Surveillance and simulation of bovine spongiform encephalopathy and scrapie in small ruminants in Switzerland

BACKGROUND: After bovine spongiform encephalopathy (BSE) emerged in European cattle livestock in 1986 a fundamental question was whether the agent established also in the small ruminants' population. In Switzerland transmissible spongiform encephalopathies (TSEs) in small ruminants have been monitored since 1990. While in the most recent TSE cases a BSE infection could be excluded, for historical cases techniques to discriminate scrapie from BSE had not been available at the time of diagnosis and thus their status remained unclear. We herein applied state-of-the-art techniques to retrospectively classify these animals and to re-analyze the affected flocks for secondary cases. These results were the basis for models, simulating the course of TSEs over a period of 70 years. The aim was to come to a statistically based overall assessment of the TSE situation in the domestic small ruminant population in Switzerland. RESULTS: In sum 16 TSE cases were identified in small ruminants in Switzerland since 1981, of which eight were atypical and six were classical scrapie. In two animals retrospective analysis did not allow any further classification due to the lack of appropriate tissue samples. We found no evidence for an infection with the BSE agent in the cases under investigation. In none of the affected flocks, secondary cases were identified. A Bayesian prevalence calculation resulted in most likely estimates of one case of BSE, five cases of classical scrapie and 21 cases of atypical scrapie per 100'000 small ruminants. According to our models none of the TSEs is considered to cause a broader epidemic in Switzerland. In a closed population, they are rather expected to fade out in the next decades or, in case of a sporadic origin, may remain at a very low level. CONCLUSIONS: In summary, these data indicate that despite a significant epidemic of BSE in cattle, there is no evidence that BSE established in the small ruminant population in Switzerland. Classical and atypical scrapie both occur at a very low level and are not expected to escalate into an epidemic. In this situation the extent of TSE surveillance in small ruminants requires reevaluation based on cost-benefit analysis

Diversity in Neuroanatomical Distribution of Abnormal Prion Protein in Atypical Scrapie

Scrapie is a transmissible spongiform encephalopathy (TSE) in sheep and goats. In recent years, atypical scrapie cases were identified that differed from classical scrapie in the molecular characteristics of the disease-associated pathological prion protein (PrPsc). In this study, we analyze the molecular and neuropathological phenotype of nine Swiss TSE cases in sheep and goats. One sheep was identified as classical scrapie, whereas six sheep, as well as two goats, were classified as atypical scrapie. The latter revealed a uniform electrophoretic mobility pattern of the proteinase K–resistant core fragment of PrPsc distinct from classical scrapie regardless of the genotype, the species, and the neuroanatomical structure. Remarkably different types of neuroanatomical PrPsc distribution were observed in atypical scrapie cases by both western immunoblotting and immunohistochemistry. Our findings indicate that the biodiversity in atypical scrapie is larger than expected and thus impacts on current sampling and testing strategies in small ruminant TSE surveillance

First report of Cytauxzoon sp. infection in domestic cats in Switzerland: natural and transfusion-transmitted infections

BACKGROUND: Cytauxzoonosis is an emerging tick-borne disease of domestic and wild felids. Cytauxzoon felis induces severe and often fatal disease in domestic cats. In Europe, clinical and subclinical infections caused by Cytauxzoon sp. are described. We report the first cases of Cytauxzoon sp. infection in domestic cats in Switzerland. METHODS: Clinical and laboratory data and results of PCR analyses were collected from Cytauxzoon sp. PCR-positive cats and the cats followed for up to 851 days. RESULTS: The cases were three two-month old kittens from the same litter (Cases 1-3) and two adult domestic shorthair cats (Cases 4 and 5). The cats originated from the north-west and west of Switzerland. Cases 1-3 presented with moderate to severe regenerative anaemia and intraerythrocytic inclusions. Cytauxzoon sp. was confirmed by PCR and sequencing. The kittens made a clinical and haematological recovery after blood transfusion and/or treatment with azithromycin and atovaquone, but erythroparasitaemia persisted. Case 4 presented with severe non-regenerative anaemia. Case 5 was healthy and used as a blood donor for Case 4. Following blood transfusion, Case 4 showed intraerythrocytic inclusions, and Cytauxzoon sp. was confirmed in both Cases 4 and 5 using PCR and sequencing. Case 4 achieved clinical and haematological remission after treatment with azithromycin, atovaquone and immunosuppressive drugs. Eight months later, Case 4 was presented again with anaemia but tested Cytauxzoon sp. PCR-negative. Sequencing of 1637 bp of the 18S rRNA gene of Cytauxzoon sp. revealed 100% nucleotide sequence identity among isolates of Cases 1-3 and between isolates of Cases 4 and 5, and 99% sequence identity between isolates of all cases. Phylogenetic analysis revealed the closest relationship of the Swiss isolates to Cytauxzoon sp. isolates from domestic cats and wild felids from France, Spain and Romania and to Cytauxzoon manul from a Pallas's cat. CONCLUSIONS: This is the first report of Cytauxzoon sp. infection in domestic cats in Switzerland. It is also the first report of infection in very young kittens and transmission of Cytauxzoon sp. to an adult cat by transfusion of blood from an asymptomatic cat. The cats recovered but some developed chronic asymptomatic erythroparasitaemia for up to 28 months. Domestic cats may act as reservoirs for Cytauxzoon sp. in Europe and blood donor cats should be screened for this agent by PCR

Doramectin-Intoxikation bei drei Katzenwelpen

Dieser Fallbericht beschreibt drei Katzenwelpen mit Verdacht auf Doramectin-Intoxikation. Ein Wurf von insgesamt 7 Katzenwelpen wurde mit Doramectin behandelt, woraufhin drei Welpen neurologische Symptome entwickeltena Ein Welpe zeigte leichte Apathie und Zittern, ein weiterer zusätzlich Verhaltensänderungen und epileptiforme Anfälle, die mit Diazepam behandelt werden mussten. Beide Welpen erholten sich vollständig. Ein dritter Welpe wurde 3 Tage nach Doramectin-Gabe stuporös vorgestellt und zeigte im weiteren Verlauf Verhaltensänderungen wie Aggressivität, Hyperästhesie, Tremor und epileptiforme Anfälle. Er verstarb 36 Stunden nach Vorstellung. Bei der histopathologischen Untersuchung des Gehirns konnten ein zytotoxisches Ödem und Polioenzephalomalazie festgestellt werden. Die Doramectin-Dosis beim verstorbenen Welpen betrug 380 μg/kg.This case report describes 3 kittens with suspected doramectin toxicity. In a litter of 7 kittens treated with doramectin, 3 developed neurological symptoms. One kitten showed mild apathy and tremors, while a second one additionally presented behavioral changes and seizures that had to be treated with diazepam. Both kittens recovered completely. A third kitten was presented to us in coma 3 days following Treatment with doramectin. Subsequently, this kitten developed behavioral changes such as aggression, hyperesthesia, tremors, and seizures and died 36 hours after presentation. Histopathologic examination of the brain showed cytotoxic edema and polioencephalomalacia. The doramectin dosage of the deceased kitten was 380 μg/kg

Association of markers of endothelial activation and dysfunction with occurrence and outcome of pulmonary hemorrhage in dogs with leptospirosis.

BACKGROUND Endothelial dysfunction might contribute to the development of leptospiral pulmonary hemorrhage syndrome (LPHS). HYPOTHESIS Serum concentrations of markers of endothelial activation and dysfunction are higher in dogs with leptospirosis and correlate with the occurrence of LPHS and a higher case fatality rate. ANIMALS Clinically healthy dogs (n = 31; 10/31 dogs confirmed healthy based on no detected abnormalities on blood work), dogs with leptospirosis with LPHS (n = 17) and without LPHS (n = 15), dogs with acute kidney injury not due to leptospirosis (AKI-nL, n = 34). METHODS Observational study. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2) at admission were compared between groups. Correlations with outcome and the accuracy to predict LPHS were examined. RESULTS Soluble intercellular adhesion molecule (sICAM-1), VEGF, and Ang-2 concentrations were higher in dogs with AKI-nL (sICAM-1 34.7 ng/mL, interquartile range [IQR] = 24.4-75.5; VEGF 43.1 pg/mL, IQR = 12.3-79.2; Ang-2 8.5 ng/mL, IQR = 6.2-12.3), leptospirosis without LPHS (sICAM-1 45.1 ng/mL, IQR = 30.6-59.0; VEGF 32.4 pg/mL, IQR = 12.5-62.6; Ang-2 9.6 ng/mL, IQR = 6.9-19.3), and LPHS (sICAM-1 69.7 ng/mL, IQR = 42.1-89.1; VEGF 51.8 pg/mL, IQR = 26.3-96.7; Ang-2 8.0 ng/mL, IQR = 5.6-12.2) compared to controls (P < .001). In dogs with leptospirosis, VEGF and sICAM-1 were higher in nonsurvivors (sICAM-1 89.4 ng/mL, IQR = 76.5-101.0; VEGF 117.0 pg/mL, IQR = 90.3-232.4) than survivors (P = .004) and sICAM-1 predicted the development of LPHS. CONCLUSIONS Soluble intercellular adhesion molecule 1, VEGF, and Ang-2 do not discriminate leptospirosis from AKI-nL. In dogs with leptospirosis, sICAM-1 and VEGF predict outcome and sICAM-1 might identify dogs at risk for LPHS

Aberrant E-cadherin, beta-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors

Expression of E-cadherin and beta-catenin has been widely studied in various human and canine epithelial tumors and has been correlated with dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are of epithelial origin, and the most important prognostic factor in human medicine is the tumor grade. Limited information is available regarding E-cadherin and beta-catenin expression in human CPTs, and no information is found in the veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and the intensity and cellular staining pattern of E-cadherin and beta-catenin were correlated with histological features, paying special attention to grade, invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found that loss of E-cadherin and beta-catenin expression was uncommon in canine CPTs. Rather, membranous expression of both molecules was increased in CPTs compared to normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant cytoplasmic or nuclear expression of both E-cadherin and beta-catenin was often observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None of these parameters were correlated with malignancy, and therefore, do not appear to be useful for prognostic information. Nevertheless, a panel of antibodies including E-cadherin and GFAP might be useful to support the diagnosis of CPTs and help to differentiate them from other tumors, such as ependymomas and metastatic epithelial tumors

Evaluation of plasma angiopoietin-2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis.

BACKGROUND: Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are regulators of endothelial permeability. OBJECTIVE: Plasma concentrations of Ang-2 and VEGF are increased in dogs with systemic inflammatory response syndrome (SIRS) and sepsis and are correlated with disease severity and outcome. ANIMALS: Healthy dogs (n = 18) and client-owned dogs with SIRS (n = 34) or sepsis (n = 25). METHODS: Prospective observational study. Ang-2 and VEGF concentrations in admission plasma samples were compared between healthy dogs and dogs with SIRS or sepsis, and between survivors and non-survivors. Correlations with the acute patient physiologic and laboratory evaluation (APPLEfast ) disease severity score were examined. RESULTS: Median Ang-2 was significantly higher in dogs with SIRS (19.3; interquartile range [IQR]: 8.6-25.7 ng/mL) and sepsis (21.2; IQR: 10.3-30.1 ng/mL) compared to healthy dogs (7.6; IQR: 6.7-9.8 ng/mL). Ang-2 was significantly higher in non-survivors (24.1; IQR: 11.9-50.0 ng/mL) than survivors (10.2; IQR: 7.2-21.5 ng/mL) but did not correlate with the APPLEfast score. Admission Ang-2 predicted negative outcome in dogs with SIRS and sepsis with reasonable accuracy (area under the curve [AUC]: 0.75, confidence interval [CI]: 0.59-0.85; sensitivity: 0.5, CI: 0.29-0.71; specificity: 0.87, CI: 0.75-0.95); differentiation between sepsis and SIRS was poor (AUC: 0.58). Plasma VEGF was significantly higher in dogs with sepsis (45; IQR: 14-107.5 pg/mL) than in dogs with SIRS (3.3; IQR: 0-35.6 pg/mL) or healthy dogs (0; IQR: 0 pg/mL; P = 0.008). VEGF was significantly (P = .0004) higher in non-survivors (34.5; IQR: 0-105.7 pg/mL) than in survivors (0; IQR: 0-55.2 pg/mL). The ability of VEGF to predict a negative outcome was poor. CONCLUSIONS AND CLINICAL IMPORTANCE: Ang-2 may represent a useful additional prognostic marker in dogs with SIRS