DRIVERS OF HUMAN EXPOSURE TO ANTIBACTERIAL RESISTANCE IN THE SRI LANKAN ENVIRONMENT

There is a growing evidence-base that the presence of antibacterials, other environmental pollutants and antibacterial resistance genes in the natural environment (i.e. wastewater systems, soils, surface waters and groundwaters) is indirectly affecting human and animal health and contributing to the global antibacterial resistance problem. The release of antibacterials, other selection pressures and resistance genes to the environment will occur from a number of sources including antibacterial manufacturing sites, hospitals and clinics, livestock facilities and from households. Once in the environment these contaminants may persist or dissipate and will be distributed around the different environmental compartments. Humans and animals can then be exposed to the antibacterial compounds and resistant organisms through: the breathing of dust; consumption of contaminated drinking water, plants, meat, fish and shellfish; through recreational and bathing activities; and via contact with wildlife. The level of exposure will be driven by a range of cultural, socio-economic, health and environmental drivers. In areas of Europe and N. America with highly regulated, centralised wastewater treatment and good quality water, the environmental exposure and occurrence of antibacterial compounds and resistance genes is likely to be controlled to some degree. However, the issue of antibacterial and antibiotic resistance pollution is likely to be much more acute in rapidly developing economies and areas with lower wastewater treatment connectivity. Given the increasing evidence-base for the occurrence of antibacterials and resistance genes in the natural environment on overall resistance levels, there is an urgent need to understand the contribution of the natural environment to the problem, and the drivers behind this, in low to middle income countries (LMICs).

In this project, we will bring together health practitioners, environmental scientists, microbiologists, modellers and social scientists to develop, parameterise and validate a spatial framework for modelling the occurrence of antibacterial substances and antibiotic resistance genes in the environment of Sri-Lanka and the subsequent exposure of the human populations to these. The framework will characterise the impacts of a range of drivers of occurrence and exposure including antibacterial manufacturing and use, land-use and the characteristics of the natural environment. By bringing this information together, we will be able to identify 'hotspots' of occurrence and exposure across the country which will allow future interventions to be targeted at scenarios and practices resulting in the highest risk of exposure. While in the project we will focus on the Sri Lankan situation, the knowledge, tools and processes developed in the project will be relevant to other LMICs.

The 8-month development phase project will combine data and literature review activities, workshops and stakeholder events to develop a conceptual model for AMR exposure in the environment of Sri Lanka and to establish the availability of data sets to parameterise the model. This phase of the project will therefore better define the work programme of the full project phase and identify the needs of key stakeholders with an interest in the problem of antibacterial resistance in Sri Lanka. A key component of the development phase will be the establishment of an interdisciplinary and intersectoral partnership comprising leading organisations from Sri Lanka, the UK and elsewhere.

In this project, we will develop, parameterise and validate a modelling framework to identify: the levels of exposure of the human population in Sri Lanka to antibacterial compounds and antibacterial resistance genes in the environment; and the health, socio-economic and environmental drivers resulting in the greatest levels of exposure. The work will be delivered using a combination of model development and parameterisation work; country-wide surveillance studies of antibacterial compounds (ACs) and antibacterial resistance genes (ARG); and ethnographical and anthropological studies. Initially, a spatially explicit model will be developed to estimate concentrations of ACs and levels of associated ARGs in different environmental media across Sri Lanka over time. Anthropological and ethnographic methods will characterise the way in which humans in the country will be exposed to ACs and ARGs in the environment. The information will be combined to develop a spatially explicit framework for estimating the level of exposure of different human sub-populations across Sri Lanka to the environmental resistome. Information on antibiotic use, land use, demographics and environmental characteristics will be used alongside data from surveillance studies for ACs and ARGs in order to parameterise and evaluate the framework. The exposure framework will then be applied to model exposure of the human population of Sri Lanka to ACs and ARGs in the environment to allow us to identify hotspots of exposure across the country and to establish which drivers are contributing the most to these exposures. This knowledge will be used to evaluate the scale of the problem and in a co-design approach, with key decision makers in Sri Lanka, to inform the design and selection of social, policy and technological interventions for minimising exposure of the citizens of the country to ARGs in the environment.

Results of our project will be beneficial to a range of stakeholders locally in Sri Lankan regions, nationally and internationally. Sectors that will benefit from the project include city and national authorities (e.g. Sri Lankan Ministries of Health and Agriculture and the National Water Supply and Drainage Board), the public health sector (e.g. hospitals and provincial health services), regulatory agencies responsible for the assessment of new and existing antibacterial substances (e.g. the European Medicines Agency), the pharmaceutical industry (e.g. large multinationals such as AstraZeneca through to smaller Sri Lankan companies), waste and wastewater treatment companies, research and scientific institutions (involved in environmental antibacterial resistance research), and society as a whole who will benefit from access to a cleaner and safer environment and food supply.

The impacts of the project will be wide ranging. The Sri Lankan (and other) public health sector, will be provided with the evidence on which they can make informed decisions regarding the importance of environmental exposure as a contributor to the problem of antibacterial resistance in the country. They will obtain the information that they need to identify scenarios and situations of highest risk which will allow them to develop mitigation measures for controlling exposure. The knowledge and tools developed during the project will allow the pharmaceutical industry to more holistically assess, and ensure, the environmental safety of their new and existing antibacterials in different geographical contexts. An understanding of the relationships between antimicrobial properties and impacts in the environment could also help the pharmaceutical industry develop 'benign-by-design' antibacterials in the future. Regulatory agencies (e.g. local Governments, Environment Agencies, Medicines Agencies etc.) will be better positioned to develop risk management guidelines for antibacterials and resistance genes that are scientifically robust, which will protect the environment while not inhibiting the introduction of new antibacterial substances. Researchers in Sri Lanka will benefit from access to and training in state-of-the-art methodologies for modelling environmental exposure to antibacterial compounds and resistance genes and chemical and microbiological techniques for surveillance of these in different environmental matrices and in food. Finally, the project aligns with the National Strategic Plan for Combating Antimicrobial Resistance in Sri Lanka 2017 - 2022 and will assist in delivery of the plan. In particular, the project will inform Strategy 1: 'To improve awareness and understanding of antimicrobial resistance through effective communication', Strategy 2: 'To strengthen the knowledge and evidence base through surveillance and research', and Strategy 3: 'To reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures'.