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
Antimicrobial resistance (AMR) is increasing worldwide, and surveillance activities play a key role in informing policies to contain AMR. Moreover, resistance to new antibiotics is emerging ever quicker after their introduction onto the market, rapidly reducing the effectiveness of even last-resort antibiotics.
As such, the sustainable introduction of a novel class antibiotic can only be achieved when accompanied by timely and informed surveillance and stewardship strategies. Affordable methodologies and tools to estimate the extent of national and local AMR are urgently needed to intelligently prioritise surveillance efforts, especially in low- and middle-income countries (LMICs).
Combining clinical, microbiological, epidemiological, and computational modelling expertise in one consortium, the project aims to satisfy that need through advanced data science and machine learning techniques at the global and (sub-)national scale, and multi-scale holistic dynamic network models at the local scale. Data and models resulting from the project will be disseminated to the benefit of various stakeholders, via their active participation in the project’s sounding board workshop, their involvement in our advisory board, the release of data and models in an international repository, and the initiation of integrating our modelling system in a web-based interactive platform.
Ultimately, our approaches aim to facilitate the sustainable potential future introduction of novel class and last-resort antimicrobial drugs. We illustrate this capacity in the specific case of Neisseria gonorrhoeae.
Filippo Castiglione, National Research Coucil of Italy, Italy (Coordinator)
Constance Schultsz, Amsterdam UMC, Faculty of Medicine, University of Amsterdam, Netherlands
Peteris Daugulis, Daugavpils University, Institute of Life Sciences and Technology, Latvia
Raquel Abad Torreblanca, Instituto de Salud Carlos III, Spain
Ramanan Laxminarayan, Center for Disease Dynamics, Economics & Policy, India
Pseudomonas aeruginosa causes severe infections in hospitalized patients. The worldwide emergence of carbapenem-resistant P. aeruginosa (CR-PA) makes infections by these pathogens almost untreatable. The World Health Organization now ranks CR-PA highest in the list of ‘urgent threats’.
Information for action to prevent further emergence has to come from insight into sources and transmission routes through smart surveillance. At present, a smart surveillance strategy is not available for CR-PA.
The aim of this project is to develop a globally-applicable smart surveillance strategy to guide action against the spread of CR-PA. Since P. aeruginosa prefers moist niches, we will focus on the human-water interface. First, highly-sensitive methods to detect CR-PA in specific environmental and human niches will be developed. Subsequently, CR-PA will be collected in three study sites with increasing prevalences of CR-PA, increasingly warmer climates, and different water situations: Rotterdam (The Netherlands), Rome (Italy), Jakarta (Indonesia). CR-PA will be searched for in a variety of niches in the environment outside and inside the hospital, and in healthy humans and hospitalized patients. Whole genome sequencing will be performed to compare the CR-PA from different sources and identify transmission routes.
Our project will provide insight into the relative contribution of the different potential reservoirs of CR-PA to its spread in different settings which will be used for the development of a globally-applicable surveillance strategy for CR-PA to guide preventive actions.
Juliëtte Severin, Erasmus MC University Medical Center, Netherlands (Coordinator)
Heike Schmitt, National Institute for Public Health and the Environment (RIVM), Netherlands
Anis Karuniawati, Universitas Indonesia, Indonesia
Bas van der Zaan, Deltares, Netherlands
Roger Levesque, University of Laval, Canada
Nicola Petrosillo, National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, Italy
OASIS aims to develop an antimicrobial resistance (AMR) surveillance strategy in a One Health context, and applicable in high-, middle-, and low-income countries. The proposed strategy challenges the strong reliance on laboratory-based AMR surveillance for meeting objectives of the Global Action Plan on AMR.
Laboratory-based AMR surveillance is hampered by selection bias and unrepresentativeness for local settings, precluding guidance on empirical treatment decisions in the human or veterinary domains. Population-based AMR surveillance is preferred but is time-, labour- and cost intensive due to large sample sizes required. OASIS moves from estimating AMR prevalence to classifying populations/settings as having a high/low AMR prevalence, by applying a Lot Quality Assurance Sampling approach, which requires much smaller sample sizes and is uniquely positioned for population-based AMR surveillance.
OASIS optimises the LQAS approach as a rapid, domain-, and setting-appropriate AMR surveillance strategy, within a One Health context that appreciates the close interplay of drivers of AMR emergence and transmission in human and livestock populations. Surveillance strategies that use a similar methodology to assess AMR prevalence in multiple domains are highly desired, strengthen the knowledge and evidence base on AMR, and optimise the use of antimicrobials in both human and animal health. Oasis’ implementation research component engages domain-specific stakeholders throughout the project to optimise knowledge utilisation, and facilitate the translation of results into policy.
Frank van Leth, Amsterdam Institute for Global Health and Development, Amsterdam UMC, Netherlands (Coordinator)
Hubert Ph. Endtz, Foundation Merieux, France
Christian Menge, Friedrich-Loeffler-Institut , Germany
Christa Ewers, Institute of Hygiene and Infectious Diseases of Animals, Justus Liebig University, Germany
Mounerou Salou, University of Lomé, Togo
Abdoul-Salam Ouedraogo, Higher National Institute of Health Sciences, Nazi Boni University, Burkina Faso