Canine Disease Research Articles

Effectiveness of fluralaner treatment regimens for the control of canine Chagas disease: A mathematical modeling study.

Canine Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by insect triatomine vectors known as kissing bugs. The agent can cause cardiac damage and long-term heart disease and death in humans, dogs, and other mammals. In laboratory settings, treatment of dogs with systemic insecticides has been shown to be highly efficacious at killing triatomines that feed on treated dogs. We developed compartmental vector-host models of T. cruzi transmission between the triatomine and dog population accounting for the impact of seasonality and triatomine migration on disease transmission dynamics. We considered a single vector-host model without seasonality, and model with seasonality, and a spatially coupled model. We used the models to evaluate the effectiveness of the insecticide fluralaner with different durations of treatment regimens for reducing T. cruzi infection in different transmission settings. In low and medium transmission settings, our model showed a marginal difference between the 3-month and 6-month regimens for reducing T. cruzi infection among dogs. The difference increases in the presence of seasonality and triatomine migration from a sylvatic transmission setting. In high transmission settings, the 3-month regimen was substantially more effective in reducing T. cruzi infections in dogs than the other regimens. Our model showed that increased migration rate reduces fluralaner effectiveness in all treatment regimens, but the relative reduction in effectiveness is minimal during the first years of treatment. However, if an additional 10% or more of triatomines killed by dog treatment were eaten by dogs, treatment could increase T. cruzi infections in the dog population at least during the first year of treatment. Our analysis shows that treating all peridomestic dogs every three to six months for at least five years could be an effective measure to reduce T. cruzi infections in dogs and triatomines in peridomestic transmission settings. However, further studies at the local scale are needed to better understand the potential impact of routine use of fluralaner treatment on increasing dogs' consumption of dead triatomines.

Characterization of the Fecal and Mucosa-Associated Microbiota in Dogs with Chronic Inflammatory Enteropathy.

Canine chronic inflammatory enteropathy implicates multifactorial pathogenesis where immunological dysregulation and gut microbiota changes have a central role. Most sequencing-based taxonomic studies have been focused on the fecal microbiota. However, the analysis of these samples does not provide complete information regarding the composition of the small intestine affected by this canine disease. Therefore, in this study, we aimed to characterize the intestinal bacterial microbiota in dogs with inflammatory bowel disease (IBD) (n = 34) by means of duodenal biopsies and fecal samples collected at the time of the diagnosis and to compare those to a group of healthy dogs (n = 12) using the 16S ribosomal RNA (16S rRNA) gene-targeted sequencing (Illumina MiSeq platform). Our study showed that IBD dogs presented differences in the fecal bacterial communities when compared with healthy dogs, with a lower relative abundance of Prevotellaceae (p = 0.005), Prevotella (p = 0.002), and Prevotellaceae Ga6A1 group (0.006); Erysipelotrichales (p = 0.019), Candidatus Stoquefichus (p < 0.001), Erysipelotrichaceae (p = 0.011), and Allobaculum (p = 0.003); Lachnospiraceae NK4A136 group (p = 0.015), Sellimonas (p = 0.042), Oscillospirales (p = 0.037), Oscillospiraceae UCG-005 (p < 0.001), Faecalibacterium (p = 0.028), and Fournierella (p = 0.034); Acidaminococcales, Acidaminococcaceae, and Phascolarctobacterium (p = 0.001); Aeromonadales (p = 0.026), Succinivibrionaceae (p = 0.037), and Succinivibrio (p = 0.031). On the other hand, a higher relative abundance of Enterococcaceae (Enterococcus; p = 0.003), Streptococcaceae (Streptococcus, p = 0.021), Enterobacterales (p = 0.027), Enterobacteriaceae (p = 0.008), and Escherichia-Shigella (p = 0.011) was detected. Moreover, when evaluating α-diversity, the dogs with IBD showed lower diversity in terms of richness and abundance of species (observed species [p = 0.031] and Shannon index [p = 0.039]). Furthermore, fecal microbiota in dogs with IBD was significantly different from healthy dogs (p = 0.006). However, only a few taxa relative abundance shifts (lower Rubrobacteria, Rubrobacterales, Rubrobacteriaceae, and Rubrobacter [p = 0.002]; Cyanobacteria [p = 0.010], Vampirivibrionia, Obscuribacterales, and Obscuribacteraceae [p = 0.005]; Neisseriaceae [p = 0.004] and Conchiformibius [p = 0.003]) were observed when assessing duodenal-associated microbiota of dogs with IBD. Thus, even if the bowel inflammation mainly affects the small intestine in the IBD-affected dogs of the study, fecal specimens may constitute a better sample due not only to their easy availability but also in terms of searching for bacterial taxa as biomarkers for canine IBD. The use of different diets in the study can also have a partial influence on the microbiota composition. Future studies encompassing multi-omics approaches should evaluate the functionality in both levels to unravel the pathophysiology of canine IBD.

Medical Management of Canine Chronic Ulcerative Stomatitis Using Cyclosporine and Metronidazole.

Canine chronic ulcerative stomatitis (CCUS) is a spontaneously occurring, painful, and often debilitating condition of the oral cavity, with a suspected immune-mediated component. The response to pharmacological treatment is generally poor, thus the need to identify more effective medical therapies for this condition. This article describes a prospective clinical trial that was designed to evaluate the efficiency of a combination of cyclosporine and metronidazole in managing CCUS. The hypothesis was that a combination of cyclosporine and metronidazole would effectively minimize clinical signs associated with CCUS. Ten client-owned dogs with a biopsy-confirmed diagnosis consistent with CCUS were prescribed cyclosporine (5 mg/kg) for 1 week, followed by the addition of metronidazole (15-20 mg/kg), both administered orally once daily. The cyclosporine dosage interval was lengthened over time. Dogs were observed for a 6-month period and evaluated using a 32-point Canine Ulcerative Stomatitis Disease Activity Index (CUSDAI). Regular cyclosporine therapeutic drug monitoring was also conducted by the measurement of whole blood cyclosporine levels and the pharmacodynamic assessment of the T-cell expression of IL-2. The results demonstrated that a combination of cyclosporine and metronidazole was effective in minimizing the clinical signs of CCUS and in reducing CUSDAI scores. Neither blood cyclosporine levels nor the T-cell expression of IL-2 predicted improvement in clinical signs and CUSDAI scores, although there was a correlation between blood drug concentrations and the suppression of T-cell IL-2 expression. The evaluation of clinical signs and CUSDAI scores appears to be the most effective means of assessing response to therapy, and therapeutic drug level monitoring does not appear to be routinely indicated.

First study on microscopic and molecular detection of Acanthocheilonema reconditum and Leishmania infantum coinfection in dogs in Southwest Colombia.

Canine vector-borne diseases represent an important issue for the welfare and health of animals, but also have great zoonotic potential. These diseases are caused by bacteria, nematodes such as filariae, and other parasites such as Leishmania spp. Given the difficulty in differentiating common microfilariae in dogs by microscopy and serological methods, molecular techniques such as polymerase chain reaction (PCR) and sequencing should be valuable for reaching a reliable diagnosis. This study aimed to use microscopy and PCR to identify the microfilarial species in dogs from Valle del Cauca, Colombia, and a possible association with Leishmania infantum parasites. This study was conducted on 270 dogs from Pradera and Florida municipalities. Microfilariae were detected in dogs by optical microscopy and amplification with 5.8S-ITS2-28S. Species identification was achieved through the amplification of the gene cytochrome oxidase I (COX1). Microscopic detection of microfilariae was possible in 4.81% (13/270) of the dogs. In addition, by PCR of COX1 and Sanger sequencing of ITS2, Acanthocheilonema reconditum was identified as the circulating microfilarial species in 12 dogs, coinfecting with the species L. infantum (Leishmania donovani complex). To the best of our knowledge, this is the first report on A. reconditum and L. infantum mixed infection in dogs in Colombia, particularly in the Valle del Cauca.

Convergence of human and veterinary medicine: leveraging canine naturally occurring neurological disorders to develop regenerative treatments.

Convergence of human and veterinary medicine: leveraging canine naturally occurring neurological disorders to develop regenerative treatments.

Construction of diagnostic prediction model for canine nasal diseases using less invasive examinations without anesthesia.

Advanced imaging techniques under general anesthesia are frequently employed to achieve a definitive diagnosis of canine nasal diseases. However, these examinations may not be performed immediately in all cases. This study aimed to construct prediction models for canine nasal diseases using less-invasive examinations such as clinical signs and radiography. Dogs diagnosed with nasal disease between 2010 and 2020 were retrospectively investigated to construct a prediction model (Group M; GM), and dogs diagnosed between 2020 and 2021 were prospectively investigated to validate the efficacy (Group V; GV). Prediction models were created using two methods: manual (Model 1) and LASSO logistic regression analysis (Model 2). In total, 103 and 86 dogs were included in GM and GV, respectively. In Model 1, the sensitivity and specificity of neoplasia (NP) and sino-nasal aspergillosis (SNA) were 0.88 and 0.81 in GM and 0.92 and 0.78 in GV, respectively. Those of non-infectious rhinitis (NIR) and rhinitis secondary to dental disease (DD) were 0.78 and 0.88 in GM and 0.64 and 0.80 in GV, respectively. In Model 2, the sensitivity and specificity of NP and SNA were 0.93 and 1 in GM and 0.93 and 0.75 in GV, respectively. Those of NIR and DD were 0.96 and 0.89 in GM and 0.80 and 0.79 in GV, respectively. This study suggest that it is possible to create a prediction model using less-invasive examinations. Utilizing these predictive models may lead to appropriate general anesthesia examinations and treatment referrals.

Ultrasonographic particularities of chronic gallbladder cholecystitis in dogs

Canine gallbladder related diseases are being reported with an increased frequency by specialists working in small animal veterinary medicine. It is presumed that these represent a direct consequence following changes in diet, lifestyle and activity levels of small animals. As a result of increased assertion towards the well-being of pets worldwide, veterinary medicine has evolved by creating and implementing new diagnostic protocols and noninvasive means of investigations, like ultrasonography, which can characterize the presence and intensity of any abnormalities encountered in the canine gallbladder.

N gene based detection and phylogenetic analysis of canine morbillivirus in dogs

Canine distemper, a highly fatal systemic disease in domestic dogs and wild carnivores, has the second highest mortality rate after rabies and is responsible for a large number of animal deaths around the world. It is considered a major pathogen in the canine infectious respiratory disease complex. This paper reports the finding of a study conducted to detect and characterise canine distemper virus (Canine Morbillivirus) based on N gene. A total of 59 samples collected from cases of respiratory infections in dogs were subjected to N gene based reverse transcriptase polymerase chain reaction (RT-PCR) and eleven of them (18.64 per cent) were found positive. Sequencing and phylogenetic analysis revealed that all the canine distemper viruses obtained in the present study were related to Indian strains that were previously reported. However, the viruses from the same district were similar among themselves.

Comparison of some cytokines, acute phase proteins and citrulline levels in healthy and canine distemper infected dogs.

Canine distemper virus (CDV) is the etiological agent of severe disease in domestic and wild carnivores. Clinical diagnosis of CDV is challenging because of its similarity to other canine respiratory and intestinal diseases. We aimed to determine certain cytokine (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor-α [TNF-α]), interferon (IFN)-γ, canine serum amyloid A (SAA), and canine citrulline (CIT) levels for the first time in CDV-positive dogs. For this purpose, 10 CDV-positive dogs with compatible clinical findings (i.e., neurological symptoms such as tremors and myoclonus, ocular and nasal discharge, and wheezing) and 10 healthy dogs based on the clinical examinations and rapid test results were enrolled. It was observed that the CIT, INF-γ, IL-1β, IL-2, IL-6, and TNF-α levels were significantly decreased in the CDV-positive dogs than that of the healthy ones (P<0.05). As a result, it was observed that CDV causes immunosuppression and accordingly, the inflammatory response might cause decreased cytokine and acute-phase protein synthesis. Therefore, it was concluded that further investigation of inflammatory pathways and CIT interactions may provide crucial clinical information at different stages of CDV, and aforementioned parameters may serve as important biomarkers for CDV in terms of demonstrating the presence of immunosuppression.

An endoscopic and histopathological assessment and correlation of endoscopic score with clinical activity index (CIBDAI) in the diagnosis of canine idiopathic inflammatory bowel disease.

Inflammatory bowel disease (IBD) in dogs is often characterized by a relapsing and remitting clinical course. Determination of inflammatory activity is important for assessing the disease extent, severity, and tailoring appropriate treatment. The study was conducted to record the macroscopic and microscopic changes associated with IBD to assess the usefulness of endoscopy in the diagnosis of the disease and to correlate the clinical activity index (CIBDAI) with endoscopic score. Thirty-three dogs with idiopathic IBD were selected after thorough examination and exclusion. Gastroduodenoscopy and colonoscopy were performed to document the gross macroscopic intestinal lesions. Histopathology of endoscopic aided biopsy samples was used to confirm the disease. Mucosal erythema and increased friability were the most predominant endoscopic findings in the stomach, duodenum, and colon of IBD dogs. Lymphoplasmacytic infiltration was predominant in the mucosal samples on histopathology and diffuse form of IBD is more common in canines. Gastroduodenoscopy and colonoscopy in combination with endoscopically guided biopsy and histopathology are of value in the assessment and diagnosis of IBD. There was no correlation between the clinical inflammatory bowel disease activity index (CIBDAI) with the endoscopic score. A diffuse form of IBD and colitis is more common in dogs in comparison to human IBD where the disease manifests in two distinct forms. Colonoscopy with ileal biopsy could act as a gold standard in the confirmation of diffuse IBD in dogs. CIBDAI can be used as a reliable measure of clinical signs of inflammation and histopathology can be used as a definitive diagnosis of intestinal inflammation.

Uterine haemodynamics and band neutrophils as recovery markers in medical management of canine pyometra

Canine pyometra is a hormonally mediated life-threatening uterine disease of canines, associated with bacterial infection and inflammation. The disease is characterized by the accumulation of pus in the uterus and systemic illness. The study was undertaken to assess the relevance of band cells in circulation and Doppler ultrasonography in the prognostic evaluation of medically managed canine pyometra. A significantly higher band of neutrophils were recorded among bitches presented with pyometra, which reduced to the physiologically normal range as treatment progressed in the animals which responded to the treatment. The resistive index, which was lower than the threshold value of 0.72, increased as the treatment progressed in the responsive animals and proved to be a reliable tool as a recovery marker.

Autochthonous infection with Ehrlichia Canis and Hepatozoon Canis in dogs from Serbia.

The epidemiological status concerning many canine tick-borne diseases (TBDs) in Serbia is still insufficiently known. Our study aimed to investigate the presence of tick-borne pathogens of the family Anaplasmataceae and Hepatozoon spp., as a cause of illnesses accompanied by clinical signs that can occur in dogs with anaplasmosis, ehrlichiosis and hepatozoonosis. Dogs are included in the study based on the presence of a minimum of three clinical and/or pathological findings that could be associated with anaplasmosis, ehrlichiosis and hepatozoonosis. During the study (April-October 2018), 11 dogs met the conditions to be included in the survey. Identification of the causative agent in the blood of diseased dogs was performed by conventional PCR followed by sequencing. The presence of the pathogens was confirmed in three animals (3/11, 27.3%). The presence of Ehrlichia canis was confirmed in 3-month-old female Rottweiler puppy, an 8-year old Miniature Schnauzer female was positive for Hepatozoon canis infection, while 4-year-old mixed breed male dog was co-infected with both mentioned pathogens. These are the first cases of autochthonous infection with E. canis and H. canis in dogs from Serbia confirmed by molecular methods. The results of our study indicate the importance of molecular methods to establish a reliable diagnosis of TBDs. Also, the confirmed presence of causative agents of canine monocytic ehrlichiosis and hepatozoonosis in Serbia appeals to veterinary practitioners that it is necessary to exclude the presence of those diseases in suspicious dogs.

Prognostic relevance of left cardiac enlargement in dogs with preclinical myxomatous mitral valve disease

IntroductionAccording to the most recent consensus guidelines on canine myxomatous mitral valve disease (MMVD), dogs with only left atrial enlargement (LAE) or left ventricular enlargement are classified as stage B1. The concomitant presence of LAE and left ventricular enlargement is needed to be classified as stage B2. The primary aim of the study was to evaluate the prognosis in stage B1 and stage B2 according to the revised definition. The secondary aim was to assess the prognostic relevance of LAE in stage B1. AnimalsA total of 440 dogs with MMVD, 276 in stage B1 and 164 in stage B2. Materials and methodsRetrospective and observational study. The left atrium-to-aorta ratio and the left ventricular end-diastolic diameter normalized were used to define cardiac dimensions. The long-term outcome was assessed by telephone interviews with owners and referring vets. Both cardiac-related and all-cause mortality were evaluated. ResultsStage B1 dogs had a longer median survival time than stage B2, considering both cardiac-related death (2344 vs. 1341 days; P<0.001) and all-cause mortality (1832 vs. 855 days; P<0.001). Age, left atrium-to-aorta ratio, and the left ventricular end-diastolic diameter normalized were independent predictors of cardiac-related death and all-cause mortality. Among stage B1, dogs with LAE lived shorter than those without LAE (1183 vs. 1882 days; P=0.005) considering all-cause mortality. Discussion and conclusionsStage B1 dogs lived longer than stage B2 dogs. Among stage B1, LAE had prognostic relevance considering all-cause mortality. This finding could add useful prognostic information in the management of preclinical MMVD.

Prospective pilot study on the predictive significance of plasma miR-30b-5p through the study of echocardiographic modifications in Cavalier King Charles Spaniels affected by different stages of myxomatous mitral valve disease: The PRIME study.

Specific microRNAs expressions may accurately characterize different stages of canine myxomatous mitral valve disease. This preliminary pilot study aimed to (1) describe the clinical and echocardiographic parameters of Cavalier King Charles Spaniels affected by myxomatous mitral valve disease at different American College of Veterinary Internal Medicine (ACVIM) stages (B1, B2 and C) and healthy control group (ACVIM A), comparing the parameters collected during the first examination (T0) and the end of the follow-up (T1); (2) assess the association between the values of echocardiographic parameters at T1 and the expression profile of miR-30b-5p at T0. Thirty-five Cavalier King Charles Spaniels (median age 4.29 years and median weight 9 Kg) in different ACVIM stages were included (7 A, 19 B1, 6 B2 and 3 C). Inverse probability weighting analysis was performed to estimate the association of the exposure variable (miR-30b-5p) with the outcome variables (clinical and echocardiographic variables). Time was included as variable. The results pointed out that high levels of plasma miR-30b-5p corresponded to lower values of left ventricular end-diastolic diameter normalized for body weight, end-diastolic and end-systolic volumes indexed for body weight, and left atrium-to aortic root ratio. Hence, higher miR-30b-5p expressions were associated with milder forms of mitral valve disease in our study population. In contrast, the results obtained for the intensity of heart murmur, the mitral regurgitation severity, and the Mitral INsufficiency Echocardiographic score) were not statistically significant. A relationship between high abundance of miR-30b-5p and myxomatous mitral valve disease that appear echocardiographically more stable over time has been demonstrated. In conclusion, Cavalier King Charles Spaniels affected by myxomatous mitral valve disease that at the first cardiologic evaluation showed an upregulation of miR-30b-5p are expected to experience lesser variations on their echocardiographic examination between T0 and T1.

Assessment of the circulation of Dirofilaria immitis in dogs from northern Portugal through combined analysis of antigens, DNA and parasite forms in blood

Dirofilariasis is a vector-borne disease frequent in many countries. Not only infected dogs, but also cats and wild canids (including wolves and foxes), represent important sources of infection for mosquitoes, which are the pathogen vectors. The disease is endemic in Mediterranean countries with increasing incidence in Italy, France, Greece and Spain, but limited epidemiological data is available from Portugal regarding its distribution and impact. Aiming to clarify this, canine whole blood samples (n = 244) from the north of Portugal were tested for Dirofilaria spp. antigens by use of a commercial rapid immunomigration test. Polymerase chain reaction (PCR) and the modified Knott test were also used to assess the presence of microfilariae. Results were also compared to assess the performance of each test used. Of the 244 animals tested, 118 (48.4%) were positive for Dirofilaria immitis (heartworm) in the serological adult worm rapid antigen detection test, and 36 (14.8%) had circulating microfilariae, identified as D. immitis. A combined positivity of 51.6% (126/244) was found. Results indicate that the risk of exposure to D. immitis in dogs is high in this region of Portugal, and that prophylaxis against the parasite is advisable to decrease the occurrence of canine infection and disease. The present study highlights the diagnostic value of serological and molecular tests in determining the prevalence of D. immitis.

Esomeprazole induces structural changes and apoptosis and alters function of in vitro canine neoplastic mast cells

Histamine-2 receptor antagonists such as famotidine and proton pump inhibitors such as esomeprazole are commonly used in canine MCT disease, but direct effects on dog MCs have not been evaluated. Omeprazole is a proton pump inhibitor which has been demonstrated to cause structural and functional changes to in vitro murine mast cells (MCs). It has not yet been determined if esomeprazole, the commercially available and commonly prescribed S-isomer of omeprazole, has similar effects. Our primary study objective was to evaluate and compare the effects of acid suppressants (esomeprazole and famotidine) on MC ultrastructure, viability, and function in vitro using both healthy and neoplastic MCs. Murine bone marrow derived mast cells (BMMC), human LAD2, and canine C2 and BR cells, were used for these studies, representing a single healthy (i.e., BMMCs) MC model and multiple neoplastic MC models (i.e., LAD2, C2, BR), respectively. The rat basophilic leukemic (RBL-2H3) and canine B cell lymphoma 17–71 cell lines served as granulocytic and agranulocytic control lines for experiments, respectively. The treatment effect of acid suppressants on MC ultrastructure was assessed via both light and transmission electron microscopy. Differences in MC viability was assessed between groups via MTS-based, colorimetric assays and flow cytometry. Degranulation was assessed by quantification of β-hexosaminidase (i.e., LAD2 and RBL-2H3). Esomeprazole-treated MCs of all lines exhibited dramatic time and concentration-dependent alterations in ultrastructure (i.e., increased vacuolization, compromise of cell membrane), increased apoptosis, and altered degranulation responses in comparison to famotidine and vehicle-treated cells. The canine B cell lymphoma cells consistently exhibited either no significant (i.e., cytotoxicity assays) or greatly diminished treatment responses (i.e., apoptosis) compared to MCs. Esomeprazole, but not famotidine, induces significant cytotoxicity, as well as alterations to cell structure and function to multiple lines of in vitro neoplastic MCs. Continued in vitro work investigating the specific mechanisms by which proton pump inhibitors induce these effects, as well as prospective, in vivo work comparing the treatment effects of acid suppressants on canine MCTs, are warranted.

Ultrasonography of the paralumbar muscles as a new aid during melarsomine treatment in canine heartworm disease. Description and illustration of the method - A preliminary study.

Melarsomine is used intramuscularly to destroy adult heartworms when treating canine heartworm disease (HWD). This drug is highly irritative and can elicit local complications. Therefore, melarsomine should be injected into the paralumbar muscles by strictly adhering to the manufacturers' prescriptions. However, it is not known how to determine the optimal location of the needle during the injection process. Ultrasonography (US) of the epaxial (paralumbar) musculature was used as a new method to measure the cross-sectional diameter of the paralumbar musculature, to determine the required location of the injection needle, and to study the local side effects in two dogs with HWD. The macroscopic appearance of the melarsomine solution during injection was demonstrated by video imaging. Melarsomine was not fully gravitating, but its majority was spreading along the thickest fascia of the musculature. Three minutes thereafter, no ultrasound signs of the melarsomine solution were seen, suggesting a full absorption at least ultrasonographically. This procedure was simulated in vitro with methylene blue solution having the same appearance. Removing the injection needle only after 5 min post-injection could prevent undesirable leakage of the drug through the injection channel into the subcutaneous tissue. Ultrasonography can be a useful aid during the treatment of HWD with melarsomine according to this preliminary study.

Intravitreal gene therapy preserves retinal function in a canine model of CLN2 neuronal ceroid lipofuscinosis

CLN2 neuronal ceroid lipofuscinosis is a rare hereditary neurodegenerative disorder characterized by deleterious sequence variants in TPP1 that result in reduced or abolished function of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). Children with this disorder experience progressive neurological decline and vision loss starting around 2–4 years of age. Ocular disease is characterized by progressive retinal degeneration and impaired retinal function culminating in total loss of vision. Similar retinal pathology occurs in a canine model of CLN2 disease with a null variant in TPP1. A study using the dog model was performed to evaluate the efficacy of ocular gene therapy to provide a continuous, long-term source of human TPP1 (hTPP1) to the retina, inhibit retinal degeneration and preserve retinal function. TPP1−/− dogs received an intravitreal injection of 1 x 1012 viral genomes of AAV2.CAG.hTPP1 in one eye and AAV2.CAG.GFP in the contralateral eye at 4 months of age. Ophthalmic exams, in vivo ocular imaging and electroretinography were repeated monthly to assess retinal structure and function. Retinal morphology, hTPP1 and GFP expression in the retina, optic nerve and lateral geniculate nucleus, and hTPP1 concentrations in the vitreous were evaluated after the dogs were euthanized at end stage neurological disease at approximately 10 months of age. Intravitreal administration of AAV2.CAG.hTPP1 resulted in stable, widespread expression of hTPP1 throughout the inner retina, prevented disease-related declines in retinal function and inhibited disease-related cell loss and storage body accumulation in the retina for at least 6 months. Uveitis occurred in eyes treated with the hTPP1 vector, but this did not prevent therapeutic efficacy. The severity of the uveitis was ameliorated with anti-inflammatory treatments. These results indicate that a single intravitreal injection of AAV2.CAG.hTPP1 is an effective treatment to inhibit ocular disease progression in canine CLN2 disease.

Across-breed genetic investigation of canine hip dysplasia, elbow dysplasia, and anterior cruciate ligament rupture using whole-genome sequencing.

Here, we report the use of genome-wide association study (GWAS) for the analysis of canine whole-genome sequencing (WGS) repository data using breed phenotypes. Single-nucleotide polymorphisms (SNPs) were called from WGS data from 648 dogs that included 119 breeds from the Dog10K Genomes Project. Next, we assigned breed phenotypes for hip dysplasia (Orthopedic Foundation for Animals (OFA) HD, n = 230 dogs from 27 breeds; hospital HD, n = 279 dogs from 38 breeds), elbow dysplasia (ED, n = 230 dogs from 27 breeds), and anterior cruciate ligament rupture (ACL rupture, n = 279 dogs from 38 breeds), the three most important canine spontaneous complex orthopedic diseases. Substantial morbidity is common with these diseases. Previous within- and between-breed GWAS for HD, ED, and ACL rupture using array SNPs have identified disease-associated loci. Individual disease phenotypes are lacking in repository data. There is a critical knowledge gap regarding the optimal approach to undertake categorical GWAS without individual phenotypes. We considered four GWAS approaches: a classical linear mixed model, a haplotype-based model, a binary case-control model, and a weighted least squares model using SNP average allelic frequency. We found that categorical GWAS was able to validate HD candidate loci. Additionally, we discovered novel candidate loci and genes for all three diseases, including FBX025, IL1A, IL1B, COL27A1, SPRED2 (HD), UGDH, FAF1 (ED), TGIF2 (ED & ACL rupture), and IL22, IL26, CSMD1, LDHA, and TNS1 (ACL rupture). Therefore, categorical GWAS of ancestral dog populations may contribute to the understanding of any disease for which breed epidemiological risk data are available, including diseases for which GWAS has not been performed and candidate loci remain elusive.

Dietary fiber aids in the management of canine and feline gastrointestinal disease.

Dietary fiber describes a diverse assortment of nondigestible carbohydrates that play a vital role in the health of animals and maintenance of gastrointestinal tract homeostasis. The main roles dietary fiber play in the gastrointestinal tract include physically altering the digesta, modulating appetite and satiety, regulating digestion, and acting as a microbial energy source through fermentation. These functions can have widespread systemic effects. Fiber is a vital component of nearly all commercial canine and feline diets. Key features of fiber types, such as fermentability, solubility, and viscosity, have been shown to have clinical implications as well as health benefits in dogs and cats. Practitioners should know how to evaluate a diet for fiber content and the current knowledge on fiber supplementation as it relates to common enteropathies including acute diarrhea, chronic diarrhea, constipation, and hairball management. Understanding the fundamentals of dietary fiber allows the practicing clinician to use fiber optimally as a management modality.