The effect of a semi-permeable, strengthening fiber coating on the expansion, mechanical properties, and residence time of gastroretentive fibrous dosage forms.

Recently, we have shown in dogs that the gastric residence time of expandable fibrous dosage forms can be prolonged by coating the fibers with a semi-permeable, strengthening coating. In this work on pigs, the effect of the volume fraction of the coating, φc, on the expansion, mechanical strength, and gastric residence time is investigated. Three methacrylic acid-ethyl acrylate-coated fibrous dosage forms with φc = 0.025, 0.041, and 0.068 were prepared and tested. Upon administering to a pig, the dosage forms expanded to a normalized radial expansion of 0.5-0.6 in 5, 8, and 10 h, respectively. The expanded dosage forms resided in the stomach and fragmented after 11, 25, and 31 h. The fragments then passed into the intestines and dissolved in 2-3 h. Models suggest that upon contact with gastric fluid, a hydrostatic pressure develops in the fibers due to the inward diffusion of water. The hydrostatic pressure in turn induces a tensile stress in the coating and the dosage form expands. The tensile stress and the expansion rate are inversely proportional to φc. The expanded dosage form eventually fractures due to the loads applied by the contracting stomach walls. The post-expansion mechanical strength and the time to fracture increase steeply with φc. The models predict the experimental results reasonably well. Thus, by increasing φc, dosage form fracture is delayed and the gastric residence time prolonged.

"EvoVax" - A rationally designed inactivated Salmonella Typhimurium vaccine induces strong and long-lasting immune responses in pigs.

Salmonella enterica subspecies enterica serovar Typhimurium (S.Tm) poses a considerable threat to public health due to its zoonotic potential. Human infections are mostly foodborne, and pork and pork products are ranked among the top culprits for transmission. In addition, the high percentage of antibiotic resistance, especially in monophasic S.Tm, limits treatment options when needed. Better S.Tm control would therefore be of benefit both for farm animals and for safety of the human food chain. A promising pre-harvest intervention is vaccination. In this study we tested safety and immunogenicity of an oral inactivated S.Tm vaccine, which has been recently shown to generate an "evolutionary trap" and to massively reduce S.Tm colonization and transmission in mice. We show that this vaccine is highly immunogenic and safe in post-weaning pigs and that administration of a single oral dose results in a strong and long-lasting serum IgG response. This has several advantages over existing - mainly live - vaccines against S.Tm, both in improved seroconversion and reduced risk of vaccine-strain persistence and reversion to virulence.

Infertility due to defective sperm flagella caused by an intronic deletion in DNAH17 that perturbs splicing.

Artificial insemination in pig (Sus scrofa domesticus) breeding involves the evaluation of the semen quality of breeding boars. Ejaculates that fulfill predefined quality requirements are processed, diluted and used for inseminations. Within short time, eight Swiss Large White boars producing immotile sperm that had multiple morphological abnormalities of the sperm flagella were noticed at a semen collection center. The eight boars were inbred on a common ancestor suggesting that the novel sperm flagella defect is a recessive trait. Transmission electron microscopy cross-sections revealed that the immotile sperm had disorganized flagellar axonemes. Haplotype-based association testing involving microarray-derived genotypes at 41,094 SNPs of six affected and 100 fertile boars yielded strong association (P = 4.22 × 10-15) at chromosome 12. Autozygosity mapping enabled us to pinpoint the causal mutation on a 1.11 Mb haplotype located between 3,473,632 and 4,587,759 bp. The haplotype carries an intronic 13-bp deletion (Chr12:3,556,401-3,556,414 bp) that is compatible with recessive inheritance. The 13-bp deletion excises the polypyrimidine tract upstream exon 56 of DNAH17 (XM_021066525.1: c.8510-17_8510-5del) encoding dynein axonemal heavy chain 17. Transcriptome analysis of the testis of two affected boars revealed that the loss of the polypyrimidine tract causes exon skipping which results in the in-frame loss of 89 amino acids from DNAH17. Disruption of DNAH17 impairs the assembly of the flagellar axoneme and manifests in multiple morphological abnormalities of the sperm flagella. Direct gene testing may now be implemented to monitor the defective allele in the Swiss Large White population and prevent the frequent manifestation of a sterilizing sperm tail disorder in breeding boars.

Antimicrobial Usage Among Different Age Categories and Herd Sizes in Swiss Farrow-to-Finish Farms.

In the Swiss pig sector, the usage of antimicrobials has been recorded, evaluated and systematically reduced on a voluntary basis since 2015. This monitoring has been carried out using various methods thereby enabling continuous national scrutiny as well as international comparisons. To gain a better understanding of the dynamics of the antimicrobial usage on Swiss farms, consumption data of farrow-to-finish farms were analyzed for (i) the within-herd relationships among different age categories and (ii) the influence of the herd size. The data were collected on 71 farms for the year 2017, encompassing the amount of active ingredients and number of defined daily doses Switzerland (nDDDch) in total, and stratified for the different age categories of piglets, weaners, fattening pigs, and sows. The differences in nDDDch per animal among the age categories were determined by a Wilcoxon test and subsequent post-hoc analysis according to Bonferroni. The within-herd relationship among the individual age categories as well as the influence of the herd size on nDDDch per animal measured as kept sows were analyzed by simple linear regression. The evaluation of the treatment days showed that 50% of the nDDDch were used in piglets, 44% for weaners, and 3% each for fattening pigs and sows. Compared to the other age categories, the examination of the number of nDDDch per animal showed a significantly higher number for sows, whereas for fattening pigs the number was significantly lower (P < 0.01). The farm-based analysis using linear regression showed a relationship between antimicrobial usage in sows and piglets (P < 0.001; adj. R 2 = 0.19). Similarly, a significant relationship between larger herd size and increased antimicrobial usage was observed (P = 0.02; adj. R 2 = 0.06). The present study provides an insight into the antimicrobial treatment dynamics of farrow-to-finish farms. In particular, the age categories piglets and sows-with their higher number of treatment days in total or per animal-are of interest regarding the potential reduction in antimicrobial usage. Likewise, larger farms with higher management requirements were found to be of particular importance for the reduction of antimicrobial usage. Monitoring programs should therefore evaluate different age categories separately to identify problems for individual farms.

Agreement of Benchmarking High Antimicrobial Usage Farms Based on Either Animal Treatment Index or Number of National Defined Daily Doses.

Introduction: While treatment frequency as an indicator of antimicrobial consumption is often assessed using defined doses, it can also be calculated directly as an Animal Treatment Index (ATI). In this study, the correlation of calculating antimicrobial usage on Swiss pig farms using either national Defined Daily Doses (DDDch) or an ATI (number of treatments per animal per year) and the agreement between the different methods for the identification of high usage farms were investigated. Material and Methods: The antimicrobial consumption of 893 Swiss pig herds was calculated separately for suckling piglets, weaned piglets, fattening pigs, lactating and gestating sows using the indicators nDDDch (number of DDDch) per animal per year and ATI. Correlations between the indicators were investigated by calculating Spearman's Rho coefficients. The 5, 10, and 25% highest usage farms were determined by applying both methods and the interrater reliability was described using Cohen's Kappa coefficients and visualized by Bland-Altman plots. Results: The Spearman's Rho coefficients showed strong correlations (r > 0.5) between nDDDch/animal/year and ATI. The lowest coefficient was shown for the correlation of both indicators in gestating sows (r = 0.657) and the highest in weaned piglets (r = 0.910). Kappa coefficients identifying high usage farms were the highest in weaned piglets (k = 0.71, 0.85, and 0.91, respectively for 5, 10, and 25% most frequent users) and the lowest in gestating sows (k = 0.54, 0.58, and 0.55 for 5, 10, and 25% most frequent users). Conclusions: In general, the investigated indicators showed strong correlations and a broad agreement in terms of the calculated levels of antimicrobial usage and the identification of high usage farms. Nevertheless, a certain proportion of the farms were defined differently depending on the indicator used. These differences varied by age category and were larger in all age categories except weaned piglets when a higher percentage benchmark was used to define high usage farms. These aspects should be considered when designing scientific studies or monitoring systems and considering which indicator to use.

Impact of the Suissano Health Programme on antimicrobial usage on 291 pig farms in Switzerland.

BACKGROUND: In 2015, in Switzerland the Suissano Health Programme was implemented in pig production to improve transparency for antimicrobial usage (AMU) and to reduce the usage of fluoroquinolones (FQ), macrolides and cephalosporins, representing highest priority critically important antimicrobials. METHODS: In the presented cohort study, the impact of the Suissano programme on the AMU of 291 pig farms between 2016 and 2017 was investigated. AMU was calculated in total numbers of defined course doses (nDCDch) for all farms in the programme. For each single farm the nDCDch/animal/year was determined for four different age categories (suckling piglets, weaned piglets, fattening pigs, sows) as well as each antimicrobial substance separately. Trends between 2016 and 2017 were investigated for all farms as well as the 25 per cent with the highest usage of antimicrobials (high users) separately. RESULTS: Total AMU measured in nDCDch declined by 23 per cent between 2016 and 2017, but statistically significant differences could not be observed when comparing the data sets of the individual farms. A significantly reduced usage of FQ could be demonstrated in suckling piglets (P=0.003), weaned piglets (P=0.006) and sows (P=0.008) in 2017 compared with 2016. For high users, a significant reduction of total AMU could be shown in suckling piglets (P=0.02), weaned piglets (P=0.0004) and fattening pigs (P=0.01). CONCLUSION: This study demonstrated a significant reduction in the usage of FQs in suckling piglets, weaned piglets and sows as well as total AMU in suckling piglets, weaned piglets and fattening pigs on high-usage farms.

Antimicrobial Drug Consumption on Swiss Pig Farms: A Comparison of Swiss and European Defined Daily and Course Doses in the Field.

Defined Daily Doses (DDD) and Defined Course Doses (DCD) have been established in both human and veterinary medicine in order to standardize the measurement of treatments in a population. In 2016 the European Medicines Agency published average defined daily dose (DDDvet) and defined course dose (DCDvet) values for antimicrobial agents used in livestock production. Similarly, national defined doses (DDDch and DCDch) for the pig sector in Switzerland have recently been determined. The aim of this study was to compare the outcome of calculating antimicrobial consumption based on either DDDvet/DCDvet or DDDch/DCDch. Data from 227 Swiss pig farms describing antimicrobial use in 2015 was collected. The numbers of treatment days and treatments were calculated using DDDvet/DCDvet and DDDch/DCDch respectively, for each farm in total and for different antimicrobial classes. Associations between calculated numbers of DDDvet/DCDvet and DDDch/DCDch on farm level were investigated. In addition, differences concerning antimicrobial use were investigated between different production types of farms (piglet-producer, finishing farm or farrow-to-finishing farm). Using DDDch/DCDch values we calculated 1,805,494 treatment days and 433,678 treatments compared to 1,456,771 treatment days (19% ratio) and 303,913 treatments (30% ratio) based on DDDvet/DCDvet. Penicillins (21.4/26.6%), polypeptides (18.6/27.6%) and fluoroquinolones (9.5/8.8%) were the most frequently used classes of antimicrobials based on calculation using both DDDch and DDDvet. Similar findings were observed for complete treatments (DCDch/vet) (penicillins: 52.8/39.6%; polypeptides: 7.8/14.2%; fluoroquinolones: 13.2/12.9%). The number of treatment days or treatments per farm was higher for piglet-producers and farrow-to-finishing farms compared to finisher farms regardless of whether Swiss or European DDD or DCD values were used for the calculation (each P < 0.001). Similar results for antimicrobial use (AMU) obtained at farm level were observed when calculated either by Swiss or European definitions. Nevertheless, marked differences could be observed in the assessment of the use of specific antimicrobial classes in the field based on DDDvet/DCDvet compared to DDDch/DCDch.