Pig farms act as reservoir of Livestock-Associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). Through occupational exposure to farm dust and contact with pigs, farm workers are at risk for acquiring LA-MRSA. Although health care institutions can cope with the current situation, it is a burden for patients, health care staff, and finances. In addition, the recent observed adaptation of LA-MRSA originating from pigs to humans in Denmark further highlights the need to reduce LA-MRSA colonization in pigs and subsequent transmission to humans. In a pilot study of the nasal microbiome we observed that piglets become LA-MRSA positive after a few days of birth. The presence of several other bacterial species, including coagulase-negative staphylococci was negatively associated with the presence of LA-MRSA. More evidence is needed regarding which bacterial species and/or strains compete with LAMRSA. The project aims to establish the effect of colonization resistance (bacterial competition) on the transmission of LA-MRSA from pigs to humans by i) identifying bacterial species that compete with LA-MRSA (S. aureus in general) in a systematic way using state of the art bioinformatics and metagenomics methods at strain level, ii) studying the efficacy of applying a nasal microflora for piglets which will be produced under GMP conditions by the industrial partner in the project and tested under field conditions at conventional farms, and iii) to estimate the risk reduction as a result from limiting MRSA transmission to humans by reducing shedding and consequently a more limited environmental contamination. Communication with farmers, veterinarians, public health workers and other stakeholders, with the help of our supporting organizations, will prepare the stakeholders for the outcome of the project, bringing it close to immediate use in practice. ExcludeMRSA will deliver a reduction of MRSA colonization or will lead to complete prevention of MRSA colonization by precolonization of piglets with microflora. The efficacy will be assessed in two countries by using proven environmental risk models for human exposure and evaluating changes in the exposure risk association. Because of the earlier performed successful pilot studies, the experience of the partners and the inclusion of an industrial partner experienced in production of live strains, this project is feasible in three years’ time

• A.A. (Abel) Vlasblom
• prof. dr. J.A. (Jaap) Wagenaar
• dr. B. (Birgitta) Duim
• dr. A.L. (Aldert) Zomer

• Marcus Claesson (UCC)
• Peadar Lawlor (Teagasc)
• Fellipe Freitas Barbosa (EW-nutrition)

MRSA-PREVENT richt zich op het verminderen van de overdracht van de methicilline-resistente Staphylococcus aureus (MRSA) bacterie van varkens naar mensen. Mensen op varkensbedrijven lopen het risico om besmet te worden met deze resistentie bacterie. In ziekenhuizen wordt door het actieve ‘search en destroy’ beleid de insleep van MRSA voorkomen maar de kosten hiervan zijn hoog.

In dit project wordt gezocht, met hightech moleculaire technieken, of bacteriën die van nature bij varkens in de neus voorkomen de groei van MRSA kunnen remmen. Modelmatig wordt onderzocht of deze bacteriën ‘kolonisatie resistentie’ geven zodat MRSA zich niet meer kan vestigen in de varkens neus. Bij een aantal varkens bedrijven wordt onderzocht hoeveel deze toediening het risico voor overdracht van MRSA naar mensen beperkt. Dit project is een interdisciplinaire aanpak, waarin artsen, onderzoekers, dierenartsen en veehouders gezamenlijk werken aan het beperken van de overdracht van MRSA van varkens naar mensen.

• prof. dr. ir. L.A. (Lidwien) Smit
• dr. A. (Arie) van Nes
• dr. A Fluit
• A.A. (Abel) Vlasblom
• prof. dr. J.A. (Jaap) Wagenaar
• dr. B. (Birgitta) Duim
• dr. A.L. (Aldert) Zomer

• Marjolein Kluytmans-van den Bergh
• Gerard van Eijden

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
• prof. dr. J.A. (Arjan) Stegeman
• P. (Panagiotis) Mallioris
• dr. L. (Lapo) Mughini Gras

• dr. N.E.M. (Nonke) Hopman
• prof. dr. J.A. (Jaap) Wagenaar
• prof. dr. Theo Verheij
• prof. dr. L.J. (Ludo) Hellebrekers
• dr. I.M. (Inge) van Geijlswijk
• dr. E.M. (Els) Broens

• Jan Prins
• Tjerk Bosje
• Marlies Hulscher
• Merel Langelaar

Intensieve veehouderij gaat gepaard met de uitstoot van fijnstof, micro-organismen, endotoxines  en andere factoren die kunnen bijdragen aan het ontstaan en/of verergeren van luchtwegklachten. Dit project onderzoekt of omwonenden van een veehouderij daadwerkelijk een verhoogde kans lopen luchtwegklachten te ontwikkelen.

• prof. dr. ir. L.A. (Lidwien) Smit
• dr. ir. I.M. (Inge) Wouters

This research project investigates the possible impact of global climate change on reproductive health in Arctic and three local European populations. The key questions to be addressed are, first, how may climate change impact on human exposure to widespread environmental contaminants and, second, how may contaminants impact on occurrence of reproductive disorders as sensitive indicators of health.

To provide affirmative answers to these questions the project will

(i) identify and describe mechanisms by which a changing climate may affect the exposure of arctic and other human populations to contaminants through change in chemical use and emissions, delivery to the arctic ecosystem as well as processing within the arctic physical environment and human food chain. This work relies on modeling of existing data.

(ii) expand the existing knowledge database on human exposure to polybrominated diphenylethers, perfluorinated surfactants and phthalates by analyses of 1000 biobanked serum samples collected in the EU FP5 programme INUENDO

(iii) increase the limited knowledge on links between human exposure to contaminants and reproductive health. This work relies on a large existing parent-child-cohort, where a follow-up survey provide new data that are fed into risk assessment

(iv) perform reviews of experimental and epidemiological literature to identify critical reproductive effects and exposure response data for the selected compounds as input to the risk assesment

(v) integrate data on relative climate induced changes in contaminant mobility and distribution and links between contaminant exposure and reproductive health into a risk evaluation providing insight into possible future risk scenarios related to global climate change.

• prof. dr. ir. R.C.H. (Roel) Vermeulen
• prof. dr. ir. L.A. (Lidwien) Smit
• dr. V.C. (Virissa) Lenters