Susceptible Dogs Research Articles

Implications of hypocobalaminemia as a negative prognostic marker in juvenile dogs with parvovirus enteritis.

Canine Parvovirus 2 (CPV-2) infection poses a significant global health risk to susceptible dogs. Hypocobalaminemia, defined as reduced serum cobalamin (CBL) concentrations, is a recognized complication in chronic enteropathies in adult dogs but remains poorly understood in the context of acute enteropathies, especially in young dogs. The aim of this study was to investigate the frequency and severity of hypocobalaminemia in young dogs with parvovirus enteritis and evaluation of CBL as a predictor of outcome. Thirty client-owned dogs diagnosed with parvovirus infection and thirty healthy controls were enrolled. Clinical, hematological, and biochemical tests, including CBL and serum methylmalonic acid (MMA) concentrations, were assessed. Results indicated a significantly higher prevalence of hypocobalaminemia in dogs with parvovirus enteritis compared to healthy controls, as well as a significant correlation with a disease severity score. Moreover, survivors demonstrated higher CBL concentrations than non-survivors, suggesting an eventual prognostic value of CBL status. However, parenteral CBL supplementation showed no significant effect on serum CBL or MMA concentrations, highlighting potential challenges in CBL uptake at the cellular level. Hypocobalaminemia in this population is caused by multiple factors such as reduced nutritional absorption, gastrointestinal losses, and increased metabolic demands. Further research is needed to develop tailored management strategies, evaluate the effectiveness of CBL supplementation, and understand the mechanisms behind hypocobalaminemia in parvovirus infection.

Hymenoptera Venom Immunotherapy in Dogs: Safety and Clinical Efficacy.

Hymenoptera allergens are the main triggers for anaphylaxis in susceptible dogs and humans. Hymenoptera venom specific immunotherapy (VIT), the only disease-modifying treatment, has the potential to prevent future life-threatening reactions in human patients. Prospective clinical data on VIT efficacy in dogs are currently lacking. Therefore, the aim of this study was to show that VIT is not only safe but also efficacious in preventing anaphylaxis in dogs allergic to Hymenoptera. This uncontrolled prospective clinical trial included 10 client-owned dogs with a history of anaphylaxis following repeated Hymenoptera stings. The sensitization to bee and wasp allergens was demonstrated by intradermal testing (IDT) and allergen-specific IgE serology. For VIT induction (induction phase), dogs received a shortened rush immunotherapy protocol with aqueous allergens, which was then followed by monthly injections of 100 µg of alum-precipitated allergen (maintenance phase). VIT efficacy was determined by observing patients' clinical reactions to re-stings. No systemic adverse events were seen during the induction and maintenance phases. From the seven re-stung dogs, only one developed a mild angioedema at the site of the sting; the remaining dogs were asymptomatic. These results show that VIT represents a safe and effective treatment option for Hymenoptera-allergic dogs.

Socioeconomic Status of Guardians as a Risk Factor for Canine Visceral Leishmaniasis: A Cohort Study in an Endemic Area of the Federal District, Brazil.

Current control measures of canine visceral leishmaniasis (CVL), a chronic and fatal zoonosis with potential transmission to humans, are not efficient enough to reduce its spread. The search for improved control measures should include studies of risk factors for infection and illness. This study aimed to identify the risk factors for CVL in an endemic locality of the Federal District, Brazil, from June 2016 to December 2018. Biologic samples and data on dog characteristics, owner household characteristics, and dog care were collected. A combination of serological and molecular tests was used to identify infected animals. The 248 dogs screened for inclusion were predominantly asymptomatic/oligosymptomatic. The baseline prevalence of infection was 27.5%. One hundred six of 162 susceptible dogs were monitored for an average period of 10.7 months. The estimated CVL incidence was 1.91 cases/100 dog-months. The multivariate analysis using a proportional Cox model included the potential risk factors, with P ≤ 0.25 in the univariate analyses. Greater purchasing power (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06; P = 0.03) and paved yard (HR, 0.19; 95% CI, 0.13-1.01; P = 0.05) remained in the final model as risk and protection factors, respectively. The use of repellent collars in dogs was associated moderately (P = 0.08) with protection against CVL. Our findings reflect the challenge of identifying strong interventions for reducing CVL incidence. Increased owner wealth had a counterintuitive effect on CVL, making the intervention scenario more complex for a zoonosis traditionally associated with poverty.

In-silico decongested trial effects on the impaired breathing function of a bulldog suffering from severe brachycephalic obstructive airway syndrome

Background and objectiveBrachycephalic obstructive airway syndrome (BOAS) susceptible dogs (e.g., French bulldog), suffer health complications related to deficient breathing primarily due to anatomical airway geometry. Surgical interventions are known to provide acceptable functional and cosmetic results; however, the long-term post-surgery outcome is not well known. In silico analysis provides an objective measure to quantify the respiratory function in postoperative dogs which is critical for successful long-term outcomes. A virtual surgery to open the airway can explore the ability for improved breathing in an obstructed airway of a patient dog, thus supporting surgeons in pre-surgery planning using computational fluid dynamics. MethodsIn this study five surgical interventions were generated with a gradual increment of decongested levels in a bulldog based on computed tomography images. The effects of the decongested airways on the breathing function of a patient bulldog, i.e., airflow characteristics, pressure drop, wall shear stress, and air-conditioning capacity, were quantified by benchmarking against a clinically healthy bulldog using computational fluid dynamics (CFD) method. ResultsOur findings demonstrated a promising decrease in excessive airstream velocity, pressure drop, and wall shear stress in virtual surgical scenarios, while constantly preserving adequate air-conditioning efficiency. A linear fit curve was proposed to correlate the reduction in the pressure drop and decongested level. ConclusionsThe in silico analysis is a viable tool providing visual and quantitative insight into new unexplored surgical techniques.

Laboratory validation of an ELISA method to measure circulating immune complexes levels in canine visceral leishmaniasis

Susceptible dogs suffering from canine leishmaniasis (CanL) develop an ineffective humoral immune response that leads to the formation of circulating immune complexes (CIC). These CIC are aggregates of Leishmania proteins and anti-Leishmania immunoglobulins. Their deposition in different tissues is considered the main cause of mortality. For this reason, CIC have been suggested as an excellent CanL biomarker for measuring the progression of the disease and the effectiveness of specific treatments. The present study aims to perform a laboratory validation of a Leishmania-specific method to isolate and quantify CIC in dog serum samples. CIC isolated from serum samples of infected dogs, grouped according to the LeishVet classification, were quantified following a PEG-ELISA procedure. The validation established a cut-off of 0.274 OD. All the parameters analyzed (including linearity, specificity, precision, and robustness) fulfilled the defined criteria, confirmed by statistical analyses. The results also proved the reproducibility and reliability of the method when samples were tested under the same conditions, and the consistency and usefulness of the method for an optimal staging of infected dogs. In conclusion, the laboratory validated method offers a potent tool to clinicians for a proper CanL management and to measure the progression of the disease.

Neospora caninum-induced NETosis in canine colostral polymorphonuclear neutrophils

Neospora caninum represents an obligate intracellular apicomplexan parasite of the family Sarcocystidae causing severe reproductive disorders in cattle, small ruminants, wild animals and canids worldwide. Neutrophil extracellular traps (NETs) were recently described as effective host defense mechanism of polymorphonuclear neutrophils (PMN) derived from cattle, dogs, goats and dolphins against N. caninum tachyzoites. Nonetheless, nothing is known so far on canine colostral PMN immune reactions against N. caninum although breeding bitches represent a susceptible dog cohort and infected bitches may spread tachyzoites through transplacental transmission to their offspring. Thus, isolated colostrum PMN from bitches were assessed for PMN phagocytic activities as well as NETs release against viable N. caninum tachyzoites. In vitro interactions of canine colostrum-derived PMN with tachyzoites were analyzed at different ratios and time spans. Extracellular chromatin staining was applied in order to unveil classical molecules of NETs, such as neutrophil elastase (NE), global histones (H1, H2A/H2B, H3, H4) and myeloperoxidase (MPO), via antibody-based immunofluorescence microscopy analysis. N. caninum tachyzoites induced canine NETs in colostral PMN and scanning electron microscopy (SEM) analysis revealed NETs formation by colostral PMN thereby ensnaring tachyzoites after exposure. In summary, NETs released from canine colostral PMN might represent an early and effective maternal defense mechanism of the definitive host helping neonates to reduce initial intracellular replication of not only parasites but of other invasive pathogens after colostrum consumption.

Optimal Control Solution for Rabies Disease Transmission within Free-ranging Dog

This paper considers deterministic model for transmission dynamics of rabies virus in the free-ranging dog population. The stability of system near by Disease Free Equilibrium point is analized using Next Generation Matrix. The effect of vaccination in susceptible dog population is considered on the model. We then present the effective reproduction number in the present of the vaccination. Further we developed the formula to obtain the optimal vaccination to eliminate the endemic equilibrium, via the Pontryagin Maximum Principle. Numerical example are presented to show the properties of the optimal control solution.

Scaling-up the delivery of dog vaccination campaigns against rabies in Tanzania.

An increasing number of countries are committing to meet the global target to eliminate human deaths from dog-mediated rabies by 2030. Mass dog vaccination is central to this strategy. To interrupt rabies transmission from dogs to humans, the World Health Organization recommends that vaccination campaigns should be carried out every year in all dog-owning communities vaccinating 70% of their susceptible dogs. Monitoring and evaluation of dog vaccination campaigns are needed to measure progress towards elimination. In this study, we measured the delivery performance of large-scale vaccination campaigns implemented in 25 districts in south-east Tanzania from 2010 until 2017. We used regression modelling to infer the factors associated with, and potentially influencing the successful delivery of vaccination campaigns. During 2010–2017, five rounds of vaccination campaigns were carried out, vaccinating in total 349,513 dogs in 2,066 administrative vaccination units (rural villages or urban wards). Progressively more dogs were vaccinated over the successive campaigns. The campaigns did not reach all vaccination units each year, with only 16–28% of districts achieving 100% campaign completeness (where all units were vaccinated). During 2013–2017 when vaccination coverage was monitored, approximately 20% of vaccination units achieved the recommended 70% coverage, with average coverage around 50%. Campaigns were also not completed at annual intervals, with the longest interval between campaigns being 27 months. Our analysis revealed that districts with higher budgets generally achieved higher completeness, with a twofold difference in district budget increasing the odds of a vaccination unit being reached by a campaign by slightly more than twofold (OR: 2.29; 95% CI: 1.69–3.09). However, higher budgets did not necessarily result in higher coverage within vaccination units that were reached. We recommend national programs regularly monitor and evaluate the performance of their vaccination campaigns, so as to identify factors hindering their effective delivery and to guide remedial action.

Genotypic and allelic frequency of a mutation in the NHEJ1 gene associated with collie eye anomaly in dogs in Italy.

BackgroundA 7.8‐kb deletion in intron 4 of the NHEJ1 canine gene is associated with Collie Eye Anomaly (CEA). This deletion has been described in sheep‐herding breeds related to the collie lineage and in several other dog breeds. A genetic test based on this association can distinguish three genotypes: normal, carrier and affected. The present study is a retrospective investigation of the presence of the CEA allele frequencies in selected breeds from the Italian dog population over a 10‐year time span.MethodsGenotype data, for the 7.8 kb deletion in intron 4 of the NHEJ1 gene, from 496 dogs belonging to Border collie (BC, n = 334), Shetland Sheepdog (SS, n = 74), Australian Shepherd (AS, n = 52), Nova Scotia Duck Tolling Retriever (NS, n = 20) and Rough Collie (RC, n = 16) were analysed. The genetic frequency of CEA allele was estimated in breeds with higher observations (BC, SS and AS).ResultsHealthy carriers were 50%, 45%, 29.6%, 17.3% and 12.5% in SS, NS, BC, AS and RC, respectively. The affected recessive homozygotes were 81.3%, 10.8% and 1.5% in RC, SS and BC, respectively. The CEA allelic frequencies were 0.36, 0.16 and 0.087 in SS, BC and AS, respectively.ConclusionThe results support the usefulness of this type of genetic analysis to optimize the care of dogs where the CEA mutation is present, including assessing the health risk to susceptible dogs within a breed and to provide an objective basis for breeding programmes.

Variability in non-core vaccination rates of dogs and cats in veterinary clinics across the United States

Vaccination guidelines for dogs and cats indicate that core vaccines (for dogs, rabies, distemper, adenovirus, parvovirus; for cats, feline parvovirus, herpes virus-1, calicivirus) are essential to maintain health, and that non-core vaccines be administered according to a clinician’s assessment of a pet’s risk of exposure and susceptibility to infection. A reliance on individual risk assessment introduces the potential for between-practice inconsistencies in non-core vaccine recommendations. A study was initiated to determine non-core vaccination rates of dogs (Leptospira, Borrelia burgdorferi, Bordetella bronchiseptica, canine influenza virus) and cats (feline leukemia virus) in patients current for core vaccines in veterinary practices across the United States. Transactional data for 5,531,866 dogs (1,670 practices) and 1,914,373 cats (1,661 practices) were retrieved from practice management systems for the period November 1, 2016 through January 1, 2020, deidentified and normalized. Non-core vaccination status was evaluated in 2,798,875 dogs and 788,772 cats that were core-vaccine current. Nationally, median clinic vaccination rates for dogs were highest for leptospirosis (70.5%) and B. bronchiseptica (68.7%), and much lower for canine influenza (4.8%). In Lyme-endemic states, the median clinic borreliosis vaccination rate was 51.8%. Feline leukemia median clinic vaccination rates were low for adult cats (34.6%) and for kittens and 1-year old cats (36.8%). Individual clinic vaccination rates ranged from 0 to 100% for leptospirosis, B. bronchiseptica and feline leukemia, 0–96% for canine influenza, and 0–94% for borreliosis. Wide variation in non-core vaccination rates between clinics in similar geographies indicates that factors other than disease risk are driving the use of non-core vaccines in pet dogs and cats, highlighting a need for veterinary practices to address gaps in patient protection. Failure to implement effective non-core vaccination strategies leaves susceptible dogs and cats unprotected against vaccine-preventable diseases.

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy.

Simple SummaryMolecular-based approaches are rapidly developing in medicine for the evaluation of physiological and pathological conditions and for the discovery of new biomarkers in prevention and therapy. Membrane fatty acid-based lipidomic analysis in healthy animals provides a benchmark to study disease conditions and was useful to evidence significant differences in dogs affected by chronic enteropathy. Such molecular information might have the potential to become a useful tool in the assessment of canine chronic enteropathy, being connected with nutritional and metabolic status of the subjects, as well as it may reflect “gut health” and suggest appropriate intervention by “lipid therapy”.Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro–inflammatory and anti–inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo–gamma–linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the “gut health”, and the non–invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.

Cytological and Histopathological Characteristics of Canine Transmissible Venereal Tumour in Male and Female Dogs Before and After Vincristine Treatment

Canine transmissible venereal tumour (CTVT) is a neoplasia naturally transmitted in susceptible dogs through coitus. CTVT has a worldwide distribution, with a high prevalence in tropical and sub-tropical urban environments. The study aimed at evaluating CTVT lesions in local breeds of dogs and to assess morphological changes based on sex before and after administration of vincristine sulphate. Clinical and gross morphology, fine needle aspirates cytology (FNAC) and routine histopathology methods were used. Two FNAC and histopathological microscopic slide sections from each of the seven sampled dogs were stained with Giemsa stain and Hematoxylin and Eosin. All dogs were treated with vincristine once weekly over a six weeks period after which clinical morphological and histopathological changes were assessed. Grossly, before treatment the tumour masses appeared irregular, cauliflower like with tendency to bleed, sizes ranged from ≥5cm to ≤2cm with or without metastasis to regional lymph nodes. Cytologically, the tumours had homogenous, sheet-like cellular mass. Cytoplasm with punctate vacuoles, anisokaryosis with anisonucleoliosis and coarse to reticulate nuclear chromatin were seen. Lymphocytoid cell pattern was dominant cell type. Histopathology showed sheets of round cells with nuclear and cytoplasmic variations. Histopathology of the treated dog revealed hyper-cellularity, absence of nucleoli, prominent mitotic figures, reduced cell size and presence of inflammatory cells. There was no difference on the cellular changes after vincristine treatment between female and male dogs. Cytology and histopathology showed that vincristine sulphate suppresses the development of tumour through alteration of cellular morphology with no difference between male and female dogs.

Deleterious Mutations in the TPO Gene Associated with Familial Thyroid Follicular Cell Carcinoma in Dutch German Longhaired Pointers.

Familial thyroid cancer originating from follicular cells accounts for 5–15% of all the thyroid carcinoma cases in humans. Previously, we described thyroid follicular cell carcinomas in a large number of the Dutch German longhaired pointers (GLPs) with a likely autosomal recessive inheritance pattern. Here, we investigated the genetic causes of the disease using a combined approach of genome-wide association study and runs of homozygosity (ROH) analysis based on 170k SNP array genotype data and whole-genome sequences. A region 0–5 Mb on chromosome 17 was identified to be associated with the disease. Whole-genome sequencing revealed many mutations fitting the recessive inheritance pattern in this region including two deleterious mutations in the TPO gene, chr17:800788G>A (686F>V) and chr17:805276C>T (845T>M). These two SNP were subsequently genotyped in 186 GLPs (59 affected and 127 unaffected) and confirmed to be highly associated with the disease. The recessive genotypes had higher relative risks of 16.94 and 16.64 compared to homozygous genotypes for the reference alleles, respectively. This study provides novel insight into the genetic causes leading to the familial thyroid follicular cell carcinoma, and we were able to develop a genetic test to screen susceptible dogs.

Efficacy of collars with allomones on dogs to control Rhipicephalus sanguineus sensu lato infestations under field conditions

Benzaldehyde and 2-hexanone are allomones produced by beagle dogs that reduce infestation by Rhipicephalus sanguineus sensu lato on these animals and on susceptible dogs which artificially release these repellents. These observations were obtained in previous laboratory tests or artificial infestations of susceptible dogs under controlled conditions. Here we evaluated the efficacy of collars delivering these repellents for suppressing the loads of R. sanguineus s.l. on naturally infested mixed-breed dogs under field conditions. Thirty dogs naturally infested with R. sanguineus s.l. were separated into two groups with 15 dogs each. The dogs from the treatment group received the collars with slow-release formulations of the allomones, and the dogs from the control group received collars without such compounds. Collar effectiveness tests were carried out over 30 days. All ticks found were removed from each dog, identified, and counted every collection day. The density of the different life stages of R. sanguineus s.l. varied greatly between groups and across evaluation times. Adult ticks were the stage most abundant and prevalent on infested dogs. The counts for larvae, nymphs and adults were similar between the control and the treatment groups within each tick collection day. Conversely, when we considered the total number of ticks over 30 days and gathered all life stages collected in the same animal, the dogs from the control group had significantly higher loads (35.3 ± 4.27) of ticks than the dogs from the treatment group (21.8 ± 2.96) (P < 0.01). In addition, the efficacy of treatment with repellent collars was high for adult ticks (30.8%) but was extremely low for reducing larval or nymphal infestation (0 or 2.6%, respectively). The present study demonstrates, for the first time, the efficacy of these volatile compounds on naturally infested dogs under field conditions. The development of a technologically enhanced device for slow release of the allomones tested here can be an advantageous alternative for reducing R. sanguineus s.l. infestation on dogs in residential environments.

Immune response dynamics and Lutzomyia longipalpis exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort.

BackgroundReports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators’ interactions, and vector exposure intensity associated with CVL resistance and susceptibility.Methodology/Principal findingsA prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11–2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE2 serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals.Conclusions/SignificanceThe biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.

Atrial dilation as a substrate for atrial fibrillation in the canine complete chronic atrioventricular block model

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia treated in clinical practice. Structural remodeling is characterized by atrial enlargement and contributes to the therapeutic resistance in patients with long-standing AF. Purpose To study the atrial arrhythmogenic and echocardiographic consequences induced by volume overload in the complete chronic atrioventricular block (CAVB) dog. Methods Echocardiographic and electrophysiological data was obtained in 14 anaesthetized Mongrel dogs, in acute AV-block (AAVB), after 6 weeks of CAVB (CAVB6) and CAVB10. Left atrial (LA) volume was determined with 2D echocardiography by using the biplane method. An electrocardiogram and monophasic action potentials (MAP) at the right atrial (RA) free wall were recorded. Atrial effective refractory period (AERP) was determined by continuous programmed electrical stimulation (PES) of 20 beats with a cycle length of 400 ms and an extrastimulus with decremental design until refractoriness was reached. A continuous PES protocol of 20 beats with an extrastimulus 5 ms longer than the AERP was applied for 150 seconds to trigger AF. After 5 min without arrhythmias, autonomic neuromodulation was performed by intravenous infusion (IV) of acetylcholine (1,5μg/kg/min to 6,0μg/kg/min) for 20 min followed by prompt IV infusion of isoprenaline (3μg/min) until the atrial heart rate increased by 20 bpm. PES with an extrastimulus was repeated for 150 seconds to induce AF. Results LA volume increased from 13.7±3.2 ml at AAVB to 20.5±5.9 ml* at CAVB6, and 22.7±6.0 ml* at CAVB10 (Fig. 1A). AERP was similar at AAVB, CAVB6, and CAVB10 (115.8±11.9, 117.3±11.7, and 106.8±12.1 ms respectively). Repetitive AF paroxysms of &amp;gt;10 seconds were induced in 1/14 (7%) dogs at AAVB, 1/11 (9%) at CAVB6, and 5/10 (50%)* at CAVB10 (*p&amp;lt;0.05) upon PES (Fig. 1B). Combined neuromodulation and PES did not increase the AF inducibility rate, but prolonged the longest episode of AF in the inducible dogs from 55±49 seconds to 236±202 seconds* at CAVB10 (Fig. 1C). LA volume was higher in inducible dogs 25.0±4.9 ml compared to 18.4±4.2 ml in non-inducible dogs at CAVB10. Conclusion Sustained atrial dilation forms a substrate for repetitive paroxysms of AF. Neuro-modulation prolongs AF episode duration in susceptible dogs. This animal model can be used to study structural remodeling of the atria and possible therapeutic advances in the management of AF. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Research

Identification of a non-host semiochemical from miniature pinscher, Canis lupus familiaris, that repels Rhipicephalus sanguineus sensu lato (Acari: Ixodidae)

It is already known that the beagle breed of domestic dogs produces semiochemicals capable of repelling the brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.). With a view to discovering new non-host semiochemicals as tick repellents, we compared the semiochemicals produced by a putative tick-resistant breed of dog, miniature pinscher, with known tick-resistant (beagle) and tick-susceptible (English cocker spaniel) breeds. Two non-host compounds produced by beagles, i.e. 2-hexanone and benzaldehyde, were shown to be present in samples collected from all three breeds. Furthermore, two compounds, 6-methyl-5-hepten-2-one and 1,2,4-trimethylbenzene, were found in higher amounts in samples collected from miniature pinscher dogs. The mean amounts of benzaldehyde, 2-hexanone and 1,2,4-trimethylbenzene were similar for beagles and miniature pinschers (P > 0.05) and higher than the means observed for cocker spaniels (P < 0.05), whereas the mean amount of 6-methyl-5-hepten-2-one produced by miniature pinschers was significantly higher (P < 0.05) than for the other breeds of dogs. In Petri-dish assays with adult R. sanguineus s.l., 6-methyl-5-hepten-2-one was repellent for all observation periods evaluated for the two highest concentrations (0.100 and 0.200 mg.cm−2, P < 0.01). The obtained results support our hypothesis that miniature pinschers are a tick-resistant dog breed and agree with previous observations of miniature pinschers being the breed least parasitized by ticks. Furthermore, the non-host semiochemical 6-methyl-5-hepten-2-one has potential to be developed for use as a repellent for the protection of susceptible dogs from R. sanguineus s.l. ticks.

A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes.

The development of a safe and efficient multivalent vaccine has great prospects for application. Both rabies virus (RABV) and canine distemper virus (CDV) are highly infectious antigens, causing lethal diseases in domestic dogs and other carnivores worldwide. In this study, a replication-deficient human adenovirus 5 (Ad5)-vectored vaccine, rAd5-G-H, expressing RABV glycoprotein (G) and CDV hemagglutinin (H) protein was constructed. The RABV G and CDV H protein of rAd5-G-H were expressed and confirmed in infected HEK-293 cells by indirect immunofluorescence assay. The rAd5-G-H retained a homogeneous icosahedral morphology similar to rAd5-GFP under an electron microscope. A single dose of 108 GFU of rAd5-G-H administered to mice by intramuscular injection elicited rapid and robust neutralizing antibodies against RABV and CDV. Flow cytometry assays indicated that the dendritic cells and B cells in inguinal lymph nodes were significantly recruited in rAd5-G-H-immunized mice in comparison with the mock and rAd5-GFP groups. rAd5-G-H also activated the Th1- and Th2-mediated cell immune responses against RABV and CDV in mice, which contributed to 100% survival of a lethal-dose RABV challenge without any clinical signs. In foxes, a single dose of 109 GFU of rAd5-G-H could elicit high levels of neutralizing antibodies against both RABV and CDV in comparison with the mock and rAd5-GFP groups. All foxes in the rAd5-GFP and mock groups died, while the foxes inoculated with rAd5-G-H all survived and showed no clinical signs of disease after being challenged with a lethal wild-type CDV strain. These results suggested that rAd5-G-H has great potential as a bivalent vaccine against rabies and canine distemper in highly susceptible dogs and wildlife animals.

The continental atlas of tsetse and African animal trypanosomosis in Nigeria

Tsetse-transmitted trypanosomosis remains a major animal health problem in Nigeria, in a context where changes in land cover, climate and control interventions are modifying its epidemiological patterns. Evidence-based decision making for the progressive control of the disease requires spatially-explicit information on its occurrence and prevalence, as well as on the distribution and abundance of the tsetse vector.In the framework of the continental Atlas of tsetse and African animal trypanosomosis (AAT), a geo-referenced database was assembled for Nigeria, based on the systematic review of 133 scientific publications (period January 1990 - March 2019).The three main species of trypanosomes responsible for the disease (i.e. Trypanosoma vivax, T. congolense and T. brucei) were found to be widespread, thus posing a national-level problem. Their geographic distribution extends beyond the tsetse-infested belt, owing to the combined effect of animal movement and mechanical transmission by non-tsetse vectors. T. simiae, the major trypanosomal pathogen in pigs, T. godfreyi and the human-infective T. brucei gambiense were also reported. AAT was reported in a number of susceptible host species, including cattle, sheep, goats, pigs, camels, horses, donkeys and dogs, while no study on wildlife was identified. Estimates of prevalence are heavily influenced by the sensitivity of the diagnostic techniques, ranging from an average of 3.5% for blood films to 31.0% for molecular techniques.Two riverine tsetse species (i.e. Glossina palpalis palpalis and G. tachinoides) were found to have the broadest geographical range, as they were detected in all six geopolitical zones of Nigeria. By contrast, the distribution of savannah species (i.e. G. morsitans submorsitans and G. longipalpis) appears to be highly fragmented, and limited to protected areas. Very little information is available for forest species, with one single paper reporting on G. fusca congolensis and G. nigrofusca nigrofusca in the Niger Delta region.The future development of a national Atlas of tsetse and AAT, relying on both published and unpublished information, could improve on the present review and provide further epidemiological evidence for decision making.

Determining the post-elimination level of vaccination needed to prevent re-establishment of dog rabies.

BackgroundOnce a canine rabies-free status has been achieved, there is little guidance available on vaccination standards to maintain that status. In areas with risk of reintroduction, it may be practical to continue vaccinating portions of susceptible dogs to prevent re-establishment of canine rabies.MethodsWe used a modified version of RabiesEcon, a deterministic mathematical model, to evaluate the potential impacts and cost-effectiveness of preventing the reintroduction of canine rabies through proactive dog vaccination. We analyzed four scenarios to simulate varying risk levels involving the reintroduction of canine rabies into an area where it is no longer present. In a sensitivity analysis, we examined the influences of reintroduction frequency and intensity, the density of susceptible dog population, dog birth rate, dog life expectancy, vaccine efficacy, rate of loss of vaccine immunity, and the basic reproduction number (R0).ResultsTo prevent the re-establishment of canine rabies, it is necessary to vaccinate 38% to 56% of free-roaming dogs that have no immunity to rabies. These coverage levels were most sensitive to adjustments in R0 followed by the vaccine efficacy and the rate of loss of vaccine immunity. Among the various preventive vaccination strategies, it was most cost-effective to continue dog vaccination at the minimum coverage required, with the average cost per human death averted ranging from $257 to $398 USD.ConclusionsWithout strong surveillance systems, rabies-free countries are vulnerable to becoming endemic when incursions happen. To prevent this, it may be necessary to vaccinate at least 38% to 56% of the susceptible dog population depending on the risk of reintroduction and transmission dynamics.