Dirofilariosis is a vector-borne disease mainly caused by Dirofilaria immitis and Dirofilaria repens. In contrast to the known endemicity of dirofilariosis in southern and south-eastern Europe, information on the distribution of D. repens in Central-Europe is fragmentary. We tested 8877 serum samples from dogs from Austria, Denmark, Germany, Italy, Lithuania, Poland, Switzerland and the UK using an ELISA detecting filarial-specific antibodies, hypothesising higher occurrence of D. repens. Based on two overlapping frequency distributions, presumed negative samples had a mean optical density (OD) value of 0.097, representing 97.45% of all samples. Presumed positive samples, representing 2.55% of all sera, had a mean OD value of 0.287. Test prevalence based on the calculated cut-off was 3.51% for all sera (4.36% for Austria, 1.94% for Denmark, 1.39% for Germany, 3.37% for Italy, 6.90% for Lithuania, 6.99% for Poland, 0.77% for Switzerland and 0.0% for the UK, respectively). The bimodal distribution, representing overlapping distributions of OD values from positive and negative dogs, enabled the assignment of a probability of true infection status to each dog. Mean probabilities of true infection status across groups, based on the postal codes of origin, allowed us to estimate and map true prevalences. For all countries, except the UK, the true prevalence was lower than the test prevalence. The large number of serum samples and the use of a non-gold standard analytical method allowed us to create a more realistic picture of the distribution of D. repens in Central Europe and the UK.
Susceptibility to Echinococcus multilocularis infection considerably varies among intermediate (mostly rodents) and dead-end host species (e.g. humans and pig), in particular regarding intestinal oncosphere invasion and subsequent hepatic metacestode development. Wistar rats are highly resistant to infection and subsequent diseases upon oral inoculation with E. multilocularis eggs, however, after immunosuppressive treatment with dexamethasone, rats become susceptible. To address the role of the cellular innate immunity, Wistar rats were individually or combined depleted of natural killer (NK) cells, macrophages (MΦ) and granulocytes (polymorphonuclear cells, PMN) prior to E. multilocularis egg inoculation. Although NK cell and MΦ depletion did not alter the resistance status of rats, the majority of PMN-depleted animals developed liver metacestodes within 10 weeks, indicating that PMN are key players in preventing oncosphere migration and/or development in Wistar rats. In vitro studies indicated that resistance is not caused by neutrophil reactive oxygen species or NETosis. Also, light microscopical examinations of the small intestine showed that oral inoculation of E. multilocularis eggs does not elicit a mucosal neutrophil response, suggesting that the interaction of oncospheres and neutrophils may occur after the former have entered the peripheral blood. We suggest to consider granulocytes as mediators of resistance in more resistant species, such as humans.
The lifecycle of the fox tapeworm Echinococcus multilocularis comprises primarily red foxes (definitive hosts) and small rodents (intermediate hosts). Dogs can additionally be definitive hosts and in rare cases they act as accidental or dead-end host species by developing alveolar echinococcosis (AE) primarily in the liver. This report describes a clinically apparent AE that appeared 5 weeks postpartum in a 3-year-old Labrador Retriever. The bitch was presented with loss of appe tite and apathy. Radiological examination revealed dense and partially calcified, space-occupying lesions in the abdomen that were sonographically further characterized as fluid-filled caverns. Intra operationem, a multifocal generalized cystic infiltration of the liver was observed with metastasis in the omentum. Because of the severe altera tions, the dog was euthanized. Histopathological examination revealed a laminated layer, which is typical for E. multilocularis and sporadic protoscoleces. E. multilocularis-specific PCR was positive. To the best of the authors' knowledge, this is the first case report of a postpartal clinically apparent AE described in a dog. Gestation may have led to progression of the disease.
There is little research explaining how affective dispositions of fans such as love and hate toward an athlete or team can determine sport rivalry. In consumer research, the concept of love and hate are often investigated related to brands. In view of the fact that sport athletes and sport teams can be described and managed as brands, the concept of brand love and brand hate is also applicable in sport marketing. Against that backdrop, the research question guiding the present chapter is: What is the impact of implicit and explicit love as well as hate toward an athlete in a rivalry competition? The current study extends the sport rivalry model as proposed by Dalakas and Melancon. With that said, the purpose of the present study is to integrate and examine fans' affective dispositions in terms of athlete love and athlete hate as potential key drivers and emotional appeal as further key outcome within a sport rivalry context.
Almost any warm-blooded creature can be an intermediate host for Toxoplasma gondii . However, sexual reproduction of T . gondii occurs only in felids, wherein fertilisation of haploid macrogametes by haploid microgametes, results in diploid zygotes, around which a protective wall develops, forming unsporulated oocysts. Unsporulated oocysts are shed in the faeces of cats and meiosis gives rise to haploid sporozoites within the oocysts. These, now infectious, sporulated oocysts contaminate the environment as a source of infection for people and their livestock. RNA-Seq analysis of cat enteric stages of T . gondii uncovered genes expressed uniquely in microgametes and macrogametes. A CRISPR/Cas9 strategy was used to create a T . gondii strain that exhibits defective fertilisation, decreased fecundity and generates oocysts that fail to produce sporozoites. Inoculation of cats with this engineered parasite strain totally prevented oocyst excretion following infection with wild-type T . gondii , demonstrating that this mutant is an attenuated, live, transmission-blocking vaccine.
Human alveolar echinococcosis (AE) is a highly pathogenic zoonotic parasitic disease caused by Echinococcus multilocularis. An ultrasound study in southern Kyrgyzstan during 2012 revealed a prevalence of 4.2% probable or confirmed AE and an additional 2.2% possible AE, representing an emerging situation. The risk for probable or confirmed AE was significantly higher in dog owners.
BACKGROUND:Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated.OBJECTIVES:To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors.ANIMALS:Sera of 30 atopic and 30 non-atopic client-owned dogs.METHODS:Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA.RESULTS:Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs.CONCLUSIONS:Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis.
ZusammenfassungDie Entwicklung des Fuchsbandwurms Echinococcus multilocularis findet typischerweise im Fuchs (Endwirt) und in Wühlmäusen (Zwischenwirte) statt. Hunde können ebenfalls als Endwirte fungieren und selten ist der Hund Fehlwirt mit einer manifestierten alveolären Echinokokkose (AE) hauptsächlich in der Leber. Dieser Fallbericht beschreibt eine klinisch manifeste AE bei einer 3-jährigen Hündin, die 5 Wochen post partum mit Inappetenz und Apathie vorgestellt wurde. Radiologisch waren weichteildichte, teilweise mineralisierte Umfangsvermehrungen zu befunden, die sich sonographisch als kavernös und flüssigkeitsgefüllt darstellten. Intra operationem zeigte sich eine multifokal generalisierte zystische Veränderung der Leber mit Metastasierung in das Omentum. Aufgrund der hochgradigen Veränderungen wurde die Hündin euthanasiert. Histopathologisch ließen sich neben der für E. multilocularis typischen Laminarschicht vereinzelnd Protoskolizes-Anschnitte darstellen. Die spezifische PCR zum Nachweis von E. multilocularis ergab einen positiven Befund. Nach bestem Wissen der Autorinnen ist bislang kein Fallbericht einer postpartal klinisch manifesten AE beim Hund beschrieben. Die Trächtigkeit könnte den progressiven Verlauf der Erkrankung begünstigt haben.
Infection with the larval stage (metacestode) of the fox tapeworm Echinococcus multilocularis leads to a primary hepatic disease referred to as alveolar echinococcosis (AE). The progressive disease can be lethal if untreated. In cases where complete parasite resection by surgery is not feasible, the current treatment regimens of AE consist of chemotherapy with the parasitostatic benzimidazoles albendazole or mebendazole over decades. Kinase-inhibitors currently administered in various cancer treatments are of increasing interest also as anti-parasitic drugs due to previous promising in vitro results. In order to search for novel drug targets and treatment regimens, nilotinib (AMN107; Tasigna®), an Abl-tyrosine kinase inhibitor and everolimus (RAD001; Afinitor®), a serine/threonine-kinase inhibitor, were tested for their treatment efficacy against metacestode vesicles of E. multilocularis in vitro and in BALB/c mice. In vitro treatment with 200 μM nilotinib caused drug-induced alterations after 12 days, and everolimus exerted parasite damage at concentrations dosing from 40 to 100 μM after 5 and 12 days of in vitro exposure. Nilotinib (100 mg/kg) + erythromycin (to increase nilotinib plasma levels: 10 mg/kg intraperitoneal) or everolimus (5 mg/kg) were formulated in honey and administered daily for three weeks and subsequently twice a week for an additional three weeks in experimentally infected mice. Treatments did not result in any reduction of parasite growth compared to untreated control groups, whereas oral treatment with albendazole (200 mg/kg) was highly effective. Combined application of the kinase-inhibitors with albendazole did not lead to a synergistic or additive treatment efficacy compared to albendazole treatment alone. These results show that neither nilotinib nor everolimus represent valuable alternatives to the current treatment regimens against AE.
Dirofilariosis is a mosquito-transmitted disease of wild and domestic carnivores. Etiological diagnosis on canine Dirofilaria-infections is generally either based on the morphological or molecular characterization of microfilariae (L1), or in case of D. immitis- infection on the detection of circulating antigens shed by mature female worms. However, these tests do not detect infections during the long prepatent period of 182-238 days. We hereby present a monoclonal antibody based sandwich-ELISA used for on-plate purification of somatic antigen of adult D. immitis stages for the detection of antibodies against D. immitis and D. repens in dog sera. Sensitivity of the assay for D. immitis patent infections was calculated to be 93.8 % (95 % CI: 79.2-99.2 %), and for patent D. repens-infections 100 % (95 % CI: 81.9-100 %). Specificity was determined to be 98.6 % (95 % CI: 92.2-100 %) with sera of 69 dogs from a non-endemic area. Cross-reactions against other nematodes such as Acantho-cheilonema and Dipetalonema spp. (50 % and 66.7 %, respectively), Crenosoma vulpis (16.7 %), Capillaria aerophila (14.3 %) and naturally, but not experimentally infected dogs with Angiostrongylus vasorum (14.3 %) were present. However, in all positive dogs a residence in a filarial endemic area cannot be excluded. No positive reactions could be shown in experimentally infected dogs with Toxocara canis, Ancylostoma caninum and Trichuris vulpis. Dogs experimentally infected with D. repens showed seroconversion between 24-80 days post inoculation (dpi), far earlier than beginning of patency (189-259 dpi). Accordingly, the presented ELISA could be a supplementary or alternative tool for the diagnosis of Dirofilaria-infected dogs in low or non-endemic areas to document the contact rate and infection pressure.
Comparable with immunocompetent humans, rats are considered highly resistant to Echinococcus multilocularis oncosphere invasion, both in nature and after experimental oral inoculation with eggs. Pharmacological immunosuppression with dexamethasone (DMX) was shown to abrogate the resistance of RccHan™:WIST rats, but due to weight losses >20%, many animals had to be excluded from previous experiments. The optimized DXM (Dexafort, MSD Animal Health, Germany) dosage regime presented in this study (each animal: 750 μg DXM at day -13 and 600 μg DXM at day -9 before inoculation) applied subcutaneously to RccHan™:WIST rats, resulted in weight losses ≤20%, but led to liver alveolar echinococcosis (AE) in all eight inoculated animals. Untreated control groups (each n = 8) including RccHan™:WIST (Wistar) and F344/DuCrl (Fischer-344) rats showed no parasite establishment. Antibodies against E. multilocularis metacestode vesicle fluid were present in 7/8 of the infected RccHan™:WIST rats 70 days after inoculation but in none of the control animals. Serology can therefore be used to diagnose AE. This optimized animal model enables a high infection rate in rats and may be applied in future immunological and experimental studies.
Susceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A-D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO). Peritoneal inoculation with NAO or metacestode tissue allowed the parasite establishment in rats. (B) T-cell-deficient athymic nude rats showed complete resistance against the metacestode establishment after oral inoculation with parasite eggs. This finding suggests that T-cell-independent parasite clearance occurred in the animals during early phase of the parasite invasion. Finally, Wistar rats that received pharmacological immunosuppression using either dexamethasone (DMS) alone or methotrexate (MTX) i.p. alone or a combination of these compounds were orally inoculated with the parasite's eggs. As a result (D), successful establishment of metacestode with protoscoleces was observed in all 3 rats treated with DMS (s.c.) alone or in all 6 rats treated with DMS (s.c.) plus MTX but not in 8 rats with MTX alone, suggesting that factors affected by DMS treatment are responsible to regulate the parasite invasion and establishment.
'Candidatus Neoehrlichia mikurensis' is an emerging tick-borne zoonotic agent that primarily affects immunocompromised human patients. Dogs and foxes are frequently exposed to ticks, and both species are in close proximity to humans. This is the first study to systematically investigate the occurrence of 'Candidatus Neoehrlichia mikurensis' in Canidae in Europa. We analyzed 1'739 blood samples from dogs in Switzerland, Italy, Spain and Portugal and 162 blood samples from free-ranging red foxes (Vulpes vulpes) in Switzerland. All samples were tested using a previously described multiplex real-time PCR for the Anaplasmataceae family, the 'Candidatus Neoehrlichia' genus and the 'Candidatus Neoehrlichia mikurensis' species. All Anaplasmataceae positive samples were subsequently tested using specific real-time PCRs for Anaplasmaphagocytophilum, Anaplasma platys, Ehrlichia canis and Rickettsia helvetica. Among the tested animals, one dog from Zurich tested positive for 'Candidatus Neoehrlichia mikurensis'. The 12-year old West Highland white terrier had been splenectomized 3 months prior to the blood collection and presented with polyuria/polydipsia. Fanconi syndrome was diagnosed based on glucosuria with normoglycemia and hyperaminoaciduria. A. platys and E. canis were detected in 14/249 dogs from Sicily and Portugal; two of the dogs were coinfected with both agents. Four Swiss foxes tested positive for A. phagocytophilium. R. helvetica was detected for the first time in a red fox. In conclusion, 'Candidatus Neoehrlichia mikurensis' infection should be considered in sick dogs, particularly when immuno-compromised. The pathogen seems not to be widespread in Canidae in the investigated countries. Conversely, other Anaplasmataceae were more readily detected in dogs and foxes.