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the European Union

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2017 EFFORT Publications on AMR !

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EFFORT at ICAHS in New Zealand: Please Save the Date !

Date: Location: Rotorua, New Zealand

Workplan

EFFORT will establish a research programme to study the complex ecology of antimicrobial resistance and the complex interactions between bacterial communities, commensals and pathogens in animals, the food chain and the environment which reaches beyond previously conducted (international) research projects. This will be conducted by a combination of epidemiological and ecological studies using newly developed molecular and bio-informatics technologies. This will include an exposure assessment of humans from animal sources. The ecological studies on isolates will be verified by in vitro and in vivo studies. Moreover, real-life intervention studies will be conducted. Focus will be on predicting and limiting the future evolution and exposure to humans of the most clinically important resistance by synthesising different sources of information in our prediction models.

Knowledge production in EFFORT is structured into 8 interrelated scientific WPs and 2 WPs on knowledge translation. These WPs range from the broad scale of metagenomic-based research, to the epidemiology and ecology, and the public health and economic impact of antimicrobial resistance in the food chain.

The project is structured around a central data collection work package (WP1)  in which all data essential for the epidemiological, ecological as well as the microbiological samples for analysis of antimicrobial resistance are obtained during the first two years of the project. The complete DNA-extracts and the bacteria identified in this work package will subsequently be used in WP2 and WP3 for further microbiological analysis, including metagenomic analysis and identification and characterization of mobile genetic elements and resistance determinants, as well as their transfer properties. The integrated phenotypic, metagenomic and genetic data, together with the risk factor and management data obtained in WP1 will be used in three work packages: focusing on the eco-epidemiology of resistance (WP4), establishing potential links between usage and resistance (WP5) and proposing and analysing intervention studies (WP6). These analyses will include the metagenomic data with the complete antimicrobial resistance determinants present in the total samples. Using the output of these three workpackages, WP7 will assess the exposure to humans through multiple routes using stochastic modelling, while WP8 will integrate the data to determine the economic impact of antimicrobial resistance. Two additional WPs on knowledge translation (WP9) and project management (WP10) will assure the dissemination both inside and outside the consortium, proper exploitation, transfer, training and the administrative and financial management of the project.

The main objectives per WP are described below.

WP-1

Integrated evidence base for the food chain


WP leader: Dik Mevius – Central Veterinary Institute (CVI) – The Netherlands

  • Establish standardise, efficient data collection methods along diverse food chains and integration of evidence in an accessible format that facilitates further analysis and comparison across food systems (phenotypic resistance data, antimicrobial consumption data and relevant meta-data
  • Together with WP2, ensure common data collection formats and create a searchable web-accessible database for meta-, phenotypic and genotypic data.

Partners involved: CVI, UUVM, UCM, ANSES, ILZLT, VION, UGent, TIHO, DTU, NVRI, NDRVI, Intomics.

WP-2

Molecular approaches for determining the molecular ecology and epidemiology of antimicrobial resistance genes


WP leader: Frank Aerestrup – National Food Institute (DTU) – Denmark

Meta-genomic analysis will provide a complete quantitative determination of all known antimicrobial resistance genes present in a sample. With the considerable reduction in costs this has now become available for large scale studies. However, the technology needed is currently not available in all places and it is still not possible to foresee whether it will be routinely available in e.g. slaughterhouses. Thus, in the current project we have decided on a hierarchical analytic strategy, where comprehensive meta-genomic analysis on selected samples will form the basis for qualitative screening of a larger number of samples using arrays, and qPCR screening of a few selected resistance genes. The array and qPCR will be initiated based on the first meta-genomic analysis and adjusted during the course of the project.

The main objectives of WP2 are:

  • To sequence single isolates and whole bacterial communities collected in WP1.
  • To develop and disseminate a protocol for complete DNA sequencing of samples collected in WP1.
  • To establish a pipeline for data storage and rapid analysis of whole community sequencing data for qualitative and quantitative identification of antibiotic resistance genes and mobile elements.
  • To analyse the sequence data and quantify the occurrence of antibiotic resistance genes as well as their relationship to species distribution and transferable elements (plasmids, transposons).
  • To provide specific, relevant, representative and targeted data for all subsequent work packages.
  • To make the analytic tools and pipeline available for other users.
  • To perform classical (array, qPCR) molecular characterisation of antimicrobial resistance genes.

Partners involved: DTU, UUVM, CVI, BfR, UCM, NVRI, Intomics.

WP-3

Ecology and transfer of resistance mechanisms


WP leader: Bruno Gonzalez-Zorn – Universidad Complutense de Madrid - Spain

  • To identify and characterise of food-chain parameters that influence the rate of genetic exchange between bacteria, bacterial fitness and expression of antimicrobial resistance determinants.
  • To identify and characterise experimentally prevalent clones, mobile genetic elements and antimicrobial resistance genes present in the food chain in Europe, and assess their potential epidemic spread in human-adapted bacterial hosts.
  • To assess the stability, fitness, and propagation characteristics of the prevalent mobile genetic elements, and determine the conditions that limit their spread and propagation in the food chain.

Partners involved: UCM, UUVM, CVI, BfR, VION, ILSI

WP-4

Epidemiological analysis of antimicrobial resistance patterns in humans and the environment


WP leader: Dick Heederik – Utrecht University – The Netherlands

  • To create a database which contains all data regarding human and environmental resistance patterns as well as farm meta-data.
  • To describe antimicrobial resistance patterns in environmental samples, and analyse relations with determinants at the farm level in order to quantify transmission through the environment to humans through different potential routes (air and ingestion, direct contact with animals, food intake, home grown food intake).
  • To describe antimicrobial resistance patterns in human sentinel populations and analyse and quantify associations with resistance patterns in production animals, biosecurity and management characteristics of farms and slaughterhouses and environmental resistance patterns.
  • The relations obtained can be used to model exposure in the general population and exposure estimation and attribution as well as cost benefit analysis in the downstream WPs.  

 Partners involved: UUVM, CVI, UGent, DTU,  SAFOSO

WP-5

Relationship between farming practices, antimicrobial usage, animal health and resistance


WP leader: Jeroen Dewulf – Gent University - Belgium

  • To describe and quantify the management and biosecurity practices applied as well as animal health and welfare situation in all herds of WP1.
  • To quantify the antimicrobial consumption in all animal production systems included in WP1 as well as companion animals across Europe.
  • To analyse and quantify the relationship between biosecurity and management characteristics as well as animal health and welfare factors and the antimicrobial consumption.
  • To analyse and quantify the relationship between antimicrobial consumption and resistance prevalence at animal, herd, sector and country level.
  • To translate results from the metagenomic into a framework for future surveillance approaches.

Partners involved: UGent, UUVM, CVI, DTU, NVRI, SAFOSO

WP-6

Intervention studies aiming at reducing antimicrobial usage and resistance in pig and poultry production


WP leader: Pascal Sanders – Agence nationale de sécurité de l’alimentation, de l’environnement et du travail - France

  • To review the potential options for reduction of antimicrobial resistance in the food chain from the peer reviewed  literature and ‘grey’ literature
  • To develop practical, science based assessment decision support (ADS) tools for both poultry and pig farms which can be applied by practitioners in the field (veterinarians, agroscientists) to implement multi-level interventions on poultry and pig farms which lead to a) abolishment of the use of fluoroquinolones and cephalosporins, b) reduction antimicrobial treatments (either group or individual).
  • To implement these intervention strategies on poultry and pig farms in five  countries and  assess the quantitative and qualitative effect of interventions on antimicrobial usage, change in antimicrobial resistance after implementation of the interventions, animal health, animal welfare, and related economic aspects (with WP3 and WP8).

Partners involved: ANSES, VION, PorQ, ø-VET, Vetworks, BEC

WP-7

Quantification of exposure to antimicrobial resistance through different transmission routes from animals to humans


WP leader: Tine Hald – National Food Institute - Denmark

  • To develop a macro-ecological (global) model that estimates the relative importance of different food and animal transmission routes for human exposure to antimicrobial resistance (AMR) determinants in the overall population.
  • To estimate the relative importance of food, animal-contact and environmental sources of AMR determinants in humans with occupational exposure at farm and slaughterhouse level.
  • To integrate estimates for occupational exposure with the output of the global model.  To refine the global model by integrating estimated transference rates of AMR determinants from commensals to pathogenic microorganisms to estimate risk of infection through the major transmission routes.
  • To explore the effect of antimicrobial usage and specific interventions for human exposure to AMR determinants.

Partners involved: DTU, UUVM, SAFOSO

WP-8

Economic impact analysis


WP leader: Helmut Saatkamp – Wageningen University – The Netherlands

The objectives of WP8 are to improve current decision making of relevant authorities through providing relevant knowledge and information for decision support, particularly on:

  • The impact of AMR on health and welfare of the individual animal;
  • Analyses for various species (e.g. pig, poultry and veal calves) and for various individual levels of the production chain (e.g. farm, slaughterhouse) of the economic impact of specific measures aimed at reducing (1) the likelihood of emergence of AMR, (2) spread and transmission of AMR and (3) the exposure and impact of AMR; particular emphasis will be on impacts at the farm level;
  • Analyses for various species and for the whole production chain of strategies against AMR (i.e. packages of measures for various chain levels, various intensities, focused on reduction of emergence, spread and transmission and/or impact); focus will be on the economic impact as such, but particularly on trade-offs between different chain levels.

Partners involved: BEC, THIO

WP-9

Project dissemination and training


WP leader: Katharina Stärk – SAFOSO - Switzerland

  • Promote dissemination of the publicly available deliverables and results from the project to the key stakeholders: farmers, veterinarians, food industry, consumers, policy makers, scientists and the European Commission
  • Inform and generate interaction between relevant stakeholders and public policy-makers working on the field of livestock production, veterinary medicine and public health
  • Provide training for capacity building in the use of novel surveillance methods and approaches.

Partners involved: SAFOSO, ARTTIC, UUVM, DTU, ILSI, BEC

WP-10

Project management


WP leader: Jaap A. Wagenaar – Utrecht University – The Netherlands

The main objective is to set up an effective management framework for the EFFORT consortium to ensure progress of the project towards its planned objectives and respect of contractual commitments. The organisational structure, decision-making mechanisms and detailed project management activities are described in section 2.1 “Management structure and procedures”.

The specific objectives are:

  • To set up the management infrastructure: management bodies and special task forces, management procedures and tools, quality plan, risk registers, remote collaboration tools
  • To ensure strategic, financial and contractual management of the consortium, including maintenance of the Consortium Agreement
  • To ensure the day-to-day operational project management
  • To manage administrative issues related to ethical and IPR aspects of the project

Partners involved: UUVM, ARTTIC