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Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an opportunistic human pathogen with main reservoir in pigs. Since LA-MRSA first was identified in Denmark in 2007 among isolates collected at two Danish pig farms in 2003, the occurrence have increased dramatically and reached a prevalence of 88% positive farms in 2016. Meanwhile a similar increase in human infections have been observed; most infections are still observed among people with livestock contact, but the development in number of infections among people without livestock contact have followed a similar increasing trend. Given the high prevalence of LA-MRSA positive farms, total eradication of LA-MRSA in the Danish pig population does not seem feasible, and thus a strong need for exploring options to control the spread of LA-MRSA in Danish pig herds exists. At present it is still not known how LA-MRSA managed to spread so quickly in the Danish pig population and a lot still needs to be understood regarding which factors that determine whether a farm becomes LA-MRSA positive or not. In the first part of this thesis two studies were conducted with the aim of identifying herd-level risk factors for: 1) herds testing MRSA positive (study 1), and 2) more specifically for herds changing status from negative to positive during 2014-2016 (study 2). The studies were based on data harvested in questionnaire-based phone interviews with farmers and supplemented with data for antimicrobial use, movement of pigs and location of neighbouring farms extracted from three national registers. Three risk factors already identified in other studies were confirmed. LA-MRSA positive status was associated with large herd size and with number of pig suppliers. In addition, sow herds tested LA-MRSA positive less frequently than herds without sows, and therefore data from sow herds were analysed separately. In univariable analysis, the following factors were associated with sow herds testing LA-MRSA positive: use of wet feed in the sow units; higher weights of piglets at weaning; availability of a delivery room on the farm; cleaning of aisles after pigs were moved; number of pigs per weaner section; number of pigs purchased in the past year, and factors related to rodent control and human traffic in the herd. In herds without sows, the univariable analysis showed that the presence of other animal species on the farm; negative pressure ventilation; full sectioning; frequent visits from the veterinarian; peroral use of tetracyclines for weaners; number of pigs purchased in the past year, and factors related to rodent control and human traffic in the herd were significantly associated with LA-MRSA status. Similar to what have been observed in other studies, many of the factors significantly associated with LA-MRSA status in study 1 was also significantly associated with herd size, and thus it was not possible to identify whether herd size itself or the related factors were the “true” risk factors. The number of observations in study 2 was small, but three variables (the number of pig suppliers, use of group medication in water vs. administration through feed, and having a company contract for mouse control) were associated with changing LA-MRSA status in the univariable analysis. Before the implementation of a national control strategy can be decided upon, it is also essential to understand how LA-MRSA spreads and persists within a pig herd, once it has been introduced. In the second part of this thesis a mechanistic model for spread of LA-MRSA within an pig herd was therefore build and subsequently used for studying transmission dynamics and within-farm prevalence after simulating different introductions of LA-MRSA on a farm. With the current parameterisation of the model, spread of LA-MRSA throughout the farm mainly followed the movement of pigs. The later in the production process LA-MRSA was introduced, the longer it took to spread to the whole farm. After spread of LA-MRSA had reached a steady state, the prevalence of LA-MRSA shedders was predicted to be highest in the farrowing unit, and lowest in the mating unit, independent of where and how LA-MRSA was introduced. Thus the farrowing unit might the area with most potential for intervention against spread of LA-MRSA. Introduction of a low number of intermittently shedding pigs was predicted to frequently result in LA-MRSA not establishing itself in the herd. Increasing the duration of carriage led to an increased median prevalence, less variance and fewer iterations where LA-MRSA did not become established in the herd. When removing the possibility of pigs becoming persistent shedders, LA-MRSA more frequently faded out and did not become established within the herd. Not much is known regarding successful interventions against LA-MRSA within pig herds. Consequently the mechanistic model for spread of LA-MRSA within a farm were used for simulating on-farm interventions within four different areas: 1) Reduced antimicrobial consumption, 2) Reduced number of pigs within each section, 3) Reduced mixing of pigs from different litters, batches or pens, and 4) Improved internal biosecurity. It is believed that a reduction in the within-farm LA-MRSA prevalence will result in less spread between farms and reduce the risk of transmission to humans working on the farm. Reducing the transmission rates after LA-MRSA had become fully established within the herd, resulted in a marked prevalence decrease in the prevalence of LA-MRSA positive pigs within the different stable units, albeit LA-MRSA rarely disappeared completely. This indicates that while reducing antimicrobial consumption might be an important step towards reducing the LA-MRSA occurrence within the herd, other preventive or intervention measures should also be implemented in order to completely clear a herd from LA-MRSA. Implementation of the other interventions after LA-MRSA had become established within a herd only resulted in marginal changes in the median within-herd prevalence. However, in relation to being able to achieve or maintain a low level of antimicrobial consumption, these factors might still be of importance. The results of the sensitivity analysis indicated that the assumptions regarding the existence of pigs persistently shedding MRSA have a noticeable influence on the model results. A secondary of objective of building the simulation model was to identify knowledge gaps regarding spread and control of LA-MRSA. Several knowledge gaps related to infection dynamics exist, including influence of the environment, LA-MRSA load and persistent carriage. Regarding control of LA-MRSA, the main problem is currently a lack of evidence for major effect of any type of intervention other than reducing antimicrobial consumption. In conclusion, the work presented in this thesis have resulted in: 1) Confirmation of already known risk factors for farms testing LA-MRSA positive (herd type, herd size, number of pig suppliers) and identification of a number of potential new risk factors, albeit many of these were related to herd size, and it therefore was impossible to conclude, whether herd size itself or these factors were the true risk factors. 2) Construction of a mechanistic model for spread of LA-MRSA within a pig herd that can be used for simulating LA-MRSA within herd dynamics following different introductions. The code for the model is publicly available, and the herd part of the model can potentially be re-used together with epidemic models for other pathogens. 3) Simulation of within-herd interventions: Reduced antimicrobial consumption, reduced number of pigs within each section, reduced mixing of pigs, and improved internal biosecurity, of which only reduced antimicrobial consumption had a marked effect on the within-herd prevalence. More intervention scenarios can be simulated, when data becomes available. 4) The observation that once LA-MRSA has become established within a herd, it will spread to all compartments within the farm and be very hard to get rid of.

DANMAP (Danish Antimicrobial Resistance Monitoring and Research Program) has monitored antimicrobial resistance and consumption of antimicrobial agents in food animals and in humans in Denmark since 1995. This report describes changes and trends in 2013.

Denne rapport giver en karakteristik af danske svinebesætninger med produktion af slagtesvin i 2007-2008. Rapporten bygger på resultaterne af telefoninterviews med 195 slagtesvineproducenter (47 økologiske producenter, 27 producenter af frilandsgrise og 121 konventionelle producenter). Producenterne blev hovedsageligt stillet spørgsmål om opstaldning, fodring, management og sundhed i besætningerne, og producenter, der havde svin på fold, blev desuden stillet en række specifikke spørgsmål om folddriften. Undersøgelsen har primært fokus på slagtesvinene, og kan anses som rimeligt repræsentativ for majoriteten af slagtesvinene i de tre besætningstyper, dog er de mindste besætninger underrepræsenteret. Oplysninger om sohold og pattegrise omfatter kun sohold i samme besætning som slagtesvineholdet eller sohold med samme ejer. En del af forskellene imellem besætningstyperne kan direkte henføres til regelsættene for økologisk svineproduktion, Friland A/S’ Frilandsgris® konceptproduktion og SPF-produktionen. De konventionelle besætninger var generelt større end besætningerne i de to alternative besætningstyper, og de største besætninger med årsleverancer på over 8000 svin fandtes udelukkende blandt de konventionelle besætninger. Også blandt frilandsbesætningerne var der mange store besætninger. De økologiske besætninger var mindst, og mange leverede under 1000 slagtesvin årligt. Knap to tredjedele af de økologiske besætninger havde søer mod kun 20% af de konventionelle besætninger og 30% af frilandsbesætningerne. I de to sidstnævnte besætningstyper var indkøb af smågrise og ungsvin mere almindeligt end i de økologiske besætninger, og der blev indkøbt flere grise men fra færre leverandørbesætninger. Størstedelen af slagtesvinene i alle besætningstyper var LYxD krydsninger. Den gennemsnitlige levende vægt ved slagtning var 107 kg for konventionelle og økologiske svin mod 111 kg for frilandssvin. Mens store kuld i de konventionelle besætninger ofte blev håndteret ved brug af ammesøer, blev der benyttet kuldudjævning i en stor del af de alternative besætninger. I stort set alle undersøgelsens besætninger blev pattegrisene kastreret. I næsten alle konventionelle besætninger fik grisene kuperet haler, og i cirka 20% af besætningerne fik pattegrisene slebet tænder. Halekupering og tandslibning blev hverken foretaget i de økologiske besætninger eller frilandsbesætningerne. Fravænningsalderen i konventionelle besætninger var i gennemsnit 30 dage, mod 34 dage i frilandsbesætninger og 53 dage i økologiske besætninger. Stort set alle de konventionelle besætninger var lukkede besætninger med alle svin på stald uden adgang til udearealer. I de alternative besætninger havde svin i alle aldersgrupper adgang til udearealer enten i form af en fold eller en begrænset udendørs løbegård i tilknytning til stalden. I alle de alternative besætninger gik diegivende søer på fold, mens de drægtige søer gik på fold i samtlige økologiske besætninger og i 60% af frilandsbesætningerne. I 20% af de økologiske besætninger gik ung- og slagtesvinene på fold, mens slagtesvin i de øvrige økologiske besætninger og frilandsbesætninger gik på stald med adgang til udendørs løbegård. På ejendomme med alternativ slagtesvineproduktion var der oftere også andre dyrearter end i de konventionelle besætninger, og adgang for hunde, katte og vilde fugle til arealer med svin og til oplagret foder og strøelse forekom også hyppigere i de alternative besætninger. Mens de alternative besætninger typisk lå længere fra andre svinebesætninger end de konventionelle besætninger, var deres afstand til kvægbesætninger kortere, og spredning af gylle eller gødning fra andre besætninger foregik tættere på de økologiske besætninger end på konventionelle og frilandsbesætninger. De konventionelle producenter vurderede hyppigere end de alternative producenter, at gnaverforekomsten på ejendommen var lille, og de havde hyppigere end de alternative producenter kontrakt med et firma om gnaverbekæmpelsen. I næsten alle konventionelle besætninger gik slagtesvinene på helt eller delvist spaltegulv med begrænset eller ingen halmstrøelse, og i halvdelen af de konventionelle besætninger gik slagtesvinene på fuldspaltet gulv uden halm. Ingen svin i de alternative besætninger gik på fuldspaltet gulv, og i en tredjedel af de alternative besætninger gik slagtesvinene udelukkende på fast gulv. Alle alternative besætninger anvendte halmstrøelse, og i to tredjedele af de alternative besætninger gik slagtesvinene på dybstrøelse. Stiarealet til slagtesvin i de konventionelle besætninger var under 1 m2 pr gris og hyppigst under 0,75 m2 pr gris. Slagtesvin i frilandsbesætningerne havde omtrent samme indeareal som konventionelle svin, og de havde desuden adgang til et begrænset udeareal. I de økologiske besætninger var både inde- og udearealet generelt større end i de to andre besætningstyper. Sammenlignet med alternative besætninger havde mange konventionelle besætninger sektionerede stalde til smågrise, ung- og slagtesvin, staldsektionerne var større, og muligheden for trynekontakt mellem stierne var mere udbredt. Over to tredjedele af de konventionelle besætninger anvendte holddrift i sektionerede stalde med udtørring og desinfektion af stierne mellem hvert hold, og de anvendte en bred vifte af midler til stalddesinfektion. Særligt blandt de økologiske besætninger var brugen af holddrift, sektionering, udtørring af stalden og desinfektionsmidler mindre udbredt, og de anvendte desinfektionsmidler færre. Der var udbredt brug af længere tomperioder mellem holdene på fold, mens længere tomperioder om vinteren ikke forekom så ofte. To tredjedele af de konventionelle besætninger fodrede slagtesvin med hjemmeblandet foder, og ca. 40% af besætningerne anvendte vådfoder. Både anvendelse af hjemmeblandet foder og vådfoder forekom hyppigst i de største konventionelle besætninger. Godt halvdelen satte valle eller gærfløde til vådfoderet. I de alternative besætninger var pelleteret færdigfoder den hyppigst anvendte fodertype. Strukturfoder blev ofte blandet i pelleteret foder i frilandsbesætninger, men sjældent i de økologiske besætninger. Mens vådfoder stort set ikke forekom i de alternative besætninger, satte de oftere organiske syrer til foderet end de konventionelle besætninger. Udover byg indeholdt foderet til konventionelle slagtesvin og frilandssvin en stor andel hvede og sjældnere andre korntyper end foderet til økologiske slagtesvin. Soja var langt den hyppigste proteinkilde til konventionelle slagtesvin og frilandssvin, mens der til økologiske slagtesvin ofte også blev benyttet andre proteinkilder som ærter, raps og kartoffelproteinkoncentrat. Alle økologiske producenter, men kun meget få konventionelle producenter og frilandsproducenter, fodrede slagtesvinene med grovfoder. Der var en tendens til, at der i konventionelle og økologiske besætninger hyppigere blev skiftet foder fra ungsvin til slagtesvin, mens der i frilandsbesætningerne oftere blev anvendt et særligt slutfoder. Næsten alle konventionelle producenter og producenter af frilandsgrise havde sundhedsrådgivningsaftale med en dyrlæge, mens det kun gjaldt 30% af de økologiske producenter. Halvdelen af de konventionelle besætninger var SPF-besætninger mod kun ca. 10% af de alternative besætninger. Der var en del forskelle i den oplyste sygdomsforekomst i de tre besætningstyper. Blandt andet var hyppigheden af almindelig lungesyge og mavesår højere i konventionelle besætninger og frilandsbesætninger end i økologiske besætninger, og ondartet lungesyge forekom hyppigere i konventionelle besætninger end i økologiske besætninger. Frilandsbesætningerne rapporterede hyppigere forekomst af PMWS end både økologiske og konventionelle besætninger. Kun få besætninger (flest økologiske) anvendte probiotika og andre alternative midler til forebyggelse eller behandling af sygdom i besætningen. This report provides a characterization of Danish pig herds with production of finishers in 2007- 2008. The report is based on the results of telephone interviews with 195 pig producers (47 organic producers, 27 producers of free range pigs and 121 conventional producers). Producers were mainly asked questions about housing, feeding, management and diseases in the herd, and producers who had pigs in paddocks, were also asked specific questions about the outdoor areas. The study focused primarily on the finishers, and may be considered reasonably representative for the majority of finishers in the three herd types, but the smallest herds are underrepresented. Information on sows and piglets was only included from integrated herds and sow herds with the same owner as the slaughter pig herd. Some of the differences between herd types can be directly attributed to the regulatory frameworks for organic pig production, the Friland A/S free range concept production and the SPF-production. Conventional finisher herds were larger than herds of the two alternative herd types. The largest herds with an annual slaughter of more than 8000 pigs were found exclusively among the conventional herds. Many large herds were also seen among free range herds. The organic herds had the lowest annual slaughter, and annual slaughters less than 1000 organic pigs were common. Close to two thirds of the organic herds had sows compared to only 20% of the conventional herds and 30% of the free range herds. Purchase of pigs was more common in conventional herds and free range herds, their number of weaners and growers purchased was higher compared to the organic herds, but they had fewer supplier herds. The majority of finishers in all herd types were LYxD hybrids. The average live weight at slaughter was 107 kg for pigs from conventional and organic herds vs. 111 kg for free range herds. While large litters in the conventional herds usually was handled by using nurse sows, cross fostering was used in most alternative herds. In virtually all herds in the study the piglets were castrated. Tail docking of pig was common practice in almost all conventional herds, and in about 20% of the herds, the piglets’ teeth were grinded. Neither tail docking nor teeth grinding were practiced in any of the organic herds or free range herds. In conventional herds piglets were weaned on average at an age of 30 days vs. 34 days in free range herds and 53 days in organic herds. Virtually all of the conventional herds were closed herds with all pigs housed without access to outdoor areas. In the alternative herds, pigs of all ages had outdoor access, either in paddocks or with access to a limited outdoor area connected to the stable. All alternative herds had lactating sows in paddocks, and pregnant sows were in paddocks in all organic herds and in 60% of the free range herds. In 20% of the organic herds weaners, growers and finisher pigs were raised in paddocks, while the rest of the organic pigs and pigs in free range herds were in stables with access to an outdoor area. The presence of animal species other than pigs on the farm was more common in the alternative herds than in conventional herds, and also access for dogs, cats and wild birds to areas with pigs and areas with stored feed and bedding material was more frequently reported in these types of herds. The distance between the alternative herds and other pig herds was generally longer than for conventional herds, but their distance to cattle herds was generally shorter. Slurry or manure from other herds was spread closer to the organic herds than to conventional and free range herds. The conventional producers more often than the alternative producers perceived the occurrence of rodents at the farm to be low, and they were more likely than the alternative producers to have contract with a company on rodent control. In almost all conventional herds finishers were housed on fully or partially slatted floors with little or no straw bedding, and half of the conventional herds had fully slatted floors without straw bedding. No pigs in alternative herds were kept on fully slatted floors, and in one third of the herds finishers only had solid floor. In all alternative herds straw bedding was used, and in two-thirds of the alternative herds, finishers were housed on deep litter. The pen area for finishers in the conventional herds was less than 1 m2 per pig and frequently less than 0.75 m2 per pig. Finishers in free range herds had about the same indoor area as conventional pigs, but had additionally access to a limited outdoor area. In the organic herds both the indoor and the outdoor areas were in general larger than in the other two herd types. Compared to alternative herds, many conventional herds had sectioned stables for piglets, growers and finishers, their sections were larger, and the possibility of snout contact between pigs in neighbouring pens was more common. More than two-thirds of the conventional herds used batch production in sectioned units with desiccation and disinfection of the batches, and they used a variety of products for disinfection. Particularly among the organic herds the use of batch production, sectioning, desiccation of the pens and disinfectants was less common, and only a few types of disinfectants were used. The paddocks were frequently kept empty between batches, while emptying the paddocks for longer periods in the cold season was not used to the same extent. In two thirds of the conventional herds, pigs were fed home-mixed feed, and in approx. 40% of the herds pigs were fed liquid feed. Both home-mixed feed and liquid feed was more frequently used in the largest conventional herds. In about one half of the herds, whey or brewer’s yeast was added to the liquid feed. In the alternative herds pelleted commercial feed was the most common feed type. In the free range herds feed components with coarse feed structure was often added to pelleted feed, but this was not common in the organic herds. While liquid feeding was not used in the alternative herd types, organic acids were more often added to the feed in these herds than in the conventional herds. Besides barley, the feed for conventional and free range finishers contained a high proportion of wheat and, compared to the feed for organic finishers, less frequently other types of grain. Soybean products was by far the most common source of protein for conventional finishers and free range finishers, while the organic finishers often were supplied with other sources of protein such as peas, canola and potato protein concentrate. As opposed to conventional herds and free range herds, the finishers were fed roughage in all organic herds. Conventional and organic producers tended to more frequently use a special diet for growers, while free range producers more often used a special feed in the last period before slaughter. Almost all conventional producers and free range producers had a health agreement contract with a veterinarian, while this only applied to 30% of the organic producers. Half of the conventional herds were SPF herds compared to only approx. 10% of the alternative herds. There were some differences in the reported presence of swine diseases in the three herd types. Among others, enzootic pneumonia and gastric ulcers were more common in conventional herds and free range herds compared to organic herds and pleuropneumonia occurred more frequently in conventional herds than in organic herds. Further, more free range herds reported presence of PMWS than both organic and conventional herds. Only few herds (mainly organic herds) used probiotics and other alternative medication to prevent or treat diseases in the herd.

I forbindelse med forskningsprojektet QUALYSAFE1 har Zoonosecenteret i DTU Fødevareinstituttet gennemført en undersøgelse af salmonellaforekomsten i slagtesvin fra forskellige svineproduktionssy-stemer. Ud over at give en sammenligning af forekomsterne i de tre besætningstyper vil undersøgel-sen indgå i en analyse af risikofaktorer for Salmonella i svinebesætninger.