A systems understanding of the flow of Antimicrobial Resistance from livestock production to the environment and humans: informing antimicrobial stewardship and optimal use
Project Lead
Challenges
Antimicrobial resistance (AMR) is a major global concern to human health. AMR occurs when microbes become resistant to clinical or veterinary drugs used to treat disease. AMR has major consequences on how to manage microbial diseases and the use of antimicrobial compounds.
The UK’s National Action Plan to tackle AMR details a One Health approach to “Better understand how AMR spreads between and among humans, animals and the environment.” The action plan recognises the lack of knowledge about AMR in the environment, including:
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The relative importance of different sources
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Transmission pathways of AMR between animals and the environment
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The risks and effects for people, animals, food, and ecosystems
In 2017, the Codex Alimentarius Commission agreed to extend and expand its code of practice for food chain actors on minimising and containing AMR. The Commission set up an ad-hoc Intergovernmental Task Force on AMR. The Task Force aims to develop science-based guidance on managing foodborne AMR. Alongside strong antimicrobial stewardship, the Task Force recommended more evidence on the links between animal health and welfare, productivity, drug usage and resistance.
Bovine Respiratory Disease (BRD) is a major challenge for cattle production, and it continues to cause serious economic losses for producers. BRD control is a major target of antimicrobial usage and an important source of AMR pathogens.
However, little is known about:
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Prevalence of AMR for the main BRD pathogens in the Scottish cattle industry
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The resistome (collection of antimicrobial resistance genes) in the respiratory tract
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The link between AMR levels and dissemination of strain(s) carrying integrative and conjugative elements (ICEs), which are associated with multidrug resistance.
To achieve global knowledge of AMR in the Scottish context an understanding of the relationships of antimicrobial use and spread of AMR is required.
Questions
- What approaches and strategies can combat zoonoses and emerging diseases to protect public health, animal health and antimicrobial resistance in Scotland?
Solutions
Antimicrobials are often the last line of defence in protecting animal health and maintaining animal welfare standards. This project is providing a deeper understanding of the consequences of antimicrobial use in livestock production to extend the useful lifespan of individual antimicrobials and reduce risk to public health and the wider environment.
Quantifying the AMR gene profiles of livestock and linked environments
We are characterising and quantifying the AMR gene profiles of co-located pig and beef production units and their environments (soil, wildlife, farm workers, and water courses) using a bottom-up system approach that uses the Easter Howgate farm as a worked example. This activity compares the AMR gene carriage of the microbiomes and E. coli isolates (AMR gene presence, richness, diversity, and phenotypic resistance). Escherichia coli is a commensal bacterium present in the gastro-intestinal tract of humans and animals. This bacterium is considered a non-pathogenic indicator of AMR as it is naturally susceptible to almost all relevant antimicrobial agents, and is inherently able to accumulate resistance genes, including transferred from other bacteria. These AMR gene profiles complement the AMR gene counts quantified in a complementary project.
Analysing the Relationships between antimicrobial use at a population level and phenotypic AMR in Scottish livestock
Food Standards Scotland (FSS) and SRUC Veterinary services monitor resistance in E. coli cultured from cattle, sheep, pigs and poultry presenting at Scottish abattoirs for slaughter (i.e., healthy animals). The E. coli isolates are tested against a panel of antimicrobials relevant to human risk, rather than veterinary practice. The reporting of the AMR test results lacks contextual information, like farm of origin or location. We are performing a descriptive analysis of the 2017-2021 national AMR data, focusing on when and where AMR has spread for pigs, sheep, cattle, and poultry. The analysis of the historic data along with the isolates collected in research elsewhere is a necessary step to study the links between the resistance patterns found and the establishment of monitoring or control plans to minimize the threat of AMR in areas or farms at risk. The analysis also places the AMR of E. coli from the pig and cattle units into a national context.
Livestock systems involve various levels of production strata (animal, group, herd). The level in which the greatest variation in AMR is found provides an indication of the factors that determine AMR in livestock systems. We are quantifying the variation in AMR across the different strata to provide an indication of what are the most important factors within the livestock system that affect AMR. Guidance on how to reduce the circulation and survival of AMR organisms by isolating animals likely to have AMR depends on estimating both the decay rate of AMR in treated animals and the transmission rate between animals in a group. We are also estimating both these parameters that describe the dynamics of AMR within a group of animals. This helps to provide policy advice to stakeholders on any effects of isolating animals that have been treated with antimicrobials to optimise their use whilst minimising the risk of AMR transfer.
Antimicrobial resistance in bovine respiratory pathogens
This activity addresses key knowledge gaps by evaluating the presence of AMR genes and integrative and conjugative elements (ICEs) associated with multidrug resistance. The presence of ICEs harbouring AMR may be significant for the effectiveness of drug therapies for the control of BRD in cattle. We are developing new diagnostic strategies for the BRD pathogens and adequate measures to mitigate the use of antimicrobial agents.
Overall, this project is providing a robust evidence base for antimicrobial stewardship and optimal use in livestock production. Understanding the consequences of antimicrobial use in livestock production will inform optimal use strategies that extend the useful lifespan of individual antimicrobials and reduce risk to humans and the wider environment.
Project Partners
Progress
Objective 1 (Characterisation of the genetic and phenotypic AMR profile of a multi-species livestock farming system and linked environments): There are several aims for this objective; the first is to determine the AMR gene carriage of bacteria from a livestock (pig and cattle) source to the wider environment. This aim is based upon an ongoing longitudinal study of which the first year of sampling is complete. The remaining aims will commence in later years of the project and include: i) determining the change in genetic and phenotypic AMR profiles of the faecal microbiome and E. coli isolates in pigs given antimicrobials, ii) determining the change in AMR profiles of soil following livestock slurry application, iii) determining the AMR gene profiles of plants grown in contaminated soils and finally iv) determining the potential for livestock production units to act as a point source of AMR gene pollution, and its diffusion to linked biological systems and the wider environment.
Objective 2 (Investigate the relationship between antimicrobial use at a population level and phenotypic AMR in Scottish livestock): This objective consists of two sections; the first uses a Food Standards Scotland national dataset on phenotypic AMR across livestock species. The first aim for this section is to describe and contrast the 2017 to 2021 phenotypic AMR of E. coli in pigs, cattle and poultry across Scotland. This has been completed for the pig dataset, the results of which has been reported to and discussed with Food Standards Scotland. Analysis of the remaining datasets are ongoing. The remaining aims for this section (which will be addressed in later years of the study) are i) characterising associations between phenotypic AMR of E. coli and antimicrobial use data for pigs, cattle, sheep and poultry across Scotland, ii) characterising emerging spatial and temporal patterns of phenotypic AMR in Years 1 to 4 of the project in comparison with the 2017 to 2021 data. iii) characterising the human and animal implications of this section's results, focusing on the historic and developing AMR trends in Scotland. The second section of this Objective uses a population study of dairy farms to characterise the relationship between levels of antimicrobial use and levels of antimicrobial resistance. There are two aims for this section; i) to quantify the variation in AMR across animal grouping strata within dairy production systems and to ii) estimate the decay rate of AMR in dairy animals. Investigation of these two aims are still ongoing.
Objective 3 (Characterisation of the AMR carriage of bovine respiratory microbiomes, and bovine respiratory disease pathogens): This Objective consists of two aims; with the first being improving the understanding of zoonotic BRD diseases present in Scotland. This aspect is ongoing with the first year's sampling complete. The second aim is the assessment of the transmissibility of AMR genes present in livestock respiratory strains of bacterial infections currently affecting Scottish livestock and is due to commence in later years of the project.
In year 2 of the project, we have made progress towards achieving the objectives and the respective Work Packages (WP):
WP1 aims to provide a detailed characterisation of the genetic and phenotypic AMR profile of a multi-species livestock farming system and linked environments. In year 2, we have continued with longitudinal environmental and livestock sampling of livestock units and linked agricultural environments to ascertain the potential of shared AMR gene carriage across livestock units and the surrounding environments. Initial findings from the year 1 sampling indicate that a wide variety of AMR genes have been detected in all sample types and there is AMR gene overlap between sample types. This longitudinal sampling will continue in years 3 and 4, providing a better understanding of how AMR spreads between animals and the environment. Year 2 also saw the commencement of a study to investigate AMR gene dynamics throughout the pig production cycle in relation to antimicrobial use on two farms with varying antimicrobial input. The sampling for this objective is complete and analysis of the samples will continue in year 3.
WP2 investigates the relationship between antimicrobial use at a population level and phenotypic AMR in Scottish livestock. There are two sub-projects for WP2. The first sub-project uses a Food Standards Scotland national dataset on phenotypic AMR across livestock species (pigs, cattle and poultry) in order to describe and contrast phenotypic AMR data of E.coli. In year 2, this has been completed for the sheep data sets, the results of which being reported and discussed with Food Standards Scotland. The second sub-project uses a population study of dairy farms to characterise the relationship between levels of antimicrobial use and levels of antimicrobial resistance. There are two objectives for this sub-project: to quantify the variation in AMR across animal grouping strata within dairy production systems and to estimate the decay rate of AMR in dairy animals. During year 2, sample collection for these objectives has been completed and lab analysis has begun.
WP3 focuses on Bovine Respiratory Disease (BRD), which is a major disease in the dairy and beef industries, and aims to assess the existence of AMR genes and integrative and conjugative elements (ICEs) linked to multidrug resistance. This involves conducting whole-genome sequencing (WGS) analysis on lung samples sourced from various origins. We have successfully met the Year 2 objective for this Work Package of collecting replicates samples from each lung of animals with respiratory symptoms. These surveillance samples (n = 189) were added to Year 1 sample collection.
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