Antimicrobial resistant microorganisms are difficult to treat and lead to increased death and treatment costs.
Antibiotic resistance is recognised as a critical threat in both human and animal medicine. Addressing this threat can be challenging when bacteria exist in complicated communities called biofilms. Biofilms form naturally and allow bacteria to survive and persist in diverse environments. Surviving bacteria facilitates the spread of antibiotic resistance genes contributing to the spread of antimicrobial resistance.
The COMBAT (COMplex Biofilms and AMR Transmission) project will identify interventions that can actually control complex biofilms in three different environments, thereby decreasing the threat of antimicrobial resistance spreading. COMBAT’s approach is based on solid novel laboratory-based biofilm study but also on the application of interventions in the domestic, healthcare and animal environments, providing a direct application to control real “One Health” antibiotic resistance problem.
Jean-Yves Maillard, Cardiff University, United Kingdom (Coordinator)
Dirk Bockmühl, Rhein-Waal-University of Applied Sciences, Germany
Mark Fielder, Kingston University London, United Kingdom
Noora Perkola, Finnish Environment Institute SYKE, Finland
Veljo Kisand, University of Tartu, Estonia
Seamus Fanning, University College Dublin, Ireland
Incorrect use of antibiotics is a major cause of antibiotic resistance. In rural Africa, people often receive antibiotics without prescription from local pharmacy shops, increasing the risk of resistance.
Substandard sanitation and hygiene practices result in frequent exchange of bacteria between humans’ guts, and their environment. How important these different sources are for the acquisition of antimicrobial resistant (AMR) bacteria in humans is still unclear, but contacts between humans and animals, in particular rodents, are frequent in much of Africa.
We will develop and evaluate a behavioural intervention for community pharmacy staff and their communities, to improve antibiotic use and hygiene practices, to ultimately reduce AMR. The intervention will be implemented over 12 months in Burkina Faso and DR Congo. We’ll measure as primary result changes in the use of specific AMR-prone and clinically vital antibiotics at community pharmacies throughout the intervention period. We will compare antibiotic use in pharmacies and surrounding communities where the intervention was implemented, and where the intervention did not take place. Also, we will assess changes in hygiene practices by surveying members of the surrounding communities. Then, we will determine how frequent AMR bacteria are transmitted by repeatedly analysing stool samples of those populations, and of rodents living in the surroundings, for bacteria and specific AMR genes. Through mathematical modelling we will quantify how changes in antibiotic use and hygiene practices will impact AMR transmission.
Marianne van der Sande, Institute of Tropical Medicine, Belgium (Coordinator)
Halidou Tinto, Institut de Recherche en Science de la Santé, Burkina Faso, Philippines
Delphin Phanzu Mavinga, Institut Médical Evangélique de Kimpese, The Democratic Republic Of The Congo
Edwin Wouters, University of Antwerp, Belgium
Tamara Giles-Vernick, Institut Pasteur, France
Stephen Baker, University of Cambridge, United Kingdom
Antimicrobials are drugs that help cure people and animals from infections with bacteria. The slogan: ‘the more you use, the faster you lose’ is definitely applicable for antimicrobials. When you use antimicrobials, more bacteria become resistant, meaning that an infection can no longer be treated. This is a worldwide challenge for the treatment of diseases in animals and humans.
The World Health Organization (WHO), like many other organizations, are advocating for reduction of use of antimicrobials when they are not needed. The COINCIDE-project explores what will happen when the use of colistin in animals is banned in Indonesia. Colistin is a specific antimicrobial that is used as last resort in humans if nothing else works, resistance against this antimicrobial means that resistant disease causing bacteria will have free reign.
In animals, colistin has been banned in 2020 and a group of human doctors, veterinarians, anthropologists and DNA researchers will look if less bacteria become resistant. We also want to reduce the colistin use in humans, as it is suspected to be used in humans without good reasons. We will work with farmers and their veterinarians, but also with people in the community and doctors and pharmacies to find out why they are still using colistin and if they can do without. The outcome of the project will help governments, farmers, veterinarians, human doctors, and everybody who really needs colistin, to safeguard this antimicrobial for use only when we cannot do without.
Anis Karuniawati, Universitas Indonesia, Indonesia (Coordinator)
Juliëtte Severin, Erasmus MC University Medical Center Rotterdam, Netherlands
Jaap Wagenaar, Utrecht University, Faculty of Veterinary Medicine, Netherlands
Sunandar Sunandar, Center for Indonesian Veterinary Analytical Studies, Indonesia
Herman Barkema, University of Calgary, Canada
Koen Peeters, Institute of Tropical Medicine, Belgium
Imron Suandy, Directorate of Veterinary Public Health, DG of Livestock and Animal Health Services, MoA-Indonesia, Indonesia
Appropriate methods for wastewater-based epidemiology (WBE) and a better understanding of the fate of pathogenic viruses and antibioticresistant bacteria from the sources to river basins and estuaries are urgently required.Ongoing project
Our project will determine the prevalence of pathogenic viruses (including SARS-CoV-2), microbial indicators, antibiotic resistance, and microbial source tracking (MST) markers in wastewater, surface water, coastal sea waters, sediment and bivalve molluscan shellfish (BMS) in catchments located in different climate areas (Sweden, Germany, France, Spain, Portugal, Israel, Mozambique, and Uganda).
The project aims are: (i) method harmonization and training of European and African partners, (ii) SARS-CoV-2 detection in raw wastewater as a biomarker of COVID-19 cases, (iii) enteric viruses, antibiotic resistances and MST markers monitoring in aquatic environments, (iv) evaluation of sediments and BMS as integral reservoirs, (v) determination of the impact of climate and extreme weather events, and (vi) microbial risk assessment for water resources.
Results and recommendations will be transferred to the scientific community by peer-reviewed papers and conference presentations. International health and environment organisations as well as authorities and waterworks that represent end-users on a global, European and African level will participate in the Stakeholder Forum.
Andreas Tiehm, DVGW-Technologiezentrum Wasser (TZW), Germany (Coordinator)
Edgar Mulogo, Mbarara University of Science and Technology (MUST), Uganda
Clemencio Nhantumbo, Eduardo Mondlane University (EMU), Moçambique
Timothy Vogel, Ecole Centrale de Lyon (ECL), France
Abidelfatah Nasser, Ministry of Health (PHLTA), Israel
Ricardo Santos, Universidade Lisboa, Instituto Superior Tecnico (IST), Portugal
Anicet Blanch, Universitat de Barcelona (UB), Spain
Magnus Simonsson, European Union Reference Laboratory for Foodborne Viruses, Swedish Food Agency (SFA), Sweden
Multiresistant bacteria are a severe problem to modern healthcare. The problem is increasing and development of novel technologies to cope with this critical situation is a necessity. Solutions include novel antibiotic drugs as well as reducing the spread of resistance genes in the environment.
Antimicrobial resistance is a worldwide problem, and many bacteria have now developed resistance towards even last-resort antibiotics. Despite significant attempts to limit this development more and more infections are identified as resistant to the treatment in hospitals. Much effort has been put into understanding the spread of resistance, and treatment thereof, within a hospital setting. It is only quite recently that an understanding that we need to also take in the environment, and development of resistance in such a setting in what now is called a One Health Approach has dawned.
Not only is the presence of resistance in hospitals important, but of equal importance is the presence of free antibiotics in nature, usage of antibiotics for food industry, handling of wastewater etc for the spread of antibiotic resistance. The wastewater treatment plants have been shown to be a hotspot for development of antibiotic resistance due to the high prevalence of bacteria and viruses there, as well as high levels of antibiotics. This will favor resistant bacteria, and exchange of resistance between microbes. A key player in this perspective are the bacterial viruses (bacteriophages) that can act as a transmission vehicle and transfer resistance between different bacteria. Our research aims at understanding the mechanisms underlying these transmission dynamics, and develop means to limit it.
The threat of AMR is rising in low and middle income countries (LMIC). The French Alliance of Health Sciences Research Institution (AVIESAN) has recently established a small network for AMR research in partnership with LMIC scientists to strengthen local research expertise. The aim is to assist in the collection of relevant evidence to advise stakeholders and policymakers on suitable control strategies for AMR reduction that are tailored to the local situation and founded on local problematics. Countries initially involved are Cambodia, Madagascar, Ivory Coast and France.
In this proposal, we intend to expand the network to integrate experts from Laos, Mauritius, Burkina Faso and Senegal, together with scientists from Belgium, Italy and the Netherlands. The intention is to reinforce the geographical distribution of the network (South-East Asia, Indian Ocean and Africa, linked with Europe), strengthen its coherence, and enrich the collaboration. The proposed multidisciplinary Network+ will develop two multicentre research projects intending to identify key determinants of AMR emergence and dissemination. It will be operated as a dynamic collaborative and synergistic process: after an initial workshop in which participants will prepare a detailed outline of the wo research projects, the protocols will be fully developed with clear indication of respective tasks and responsibilities, and piloted for feasibility. A second workshop will take place to gather progress and results, and final protocols submitted for funding. Partners will prepare for the implementation of the research protocols, with supporting best practice activities.
This Network will contribute to the collection of a large dataset that will enrich AMR knowledge, and assist in implementation of efficient strategies for AMR control in LMICs. Contents and expected deliverables of the projects will be described in Communication Notes to be placed on JPIAMR-VRI.
Christian Lienhardt, Institut de Recherche pour le Developpement, France (Coordinator)
An integrated approach to surveillance spanning different sectors has been promoted by international organisations for more than a decade and constitutes a central recommendation of the WHO action plan on AMR. The objective of the CoEval-AMR Network is to develop consolidated guidance for evaluation that addresses the specific needs of integrated One Health surveillance systems for AMR and AMU.
Activities targeted for this proposal called “Co-Eval-AMR PHASE 2” include the development of methods and metrics for the evaluation of governance and impacts of One Health surveillance, and their application to selected country-based case studies. Two scientific workshops will be held to build on researchers’ experience and expertise, and consolidated guidance will be developed and made publicly available through the existing online websites. Results will allow for a better understanding of the added value of integrated surveillance for AMR, and to compare integrated surveillance governance strategies across countries in order to identify the most effective and efficient approaches.
Cécile Aenishaenslin, Université de Montréal, Canada (Coordinator)
The impact of antimicrobial resistance (AMR) is an almost invisible enemy, which slowly, but steadily has impacted society as a whole. Multi-, and/or pan-drug resistant strains have emerged, and have been spreading readily, causing deaths, disabilities and economic losses.
Like for viruses, emergence of successful clones could further aggravate the immense impact of AMR on the global economy, especially if there is an outbreak of multi- or pan-resistant infections. As AMR has been rising slowly, little data has been available about its impact, especially for low- and middle income countries, and especially with regards to economic costs. Understanding how AMR currently affects health care expenditure and economic productivity in health care and agriculture, and how it is likely to do so in times of greater transmission in the future, are key to being able to making informed decision-making with regards to public health interventions, including economically-sound decisions such as surrounding the relative cost-effectiveness of interventions.
To address the complex issue of building the cost picture associated with AMR, we have a three-step roadmap. In the first step, a cost framework completed by the GAP-ON€ network, funded under the 2018 Network Call. Also, GAP-ON€ also identified and contacted a list of 102 key stakeholders. The second step is to gather a smaller group of critical experts from all the One Health areas to co-write a much larger proposal detailing relevant data sources, data gaps, applicable methodologies, and their interconnectedness. The third step will be the actual cost study that needs to be undertaken to gauge the real cost magnitude associated with AMR. Such a major undertaking will require careful planning, and sufficient resources to carry out and coordinate.
We plan to hold one F2F meeting amongst key experts to develop these study structures, map out potential funding sources, and write a coherent project proposal worthy of funding.
Luigia Scudeller, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano Foundation, Italy (Coordinator)
Main Questions/Approach: How can we best identify and promote collaboration and implementation between AMR NGS stakeholders that link the individual fields of (new) NGS technologies, algorithms, quality standards, teaching/training and sequence databanks?
Answer – By establishing an international and interdisciplinary OneHealth network of public and private experts to take the lead in identifying potential knowledge gaps and solutions. Further, by developing AMR NGS-dedicated quality and teaching/training materials. Finally, by promoting discussion and interactions between AMR NGS stakeholders and other working groups with cross-cutting priorities – including extensive use of JPIAMR VRI.
Promote active collaboration between interdisciplinary OneHealth AMR NGS stakeholders
Identify knowledge gaps and provide solutions to current/future AMR NGS issues
Formulate recommendations on quality and quality materials
Educate AMR NGS stakeholders via interdisciplinary-directed AMR NGS teaching/training materials
Dedicated website and access to network materials
Face-to-face network meetings and regular teleconferences (in collaboration with other relevant JPIAMR working groups)
Open access publications and collation of a Seq4AMR Strategic Roadmap
Dedicated interdisciplinary Seq4AMR webinar(s) and course(s)
Dedicated Seq4AMR workshop at a relevant international meeting
Promotion of Seq4AMR and JPIAMR during conferences.
Establish new OneHealth AMR synergies between international and interdisciplinary experts for knowledge exchange, joint publications grant writing etc.
Identify current knowledge gaps and how to best fill these gaps
Formulate quality recommendations and access to materials
Develop new interdisciplinary AMR teaching/training/ materials
To publish a Seq4AMR Strategic Roadmap
To contribute and strengthen the activities of JPIAMR VRI
John Hays, Erasmus MC University Medical Center, Netherlands (Coordinator)
A. Stubbs, Erasmus MC University Medical Center, Netherlands
A. Heikema, Erasmus MC University Medical Center, Netherlands
A. van Belkum, BioMérieu France, Craponne, France
W. A. Valdivia, Orion Integrated Biosciences (OIB), Kansas, USA
Liping Ma, East China Normal University, Shanghai, China
E. Kristiansson, University of Gothenburg, Gothenburg, Sweden
S. Bruchmann, Cambridge University, Cambridge, UK
A. McArthur, McMaster University, Hamilton, Canada (CARD Database)
S. Emler, SmartGene GmbH, Lausanne, Switzerland
E. Claas, Leiden University Hospital, Leiden, the Netherlands
S. Beisken, Ares Genetics GmbH, Vienna, Austria
R. Stabler, London School for Hygiene and Tropical Medicine, London, UK
A. Lebrand, Swiss Institute of Bioinformatics, Lausanne, Switzerland
M. Petrillo, European Commission, Joint Research Centre (JRC), Ispra, Italy
S. Capella-Gutierrez, Barcelona Supercomputing Centre (BSC), Barcelona, Spain
L. Portell, Barcelona Supercomputing Centre (BSC), Barcelona, Spain
B. Grüning, Freiburg Galaxy Team, Freiburg, Germany
G. Cuccuru, Freiburg Galaxy Team, Freiburg, Germany
C. Carrillo, Canadian Food Inspection Agency, Ottawa, Canada
B. Blais, Canadian Food Inspection Agency, Ottawa, Canada
B. Gruening, University of Freiburg, Freiburg, Germany
W. Meier, University of Freiburg, Freiburg, Germany
B. Batut, University of Freiburg, Freiburg, Germany
K. Vanneste, Sciensano, Brussels, Belgium
J. Bengtsson-Palme, University of Gothenburg, Gothenburg, Sweden
T. Naas, Hopital de Bicêtre, Paris, France
N. Strepis, Erasmus University Medical Centre (Erasmus MC), the Netherlands
A. Rhod Larsen, Statens Serum Institut, Copenhagen, Denmark
B. Helwigh, National Food Institute, Lyngby, Denmark
H. Hasman, National Food Institute, Lyngby, Denmark
R. Hendriksen, National Food Institute, Lyngby, Denmark
S. Forslund, Max Delbrück Center for Molecular Medicine, Berlin, Germany
L. Pedro Coelho, Institute of Science and Technology, Fudan University, Shanghai, China
A. Patak, Molecular Biology and Genomics Unit, Institute for Health and Consumer Protection, Ispra, Italy
M. Querci, Deputy Head of Unit, Joint Research Centre European Commission, Brussels, Belgium
G. van den Eede, Head of Unit, Health, Consumer and Reference Materials, European Union, Brussels, Belgium
There is a growing recognition that interventions within the healthcare sector are not enough to curb antibiotic resistance development. Instead, a one-health perspective incorporating animal husbandry and external environments is needed. This calls for monitoring antibiotic resistance outside of the healthcare setting.
Unfortunately, antimicrobial resistance monitoring lacks comprehensive reference data for the vast majority of environments. Therefore, there is little knowledge on the range of background abundance and prevalence of antibiotic resistance genes (ARGs) occurring naturally. Furthermore, the few milieus where reference data exist are biased towards a small number of environments and there is no standardized methodology or any well-defined set of relevant ARGs that routinely are tested for monitoring purposes. This project will solve or alleviate these problems by integrating several approaches under one umbrella framework.
We will 1) establish baseline ranges for background ARG abundances and diversity in different environments, 2) standardize different methods for monitoring ARGs and provide a means for making them comparable, 3) identify sets of priority target ARGs for monitoring, 4) develop methods to detect emerging resistance threats and thereby provide an early-warning system for resistance, and 5) suggest a monitoring scheme that can be used in a modular fashion depending on the available resources. Establishing a coherent monitoring scheme is imperative for efficient monitoring, which in turn is essential for limiting future resistance development.
Johan Bengtsson-Palme, University of Gothenburg, Sweden (Coordinator)
Thomas U Berendonk, Technische Universität Dresden, Germany
Etienne Ruppé, INSERM, France
Sofia Forslund, Max-Delbrück-Centrum für Molekulare Medizin, Germany