Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Wind waves in sea ice of the western Arctic and a global coupled wave-ice model.

The retreat of Arctic sea ice is enabling increased ocean wave activity at the sea ice edge, yet the interactions between surface waves and sea ice are not fully understood. Here, we examine in situ observations of wave spectra spanning 2012-2021 in the western Arctic marginal ice zone (MIZ). Swells exceeding 30 cm are rarely observed beyond 100 km inside the MIZ. However, local wind waves are observed in patches of open water amid partial ice cover during the summer. These local waves remain fetch-limited between ice floes with heights less than 1 m. To investigate these waves at climate scales, we conduct experiments varying wave attenuation and generation in ice with a global model including coupled interactions between waves and sea ice. A weak high-frequency attenuation rate is required to simulate the local waves in observations. The choices of attenuation scheme and wind input in ice have a remarkable impact on the extent of wave activity across ice-covered oceans, particularly in the Antarctic. As well as demonstrating the need for stronger constraints on wave attenuation, our results suggest that further attention should be directed towards locally generated wind waves and their role in sea ice evolution. This article is part of the theme issue 'Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks'.

Marginal ice zone dynamics: future research perspectives and pathways.

Perspectives are discussed on future directions for the field of marginal ice zone (MIZ) dynamics, based on the extraordinary progress made over the past decade in its theory, modelling and observations. Research themes are proposed that would shift the field's focus towards the broader implications of MIZ dynamics in the climate system. In particular, pathways are recommended for research that highlights the impacts of trends in the MIZ on the responses of Arctic and Antarctic sea ice to climate change. This article is part of the theme issue 'Theory, modelling and observations of marginal ice zone dynamics: multidisciplinary perspectives and outlooks'.

Antimicrobial susceptibility in E. coli and Pasteurellaceae at the beginning and at the end of the fattening process in veal calves: Comparing 'outdoor veal calf' and conventional operations.

Animal husbandry requires practical measures to limit antimicrobial resistance (AMR). Therefore, a novel management and housing concept for veal calf fattening was implemented on 19 intervention farms (IF) and evaluated regarding its effects on AMR in Escherichia (E.) coli, Pasteurella (P.) multocida and Mannheimia (M.) haemolytica in comparison with 19 conventional control farms (CF). Treatment intensity (-80%) and mortality (-50%) were significantly lower in IF than in CF, however, production parameters did not differ significantly between groups. Rectal and nasopharyngeal swabs were taken at the beginning and the end of the fattening period. Susceptibility testing by determination of the minimum inhibitory concentration was performed on 5420 isolates. The presence of AMR was described as prevalence of resistant isolates (%), by calculating the Antimicrobial Resistance Index (ARI: number of resistance of one isolate to single drugs/total number of drugs tested), by the occurrence of pansusceptible isolates (susceptible to all tested drugs, ARI=0), and by calculating the prevalence of multidrug (≥3) resistant isolates (MDR). Before slaughter, odds for carrying pansusceptible E. coli were higher in IF than in CF (+65%, p=0.022), whereas ARI was lower (-16%, p=0.003), and MDR isolates were less prevalent (-65%, p=0.001). For P. multocida, odds for carrying pansusceptible isolates were higher in IF before slaughter compared to CF (+990%, p=0.009). No differences between IF and CF were seen regarding the prevalence of pansuceptible M. haemolytica. These findings indicate that easy-to-implement measures to improve calf management can lead to a limitation of AMR in Swiss veal fattening farms.

[Evaluation of associations between barn characteristics, results of barn climate parameter measurements and health indicators in Swiss veal calf herds]. / Evaluation der Zusammenhänge zwischen Stallmerkmalen, gemessenen Stallklimaparametern und Indikatoren für Tiergesundheit in Schweizer Kälbermastbetrieben.

INTRODUCTION: Easy-to-use digital devices to measure climate parameters that can also be used in calf barns have become available commercially in recent years. Data collected in a prospective cohort study in 43 Swiss veal calf operations were evaluated with regard to validity of measured climate parameters, potential associations of those with barn features, and relationships between values of climate parameters and barn characteristics, respectively, with indicators of calf health. Barn parameters, such as ventilation system, access to an outdoor pen and barn size, were recorded, and temperature, air humidity, ammonia and carbone dioxide concentrations were measured at five different locations in each barn during an average of six farm visits over a year. Furthermore, continuous measurements of temperature and humidity (over a period of 72 hours each) were performed once in summer and once in winter in each farm. Whether barn parameters and measured barn climate values are associated as significant risk factors with indicators of calf health (antimicrobial use, mortality and daily weight gain) was explored with statistical methods. Values outside the optimal range were observed for all parameters measured punctually during farm visits and in all seasons. Values of temperature and humidity outside the optimal range were observed more often by continuous than by punctual measurements. Relevant correlations were observed neither among the barn climate values measured punctually nor among measured barn climate values and number of calves, barn surface, bedded surface and barn volume. High maximal group size and presence of mechanic ventilation were positively associated with high antimicrobial use, and high maximal group size and high number of fattening groups were associated with mortality >3%. Farms in lowland regions and high air volume per calf were positively associated with daily weight gain. None of the measured barn climate parameters was associated with the calf health indicators antimicrobial use, mortality and daily weight gain. Therefore, climate parameter measurements appear inadequate to predict calf health in veal fattening operations. The present results show that these (easily) measured parameters are difficult to interpret and should be considered critically.

INTRODUCTION: Des instruments de mesure digitaux faciles à l'emploi pour les paramètres climatiques, qui peuvent aussi être utilisés dans les étables, sont disponibles depuis quelque temps.Afin d'évaluer la validité des valeurs de paramètres du climat mesurées, d'éventuelles associations de ces mesures avec certaines caractéristiques des étables, et les relations des mesures de paramètres associés au climat, respectivement des spécificités des étables, avec des indicateurs de santé animale, des données récoltées dans le cadre d'une étude prospective dans 43 exploitations d'engraissement de veaux en Suisse ont été analysées. D'une part, différents paramètres des étables (tels que le système d'aération, l'accès à un enclos externe, la surface de l'étable) ont été répertoriés. D'autre part, des mesures ponctuelles de la température, de l'humidité de l'air et des concentrations d'ammoniac et de dioxide de carbone ont été effectuées à cinq endroits de chaque étable lors de visites d'exploitation (en moyenne six par ferme sur une durée d'une année). De plus, des mesures continues de la température et de l'humidité ont été conduites sur 72 heures, une fois en été et une fois en hiver, dans chaque exploitation. À l'aide de méthodes statistiques, on a évalué si les caractéristiques des étables et les valeurs de climat mesurées sont associées en tant que facteurs de risque significatifs avec les indicateurs de santé animale (usage d'antibiotiques, mortalité et gain de poids journalier). Lors des mesures ponctuelles, des valeurs en dehors des domaines optimaux ont été observées pour tous les paramètres mesurés et à chaque saison. Des valeurs en dehors des domaines optimaux pour la température et l'humidité ont été constatées plus souvent par les mesures continues que par les mesures ponctuelles. Aucune corrélation significatrice n'a été observée entre les valeurs des paramètres de climat mesurées ponctuellement ou entre les valeurs des paramètres du climat mesurées et le nombre de veaux présents dans l'étable, la surface totale de l'étable, la surface paillée ou le volume de l'étable. Les groupes comptant beaucoup de veaux et la présence d'une ventilation mécanique étaient associés positivement à un usage élevé d'antibiotiques. Les groupes comprenant beaucoup de veaux et la présence d'un grand nombre de groupes étaient associés avec un taux de mortalité supérieur à 3%. Les exploitations en zone de plaine et le volume d'air par veau étaient associés positivement avec le gain de poids journalier. Aucun des paramètres de climat mesurés ne montrait d'association avec les indicateurs de santé animale (usage des antibiotiques, mortalité et gain de poids journalier). Ils semblent donc être inadéquats pour évaluer la santé des veaux dans des exploitations d'engraissement. Nos résultats montrent que les mesures de paramètres du climat sont difficiles à interpréter et doivent être considérés de manière critique.

Potential of a rumen bolus containing 1,25-dihydroxyvitamin D3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows.

Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves' blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day -2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves' blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves.

Pharmacokinetics of 1,25-dihydroxyvitamin D3 glycosides from Solanum glaucophyllum extract given in a rumen bolus on blood mineral profiles in dry pregnant dairy cows.

Providing tablets of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active metabolite of vitamin D3, in a rumen bolus may be used as prevention for periparturient hypocalcemia in dairy cows. This study investigated the pharmacokinetics of 1,25(OH)2D3 glycosides extracted from Solanum glaucophyllum (SGE) on blood serum 1,25(OH)2D3, Ca, P and Mg response in dry pregnant dairy cows. Boluses contained tablets of SGE which differed in their release properties (rapid release, slow release and combination) and galenics (200 µg uncoated, 300 µg and 500 µg uncoated or coated, 2 × 500 µg uncoated). Nineteen blood samples were collected from 29 cows between 96 h before and 336 h after bolus administration. Blood serum 1,25(OH)2D3, Ca and P increased between 12 h and 120 h, 12 h and 264 h and 24 h and 264 h, respectively. Highest values were reached at 30 h, 72 h and 120 h for 1,25(OH)2D3, Ca and P, respectively. Baseline values were then reached at 216 h for 1,25(OH)2D3 and 336 h for Ca and P. Concentration of Mg decreased between 24 h and 216 h, before reaching values comparable to baseline at 264 h. Highest Ca values were obtained with the combined rapid and slow release properties (500 µg) and there was no effect from coating on pharmacokinetics. In conclusion, the antepartum oral SGE bolus administration may be suitable for the prevention of periparturient hypocalcemia.

[Meta-analysis to estimate the economic losses caused by reduced milk yield and reproductive performance associated with bovine paratuberculosis in Switzerland]. / Eine Meta-Analyse zur Schätzung der wirtschaftlichen Einbussen durch Milch- und Reproduktionsverluste infolge boviner Paratuberkulose in der Schweiz.

INTRODUCTION: Especially in regions with intensive cattle farming, paratuberculosis in ruminants can cause considerable economic losses for example through loss of sick animals, reduced milk yield and decreased reproduction performance. Although quantifying the actual economic losses is complex, this study attempts to quantify the losses caused by paratuberculosis in infected dairy farms in Switzerland by means of meta-analyses. For this purpose, in an elaborate selection process, data from 12 studies on milk yield and from three studies on the calving to conception interval were finally selected for further calculations. In addition, data from eight studies each on milk fat concentration and milk protein concentration were evaluated. For the meta-analyses, only studies in which «sick¼ (seropositive) and «healthy¼ (seronegative) animals based on the results of serum ELISA tests were compared at the individual animal level were considered. With a paratuberculosis prevalence of 5,99 % in cattle in Switzerland, a total loss of CHF 12 034 329,96 (95 % CI [CHF 8 625 406,02; CHF 16 409 276,30]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) per year was calculated for a population of 559 900 dairy cows. The main part of the losses is caused by an extended calving to conception interval: Seropositive animals need an average of 14,93 days longer (95 % CI [1,73; 28,13]) from calving to successful insemination as seronegative animals. This results in total costs for the extended calving to conception interval due to paratuberculosis of CHF 7 365 591,21 per year (95 % CI [CHF 900 394,95; CHF 14 838 087,61]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). Milk yield reduction based on a lactation period of 305 days results in an economic loss of CHF 4 668 738,75 per year (95 % CI [CHF 1 571 188,69; CHF 7 725 011,07]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Milk fat and milk protein content were not found to be significantly changed. Despite a large number of studies in the screening phase, it was not possible to calculate all types of losses attributable to paratuberculosis due to lack of comparability between the studies, which is essential for meta-analyses. Nevertheless, it was possible to carry out four different meta-analyses, the results of which give a first impression of the economic importance of paratuberculosis in dairy cows in Switzerland.

INTRODUCTION: La paratuberculose des ruminants cause, particulièrement dans les régions ayant une industrie laitière intensive, des pertes économiques considérables, par exemple par la perte d'animaux malades, la réduction de la production laitière et une reproduction diminuée. Malgré la complexité de la quantification des pertes économiques effectives, on a essayé dans l'étude présentée ici de calculer les pertes causées par la paratuberculose dans les exploitations laitières en Suisse au moyen de méta-analyses. Dans ce but, des données extraites par un processus de sélection compliqué de 12 études sur la production laitière et de trois études sur la période de tarissement ont été utilisées pour calculer les pertes dues à la paratuberculose. De plus, huit études chacune sur la concentration de graisse et des protéines du lait ont été prises en compte. Seules des études où les animaux étaient classifiés comme «sains¼ (séronégatifs) et «malades¼ (séropositifs) sur la base d'un test ELISA sérique ont été prises en considération pour les méta-analyses. Pour une prévalence de la paratuberculose de 5,99 % chez les bovins en Suisse, on a pu calculer pour une population de 559 900 vaches laitières une perte totale de 12 034 329,96 CHF (IC 95 % [8 625 406,02 CHF; 16 409 276,30 CHF]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) par année. La plus grande partie de ces pertes sont dues à une période de tarissement prolongée: les vaches séropositifs ont besoin en moyenne de 14,93 jours de plus (IC 95 % [1,73; 28,13]) du vêlage à une insémination menant à une gestation que les animaux séronégatifs. Il en résulte des coûts dus à la paratuberculose en raison d'une période de tarissement prolongée de 7 365 591,21 CHF par année (IC 95 % [900 394,95 CHF; 14 838 087,61 CHF]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). La diminution de la production laitière cause pour une durée de lactation de 305 jours une perte économique de 4 668 738,75 CHF par année (IC 95 % [1 571 188,69 CHF; 7 725 011,07 CHF]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Les pertes en valeurs de graisse et de protéines du lait n'étaient pas significatives. Malgré le nombre élevé d'études prises en compte dans la phase de recherche de publications pertinentes, il n'a pas été possible de calculer tous les types de pertes, car les études n'étaient pas suffisamment comparables entre elles, ce qui est une condition essentielle pour une méta-analyse. Il a cependant été possible de procéder à quatre méta-analyses différentes, dont les résultats donnent une idée de l'importance économique des pertes liées à la paratuberculose chez les vaches laitières en Suisse.

[Comparative economic analysis of the new concept for veal calf fattening «outdoor veal calf¼ and the conventional IP-SUISSE label]. / Vergleichende Wirtschaftlichkeitsanalyse des Kälbermastsystems «Freiluftkalb¼ und der konventionellen IP-SUISSE-Labelmast.

INTRODUCTION: The evaluation of new animal husbandry concepts includes, beyond the exploration of chosen parameters, that the question is addressed whether economic benefits for producers and ethical benefits for society result of the new system when compared to traditional systems. In a previous study, a novel management and housing concept for veal production («outdoor veal calf¼, OVC) was tested from October 2016 to July 2018. The OVC concept was associated with distinctly lower antimicrobial use while average daily weight gain was similar and calf welfare better; furthermore mortality was lower compared to conventional label fattening. The aim of the present study was to compare economics between the OVC concept on intervention farms (IF) and the IP-SUISSE label concept on control farms (CF) by calculating contribution margins (CM). The CM indicates the difference between the performance of a production branch (e. g. slaughter return) and the allocable costs for this production branch (e. g. feed costs). In the present study, two different approaches were used for CM calculation to analyze the available data in detail. No substantial differences in CM between the OVC concept and the IP-SUISSE concept were found in either approach. However, the specific CM varied between the approaches as different calculation criteria for quantities and prices were applied (approach «real¼ with accurate costs and returns from the OVC study and approach «standardized¼ with costs and returns based on the CM catalogue). The CM varied slightly for the CM per man-hour (IF «real¼: 6.96 CHF/man-hour, «standardized¼: 4.49 CHF/man-hour; CF: 7.90 CHF/man-hour and 8.08 CHF/man-hour, respectively) and considerably for the CM per fattening space and year (IF «real¼: -380.36 CHF, «standardized¼: -559.50 CHF; CF: -244.70 CHF and -318.80 CHF, -respectively). Producing veal with the OVC concept -allowed for achieving comparable CM/man-hour as in conventional label production. Thus, the farmers' economic interests should be warranted when implementing the OVC concept.

INTRODUCTION: Lors du développement de nouveaux systèmes d'élevage, on s'efforce de les tester par rapport à des paramètres sélectionnés pour évaluer si un changement apporterait une valeur ajoutée économique ou sociétale par rapport aux systèmes déjà établis. Dans une étude précédente, un nouveau type de système d'engraissement des veaux (système «veau en plein air¼, VPA) a été testé d'octobre 2016 à juillet 2018. Par rapport à l'engraissement conventionnel labellisé, considérablement moins d'antibiotiques ont été utilisés avec ce système tout en conservant les mêmes performances de croissance quotidienne et en améliorant le bien-être des animaux; de plus, la mortalité des veaux d'engraissement était plus faible. Le but de la présente étude était de procéder à une analyse économique comparative des deux systèmes de détention, VPA et label IP-SUISSE (IPS), à l'aide du calcul des marges brutes (MB). La MB indique la différence entre les performances d'une branche de production (par exemple les revenus d'abattage) et les coûts imputables à cette branche de production (par exemple les coûts d'alimentation). Dans cette étude, deux variantes des marges brutes ont été calculées afin d'évaluer en détail les données disponibles. Les deux variantes sont arrivées à la conclusion qu'il n'y avait pas de différences majeures dans la MB entre le nouveau système VPA et le système du label IP-SUISSE. Cependant, la MB spécifique différait entre les variantes, en raison des bases de calcul différentes utilisées pour chaque variante pour les quantités et les prix (variante «réelle¼ aves des revenus et coûts concrets dérivés de l'étude VPA et variante «standardisée¼ avec des revenus et des prix basés sur le catalogue des MB). Les MB variaient légèrement en ce qui concerne la MB par heure de travail productive (VPA: variante «réelle¼: 6.96 CHF/heure, «standardisée¼: 4.49 CHF/heure; IPS: variante «réelle¼ 7.90 CHF/heure, «standardisée¼ 8.08 CHF/heure) et considérablement pour la MB par place d'engraissement et par année (VPA: variante «réelle¼: ­380.36 CHF, «standardisée¼: ­559.50 CHF; IPS: variante «réelle¼: ­244.70 CHF, «standardisée¼: ­318.80 CHF). La production de viande de veau selon le système VPA permet de générer une MB/heure de travail positive similaire à celle de l'engraissement conventionnel labellisé IP-SUISSE. En conséquence, les intérêts économiques des producteurs ne paraissent pas être prétérités dans ce nouveau système d'élevage.

On the Wiener-Hopf solution of water-wave interaction with a submerged elastic or poroelastic plate.

A solution to the problem of water-wave scattering by a semi-infinite submerged thin elastic plate, which is either porous or non-porous, is presented using the Wiener-Hopf technique. The derivation of the Wiener-Hopf equation is rather different from that which is used traditionally in water-waves problems, and it leads to the required equations directly. It is also shown how the solution can be computed straightforwardly using Cauchy-type integrals, which avoids the need to find the roots of the highly non-trivial dispersion equations. We illustrate the method with some numerical computations, focusing on the evolution of an incident wave pulse which illustrates the existence of two transmitted waves in the submerged plate system. The effect of the porosity is studied, and it is shown to influence the shorter-wavelength pulse much more strongly than the longer-wavelength pulse.

Prevalence and antimicrobial resistance of opportunistic pathogens associated with bovine respiratory disease isolated from nasopharyngeal swabs of veal calves in Switzerland.

The composition of the bacterial flora in the calf nasopharynx might influence the risk of bovine respiratory disease (BRD). The aims of the present study were, firstly, to investigate the prevalence of bacteria potentially involved in BRD in the nasopharynx of veal calves and to identify associated risk factors for their presence, and, secondly, to provide data on antimicrobial resistance levels in these bacteria. Deep nasopharyngeal swabs were collected from veal calves on 12 Swiss farms over a period of one year by non-random, but systematic sampling for isolation of Pasteurellaceae and Mycoplasma (M.) bovis and dispar. Associations of potential risk factors with occurrence of these bacteria were tested in multivariable mixed logistic regression analyses, based on information gained from extensive questionnaires completed with the farmers. Antimicrobial susceptibility testing was performed for Pasteurellaceae by broth microdilution method to obtain minimal inhibitory concentrations (MIC). Pasteurellaceae, including Pasteurella (P.) multocida, Mannheimia (M.) haemolytica, Bisgaard Taxon 39 and Histophilus (H.) somni, were almost twice as prevalent as M. bovis and dispar in this study. Continuous stocking was a risk factor for the presence of Pasteurellaceae, especially when calves originated from more than six suppliers. In young calves (≤ 91 days), feeding of California Mastitis Test (CMT) positive milk was an additional risk factor for the presence of Pasteurellaceae whereas transport of calves by farmers and livestock traders (as opposed to transport only by farmers) increased the risk in older calves (> 91 days). Risk factors for the presence of M. bovis/dispar were higher number of calves per drinking nipple in young calves, and no access to an outside pen and feeding of CMT positive milk in older calves, respectively. While further research will have to investigate the observed associations in more detail, this suggests that management can play an important role in the prevalence of nasopharyngeal bacteria with a potential subsequent involvement in BRD. Antimicrobial resistance differed between the three bacterial species tested in this study and was highest to oxytetracycline and spectinomycin in P. multocida, oxytetracycline and penicillin in M. haemolytica, and ampicillin and penicillin in H. somni. Only two European VetCAST breakpoints (for florfenicol in P. multocida and M. haemolytica) have been published to date, matching the MIC distribution of the present isolate populations well, in contrast to certain commonly applied American Clinical and Laboratory Institute interpretive criteria. This highlights the potential for further refinement of clinical breakpoints in veterinary medicine.

Effects of the novel concept 'outdoor veal calf' on antimicrobial use, mortality and weight gain in Switzerland.

The aim of the intervention study 'outdoor veal calf' was to evaluate a novel concept for calf fattening which aimed at reducing antimicrobial use without compromising animal health. Management practices such as commingling of calves from multiple birth farms, crowding, and suboptimal barn climate are responsible for high antimicrobial use and mortality in the veal calf population. The risk of selecting bacteria resistant to antimicrobials and of economic losses is accordingly elevated. The 'outdoor veal calf' concept, implemented in nineteen intervention farms (IF), is based on three main measures: 1. purchased calves are transported directly from neighboring birth farms to the fattening facility instead of commingling calves in livestock dealer trucks; 2. each calf is vaccinated against pneumonia after arrival and completes a three-week quarantine in an individual hutch; and 3. the calves spend the rest of the fattening period in outdoor hutches in groups not exceeding 10 calves. The covered and bedded paddock and the group hutches provide shelter from cold weather and direct sunshine, constant access to fresh air is warranted. Nineteen conventional calf fattening operations of similar size served as controls (CF). Every farm was visited once a month for a one-year period, and data regarding animal health, treatments, and production parameters were collected. Treatment intensity was assessed by use of the defined daily dose method (TIDDD in days per animal year), and calf mortality and daily weight gain were recorded in both farm groups. Mean TIDDD was 5.3-fold lower in IF compared to CF (5.9 ±â€¯6.5 vs. 31.5 ±â€¯27.4 days per animal year; p < 0.001). Mortality was 2.1-fold lower in IF than in CF (3.1% ± 2.3 vs. 6.3 % ± 4.9; p = 0.020). Average daily gain did not differ between groups (1.29 ±â€¯0.17 kg/day in IF vs. 1.35 ±â€¯0.16 kg/day in CF; p = 0.244). A drastic reduction in antimicrobial use and mortality was achieved in the novel 'outdoor veal calf' system without compromising animal health. The principles of risk reduction used in designing the system can be used to improve management and animal health, decrease the need for antimicrobial treatments and thus selection pressure on bacteria in veal operations.

Antibiotic and quaternary ammonium compound resistance in Escherichia coli from calves at the beginning of the -fattening period in Switzerland (2017).

INTRODUCTION: In the Swiss veal calf production, antimicrobials and disinfectants are used to control bacterial infectious diseases, leading to a risk of selecting for a resistant bacterial population. While the prevalence of antibiotic resistance in E. coli from calves has been monitored at slaughterhouses in Switzerland since 2006, the resistance situation of E. coli from young calves entering the fattening period is not known. A total of 100 calves entering the fattening period in 20 geographically distant farms in Switzerland were screened for the presence of E. coli using rectal swabs in 2017. Genetic diversity between isolates was determined using repetitive palindromic Polymerase Chain Reaction (rep-PCR) revealing a genetically diverse E. coli population. Susceptibility to 13 antibiotics and to alkyldimethylbenzylammonium (ADBAC) was determined by the measurement of the minimal inhibitory concentration. Antibiotic and quaternary ammonium compound (QAC) resistance genes were identified using microarray and Polymerase Chain Reaction (PCR). Sixty-four percent of the isolates were resistant to at least one antibiotic, and 52% also exhibited decreased susceptibility to ADBAC. Resistance to more than 3 antibiotics was found in 40% of the isolates. Isolates exhibited resistance to tetracycline (57%) associated with the presence of tet genes (tet(A), (B), (E), (G)), to sulfonamides (61%) (sul1, sul2, sul3), ampicillin (56%) (blaTEM-1), trimethoprim (32%) (dfrA), phenicols (31%) (catA1, cmlA1, floR), gentamicin (27%) (ant(2")-Ia, aac(3)-IVa, aac(3)-VIa), and cefotaxime (2%) (blaCTX-M-14 (ESBL)). Mutations in GyrA (S83L) and ParC (S80I) were found in the fluoroquinolone-resistant isolates (6%). All isolates were susceptible to colistin, tigecycline and meropenem. No association between the presence of decreased susceptibility to ADBAC and qac genes was observed. In conclusion, antibiotic and QAC resistant E. coli are present in the gastrointestinal tract of young calves at the beginning of the fattening period, emphasizing the need for appropriate and reduced use of antibiotics and QAC-containing disinfectants in order to limit further selection of these bacteria during the fattening period.

INTRODUCTION: Dans la production de veaux en Suisses, des antimicrobiens et des désinfectants sont utilisés pour contrôler les maladies infectieuses bactériennes, ce qui entraîne un risque de sélection d'une population bactérienne résistante. Si la prévalence de la résistance de E. coli aux antibiotiques chez les veaux est surveillée dans les abattoirs suisses depuis 2006, la situation de la résistance de E. coli chez les jeunes veaux au début de la période d'engraissement n'est pas connue. Un total de 100 veaux entrant dans la période d'engraissement dans 20 exploitations géographiquement éloignées de Suisse ont été testés en 2017 pour détecter la présence de E. Coli à l'aide de prélèvements rectaux. La diversité génétique entre les isolats a été déterminée à l'aide de la réaction de polymérase en chaîne répétitive palindrome (rep-PCR) révélant une population de E.coli génétiquement diversifié. La sensibilité à 13 antibiotiques et au chlorure d'alkyldiméthylbenzylammonium (ADBAC) a été déterminée par la mesure de la concentration inhibitrice minimale. Les gènes de résistance aux antibiotiques et aux composés d'ammonium quaternaire (QAC) ont été identifiés à l'aide d'une puce à ADN et de la réaction de polymérase en chaîne (PCR). Soixante-quatre pour cent des isolats étaient résistants à au moins un antibiotique et 52% présentaient également une diminution de la sensibilité à l'ADBAC. Une résistance à plus de 3 antibiotiques a été trouvée dans 40% des isolats. Les isolats présentaient une résistance à la tétracycline (57%) associée à la présence de gènes tet (tet (A), (B), (E), (G)), aux sulfonamides (61%) (sul1, sul2, sul3), à l'ampicilline (56%) (blaTEM-1), au triméthoprime (32%) (dfrA), aux phénicols (31%) (catA1, cmlA1, floR), à la gentamicine (27%) (ant(2'')-Ia, aac (3) -IVa, aac (3) -VIa) et à la céfotaxime (2%) (blaCTX-M-14 (BLSE)). Les isolats résistants aux fluoroquinolones (6%) présentaient des mutations dans GyrA (S83L) et ParC (S80I). Tous les isolats étaient sensibles à la colistine, à la tigécycline et au méropénème. Aucune association entre la présence d'une sensibilité diminuée à l'ADBAC et les gènes qac n'a été observée. En conclusion, des E. coli résistants aux antibiotiques et aux QAC sont présents dans le tractus gastro-intestinal des jeunes veaux au début de la période d'engraissement, ce qui souligne la nécessité d'un usage approprié et réduit d'antibiotiques et de désinfectants contenant un QAC afin de limiter la sélection ultérieure de ces bactéries au cours de la période d'engraissement.

[Acute outbreak of lameness due to inflammatory claw disease in a beef herd]. / Akuter Ausbruch von Lahmheit infolge entzündlicher Klauenhauterkrankungen in einem Mastbetrieb.

INTRODUCTION: Several young bulls in a beef farm showed large, foul-smelling skin lesions in the plantar region of the coronary band and in the interdigital space. Some of the animals also had a painful, warm swelling in the palmar fetlock area. All bulls were lame (score 4/5), the most severely affected animal had a lameness score of 5/5. Initial local treatment was unsuccessful, therefore the animals received parenteral antimicrobial treatment leading to improvement of clinical signs and weight bearing in most animals. However, several animals were slaughtered prematurely due to severe foot lesions. The diverse clinical picture did not allow for diagnosing one specific claw affection without further diagnostic investigations. Histopathological and bacteriological examinations confirmed the diagnosis of digital dermatitis (DD) in combination with an interdigital phlegmon, whereby five of the seven examined specimens were positive for one or more Treponema spp. Treponemes belong to the spirochetes, the ones commonly involved in DD in dairy cows include Treponema medium, Treponema phagedenis and Treponema pedis. The last two species were detected in the present cases. The clinical findings and results of diagnostic investigations indicate that a severe form of DD complicated by a secondary infection and interdigital phlegmon caused an outbreak of severe lameness in young bulls in a beef farm. Single or combined claw diseases can be associated with severe losses not only in dairy but also in beef herds.

INTRODUCTION: Plusieurs jeunes taureaux dans une exploitation d'engraissement ont présenté, en particulier aux membres postérieurs, des lésions étendues et malodorantes au niveau plantaire de la couronne, qui s'étendaient jusqu'à l'espace interdigital. Certains animaux présentaient une enflure chaude et très douloureuse dans le pli du boulet. Les animaux étaient fortement boiteux (4/5), le taureau le plus atteint présentait une boiterie très sévère (5/5). Un traitement initial local a été mis en place, cependant, en l'absence de succès thérapeutique, les animaux ont été ensuite traités par voie parentérale avec un antibiotique, ce qui permis de réduire la sévérité du tableau clinique et d'améliorer la charge des membres atteints. En raison de la gravité des lésions, plusieurs animaux ont toutefois dû être abattus prématurément. Au vu de la diversité du tableau clinique, la maladie n'a pas pu être attribuée à une maladie des onglons particulière sans clarification supplémentaire du diagnostic. Un diagnostic de dermatite digitale en combinaison avec un phlegmon interdigital a été confirmé par l'analyse histopathologique ainsi que l'examen bactériologique: cinq des sept écouvillons examinés étaient positifs pour un ou plusieurs Treponema spp. Dans la famille des spirochètes, Treponema medium, Treponema phagedenis et Treponema pedis sont les tréponèmes le plus souvent impliqués dans la dermatite digitale chez les vaches laitières. Les deux germes mentionnés en dernier ont été mis en évidence dans les échantillons prélevés sur les taureaux d'engraissement décrits ici. L'image clinique et les résultats d'analyses des échantillons examinés suggèrent qu'une forme sévère de dermatite digitale compliquée par une infection secondaire et le développement d'un phlegmon interdigital s'est développée lors de l'épidémie de forte boiterie observée dans une exploitation d'engraissement. Les maladies des onglons, individuellement ou en combinaison, peuvent donc occasionner des pertes importantes dans les exploitations d'engraissement.

Associations between antimicrobial treatment modalities and antimicrobial susceptibility in Pasteurellaceae and E. coli isolated from veal calves under field conditions.

Antimicrobial consumption, with bovine respiratory disease as main indication, is higher in the veal calf industry compared to other livestock production branches. The aim of the present study was to investigate possible associations between antimicrobial drug use and resistance in Pasteurellaceae and indicator Escherichia (E.) coli from veal calves under field conditions in a prospective trial. Over a period of one year, nasopharyngeal and rectal swabs were collected from 2587 animals on 12 and 43 farms, respectively. Antimicrobial susceptibility testing was performed on 346 Mannheimia (M.) haemolytica, 1162 Pasteurella (P.) multocida and 2138 E. coli. Drug use was quantified as treatment incidence for each farm based on the used daily dose methodology (TIUDD), separately for group and individual treatments, and for antimicrobial classes. In multivariable mixed logistic regression analyses, risk factors could be identified for reduced susceptibility to certain antimicrobial classes. Group treatment was generally associated with higher rates of not susceptible (NS) M. haemolytica and P. multocida and non-wildtype (non-WT) E. coli. Individual treatment was associated with less NS and non-WT isolates. Age and entry protocol were important confounders with younger animals showing higher rates of NS and non-WT strains. The present findings suggest that, under field conditions, targeted individual treatment of calves can reduce the development of antimicrobial resistance compared to oral group treatment. For the different microorganisms, risk factors for resistance were partially different. This demonstrates that indicator organisms like E. coli do not necessarily reflect the associations observed in respiratory pathogens.

[Transport of veal calves from birth farms to veal farms and calf management in Swiss dairy farms]. / Transporte von Mastkälbern vom Geburts- auf den Mastbetrieb und Kälbermanagement in Schweizer Geburtsbetrieben.

INTRODUCTION: The calf transports of 34 veal farms were documented over a one-year period in order to describe the transport from dairy to veal farms. Veal farms were visited four to eight times, and general farm management data and information on calf purchase were collected. Thirty-five transports were accompanied and documented in detail by the project team. Whenever possible during the accompanied transports, a questionnaire on calf management prior to purchase (calving location, colostrum feeding, vaccinations, iron and selenium supplementation) was filled in with the manager of the dairy (birth) farm. Unaccompanied transports were recorded using a form completed by the veal farmers and the transporters. Information was collected on the number and origin of the calves, transport duration and distance, and stops on farms and markets. A total of 721 transports from dairy to veal farms (531 transports by veal farmers and 190 by suppliers/livestock traders) were documented in the course of the project. Six veal farmers always collected and transported their own calves, nine received their calves from cattle traders only, and 19 used both systems. Veal farmers transported a median of 2.0 (1-21 calves) and traders 3.0 calves (1-74 calves) per transport. The median number of dairy farms per 10 transported calves was 10.0 (1.2-10 dairy farms per 10 transported calves) for transports performed by veal farmers, and 10.0 (2.5-10 dairy farms per 10 transported calves) by traders. The median transport duration was 20.0 minutes (1-330 minutes) with veal farmers and 45.0 minutes (2-414 minutes) with traders. The median available surface per calf during transport was 2 m2 (0.4-6 m2) in transports by veal farmers and 0.6 m2 (0.4-2.7 m2) in those by traders. No bedding was provided on three transports performed by veal farmers although this is prescribed by law. Intranasal vaccination against respiratory disease was performed in 7% of the 88 birth farms included in the study.

INTRODUCTION: Afin de documenter les transports de veaux des exploitations de naissance aux exploitations d'engraissement, les transports dans 34 fermes d'engraissement ont été documentés pendant un an. Les exploitations d'engraissement ont été visitées quatre à huit fois au cours de cette période et des données générales ont été recueillies sur l'exploitation et sur l'achat des veaux. Trente-cinq transports ont été accompagnés et documentés avec précision par l'équipe du projet. Si possible, un questionnaire sur la gestion des veaux avant la vente (lieu de naissance, apport en colostrum, vaccinations, administration de fer et de sélénium) a été rempli avec les responsables de l'exploitation de naissance lors des transports accompagnés. Les autres transports (non accompagnés) ont été documentés à l'aide d'un formulaire que les agriculteurs ont rempli avec les transporteurs. Des informations ont été recueillies sur le nombre et l'origine des veaux, la durée et la distance de transport, ainsi que les arrêts dans les fermes et les marchés. Au total, 721 transports de l'exploitation de naissance à celle d'engraissement ont pu être documentés au cours du projet (531 transports par les engraisseurs eux-mêmes et 190 par des fournisseurs/marchands de bétail). Sur les 34 engraisseurs, six allaient toujours chercher leurs veaux eux-mêmes, neuf les achetaient toujours à un fournisseur, et 19 faisaient les deux. Les engraisseurs transportaient un médian de 2,0 veaux (1-21 veaux) et les fournisseurs de 3,0 veaux (1-74 veaux) par transport. Le nombre médian d'exploitations de naissance par 10 veaux transportés était 10,0 (1,2 à 10 exploitations par 10 veaux) pour les transports effectués par les engraisseurs et de 10,0 pour ceux effectués par les fournisseurs (2,5 à 10 exploitations par 10 veaux). La durée médiane des transports était de 20,0 minutes (1-330 minutes) pour les engraisseurs et de 45,0 minutes (2-414 minutes) pour les marchands de bétail. Pour les transports accompagnés, la surface médiane par veau était de 2 m2 (0,4 à 6 m2) pour les engraisseurs et de 0,6 m2 (0,4 à 2,7 m2) pour les marchands. Il n'y avait pas de litière sur trois transports d'engraisseurs, bien que cela soit exigé par la loi. Une vaccination intranasale contre les maladies respiratoires était réalisée dans 7% des 88 fermes de naissance pour lesquelles un questionnaire a été rempli.

Effects of management practices, animal transport and barn climate on animal health and antimicrobial use in Swiss veal calf operations.

To assess the effects of transport, management factors and barn climate on calf health, 43 Swiss veal farms (11 large farms fattening ≥100 calves and 32 small farms fattening >20 but <100 calves per year) were monitored in a prospective cohort study over a period of one year. Detailed questionnaires on farm structure, management, housing system and animal health were filled out with the farmers during bimonthly visits, and barn temperature, humidity, ammonia and CO2 concentrations were measured. Temperature and humidity were also measured continuously over 72 h once each in winter and summer. In addition, calf purchase and transport from birth farm to fattening unit were documented by the farmers, and the study team accompanied one transport per farm whenever possible. Antimicrobial treatment incidence was calculated from the used daily dose (TIUDD). Risk factors for mortality, average daily weight gain (ADG) and antimicrobial use, as well as factors related to transport and barn climate measures were evaluated with mixed regression models. The overall mortality rate was 5.1% (6.2% in large herds and 3.1% in small ones). Identified risk factors for mortality >3% included a lower number of calves fattened per year and a good hygiene of the feeder. This surprising result was likely due to the fact that the threshold of 3% mortality was rather exceeded in smaller farms. Furthemore, higher temperature variation (range between maximal and minimal temperature over 3 measurement days) in the calf pen was associated with mortality >3% in the univariable analysis. The overall mean ADG was 1.40 ± 0.16 kg. Calf purchase was significantly associated with decreased ADG. The median overall TIUDD was eight daily doses per calf and year (2.1 in small farms and 26 in large farms, respectively); the main indication for treatment was respiratory disease (81.1%). Risk factors for increased TI were no quarantine upon arrival, access to an outside pen, higher numbers of calves per drinking nipple, mechanical ventilation, vaccination against bovine respiratory disease, and a maximum ammonia value >10 ppm in the calf pen. In addition, a higher number of birth farms and calf purchase from markets were associated with increased TI in the univariable analysis. The identified risk factors associated with increased TI and mortality and with decreased ADG should be addressed in priority in veal calf operations to improve calf health and reduce antimicrobial use.

Three-dimensional time-domain scattering of waves in the marginal ice zone.

Three-dimensional scattering of ocean surface waves in the marginal ice zone (MIZ) is determined in the time domain. The solution is found using spectral analysis of the linear operator for the Boltzmann equation. The method to calculate the scattering kernel that arises in the Boltzmann model from the single-floe solution is also presented along with new identities for the far-field scattering, which can be used to validate the single-floe solution. The spectrum of the operator is computed, and it is shown to have a universal structure under a special non-dimensionalization. This universal structure implies that under a scaling wave scattering in the MIZ has similar properties for a large range of ice types and wave periods. A scattering theory solution using fast Fourier transforms is given to find the solution for directional incident wave packets. A numerical solution method is also given using the split-step method and this is used to validate the spectral solution. Numerical calculations of the evolution of a typical wave field are presented.This article is part of the theme issue 'Modelling of sea-ice phenomena'.

[The significance of cryptosporidiosis for the health of calves in Switzerland]. / Die Bedeutung der Cryptosporidiose für die Kälbergesundheit in der Schweiz.

INTRODUCTION: Diarrhea in calves is one of the most important cattle diseases in Switzerland. The diagnosis and treatment of calf diarrhea represent a major challenge. Single-celled Cryptosporidium parasites are the most prevalent causative agents of calf diarrhea besides rotavirus in the first weeks of life, and are responsible for about 50% of diarrheal cases. Cryptosporidium parvum has been described as a cause of diarrhea in one to three weeks old calves since the 1970s. Oral ingestion of persistent environmental oocysts results in severe diarrhea lasting four to six days and shedding of large numbers of infectious oocysts. A tiny amount of 10 oocysts is already sufficient to cause disease. Detailed knowledge about the epidemiology and virulence of the different C. parvum strains is still lacking. In addition, current diagnostic tests cannot reliably distinguish between non-pathogenic (e.g. C. bovis) and pathogenic Cryptosporidium species. Until now, no effective therapeutic drug or vaccine against calf cryptosporidiosis has been found. Water-borne epidemics and the zoonotic potential of Cryptosporidium in immunodeficient patients are of great medical importance. The increasing number of cryptosporidiosis cases associated with high infant mortality in less industrialized and impoverished regions (including South-East Asia and sub-Saharan Africa) has intensified the research in recent years. The recent discoveries of new therapeutics against C. parvum may benefit calf medicine in the near future. This review article reports on these new developments, highlights calf cryptosporidiosis in Switzerland and draws attention to a new research project.

INTRODUCTION: La diarrhée chez les veaux est l'une des maladies du bétail les plus courantes en Suisse. Le diagnostic de la cause et le traitement de la diarrhée des veaux représentent un défi majeur. En Suisse, les cryptosporidies sont, avec les rotavirus, l'agent causal le plus fréquent de diarrhée du veau dans les premières semaines et elles sont responsables d'environ 50% des cas. Le parasite unicellulaire Cryptosporidium parvum a été décrit depuis les années 1970 comme un agent de diarrhée chez les veaux d'une à trois semaines. Après ingestion orale d'oocystes persistants dans l'environnement, il se produit après quelques jours une diarrhée sévère de quatre à six jours avec excrétion massive d'oocystes déjà infectieux. Même quelques oocystes persistants dans l'environnement peuvent être pathogènes. Du point de vue épidémiologique, il existe encore de grandes lacunes dans la connaissance de la variabilité suspectée dans la virulence de diverses souches de C. parvum. En outre, des espèces non pathogènes (entre autres Cryptosporidium bovis) peuvent être présentes chez les veaux, qui ne se distinguent pas de C. parvum avec les tests diagnostiques actuels. Jusqu'à présent, aucun médicament efficace sur le plan thérapeutique et aucun vaccin contre la cryptosporidiose du veau n'ont été trouvés. En médecine humaine, les épidémies transmises par l'eau (en particulier aux États-Unis) et l'importance zoonotique des cryptosporidies comme pathogènes opportunistes chez les personnes immunodéficientes jouent un rôle de premier plan. La forte morbidité de la cryptosporidiose associée à une forte mortalité infantile dans les régions les moins industrialisées et les plus pauvres (entre autres en Asie du Sud-Est et en Afrique subsaharienne) ont relancé la recherche sur ces parasites au cours des dernières années. En particulier, la découverte de nouveaux médicaments contre C. parvum est susceptible de bénéficier à la médecine du veau dans un proche avenir. Cet article de synthèse fait le point sur ces nouveaux développements mais surtout sur la cryptosporidiose du veau en Suisse et attire l'attention sur un nouveau projet de recherche.

[Bovine dilated cardiomyopathy: Almost forgotten but still present]. / Bovine dilatative Kardiomyopathie: Altbekannt und dennoch gegenwärtig.

INTRODUCTION: Numerous cases of bovine dilatative cardiomyopathy (BDCMP) were registered in the nineteen-eighties, but the prevalence decreased steadily thanks to classical selection measures, i.e. excluding putative carrier animals from breeding. The cases described here show that the recessively inherited disease is still present in the Swiss cattle population. By use of a direct gene test developed a few years ago, a clinical tentative diagnosis can be confirmed. Since the end of the year 2016, carriers are officially labelled as such in Switzerland. Currently, about 2% of the insemination sires of the Holstein, Red Holstein and Swiss Fleckvieh breeds carry the causative mutation in the OPA3 gene. A combination of increased awareness of the disease and use of the gene test should allow for complete elimination of the disease from the Swiss cattle population.

INTRODUCTION: De nombreux cas de cardiomyopathie dilatative bovine (CMPDB) ont été rapportés dans les années 1980. Leur prévalence a ensuite fortement diminué grâce à des mesures classiques de sélection, à savoir l'exclusion de l'élevage des porteurs potentiels. Les cas décrits ici montrent que cette maladie héréditaire récessive, quoique rare, est toujours bien présente dans la population bovine suisse. Un test génétique direct développé il y a quelques années permet de confirmer définitivement un diagnostic de suspicion clinique. Depuis fin 2016, les porteurs de la mutation sont signalés officiellement en Suisse: environ 2% des taureaux d'insémination des races Holstein, Red Holstein et tachetée rouge sont porteurs de la mutation causative du gène OPA3. Une attention augmentée et un usage accru du test génétique rendent possible pour la première fois une éradication complète de la maladie du cheptel bovin suisse.