Mapping the evidence for the risks of human exposure and transmission of AMR in the natural environment

Lead Research Organisation: University of Exeter
Department Name: Institute of Health Research

Abstract

Antimicrobials (such as antibacterial and antifungal medicines) are used to treat and prevent infections in humans and animals. Effective antimicrobial drugs are essential to modern medicine and to food production practices. However, the microorganisms that cause many common infections are developing the ability to survive and grow even in the presence of antimicrobials, particularly antibiotics. This antimicrobial resistance (AMR) leads to treatment failure, with consequent poor health outcomes and even death. There has been a rapid recognition both by national and international organisations that AMR is a critical emerging threat to our health and wellbeing. If current trends continue AMR infections could be the leading cause of death globally by 2050. Until recently, most attention has focused on the role that clinical settings, like hospitals, and agricultural settings, such as farms, play in contributing to the development and spread of AMR. But, as a large proportion of AMR infections are now known to be acquired in the community, and many resistance mechanisms to have evolved in environmental bacteria before spread to human pathogens, environmental sources are increasingly recognised as key.

However, the research that has been conducted about human health risks from environmental sources of AMR risk is disparate, covers a wide range of topic areas, and has not previously been brought together systematically. This study will establish what research has been undertaken to assess the role of the environment in AMR acquisition. It will use a research method called "systematic evidence mapping" to ensure that all the relevant research evidence is identified in a robust and non-biased way. The aim is to identify, categorise and describe the range of research evidence available. As well as written descriptions, a series of graphics and tables will be generated as a quick reference to how much research has addressed particular types of issues. This will allow us to see easily where there has been a lot of research and where there has been little or none. This "evidence gap" identification can show where research still needs to be done. We will work with stakeholders to prioritise which evidence gaps are most pressing to fill. Where there is already a body of research, this can in the future be brought together using full systematic review methodologies to form a better understanding of a topic area for policy and practitioners to make evidence based decisions.

Planned Impact

Through the focus on AMR, which is acknowledged as a key challenge nationally and internationally, we will identify where, across a range of policy areas, key actions may be needed in environmental policy to contain and reduce the human health risks from AMR in the environment. We will also help identify where more research is needed in an integrated manner across the processes involved in AMR as detailed in the DPSEEA model shown in Figure 1 of the Case for Support. Our ability to access an optimal stakeholder group through existing NERC funded Knowledge Exchange adds considerable value to this project because it facilitates our ability to include stakeholder input across the evidence mapping project - particularly in refining the final scope and identifying priority evidence gaps and gluts. The outputs of the evidence mapping project will be made available to all stakeholders and the wider community through the website being developed as part of existing knowledge exchange activity.

The desire and need for evidence by key stakeholders is demonstrated by the close working relationship between Gaze, Defra and EA. Both the KE Fellowship and JPIAMR network grant were written in response to demand from Defra/EA partners for information and evidence on AMR from an environmental perspective. The proposed evidence mapping exercise will consider evidence on human exposure, colonisation and infection from all environmental matrices (not just water) and will include a UK focused assessment of environmental AMR prevalence in environmental matrices that can be used in future human exposure risk assessments. The issue of AMR and environment has been prioritised by the United Nations Environment Programme (Gaze co-ordinating the UNEP report on AMR in the environment to be considered at the next UN Environment Assembly), the European Environment Agency (Gaze recently co-organised a meeting on AMR and environment at EEA headquarters in Copenhagen) and at EU level demonstrating the importance and timeliness of this proposal in contributing to understanding of what is undoubtedly a huge global issue.
 
Description Mapping the research evidence shows how people can be exposed to, infected and colonised by bacteria resistant to antibiotics from environmental sources.

Antimicrobial resistance is predicted to become the leading cause of death by 2050 with antibiotic resistance being an important component. Previous research has tended to focus on antimicrobial resistance in clinical settings like hospitals, and there is currently limited empirical evidence demonstrating whether humans are exposed to environmental antimicrobial resistance and whether this exposure can impact on human health.

We undertook two systematic evidence maps to explore:
1. What research evidence is there about exposure and transmission of antibiotic resistance bacteria to humans from the environment?
2. What research evidence is there measuring the prevalence of antibiotic resistance bacteria in the environment in the UK?

We mapped the geographical location of identified studies, and catalogued their dates and study designs. We also examined what had been researched in terms of people's exposure routes (such as inhalation, consumption, direct contact), the types of bacterial species investigated (such as e. coli, campylobacter, salmonella), and the environmental source examined (such as water, soil, food (eg wild meat, raw vegetables, food), air).

Map 1: What research evidence is there about exposure and transmission of bacteria resistant to antibiotics to humans from the environment?
40 studies were identified, mostly from Europe, from 2009 to 2020 assessing whether people had been exposed to, infected or colonised by antimicrobial resistant bacteria from environmental sources. These studies were from Europe, South East Asia, North America and Africa.
In Map 1, E. coli was the most highly studied bacterium (16 studies). Consumption/ingestion was the most commonly studied transmission route (30 studies), followed by direct contact (9 studies) and inhalation (7 studies). Research is focused on water sources, followed by wild meat or raw vegetable consumption. In terms of human health outcomes, most studies only looked at whether people had been exposed to, (17 studies) or colonised by (11 studies), antibiotic resistant bacteria. Fewer studies looked at direct human health impacts, with 16 assessing whether this led to infection, and impact on mortality researched by 2 studies.

Map 2: What research evidence is there measuring the prevalence of antibiotic resistant bacteria in the environment in the UK?
62 studies where identified from 2005 to 2020 measuring the prevalence of antimicrobial resistant bacteria in the UK environment.
For Map 2, mixed communities of bacteria were studied the most (32), with bacteria found in faeces (such as E. coli, Campylobacter) also frequently studied (27 studies). Phenotypic testing was the most common method (used in 37 studies). The most commonly reported outcome was characterisation of antibiotic resistant bacteria (40 studies), followed by characterisation of antibiotic resistance genes (35 studies). Most research was focused on environmental water sources.

Research on environmental antimicrobial resistance is a rapidly growing field and these maps identify and catalogue recent research that investigates this and its impacts on human health. This is relevant to various decision-makers both globally and in the UK.
The United Nations Environment Programme highlighted the environmental dimension of antimicrobial resistance as one of the most serious environmental pollution issues. Currently, however, environmental policy is often more focused on chemicals than microorganisms. To the best of our knowledge this map constitutes the first co-ordinated effort to collate data on the human impacts of antimicrobial resistance in the environment.
Policy-makers are able to search our maps to find evidence that may support or contradict current or planned initiatives to manage environmental antimicrobial resistance and/or public health.
Articles identified by these two maps evidencing transmission from the environment to humans may be used to support the need for surveillance and policy in this area to protect health. Likewise, this mapping exercise identifies topics where little evidence exists to underpin policy and management, where further research is necessary.


The paper has been accepted for Publication by Environmental Evidence (March 2022)
Exploitation Route Research on environmental antimicrobial resistance is a rapidly growing field and these maps identify and catalogue recent research that investigates this and its impacts on human health. This is relevant to various decision-makers both globally and in the UK.
The United Nations Environment Programme highlighted the environmental dimension of antimicrobial resistance as one of the most serious environmental pollution issues. Currently, however, environmental policy is often more focused on chemicals than microorganisms. To the best of our knowledge this map constitutes the first co-ordinated effort to collate data on the human impacts of antimicrobial resistance in the environment.
Policy-makers are able to search our maps to find evidence that may support or contradict current or planned initiatives to manage environmental antimicrobial resistance and/or public health.
Articles identified by these two maps evidencing transmission from the environment to humans may be used to support the need for surveillance and policy in this area to protect health. Likewise, this mapping exercise identifies topics where little evidence exists to underpin policy and management, where further research is necessary.
Sectors Agriculture, Food and Drink,Environment,Healthcare

 
Description The report has been forwarded to AMR leads at the Environment Agency and Defra.
First Year Of Impact 2022
Sector Environment
Impact Types Policy & public services

 
Description AMR evidence map discussed in an article by The Conversation 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact In an article in The Conversation 28/11/22, linked to the article from this project in a discussion of the risk of transmission of AMR to humans from environmental sources.
Year(s) Of Engagement Activity 2022
URL https://theconversation.com/superbugs-in-the-environment-rarely-transfer-to-humans-new-study-195075
 
Description AMR evidence map linked to by online BBC news article 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An online BBC news article 22/11/22 "Superbug fight 'needs farmers to reduce antibiotic use'" included a link to the article resulting from this project (https://environmentalevidencejournal.biomedcentral.com/articles/10.1186/s13750-022-00262-2) in relation to a quote from Professor Isabelle Durance, director of the Cardiff Water Research Institute, about faecal matter entering water bodies carrying drug-resistant bacteria and genes, and that could come from farming.
Year(s) Of Engagement Activity 2022
URL https://www.bbc.co.uk/news/science-environment-63666024
 
Description Presentation and workshop to consult about aspects of the AMT mapping reviews with stakeholders 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact As part of a larger meeting on AMR in the environment, a dedicated session on the evidnce maps was intriduced and feedback, consulttaion about the scope, sources of grey literature, outputs and dissemination was undertaken. Professionals from government agencies, water industry, and policy bodies were present.
Year(s) Of Engagement Activity 2019
 
Description Stakeholder consultation re the scope of the evidence maps 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact We met with an expert from the Environment Agency, and consulted virtually with others from DEFRA, SEPA, the Welsh government, relevant industrial partners (such as AstraZeneca) and Water Industry managers to ensure the scope of the maps is appropriate.
Year(s) Of Engagement Activity 2019