Suppressive antibiotic therapy for infectious endocarditis.

OBJECTIVES: Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. METHODS: We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. RESULTS: The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. CONCLUSION: Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

[Importance of biopsy in the diagnostic assessment of chronic wounds-position paper of the Initiative Chronische Wunden (ICW) e. V.] / Stellenwert der Biopsie in der Diagnostik chronischer Wunden ­ ein Positionspapier der Initiative Chronische Wunden (ICW) e. V.

Diagnostic assessment of chronic wounds is essential for the initiation of causal therapeutic treatment. For diagnostic classification of the wound genesis, it may be necessary to take a tissue sample for histological and/or microbiological processing. If there is clinical suspicion of a specific cause of the wound such as a neoplasm, an inflammatory dermatosis or a pathogen-induced wound, a tissue sample for further diagnosis is required immediately. If the ulceration does not respond sufficiently to adequate causal therapy, a tissue sample for further evaluation is recommended after 12 weeks. The choice of the correct sampling technique, further storage, transport and processing are just as decisive for a reliable result as the specific question for the diagnostic laboratory.

[DDB2-associated incidence of squamous cell carcinoma in Haflingers: risk minimization by genotyping]. / DDB2-assoziiertes Vorkommen von Plattenepithelkarzinomen beim Haflinger: Risikominimierung durch Genotypisierung.

INTRODUCTION: SCC (squamous cell carinomas) are among the most common eye neoplasms in horses. In recent studies Haflinger horses with a homozygous genotype for a missense variant in the DDB2 gene (damage specific DNA binding protein 2) had a significant increased risk of developing ocular SCC. The aims of this study were to determine the frequency of the SCC-associated risk allele in the DDB2 gene in Swiss and Austrian Haflinger populations and to validate the previously described phenotypic correlation. For this purpose, Haflingers presented at various horse clinics in Switzerland (n = 21, including 11 SCC cases), privately kept Haflingers (n = 52, including 1 SCC case), and Haflingers from a stud farm in the Austrian Tyrol (n = 53) were recruited. The individual DDB2 genotype of the animals was determined using a polymerase chain ceaction (PCR) test using hair follicle or whole blood samples. Of the 12 horses suffering from SCC, nine had ocular SCC and three had non-ocular SCC. Six of the nine Haflingers with ocular SCC and one of the three Haflingers with non-ocular SCC were homozygous for the DDB2 variant. Of the 113 clinically normal animals, 7/113 were homozygous (6 %) and 42/113 were heterozygous (37 %), which corresponds to an allele frequency of 24,8 % in the control cohort. The risk of ocular SCC occurring in Haflingers is significantly increased with the homozygous DDB2 genotype. However, not all animals with SCC carry this gene variant and not all DDB2 homozygous animals develop SCC, which can be explained by the multifactorial genesis of the disease. Due to the high frequency of the undesirable allele, we recommend taking the individual DDB2 genotype of breeding animals into account in order to avoid homozygous offspring with a greatly increased SCC risk by excluding high-risk matings.

INTRODUCTION: Les carcinomes épidermoïdes (CE) sont parmi les néoplasmes oculaires les plus fréquents chez les chevaux. Des études récentes ont montré que les chevaux Haflinger présentant un génotype homozygote pour un variant faux-sens dans le gène DDB2 (damage specific DNA binding protein 2) avaient un risque significativement plus élevé de développer un CE oculaire. Les objectifs de cette étude étaient de déterminer la fréquence de l'allèle à risque associé au CE dans le gène DDB2 dans les populations suisses et autrichiennes de Haflinger et de valider la corrélation phénotypique décrite précédemment. Pour ce faire, des Haflingers présentés dans différentes cliniques équines en Suisse (n = 21, dont 11 cas de CE), des Haflingers privés (n = 52, dont 1 cas de CE) et des Haflingers d'un haras du Tyrol autrichien (n = 53) ont été recrutés. Le génotype DDB2 individuel des animaux a été déterminé à l'aide d'un test de réaction en chaîne par polymérase (PCR) utilisant des échantillons de follicules pileux ou de sang total. Sur les 12 chevaux souffrant de CE, neuf avaient un CE oculaire et trois un CE non oculaire. Six des neuf Haflingers atteints de CE oculaire et un des trois Haflingers atteints de CE non oculaire étaient homozygotes pour la variante DDB2. Sur les 113 animaux cliniquement normaux, 7/113 étaient homozygotes (6 %) et 42/113 étaient hétérozygotes (37 %), ce qui correspond à une fréquence d'allèle de 24,8 % dans la cohorte de contrôle. Le risque de CE oculaire chez les Haflingers augmente de manière significative avec le génotype DDB2 homozygote. Cependant, tous les animaux atteints de CE ne sont pas porteurs de cette variante génétique et tous les animaux homozygotes DDB2 ne développent pas de CE, ce qui peut s'expliquer par la genèse multifactorielle de la maladie. En raison de la fréquence élevée de l'allèle indésirable, nous recommandons de tenir compte du génotype DDB2 individuel des animaux reproducteurs afin d'éviter une progéniture homozygote présentant un risque fortement accru de CE en excluant les accouplements à haut risque.

[Ocular and non-ocular squamous cell carcinomas in the Haflinger: Eight cases at the Institut Suisse de Médecine Equine (2015-2022)]. / Okuläre und nicht-okuläre Platten­-epithel­karzinome beim Haflinger: Acht Fälle am Institut Suisse de Médecine Equine (2015­2022).

INTRODUCTION: This case series describes the clinical course of ocular and non-ocular squamous cell carinoma (SCC) in the Haflinger horse and is intended to raise awareness of the high recurrence rate and tendency to metastasize. Eight Haflingers with histologically confirmed SCC were included, five ocular and three non-ocular, who were presented at the Institut Suisse de Médecine Équine (ISME) Bern between July 2015 and January 2022. The ocular SCC cases were all presented because of an apparent mass, which in most cases was post-treatment recurrence. The occurrence of recurrences was observed between 3 weeks and 16 years after initial therapy. Four of five Haflingers with ocular SCC had an enucleation, three of which were clinically normal at the time of the completion of this study, one case was euthanized due to confirmed metastases and one due to lameness. The result of enucleations for therapy of ocular SCC was good if no metastases occurred. Of the three non-ocular SCC cases, only one case, a penile SCC, had an apparent mass. Therapy was initiated in this case, while the other two cases were euthanized shortly after diagnosis due to the poor prognosis of SCC in the appropriate locations (maxillary sinus, mandible). Metastases occurred three and two years after removal of the primary tumor in ocular SCC in the scapula, liver and lungs and in non-ocular SCC from the penis to the nostrils. Since a postmortem pathological examination was not carried out on all Haflingers, further metastases cannot be ruled out. Haflingers with SCC should be monitored by a veterinarian over the long term, as recurrences and/or metastases can still occur years later.

INTRODUCTION: Cette série de cas décrit l'évolution clinique des carcinomes épidermoïdes (CE) oculaires et non oculaires chez le cheval Haflinger et vise à faire prendre conscience du taux de récidive élevé et de la tendance à la formation de métastases. Huit Haflinger avec un CE confirmé histologiquement, cinq oculaires et trois non-oculaires, qui ont été présentés à l'Institut Suisse de Médecine Équine (ISME) Berne entre juillet 2015 et janvier 2022, ont été inclus. Les cas de CE oculaires ont tous été présentés en raison d'une masse apparente, qui dans la plupart des cas était une récidive post-traitement. La survenue des récidives a été observée entre 3 semaines et 16 ans après le traitement initial. Quatre des cinq Haflinger atteints de CE oculaire ont subi une énucléation, dont trois étaient cliniquement normaux au moment de l'achèvement de l'étude, un cas ayant été euthanasié en raison de métastases confirmées et un autre en raison d'une boiterie. Le résultat des énucléations pour la thérapie du CE oculaire était bon s'il n'y avait pas de métastases. Sur les trois cas de CE non oculaires, seul un cas, un CE pénien, présentait une masse apparente. Le traitement a été initié dans ce cas, tandis que les deux autres cas ont été euthanasiés peu de temps après le diagnostic en raison du mauvais pronostic des CE dans les localisations constatées (sinus maxillaire, mandibule). Des métastases sont apparues trois et deux ans après l'ablation de la tumeur primaire dans le cas du CE oculaire, au niveau de l'omoplate, du foie et des poumons et, dans un cas de CE non oculaire, celui du pénis, aux narines. Étant donné que tous les Haflinger n'ont pas fait l'objet d'un examen pathologique post-mortem, on ne peut exclure la possibilité d'autres métastases. Les Haflinger atteints de CE doivent être suivis à long terme par un vétérinaire, car des récidives et/ou des métastases peuvent encore survenir des années plus tard.

The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids.

MicroRNAs (miRNAs) have been proposed as biomarkers for equine sarcoid (ES) disease. In this study, the suitability of three whole blood miRNAs to diagnose ES and to predict and monitor the outcome of therapy was explored. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), expression levels of eca-miR-127, eca-miR-379, and eca-miR-432 in whole blood of ES-affected equids before and at least one year after therapy were compared to those of unaffected control equids. Associations of age, sex, species, diagnosis, and therapy outcome with miRNA expression levels were examined using general linear models. In total, 48 ES-affected equids and 47 control equids were recruited. From the affected animals, 31 responded favorably to treatment, and 17 demonstrated a failure of therapy. None of the tested miRNAs were influenced by age. Male equids showed increased expression of eca-miR-127 compared to females and horses showed higher expression levels of eca-miR-379 and eca-miR-432 than donkeys. Eca-miR-127 was confirmed as a diagnostic discriminator between ES-affected and control equids. No difference in miRNA profiles before therapy was found when comparing ES-affected equids with success vs. failure of therapy. Eca-miR-379 and eca-miR-432 decreased over time in horses where therapy was successful, but not in those cases where it failed. Biological variables influence equine whole blood miRNA expression, which may complicate biomarker validation. While none of the tested miRNAs could predict the response to therapy in ES-affected equids and eca-miR-127 showed poor diagnostic accuracy for ES, eca-miR-379 and eca-miR-432 miRNAs might allow refinement of monitoring of success of ES therapy.

[Prevalence of health problems in midlife Swiss warm-blooded horses]. / Auftreten gesundheitlicher Probleme beim Schweizer Warmblutpferd ­mittleren Alters.

INTRODUCTION: The breeding of a healthy horse is the basic requirement for optimal performance. This is also specifically stated in the breeding goal of the Swiss warmblood horse and should be achieved through a strict selection of the stallions. The aim of this retrospective study was to assess the current state of the population to optimize breeding. Data on the health status of Swiss warmblood horses in the age between 6 and 16 years (midlife) were collected by a telephone survey and analyzed descriptively. Following the heritability of the most common health problems were estimated. Data on 1,861 horses were collected between 2016 and 2018. Lameness (34%), colic (22%), sarcoids (19%), and pastern dermatitis (16%) were among the most common health problems, followed by back problems (13%), cough (10%), urticaria (10%), free fecal water syndrome (9%), nasal discharge (8%) and sweet itch (4%). Lameness was observed in 49% of the cases in the forelimbs, in 25% in the hindlimbs and in 26% in both. 27% of horses with colic have been hospitalized once and 8% have undergone colic surgery. Sarcoids became fewer or smaller in 89% of the treated and in 58% of the untreated horses. A significant relationship between treatment and the status of the sarcoids was demonstrated (p .

INTRODUCTION: L'élevage d'un cheval en bonne santé représente une condition de base pour une performance optimale. Ceci est également spécifiquement mentionné dans l'objectif d'élevage du cheval de sang suisse et doit être atteint par une sélection stricte des étalons. Afin d'optimiser l'élevage, il faut connaître l'état actuel de la population, ce qui était le but de cette étude rétrospective. Au moyen d'une enquête téléphonique, des données sur l'état de santé des chevaux de sang suisses âgés de 6 à 16 ans (âge moyen) ont été collectées et traitées de manière descriptive. Les héritabilités des problèmes de santé les plus courants ont ensuite été estimées. Au total, les données de1861 chevaux ont été collectés entre 2016 et 2018. Les boiteries (34%), les coliques (22%), les sarcoïdes (19%) et les crevasses (16%) figuraient parmi les problèmes de santé les plus courants, suivis des problèmes de dos (13%), de la toux (10%), des urticaires (10%), d'écoulements anaux (« Kotwasser ¼) (9%), d'écoulements nasaux (8%) et de dermite estivale (4%). Chez 49% des chevaux boiteux, il s'agissait d'une boiterie antérieure, chez 25% d'une boiterie postérieure et chez 26% d'une boiterie impliquant antérieurs et postérieurs. 27% des chevaux présentant des coliques avaient été hospitalisés et 8% avaient subi une chirurgie de coliques. Les sarcoïdes sont devenus moins nombreux ou plus petits chez 89% des chevaux traités mais également chez 58% des chevaux non traités. Une relation significative entre le traitement et l'état des sarcoïdes a pu être démontrée (p .

Age over 25 years, but not plasma adrenocorticotropic hormone con-cen-tration above the seasonally adjusted reference range is predictive for radio-graphically assessed changes of chronic laminitis in elderly horses.

INTRODUCTION: Endocrinopathic laminitis occurs as a consequence of hormonal derangements like pituitary pars intermedia dysfunction (PPID). The objective of the present study was to assess the occurrence of radiographic changes associated with chronic laminitis in elderly, clinically sound horses. Fifty-one horses were included in the study. Horses were assigned to different age groups, in groups according to their BCS and CNS as well as to groups with different ACTH concentrations in order to assess their risk of chronic laminitis (reported as odds ratios (OR) and confidence intervals (CI)). Horses assigned to an older age group (26-32 years) were significantly more likely to have radiographically assessed changes of chronic laminitis than horses in a younger age group (15-25 years) (OR 3.33; CI 1.05-10.59). The other variables (body condition score, cresty neck score, ACTH concentration) were not associated with an increased risk of having laminitic changes in these horses.

INTRODUCTION: La fourbure endocrinopathique survient à la suite de troubles hormonaux tels que le dysfonctionnement de la pars intermedia de l'hypophyse (DPIH). L'objectif de la présente étude était d'évaluer les changements radiographiques associés à la fourbure subclinique chez les chevaux âgés cliniquement sains. Cinquante et un chevaux ont été inclus dans l'étude. Les chevaux ont été assignés à différents groupes d'âge, en groupes en fonction de leur Body Condition Score (BCS) et de leur Cresty Neck Score (CNS) ainsi que des groupes avec différentes concentrations d'ACTH afin d'évaluer leur risque de fourbure chronique (rapportés sous forme de rapports de cotes (Odds-Ratio, OR) et d'intervalles de confiance (IC)). Les chevaux faisant partie d'un groupe d'âge plus avancé (26 à 32 ans) étaient significativement plus susceptibles de présenter des signes radiographiques de fourbure chronique que les chevaux d'un groupe d'âge plus jeune (15 à 25 ans) (OR 3,33; IC 1,05­10,59). Les autres variables (BCS, CNS, concentration d'ACTH) n'étaient pas associées à un risque accru de modifications de type fourbure chez ces chevaux.

Quantitative motor unit action potential analysis of paraspinal muscles, diagnostic imaging and necropsy findings in 36 horses suspected of cervical impairment.

INTRODUCTION: Aims: To determine the relation between quantitative electromyography (QEMG) of the cervical ventral serratus muscle, radiographic findings and post-mortem gross and histopathological examination in order to calculate the ability of QEMG to localize the region of cervical compressive neuropathy and myelopathy in horses. Methods: In this clinical, non-randomised, partially blinded study (QEMG and histology), 36 warmblood horses with clinical suspicion of cervical spine disease were examined with QEMG in different segments of the ventral serratus muscle. Results were compared to normative data. Diagnostic imaging was performed in 28 cases. All horses were euthanized because of poor clinical prognoses and/or recurrent clinical neurological signs despite treatment and underwent necropsy with emphasis on the cervical nervous tissue and vertebrae. Clinical and diagnostic imaging findings, QEMG results and post mortem findings were compared with each other. Results: Overall mean values of duration (9.54 ms), polyphasia, number of phases (3.6) and size index (0.67) in horses with cervical lesions were significantly (P.

INTRODUCTION: Objectifs: Déterminer la relation entre l>électromyographie quantitative (QEMG) du muscle serratus ventral cervical, les résultats radiographiques et les examens macroscopiques et histopathologiques post mortem afin de calculer la capacité de la QEMG à localiser la région de compression neurogène dans l'encolure des chevaux. Méthodes: Dans cette étude clinique, non randomisée, partiellement aveugle (histologie et QEMG), 36 chevaux de sang soupçonnés d'affection du rachis cervical ont été examinés par QEMG sur différents segments du muscle serratus ventral. Les résultats ont été comparés aux données de référence. L'imagerie diagnostique a été réalisée dans 28 cas. Tous les chevaux ont été euthanasiés en raison de mauvais pronostics cliniques et/ou de signes neurologiques cliniques récurrents malgré le traitement et ont subi une autopsie en mettant l'accent sur le tissu nerveux cervical et les vertèbres. Les résultats de l'imagerie clinique et diagnostique, les résultats de la QEMG et les résultats post mortem ont été comparés les uns aux autres. Résultats: Les valeurs moyennes globales de durée (9,54 ms), de polyphasie, de nombre de phases (3,6) et d'indice de taille (0,67) chez les chevaux présentant des lésions cervicales étaient significativement (P.

The clinical diagnosis of equine sarcoids-Part 2: Assessment of case features typical of equine sarcoids and validation of a diagnostic protocol to guide equine clinicians in the diagnosis of equine sarcoids.

Research has shown that the accuracy of the clinical diagnosis of equine sarcoids (ES) can be improved. Particularly, less experienced veterinarians are often mistaken in their clinical judgement despite a high level of diagnostic confidence. The aim of this study was to develop and assess the performance of a diagnostic protocol (DP) to improve diagnostic accuracy and identify diagnostically challenging cases. The design of the DP was based on typical clinical features of ES and its algorithm was optimised through repeated tests on clinical cases prior to validating its performance in a representative online examination. A total of 22 equine practitioners and 31 veterinary students used the DP to diagnose 40 standardised ES and non-ES cases in an online examination. Scores of these 53 respondents were compared to scores of 128 respondents of comparable levels of expertise, and 14 experts, all assessing the same cases without using the DP. Overall, respondents using the DP were significantly more likely (odds ratio (OR) 1.25; 95% confidence interval (95% CI) 1.09-1.43) to diagnose a case correctly compared to respondents not using the DP and felt significantly more confident of their diagnosis (OR 1.53; 95% CI 1.39-1.67). Thus, the DP proved to be a reliable tool to increase clinical diagnostic accuracy and diagnostic confidence. The DP algorithms may be further improved with experiences gained from its application in equine practice and clinicians will be able to optimise their diagnostic accuracy and selection of lesions requiring a biopsy.

The clinical diagnosis of equine sarcoids - Part 1: Assessment of sensitivity and specificity using a multicentre case-based online examination.

Equine clinicians and researchers often make the diagnosis of equine sarcoids (ES) on clinical assessment alone, without histopathological confirmation. However, the accuracy of the clinical diagnosis of ES has not been critically assessed. To assess sensitivity, specificity, positive and negative predictive values of the clinical diagnosis of ES, 40 clinical cases with histologically confirmed equine skin lesions (26 ES and 14 non-ES) were compiled in a representative online examination. For each case and lesion, at least one photograph and all relevant information were presented in a standardised format. This included the horse's signalment, lesion localisation, lesion progression, presence of other skin lesions, earlier treatments and response to treatment. No information relevant for the assessment of the lesion was intentionally withheld. Fourteen ES experts, 39 board-certified equine specialists, 103 equine practitioners and 25 novices categorised the cases into ES or non-ES and graded their level of diagnostic confidence on a scale from 1 to 6 for each case. The overall success rate was 82.0% while sensitivity and specificity were 83.3% and 79.6%, respectively. The positive and negative predictive values were 88.4% and 72.0%, respectively, in the tested population with a 66% prevalence of ES. However, less experienced veterinarians were frequently wrong in their clinical judgement despite a high level of diagnostic confidence. Therefore, the authors propose to develop a diagnostic tool to help clinicians optimise their selection of lesions requiring a biopsy. Ultimately, this will help reduce costs and morbidity generated by unnecessary diagnostic and therapeutic efforts.

Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10-5 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10-14 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.

Genomic comparison of bovine papillomavirus 1 isolates from bovine, equine and asinine lesional tissue samples.

Several attempts have been made to categorize equid- and bovid-specific bovine papillomavirus 1 (BPV1) isolates based on sequence tags. This study includes newly determined sequence information from 33 BPV1 isolates of equine, asinine and bovine origin and investigates sequence bias due to host species. Twenty of the viral genomes were sequenced over their entire length and a further thirteen were sequenced, including flanking sequences, at two specific sites, the LCR and the E5 ORF. Alignment and analyses of the sequences did not reveal statistically significant site differences between the sequences of bovine and equid origin. None of the proposed sites of divergence noted by other authors demonstrated significant species-specific characteristics. Our results suggest that BPV1 is shared between equine, asinine and bovine host species, and that viral transfer between bovines and equids is a repeated and ongoing phenomenon.

In vitro effects of the toll-like receptor agonists monophosphoryl lipid A and CpG-rich oligonucleotides on cytokine production by equine cells.

Insect bite hypersensitivity (IBH) is an equine allergic dermatitis to Culicoides spp. antigens. Attempts at using allergen-specific immunotherapy (AIT) as a treatment for IBH have so far proven unsuccessful. Toll-like receptor (TLR) agonists can promote a shift in the immune response from the allergy-promoting T helper cell 2 (Th2) response towards a Th1 and/or regulatory response. The aim of this study was to evaluate two immunomodulatory TLR agonists in vitro as potential vaccine adjuvants for a more efficacious AIT in IBH. Peripheral blood mononuclear cells (PBMCs) from healthy and IBH-affected horses were stimulated with the TLR-agonists monophosphoryl lipid A (MPLA) or CpG-rich oligodeoxynucleotides (CpG-ODN) in the presence or absence of Culicoides spp. allergens. Cytokine concentrations of interferon (IFN)-α, IFN-γ, interleukin (IL)-4, IL-10 and IL-17 were quantified in the supernatants of stimulated PBMCs. MPLA induced IL-10 secretion in all horses, regardless of presence and nature of antigens, while suppressing antigen-induced production of IFN-γ, IL-4 and IL-17. CpG-ODN significantly increased IFN-α, IFN-γ and IL-4 production, but had little effect on IL-10 production. In conclusion, MPLA promotes a regulatory immune response and is therefore a promising adjuvant candidate for allergy vaccines in horses. While C-class CpG-ODN is an unsuitable adjuvant for AIT, it induces IFN-γ and IFN-α, and thus may be a useful adjuvant in combination with vaccines for equine infectious or neoplastic diseases.

Quantitative analysis of infiltrating immune cells and bovine papillomavirus type 1 E2-positive cells in equine sarcoids.

Sarcoids are the most frequently observed skin tumours in equids and consist of cutaneous accumulations of transformed fibroblasts. Their aetiopathogenesis is closely linked to a presumably abortive infection by bovine papillomavirus (BPV) types 1 and 2. In cattle, dermal fibropapillomas induced by BPV1/2 usually regress spontaneously due to a local, cell-mediated, immune response; however, equids appear to lack an effective immune response to BPV1/2 and mechanisms of immune evasion have been postulated. As a consequence, equine sarcoids tend to persist and are prone to recur. In this study, cryosections were analysed by immunofluorescent staining and a high content analysis system to determine the presence and distribution of CD4(+), CD8(+), FoxP3(+), RORγt(-), CD206(+) and CD14(+) cells, along with expression of the BPV1 early regulatory protein E2. A higher density of cells was positive for BPV1 E2(+) within the transformed tissue than in perilesional tissue or normal skin of horses with sarcoids and control horses. The proportion of CD8(+) cytotoxic T cells was significantly increased in perilesional and lesional tissues, whereas CD4(+) T helper cells were present in higher density only in lesional tissue compared to normal skin from horses with and without sarcoids. The proportion of pro-inflammatory CD4(+)FoxP3(+)RORγt(+) regulatory T cells was decreased in sarcoid tissue compared to perilesional, distant and control tissue. There were no significant differences in densities of CD4(+)FoxP3(+) RORγt(-) regulatory T cells between sarcoids and control tissues. Equine sarcoids are characterised by infiltrations of CD8(+) and CD4(+) T cells, with decreased representation by pro-inflammatory CD4(+)FoxP3(+)RORγt(+) regulatory T cells.

A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis.

In this review, we address the function of the hypothalamus-pituitary-adrenocortical (HPA) axis with special emphasis on the comparison between the bovine and equine species. The pars intermedia of the pituitary gland is particularly well developed in horses and cattle. However, its function is not well appreciated in cattle yet. The Wulzen's cone of the adenohypophysis is a special feature of ruminants. Total basal cortisol concentration is much higher in horses than that in cows with similar free cortisol fractions. Corticotropin-releasing factor (CRF) concentrations in equine pituitary venous blood are lower compared with other species, whereas plasma ACTH concentrations in cows are higher than those in horses. A CRF challenge test induced a more pronounced cortisol response in horses compared with cattle, whereas regarding ACTH challenge testing, the opposite seems true. Based on data from literature, the bovine species is characterized by relatively high basal blood CRF and ACTH and low cortisol and glucose concentrations. Obviously, further lowering of blood cortisol in cattle is easily prevented by the high sensitivity to ACTH, and as a consequence, subsequent increased gluconeogenesis prevents imminent hypoglycemia. Hypoglycemia is less likely in horses given their high muscle glycogen content and their relatively high cortisol concentration. When assessing HPA axis reactivity, response patterns to exogenous ACTH or CRH might be used as a reliable indicator of animal welfare status in cows and horses, respectively, although it is emphasized that considerable caution should be exercised in using measures of HPA activity solely to assess animal welfare.

Clinical course of sarcoids in 61 Franches-Montagnes horses over a 5-7 year period.

BACKGROUND: The progression of equine sarcoids (ES) is notoriously unpredictable. Making a choice for the appropriate treatment is challenging when dealing with milder manifestations of ES. OBJECTIVE: The aim of this study was to investigate the clinical course of ES in young horses. ANIMALS AND METHODS: A cohort of 61 ES-affected three-year-old Franches-Montagnes horses and a breed-, age- and geographically matched control group of 75 ES-free peers were examined twice over a period of 5-7 years. Owners and caretakers were queried, using a standardized questionnaire. RESULTS: More than half of the 38/61 (62%) horses that were ES-affected at the age of three, had become ES-free at the time of follow-up. In 29 of 38 horses, representing 48% of the entire study population, ES lesions had spontaneously disappeared without therapy. When differentiating the clinical types of ES lesions, occult ES underwent complete spontaneous regression in 65% (11/17), while verrucous lesions regressed spontaneously in 32% (9/28). None of the evaluated intrinsic or environmental factors showed a significant effect on the risk for development, regression or exacerbation of ES disease. CONCLUSIONS: Our results document a surprisingly high rate of spontaneous ES regression for young horses affected with milder manifestations of ES disease. These findings justify a 'wait-and-see' approach in selected cases of occult and verrucous ES, provided that all lesions are closely monitored. Furthermore, results of this study should also be considered when critically assessing treatment effects of therapies directed against ES, especially in the context of uncontrolled studies.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression.

Whole genome scan identifies several chromosomal regions linked to equine sarcoids.

Despite the evidence for a genetic predisposition to develop equine sarcoids (ES), no whole genome scan for ES has been performed to date. The objective of this explorative study was to identify chromosome regions associated with ES. The studied population was comprised of two half-sibling sire families, involving a total of 222 horses. Twenty-six of these horses were affected with ES. All horses had been previously genotyped with 315 microsatellite markers. Quantitative trait locus (QTL) signals were suggested where the F statistic exceeded chromosome-wide significance at P < 0.05. The QTL analyses revealed significant signals reaching P < 0.05 on equine chromosome (ECA) 20, 23 and 25, suggesting a polygenic character for this trait. The candidate regions identified on ECA 20, 23 and 25 include genes regulating virus replication and host immune response. Further investigation of the chromosome regions associated with ES and of genes potentially responsible for the development of ES could form the basis for early identification of susceptible animals, breeding selection or the development of new therapeutic targets.