Dataset Information

Drivers for Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Spread Among Danish Pig Herds - A Simulation Study.

ABSTRACT: To gain insight into the rapid increase in the number of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA)-positive herds in Denmark, we developed an individual-based Monte Carlo simulation model. We aimed to assess whether transmission of LA-MRSA via pig movements could explain the observed increase in the number of positive herds in Denmark, and to evaluate the effect of other between-herd transmission mechanisms. Pig movements alone were not sufficient to mimic the observed increase in LA-MRSA-positive herds in Denmark in any of the modelled scenarios. The model identified three factors that played important roles in the between-herd spread of LA-MRSA: (1) the within-herd dynamics, (2) the frequency and effectiveness of indirect transmissions, and (3) unexplainable introduction of LA-MRSA to swine herds. These factors can act as starting points for the development of LA-MRSA control programs in pig herds in order to limit the risk of its transmission to humans.

SUBMITTER: Schulz J

PROVIDER: S-EPMC6240036 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Drivers for Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Spread Among Danish Pig Herds - A Simulation Study.

Schulz Jana J Boklund Anette A Toft Nils N Halasa Tariq T

Scientific reports 20181116 1

To gain insight into the rapid increase in the number of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA)-positive herds in Denmark, we developed an individual-based Monte Carlo simulation model. We aimed to assess whether transmission of LA-MRSA via pig movements could explain the observed increase in the number of positive herds in Denmark, and to evaluate the effect of other between-herd transmission mechanisms. Pig movements alone were not sufficient to mimic the ob ...[more]

PMID: 30446719

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Project description:Knowledge on successful interventions against livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) within pig herds is sparse. In situations like this, a mechanistic simulation model can be a valuable tool for assessing the effect of potential intervention strategies, and prioritising which should be tested in the field. We have simulated on-farm interventions in a farrow-to-finish pig herd, with a previously published LA-MRSA spread model, within four different areas: 1) Reduced antimicrobial consumption, 2) Reduced number of pigs within each section, 3) Reduced mixing of pigs, and 4) Improved internal biosecurity. To model a decrease in the selective pressure, the transmission rates were reduced after LA-MRSA had become fully established within a herd, which resulted in a marked decrease in the prevalence within all stable units. However, LA-MRSA rarely disappeared completely from the herd; this was only observed in scenarios where the transmission rates were reduced to ≤ 30% of the original level. While changes in antimicrobial consumption patterns might be a very important step towards reducing the spread of LA-MRSA, the simulation results indicate that it may need to be paired with other preventive or intervention measures. Reducing the number of pigs within each section, reducing mixing of pigs, or improving internal biosecurity after LA-MRSA had become established within the herd only resulted in marginal changes in the median prevalence within the herd. However, these factors might be important in relation to being able to achieve or maintain a low level of antimicrobial consumption, and thus still indirectly influence the LA-MRSA prevalence within the herd. The results of a sensitivity analysis indicated the assumptions regarding the existence of pigs persistently shedding MRSA have a noticeable influence on the model results. The assumptions regarding transmission from sow to offspring at the day of birth also had a considerable influence on the MRSA prevalence within the farrowing unit but did not cause any marked changes in the simulated effect of interventions. Effects might differ between different farm types contaminated in different levels and this simulation study highlights a strong need for more knowledge from on-farm trials.

Project description:The spread of livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) within the Danish pig production system has been linked to an increased number of human infections. Yet, the population structure and transmission dynamics of this important pathogen remain poorly understood. In this study, whole-genome sequences from 371 LA-MRSA CC398 isolates collected between 2004 and 2015 were subjected to bioinformatic analyses. The isolates originated from Danish pig farms (n = 209) and people having livestock contact (n = 79). In addition, whole-genome sequence data from 82 isolates representing an international reference collection and 83 isolates from Danish patients were included in the analysis. The results demonstrated that the increasing prevalence of LA-MRSA CC398 in Danish pigs and patients was caused by clonal expansion of three dominant lineages. The results also showed that these lineages were enriched for the tetracycline resistance gene tet(K) and other determinants conferring resistance to some of the most frequently used antimicrobials in Danish pigs. The association between pig movements and the spread of LA-MRSA CC398 was assessed in a Poisson regression analysis of 17,009 pig movements into 273 farms with known LA-MRSA CC398 status. The results demonstrated that animal movements have played a critical role in the dissemination of LA-MRSA CC398 within the Danish pig production system, although other transmission routes may also have contributed. Consistent with this scenario, the genetic relatedness of isolates from different farms was positively correlated with the number of animal movements between the farms.IMPORTANCE Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex CC398 (LA-MRSA CC398) is resistant to nearly all ?-lactams and several non-?-lactam antimicrobials. Over the last decade, it has become widespread in pig farms across Europe and is now an important cause of human infections in countries with previously low levels of MRSA, such as the Netherlands and Denmark. The hitherto uncontrolled spread of LA-MRSA CC398 underscores an urgent need to understand its epidemiology in order to develop evidence-based interventions. This study demonstrates that pig movements between farms in combination with increased bacterial resistance to specific antibiotics and heavy metals were important drivers of the rapid spread of LA-MRSA CC398 in the Danish pig production system. These findings should be taken into consideration when researchers and policy makers evaluate and decide on actions and policies to limit the spread of LA-MRSA CC398 and other pathogens in food animals.

Project description:UNLABELLED:Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. IMPORTANCE:Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.

Dataset Information

Drivers for Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Spread Among Danish Pig Herds - A Simulation Study.

Publications

Drivers for Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Spread Among Danish Pig Herds - A Simulation Study.

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