Predicting effects of changed antimicrobial usage on the abundance of antimicrobial resistance genes in finisher' gut microbiomes.

It is accepted that usage of antimicrobials (AMs) in food animals causes the emergence and spread of antimicrobial resistance (AMR) in this sector, while also contributing to the burden of AMR in humans. Curbing the increasing occurrence of AMR in food animals requires in-depth knowledge of the quantitative relationship between antimicrobial usage (AMU) and AMR to achieve desired resistance reductions from interventions targeting AMU. In the observational study, the relationships between lifetime AMU in 83 finisher batches from Danish farms and the AMR gene abundances of seven antimicrobial classes in their gut microbiomes were quantified using multi-variable linear regression models. These relationships and the national lifetime AMU in pigs were included in the predictive modelling that allowed for testing of scenarios with changed lifetime AMU for finishers produced in Denmark in 2014. A total of 50 farms from the observational study were included in validating the observational study and the predictive modelling. The results from the observational study showed that the relationship was linear, and that the parenteral usage of AMs had a high effect on specific AM-classes of resistance, whereas the peroral usage had a lower but broader effect on several classes. Three different scenarios of changed lifetime AMU were simulated in the predictive modelling. When all tetracycline usage ceased, the predicted interval reductions of aminoglycoside, lincosamide and tetracycline resistance were 4-42 %, 0-8 % and 9-18 %, respectively. When the peroral tetracycline usage of the 10 % highest users was replaced with peroral macrolide usage, the tetracycline resistance fell by 1-2 % and the macrolide and MLSb resistance increased by 5-8 %. When all extended-spectrum penicillin usage was replaced with parenteral lincosamide usage, the beta-lactam resistance fell by 2-7 %, but the lincosamide usage and resistance increased by 194 % and 10-45 %, respectively. The external validation provided results within the 95 % CI of the predictive modelling outcome at national level, while the external validation at farm level was less accurate. In conclusion, interventions targeting AMU will reduce AMR abundance, though differently depending on the targeted AM-class and provided the reduction of one AM-class usage is not replaced with usage of another AM-class. Predicting several classes of AMR gene abundance simultaneously will support stakeholders when deciding on interventions targeting AMU in the finisher production to avoid adverse and unforeseen effects on the AMR abundance. This study provides a sound predictive modelling framework for further development, including the dynamics of AMU on AMR in finishers at national level.

Validation of the register-based lifetime antimicrobial usage measurement for finisher batches based on comparison with recorded antimicrobial usage at farm level.

Assessing the relationship between antimicrobial usage (AMU) and antimicrobial resistance (AMR) requires the accurate and precise utilisation of register data. Therefore, validation of register-based data is essential for evaluating the quality and, subsequently, the internal validity of studies based on the data. In this study, different smoothing methods for Veterinary Medicine Statistic Program database (VetStat)-records were validated by comparing these with farm-records. Comparison between measurements included accuracy as; completeness and correctness, and precision as; a relative difference of the error, correlation with Fisher's z transformation and reliability coefficient. The most valid methods of those examined were then used in re-analyses of the abundance of AMR genes in 10 finisher batches from a previous study. Improved accuracy was found when detailed smoothing methods were applied. Although the precision also increased, the effect was not as pronounced, as the usage estimate of all smoothing methods deviated moderately compared with the farm-registrations. Applying the most valid methods to the 10 finisher batches increased estimates of statistical model fit for aminoglycosides, lincosamides, tetracyclines and decreased estimates of statistical model fit for macrolides. The estimates of statistical model fit for sulfonamides and broad-spectrum penicillins remained the same. Through refined data transformation, VetStat-records can be used to calculate a daily amount of AMU per pig reflecting the true usage accurately and moderately precisely, which is the foundation for calculating lifetime AMU.

The association between measurements of antimicrobial use and resistance in the faeces microbiota of finisher batches.

The objectives were to present three approaches for calculating antimicrobial (AM) use in pigs that take into account the rearing period and rearing site, and to study the association between these measurements and phenotypical resistance and abundance of resistance genes in faeces samples from 10 finisher batches. The AM use was calculated relative to the rearing period of the batches as (i) 'Finisher Unit Exposure' at unit level, (ii) 'Lifetime Exposure' at batch level and (iii) 'Herd Exposure' at herd level. A significant effect on the occurrence of tetracycline resistance measured by cultivation was identified for Lifetime Exposure for the AM class: tetracycline. Furthermore, for Lifetime Exposure for the AM classes: macrolide, broad-spectrum penicillin, sulfonamide and tetracycline use as well as Herd Unit Exposure for the AM classes: aminoglycoside, lincosamide and tetracycline use, a significant effect was observed on the occurrence of genes coding for the AM resistance classes: aminoglycoside, lincosamide, macrolide, ß-lactam, sulfonamide and tetracycline. No effect was observed for Finisher Unit Exposure. Overall, the study shows that Lifetime Exposure is an efficient measurement of AM use in finisher batches, and has a significant effect on the occurrence of resistance, measured either by cultivation or metagenomics.

Attributing foodborne salmonellosis in humans to animal reservoirs in the European Union using a multi-country stochastic model.

A Bayesian modelling approach comparing the occurrence of Salmonella serovars in animals and humans was used to attribute salmonellosis cases to broilers, turkeys, pigs, laying hens, travel and outbreaks in 24 European Union countries. Salmonella data for animals and humans, covering the period from 2007 to 2009, were mainly obtained from studies and reports published by the European Food Safety Authority. Availability of food sources for consumption was derived from trade and production data from the European Statistical Office. Results showed layers as the most important reservoir of human salmonellosis in Europe, with 42·4% (7 903 000 cases, 95% credibility interval 4 181 000-14 510 000) of cases, 95·9% of which was caused by S. Enteritidis. In Finland and Sweden, most cases were travel-related, while in most other countries the main sources were related to the laying hen or pig reservoir, highlighting differences in the epidemiology of Salmonella, surveillance focus and eating habits across the European Union.

Using surveillance and monitoring data of different origins in a Salmonella source attribution model: a European Union example with challenges and proposed solutions.

Microbial subtyping approaches are commonly used for source attribution of human salmonellosis. Such methods require data on Salmonella in animals and humans, outbreaks, infection abroad and amounts of food available for consumption. A source attribution model was applied to 24 European countries, requiring special data management to produce a standardized dataset. Salmonellosis data on animals and humans were obtained from datasets provided by the European Food Safety Authority. The amount of food available for consumption was calculated based on production and trade data. Limitations included different types of underreporting, non-participation in prevalence studies, and non-availability of trade data. Cases without travel information were assumed to be domestic; non-subtyped human or animal records were re-identified according to proportions observed in reference datasets; missing trade information was estimated based on previous years. The resulting dataset included data on 24 serovars in humans, broilers, laying hens, pigs and turkeys in 24 countries.

Temporal relationship between decrease in antimicrobial prescription for Danish pigs and the "Yellow Card" legal intervention directed at reduction of antimicrobial use.

The potential effects of the "Yellow Card" intervention, enforced by Danish authorities in December 2010, on the antimicrobial prescription in the Danish pig production were investigated. Data on antimicrobial prescription for pigs during 2002-2012 was obtained from the national database on veterinary prescribed medicines, VetStat. Descriptive analysis of temporal trends in quantitative antimicrobial prescription for pigs on national level was performed for each administration route, age group and disease group. In addition, prescription patterns of the three most prescribed antimicrobial classes (tetracyclines, macrolides and pleuromutilins) for weaners and finishers were studied at herd level. A 25% decline in the total antimicrobial use per pig produced occurred between 2009 and 2011. A decline was observed both in sows and piglets (31%), weaners (34%) and finishers (19%). Reduced prescription of tetracycline, macrolides and pleuromutilins for oral use, mainly for gastrointestinal disease (GI) in weaners and finishers, explained 76% of the total reduction. In 2012, the overall antimicrobial use increased by 10%, as a partial reversal of the preceding changes in prescription pattern. On herd level, the decline and subsequent increase was mainly related to changes in number of herds receiving regular monthly prescriptions. This study demonstrated that the steep decrease in antimicrobial use in the Danish pig production was temporally related with the announcement and introduction of the Yellow Card intervention.

Morcegos capturados no município de Belo Horizonte, 1999-2003 / Bats found in the city of Belo Horizonte, MG, 1999-2003

Entre os anos de 1999 e 2001, realizaram-se 18 capturas de morcegos em Belo Horizonte, sendo uma na estacão seca e uma na estacão chuvosa em cada regional administrativa. Foram capturados 316 exemplares, com predominância de Artibeus lituratus (Olfers, 1818), 55,1 por cento, Platyrrhinus lineatus (Geoffroy, 1810), 24,4 por cento e Glossophaga soricina (Pallas, 1766), 10,1 por cento, além de Sturnira lilium (Geoffroy, 1810), Phyllostomus discolor (Wagner, 1843), Carollia perspicillata (Linnaeus, 1758), Myotis nigricans (Schinz, 1821) e Anoura caudifer (Geoffroy, 1818), totalizando oito espécies, pertencentes às famílias Phyllostomidae e Vespertilionidae. Observou-se concentracão de partos próximos à estacão chuvosa, coincidindo com a maior disponibilidade de alimento para os períodos de prenhez e lactacão. Partos esporádicos ocorreram durante todo o ano. Entre 2002 e 2003, foi feita uma busca em diversos tipos de abrigos nas mesmas regionais. Os abrigos foram registrados, e as espécies encontradas foram somadas às já observadas na primeira parte deste estudo, bem como às citadas em diversas fontes bibliográficas e disponíveis em colecões acadêmicas, gerando um relato atualizado das espécies de morcegos já encontrados no município.