A Horizon 2020 project entiteld: “Data-driven control and prioritisation of non-EU-regulated contagious animal diseases (DECIDE)” with19 partners from 11 countries coordinated by Gerdien van Schaik. The main goal of the DECIDE project is to develop data-driven decision support tools and workflows with which farmers and veterinarians can make informed decisions for the control of endemic contagious diseases in calves, broilers, piglets and salmon. These decisions take into account the presence of the infection, the direct production losses, the impact on welfare and the costs and benefits of any treatment. The DECIDE consortium consists of experts from different disciplines and sectors, namely veterinary epidemiology and diagnostics, social sciences, economics, animal welfare, information technology, artificial intelligence, data sciences, and mechanistic and predictive modelling.

• prof. dr. M. (Mirjam) Nielen
• prof. dr. J.J. (Sjaak) de Wit
• dr. ir. W. (Wilma) Steeneveld
• prof. dr. ir. G. (Gerdien) van Schaik
• Y. (Yara) Slegers

https://www.uu.nl/en/organisation/faculty-of-veterinary-medicine/veterinary-research/partnerships/netherlands-centre-for-one-health-ncoh/fighting-covid-19-in-animals-and-humans

• prof. dr. H.S. (Hans) Kooistra
• prof. dr. J.A. (Jaap) Wagenaar
• drs. W.J.R. (Ruth) van der Leij
• drs. M.M. (Marleen) Kannekens-Jager
• dr. H.F. (Herman) Egberink
• dr. E.M. (Els) Broens
• prof. dr. Merel Langelaar

• NCOH
• WUR
• Erasmus MC
• WBVR

Sustainable control of antimicrobial resistance (AMR) requires a One Health approach, because humans and animals can exchange bacteria and genetic mobile elements encoding for AMR. Responsible use of antimicrobials in animals is essential, but AMR genes may also spread in the absence of selection pressure. Thus, AMR surveillance has been implemented to evaluate AMR trends in animal populations. Current surveillance programs are, however, not fit for early detection of newly emerging AMR. The latter is important in case of resistance to antimicrobials of critical importance to humans. When only a few farms are positive at the time of first detection, measures like quarantine or culling could be implemented to minimize exposure of humans. In case many farms are affected at first detection, implementation of such measures is not feasible. 

Methicilin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant enterococci (VRE) and Extended Spectrum Beta-Lactamase Enterobacteriaceae (ESBL) are all examples of AMR’s with a large impact on human health that emerged in animal populations in the Netherlands and many other countries and that were already wide spread at the time of detection. The goal of BEWARE is to develop a blueprint for detecting emerging AMR in livestock when the number of affected farms is still low. This early warning blueprint is unique, because it takes account of the most likely routes of introduction, the transmission of AMR between animals and between farms and the diagnostic quality of the assay used. Although the blueprint will be applicable to all AMR’s and animal sectors, BEWARE will focus on carbapenemase producing Enterobacteriaceae (CPE) in veal calves, pigs and broilers. These are the most relevant livestock sectors regarding AMR and CPE emerging in animals is of critical importance in human health care. Specific goals are: 1) identify AMR introduction routes, their association with human behavior, and rank them according to their importance; 2) calculate transmission parameters for AMR-carrying bacteria within and between animal populations; 3) develop a sensitive and specific assay for early detection of CP-genes; and 4) generate a dynamic mathematical model to integrate the results to predict the numbers of affected farms at first detection as function of the selected sampling strategy. 

Developing such an early warning blueprint requires an interdisciplinary project subdivided in 4 work packages (WP). In WP1 AMR introduction routes will be identified, including their association with human behavior, and combined into a risk model of AMR introduction into the livestock populations that allows to rank the sites of possible introduction according to their relevance. The model will include both national and international routes of introduction and information will be collected from literature, available databases and by expert elicitation. 

In WP2 transmission of AMR carrying bacteria within and between populations determines the speed of AMR emergence. Parameters for AMR transmission in veal calf, broiler and pig farms will be estimated from available data sets, assuming transmission of emerging CPE carrying bacteria is like transmission of ESBL carrying Enterobacteriaceae. We will test this assumption in vivo in broilers. The network of animal movements between farms will be created from data available to the research consortium. 

In WP3 an assay for sensitive and specific metagenomics detection of CPE will be made. Following enrichment, DNA will be isolated and used for RT-PCR and for targeted metagenomics. Furthermore, we will perform a second enrichment step using the ResCap platform and samples will be sequenced using Illumina and Nanopore sequencing. Finally, test quality parameters will be estimated. 

In WP4 an early detection surveillance framework will be developed using a dynamic mathematical model. The framework will consist of three parts that integrate the results of WP 1-3: introduction of AMR genes/plasmids in the livestock population, transmission between animals and between farms, and detection. Using the fully parameterized framework, the sensitivity and specificity of early warning is evaluated. By varying the sampling strategy (i.e. frequency and sample size) the effects on the performance of the early detection system are studied. The blueprint can be easily adapted to other types of emerging AMR, provided their transmission and test quality parameters are available. The flexibility of the model regarding selected sampling strategy will enable policy makers to develop an AMR early warning program according their needs.

• dr. N. (Natcha) Dankittipong
• prof. dr. J.A. (Jaap) Wagenaar
• dr. A.L. (Aldert) Zomer

• Jantien Backer (RIVM)
• Alex Bossers (WUR)
• Clazien de Vos (WUR)
• Manon Swanenburg (WUR)

Since the 1950s, antimicrobials have been increasingly used in modern intensive livestock production systems. Besides preventive and therapeutic use, antimicrobials were used as growth promoters in the European Union (EU) until their ban in 2006. This was preceded by decades of growing evidence and concerns about the public health impact of widespread veterinary antimicrobial use (AMU) and associated increasing antimicrobial resistance (AMR). As AMU in livestock favors AMR development in bacterial populations as it does in humans, the public health risks of veterinary AMU are threefold: 1) resistant bacteria can pass onto humans via direct contact with animals; 2) these bacteria can pass on via food of either animal origin or cross-contaminated during production; 3) these bacteria can spread into the environment via farm runoff or unprocessed manure used as fertilizer. Moreover, large volumes of antimicrobial residues in manure cause further environmental exposure and potential selective pressure. In 2007, the Netherlands was the largest veterinary antimicrobial consumer per biomass unit of animal production among 10 EU countries. Together with the discovery of large reservoirs of methicillin-resistant S. aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria in Dutch livestock, this led to considerable socio-political pressure, with the government imposing 20%, 50% and 70% AMU reductions in livestock in 2011, 2013 and 2015, respectively. After an initial rapid AMU reduction (56% in 2013), mostly attributable to replacing group treatments, adopting herd health and treatment plans, guidelines, benchmarking systems and transparency in prescriptions, a 58% AMU reduction was reported in 2015, indicating that a 70% of higher AMU reduction would require more fundamental changes in the livestock production systems rather than in prescribing procedures alone. Indeed some structural differences in AMU still exist between Dutch livestock farms and overall AMU remains high in a subset of them, mainly because of the highly intensive nature of the Dutch farming industry. Moreover, in recent years AMU reduction has levelled off despite further reduction is sought after, particularly in broilers, weaned piglets and veal calves, whose groups now account for most AMU in Dutch livestock. An important counter argument is the increased economic burden placed on the farmers and eventually on the consumers through further restriction to veterinary AMU when this is needed for therapeutic purposes. A rise in livestock production costs would be unbearable in the highly competitive international agricultural market wherein the Dutch livestock industry relies heavily on exports. Providing the right conditions for incentivizing further AMU reduction in Dutch livestock requires an assessment of the potential impact on AMU and associated (negative or positive) financial effects of the available interventions aiming at keeping livestock healthy, on the principle that every infection prevented is an opportunity for no treatment. Policy makers and livestock producers would then be able to consider supporting the implementation of a specific intervention instead of another based their cost-effectiveness. These interventions include: (i) infection control (i.e. enhanced farm biosecurity and hygiene standards), (ii) animal husbandry practices (i.e. enhanced farm management, e.g. low-stock density farming, all-in/all-out production systems, rearing of slow-growing breeds, etc.), (iii) vaccination (for bacterial diseases, but also viral diseases often complicated by secondary bacterial infections). Indeed, there is still no quantitative evidence for the impact of these interventions on AMU, and even less evidence for their sustainability. Consequently, comprehensive recommendations to farmers about which interventions are most cost-effective and would best suit their specific situations in relation to the public health needs remain rather vague (e.g. as general statements like ‘increased vaccination’ or ‘improved biosecurity’) or are based on individual veterinarians’ personal experience and opinion. As a collaboration of two leading institutions in animal and public health in the Netherlands (Veterinary Medicine Faculty of Utrecht University and the RIVM) and using both existing and newly collected data, we will quantify in a scenario-based modelling framework the impact of different biosecurity/hygiene standards, vaccination schemes and husbandry practices on AMU reduction (overall and for specific antimicrobials) in broilers, weaned piglets and veal calves, including their cost-effectiveness. Determining the impact and feasibility of these interventions will provide livestock producers and policy makers with a management tool to set targets and draw plans for the implementation of those interventions with the highest potential for AMU reduction, and so decreasing AMR in a rational and sustainable way.

• prof. dr. J.A. (Jaap) Wagenaar
• P. (Panagiotis) Mallioris
• dr. L. (Lapo) Mughini Gras