferring antimicrobial resistance. Contamination of the food chain allows the transport of resistant and difficult-to-treat pathogens to humans and animals9.

Dynamics of resistance in the environment

The environment has a continuous inflow of effluents from the pharmaceutical industry, sewage from human and animal healthcare facilities and agricultural and municipal waste13. These are rich in live pathogens, their genes and antibiotic residues as well as several metals. These move into available soil surface and water, which also provides a conducive milieu for the horizontal transfer of resistance coding genetic material, thus amplifying the quantum of resistance burden.

The magnitude of sources of effluents, sewage and large water and soil area available in India is significant (Table I). All these materials can find their way into vast length of rivers and 2.4 million water bodies21 with a capacity of 8.5 million ha. This is the wide spectrum of environment that plays a critical role in the genesis, spread and evolution of AMR (Figure). Waste, sewage and effluents rich in a variety of bacteria and antibiotic residues are generated on multiple and extensive sources with little information about efficient processing. Addressing such a spectrum is a huge challenge.

Table I.

Potential sources of environment contamination with antimicrobials and resistant genes in India

Sources of contamination	Estimated numbers
Number of pharmaceutical manufacturing units	10,50017
Number of healthcare facilities	69,00018
Municipal solid waste generated (/yr million metric tons)	6219
Rivers and canals (km)	191,00020
Number of livestock and poultry (billion)	11.3
Human population (billion)	1.4

Figure.

Dynamics of antimicrobial resistance in the environment.

Activities undertaken in India in the context of environment and antimicrobial resistance

India’s NAP (2017-2021)22 did articulate numerous environment-related activities, but these were essentially aspirational and somehow could not be implemented due to the COVID-19 pandemic and more importantly due to the belief that the evidence base linking the environment with AMR is inadequate in the Indian context. This reiterates the importance of the One Health approach to address AMR and undertaking research to generate evidence in the local context. The expertise available within India can be utilized to answer a variety of research questions as well as to develop/evaluate affordable and efficient interventions in the context of Indian context.

Environment-related activities in India’s National Action Plan on AMR (2017-2021)22 find mention in its all strategic priorities. Strategic priorities (1) called upon improved awareness and understanding of AMR through effective communication, education and training to raise awareness among all stakeholders, including policymakers, professionals and other stakeholders, including the general public; (2) advocated for surveillance to enable evidence-informed policymaking; (3) recommended infection prevention and control measures to reduce the spread of AMR and antimicrobials in the community and environment; (4) optimizing the use of antimicrobials in all sectors was recommended to minimize contamination of the environment through regulations and rational use of these agents; sustainable access to resources to contain AMR was recommended in strategic priority (5), while (6) referred to collaborative efforts at global, national and subnational levels to promote all activities that influence development and spread of resistance in pathogens. Stronger advocacy with appropriate legislative support and preparedness for environment-related activities remains the need of the hour. India was the only country to announce a draft law in 2019 for pharmaceutical manufacturing and AMR to limit the amount of antibiotics in waste released from pharmaceutical manufacturing plants into surrounding waterways. It is, however, yet to be fully promulgated23.

Advocacy and technical support from the global community

A quadripartite arrangement between FAO, WHO, WOAH and UNEP, through their Joint Action Plan24, has been collectively advocating and supporting the acceleration of national efforts in building capacity and undertaking actions that minimize the emergence and spread of resistant pathogens.

UN agencies, especially UNEP, have been undertaking global advocacy, awareness and evidence dissemination role. During the past five years, the United Nations Environment Assembly has advocated impact of climate change, biodiversity loss and pollution on AMR through its resolutions (UNEP/EA.3/R4: 201825 and UNEP/EA.5/R6: 202226) calling upon countries and UN agencies to accelerate activities on environmental aspects of AMR.

The UNEP commissioned research in 2019 through the ICMR-National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India, to enhance understanding of environmental dimensions of AMR in India15. The study recommendations included institutional as well as regulatory strengthening for improved effluent treatment and handling across sectors, environmental policies should include antibiotic management and guidelines from both manufacturing as well as antibiotic use perspective, provision for subsidy or incentives to farmers in order to encourage them to adopt alternatives to antibiotic growth promoters and finally enhanced participation of pharmaceutical companies towards adopting sustainable practices for antibiotic manufacturing. The UNEP has also developed guidelines and knowledge documents for possible adoption by the countries11 which India may adapt as it moves forward in containment of AMR through its NAP 2.022.

India can also learn from the standards being established by the pharmaceutical industry. The members of the AMR Industry Alliance have developed a unified approach for establishing discharge targets for antibiotic manufacturing, based on predicted no-effect concentrations (PNECs) for use in environmental risk assessments of antibiotics27. In addition, the European Food Safety Authority has recommended modalities for risk assessment of environmental contamination with AMR28.

Way forward for India for strengthening environmental component of antimicrobial resistance

The establishment of the National One Health Mission under the Principal Scientific Adviser to the Prime Minister augurs well for India. This mission will facilitate seamless intersectoral collaboration and national oversight.

During the past decade, India has created greater awareness on AMR, augmented capacity, especially in surveillance, antimicrobial stewardship programme and infection prevention and control and improved engagement of community and professionals. Prioritizing understanding and responding to AMR-related issues in the environmental sector and engaging major stakeholders from this sector are critical for a comprehensive response to the burgeoning problem of AMR.

Several components that should be discussed and considered for possible incorporation in proposed NAP 2.022 are suggested in Table II. Most of the activities mentioned in Table II conform to the strategic priorities as have been envisaged in India’s NAP (2017-2021)22 and the Global Action Plan on AMR (GAP)29. These can be incorporated and implemented seamlessly in NAP 2.022. The lead for environment-related activities in India must be taken by the Union Ministry of Environment, Forest and Climate Change. A comprehensive action plan with the active participation of all stakeholders, mainly State governments and existing related programmes, need be developed and funded. A high-power multisectoral committee can oversee the implementation of the action plan. The establishment of surveillance networks for both antimicrobial residues and resistant genes/pathogens through the engagement of several national institutes will provide evidence on the quantum of the problem and detect trends to assess the impact of the programme and to modify activities. Developing legislations and ensuring their effective enforcement through active engagement with the pharmaceutical industry, health facilities and veterinary institutions shall substantially reduce the inflow of resistance parameters into the environment. Finally, indigenous research to develop affordable tools to effectively treat effluents and sewage before their discharge into the environment must be encouraged and supported.

Table II.

Suggest activities for environmental sector in India’s National Action Plan 2.022

Strategic objective	Major activities
Governance and intersectoral coordination	•Mechanism to mainstream environment in the One Health-guided approach
	•Multisectoral technical working group for programmatic approach
	•Empowered national focal point for AMR in the environment
	•Legislation, regulation and enforcement to minimize source contamination
	•Harness national-specific expertise and related ongoing initiatives Namami Gange, Swachh Bharat, Kayakalp and Smart City.
Advocacy and awareness	•Engagement of policymakers and communities
National surveillance networks	•Mapping of resources and expertise in the environment sector
	•Capacity augmentation Collaboration with human and animal health networks
Best source contamination containment practices	•Mitigation contamination at source/origin Incentives to implement technology-driven interventions
Research: Ops and basic	•Understand the dynamics of resistance transfer in the environment
	•Innovations and low-cost technologies and interventions

AMR, antimicrobial resistance

A national consensus from policymakers, implementers and national technical experts within India shall facilitate priority implementation of these interventions and make significant contributions to national and global efforts in containing AMR.

Financial support and sponsorship

None.

Conflicts of interest

None.