Contrasting Treatment- and Farm-Level Metrics of Antimicrobial Use Based on Used Daily Dose vs. Defined Daily Dose for the German Antibiotics Minimization Concept.

The German Antibiotics Minimization Concept defines a farm-level benchmarking process based on half-yearly treatment frequencies that applies to six animal populations for fattening: calves (≤ 8 months), cattle (> 8 months), piglets (≤ 30 kg), pigs (> 30 kg), broiler chickens, and turkeys. The treatment frequency defined in the Minimization Concept takes into account the number of animals treated, the treatment duration, and the number of active antimicrobial ingredients, for each individual treatment, and is equivalent to a treatment frequency based on the used daily dose (UDD) and the actual weight of the animals at the time of treatment. With data from the German benchmarking system for the seven half-year periods from the second semester 2014 to the end of 2017, we compared UDD-based metrics of antimicrobial use (AMU) at the treatment and the farm level with metrics based on defined daily doses for animals (DDDvet) and standardized animal weights assumed at the time most likely for treatment. We show the extent to which DDDvet-based metrics would introduce errors into the measurement of AMU at the treatment level and consequently at the farm level. To that end, we introduce the average animal daily dose ratio, an aggregate measure that quantifies how choice of antimicrobial substances, deviations of used doses from recommended doses, of recommended doses from DDDvet values, and of treatment weights from standardized weights, affect a farm's AMU metrics. Our results show that in all animal populations considered benchmarking processes would become less successful at targeting high users. This would be especially true for broiler chickens and turkeys where the relative weight gain during fattening is the largest and overdosing appears to be common practice. Therefore, in AMU monitoring systems with the purpose of benchmarking farms UDD-based metrics are preferable to DDDvet-based metrics.

Association of Antimicrobial Resistance in Campylobacter spp. in Broilers and Turkeys with Antimicrobial Use.

We investigated trends in antimicrobial resistance (AMR) in Campylobacter jejuni and Campylobacter coli in poultry between 2010 and 2016 in Germany and their association with antimicrobial use. Campylobacter had been isolated from the caeca of broilers and turkeys at slaughter by regional laboratories according to current ISO methods in the framework of a national monitoring program. Isolates were submitted to the National Reference Laboratory for Campylobacter and tested for AMR using broth microdilution methods. Minimum inhibitory concentrations were evaluated according to epidemiological cut-off values. Antimicrobial use (AMU) data from 2014 to 2016 were taken from a government report. AMR was higher in C. coli than in C. jejuni and higher in turkeys than in broilers. AMR was highest to tetracycline and the tested (fluoro)quinolones while it was rare to gentamicin in both bacterial species, infrequent to erythromycin in C. jejuni, and moderate in C. coli. AMR to tetracycline and erythromycin decreased over time while it increased to (fluoro)quinolones. An association of AMU and AMR was observed for resistance to tetracycline and erythromycin, while it was not observed for the aminoglycosides. Resistance to nalidixic acid and ciprofloxacin increased despite a decrease of fluoroquinolone use between 2014 and 2016, indicating that other factors have a strong influence on resistance to (fluoro)quinolones in Campylobacter.

Comparison of Consumption Data and Phenotypical Antimicrobial Resistance in E. coli Isolates of Human Urinary Samples and of Weaning and Fattening Pigs from Surveillance and Monitoring Systems in Germany.

Antimicrobial resistance (AMR) data from humans are mostly collected from clinical isolates, whereas from livestock data also exist from colonizing pathogens. In Germany, livestock data are collected from clinical and nonclinical isolates. We compared resistance levels of clinical and nonclinical isolates of Escherichia coli from weaning and fattening pigs with clinical outpatient isolates of humans from urban and rural areas. We also studied the association of AMR with available antimicrobial use (AMU) data from humans and pigs. Differences between rural and urban isolates were minor and did not affect the comparison between human and pig isolates. We found higher resistance levels to most antimicrobials in human isolates compared to nonclinical isolates of fattening pigs. Resistance to ampicillin, however, was significantly more frequent in clinical isolates of fattening pigs and in clinical and nonclinical isolates of weaning pigs compared to isolates from humans. The opposite was observed for ciprofloxacin. Co-trimoxazole resistance proportions were higher in clinical isolates of weaning and fattening pigs as compared to isolates from humans. Resistance proportions were higher in clinical isolates than in nonclinical isolates from pigs of the same age group and were also higher in weaner than in fattening pigs. Significant associations of AMU and AMR were found for gentamicin resistance and aminoglycoside use in humans (borderline) and for ampicillin resistance in clinical isolates and penicillin use in fattening pigs. In summary, we found significant differences between isolates from all populations, requiring more detailed analyses supported by molecular data and better harmonized data on AMU and AMR.

Comparison of Bayesian and frequentist methods for prevalence estimation under misclassification.

BACKGROUND: Various methods exist for statistical inference about a prevalence that consider misclassifications due to an imperfect diagnostic test. However, traditional methods are known to suffer from truncation of the prevalence estimate and the confidence intervals constructed around the point estimate, as well as from under-performance of the confidence intervals' coverage. METHODS: In this study, we used simulated data sets to validate a Bayesian prevalence estimation method and compare its performance to frequentist methods, i.e. the Rogan-Gladen estimate for prevalence, RGE, in combination with several methods of confidence interval construction. Our performance measures are (i) error distribution of the point estimate against the simulated true prevalence and (ii) coverage and length of the confidence interval, or credible interval in the case of the Bayesian method. RESULTS: Across all data sets, the Bayesian point estimate and the RGE produced similar error distributions with slight advantages of the former over the latter. In addition, the Bayesian estimate did not suffer from the RGE's truncation problem at zero or unity. With respect to coverage performance of the confidence and credible intervals, all of the traditional frequentist methods exhibited strong under-coverage, whereas the Bayesian credible interval as well as a newly developed frequentist method by Lang and Reiczigel performed as desired, with the Bayesian method having a very slight advantage in terms of interval length. CONCLUSION: The Bayesian prevalence estimation method should be prefered over traditional frequentist methods. An acceptable alternative is to combine the Rogan-Gladen point estimate with the Lang-Reiczigel confidence interval.

The Quantity and Quality of Illegally Imported Products of Animal Origin in Personal Consignments into the European Union Seized at Two German Airports between 2010 And 2014.

The import of products of animal origin (POAO) in travellers' personal consignments presents a considerable risk of introducing animal diseases and emerging zoonoses into the European Union. The current regulation (EU) 206/2009 implements strict measures for illegally imported POAO, whereupon non-complying products have to be seized and destroyed regardless. Especially airports serve as global bottlenecks for illegally imported POAO where passenger controls of non-European flights are performed by customs and veterinary services in collaboration. Results of these control measures have to be submitted in the form of annual reports to the European Commission. However, few data on qualities and quantities of seizures have been published so far. In this study, POAO seized at two German airports between 2010 and 2014 were analysed in terms of quantities, qualitative categories and region of origin. In most years considered, more than 20 tonnes POAO were seized at each airport. However, reported amounts of seizures seem to be only the tip of the iceberg as an all-passenger control is not feasible and therefore travellers are only spot-checked. The analysis suggests that the organisational structures of both customs and official veterinary services and their different risk perceptions interfere in completing an effective ban on the illegal import of POAO.

The effect of sibmating on the infection dynamics of male-killing bacteria.

Male-killing (MK) bacteria are vertically transmitted endosymbionts that selectively kill the male offspring of their hosts. Simple mathematical models describe the infection dynamics using two parameters, the bacterial transmission rate and a fitness compensation for siblings of killed males. These models cannot explain two phenomena that have been observed in nature: the persistence of extreme MK causing all-female broods, and the coexistence of two different strains of MK bacteria in the same host population. In the present study, we extend the simple MK models and investigate theoretically the effects of sibmating on the infection dynamics. We demonstrate analytically that, in general, sibmating reduces MK prevalence, and can even cause its extinction. As a special case of this finding, we show that sibmating allows a stable coexistence between no infection and extreme MK. Furthermore, we performed computer simulations and showed that, depending on male mating capacity, a stable coexistence of two strains is possible if sibmating occurs but is below a threshold. The results suggest that sibmating might be an important factor for understanding the infection dynamics of MK bacteria.

Wolbachia-induced unidirectional cytoplasmic incompatibility and speciation: mainland-island model.

Bacteria of the genus Wolbachia are among the most common endosymbionts in the world. In many insect species these bacteria induce a sperm-egg incompatibility between the gametes of infected males and uninfected females, commonly called unidirectional cytoplasmic incompatibility (CI). It is generally believed that unidirectional CI cannot promote speciation in hosts because infection differences between populations will be unstable and subsequent gene flow will eliminate genetic differences between diverging populations. In the present study we investigate this question theoretically in a mainland-island model with migration from mainland to island. Our analysis shows that (a) the infection polymorphism is stable below a critical migration rate, (b) an (initially) uninfected "island" can better maintain divergence at a selected locus (e.g. can adapt locally) in the presence of CI, and (c) unidirectional CI selects for premating isolation in (initially) uninfected island populations if they receive migration from a Wolbachia-infected mainland. Interestingly, premating isolation is most likely to evolve if levels of incompatibility are intermediate and if either the infection causes fecundity reductions or Wolbachia transmission is incomplete. This is because under these circumstances an infection pattern with an infected mainland and a mostly uninfected island can persist in the face of comparably high migration. We present analytical results for all three findings: (a) a lower estimation of the critical migration rate in the presence of local adaptation, (b) an analytical approximation for the gene flow reduction caused by unidirectional CI, and (c) a heuristic formula describing the invasion success of mutants at a mate preference locus. These findings generally suggest that Wolbachia-induced unidirectional CI can be a factor in divergence and speciation of hosts.