Feline Disease Research Articles

Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats.

Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus-1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-α2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols.

GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido, Japan.

A male Japanese domestic cat with retarded growth in Hokkaido, Japan, showed progressive motor dysfunction, such as ataxia starting at 3 months of age and tremors, visual disorder and seizure after 4 months of age. Finally, the cat died of neurological deterioration at 9 months of age. Approximately half of the peripheral blood lymphocytes had multiple abnormal vacuoles. Magnetic resonance imaging showed bisymmetrical hyperintensity in the white matter of the parietal and occipital lobes in the forebrain on T2-weighted and fluid-attenuated inversion recovery images, and mild encephalatrophy of the olfactory bulbs and temporal lobes. The activity of lysosomal acid β-galactosidase in leukocytes was negligible, resulting in the biochemical diagnosis of GM1 gangliosidosis. Histologically, swollen neurons characterized by accumulation of pale, slightly granular cytoplasmic materials were observed throughout the central nervous system. Dysmyelination or demyelination and gemistocytic astrocytosis were observed in the white matter. Ultrastructually, membranous cytoplasmic bodies were detected in the lysosomes of neurons. However, genetic analysis did not identify the c.1448G>C mutation, which is the single known mutation of feline GM1 gangliosidosis, suggesting that the cat was affected with a new variant of the feline disease.

Nosocomial feline calicivirus-associated virulent systemic disease in a veterinary emergency and critical care unit in France.

Case series summaryIn October 2011, an abnormally large morbidity and mortality event was noted in the intensive care unit (ICU) of a veterinary school hospital in Nantes, France. Cats, and cats only, transferred from the emergency room presented with fever, ulcers on the tongue and cutaneous lesions around venepuncture or surgical incision sites, leading to suspicion of a feline calicivirus-associated virulent systemic disease confirmed with reverse transcriptase-polymerase chain reaction. A total of 14 cats were suspected. The clinical features and the origin of the contamination were described for each cat. The median length of incubation was 4.5 days. Fifty-seven percent of the cats were euthanased (8/14) and 21% died (3/14), with a combined mortality of 79% (11/14) – the highest ever reported. Median survival was 12 days. The recovery rate was 21% (3/14).Relevance and novel informationEight outbreaks have been reported, in veterinary clinics or in group-housed cats. The main unusual aspects of the present outbreak were: (1) the extreme flare-up of lesions at sites of skin breach, precluding any puncture/incision; (2) the suggested better survival rate at home than in hospital; and (3) the immediate control of the outbreak after recognition of the disease. Other striking but less unusual features of this outbreak were: (4) the increasing of the virulence of the calicivirus with the passage of time; and (5) the primary role that the caregivers’ hands played in the spread of the outbreak.

What do we know about feline leishmaniosis?

According to the World Health Organization (WHO), endemic areas of leishmaniosis have spread and the number of reported cases has increased. Europe is one of the continents with greatest risk of the re-emergence of this zoonosis. The significance of the cat as a reservoir of Leishmania species and not simply an accidental host seems to be gaining ground, mainly because: (i) cats can present increased seropositivity between serological analyses, but the pattern of seropositivity is not consistent between cats; (ii) cats can be infected for some months and thus are available for sandflies; and (iii) cats transmit the Leishmania species agent in a competent form. Furthermore, cats have behavioural characteristics that contribute to infection by Leishmania infantum and, as such, feline leishmaniosis (FeL) has been reported worldwide. When clinical signs of FeL are present, they are non-specific and frequently occur in other feline diseases. If they go undiagnosed, they can contribute to an underestimation of the actual occurrence of the disease in cats. The low seroprevalence titres, along with the commonly asymptomatic infection in cats, can further contribute to the underestimation of FeL occurrence. This work aims to raise awareness about FeL among veterinarians by providing a review of the current status of FeL infection caused by L infantum worldwide, the major clinicopathological features of infection, along with recent developments on FeL diagnosis, treatment and prevention.

Feline diabetic remission: what is the recipe?

Diabetes mellitus is a common feline disease that can compromise the wellbeing of affected cats and places numerous obligations on pet owners. A proportion of diabetic cats can enter a state of remission and no longer require exogenous insulin therapy. Achieving remission significantly improves the quality of life of diabetic cats and their owners, so would be an ideal outcome when treating diabetic cats. Although there is little strong evidence on the best management protocols to encourage remission in diabetic cats, it is likely that treatments which promote good glycaemic control provide the greatest likelihood of remission. This article reviews current evidence on the best management strategies to achieve good diabetic control and increase the chance of remission in diabetic cats. It also reviews predictors of which cats are most likely to achieve remission, and management of cats that have successfully achieved diabetic remission.

Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.

Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme β-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease.

Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats.

Feline chronic kidney disease (CKD) is characterized by chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. Mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and antifibrotic effects in rodent CKD models. However, few randomized trials evaluating the effectiveness of MSC therapy for diseases in companion animals have been reported. The purpose of this study was to evaluate the effectiveness of allogeneic MSCs for the treatment of feline CKD using a randomized, placebo-controlled trial. MSCs were isolated from the cryopreserved adipose tissues of specific pathogen-free research cats and culture expanded. CKD cats were enrolled in a randomized, placebo-controlled, blinded one-way crossover clinical study. Four CKD cats were randomized to receive 2 × 10(6) MSCs/kg intravenously at 2, 4 and 6 weeks. Four CKD cats were randomized to receive placebo, with two cats crossing over to the MSC treatment group and one cat failing to complete the trial. Complete blood counts, chemistry and urinalysis were performed at weeks 0, 2, 4, 6 and 8. Glomerular filtration rate (GFR) via nuclear scintigraphy and urine protein:creatinine ratio (UPC) were determined at weeks 0 and 8. Six cats received three doses of allogeneic MSC culture expanded from cryopreserved adipose without adverse effects. No significant change in serum creatinine, blood urea nitrogen, potassium, phosphorus, GFR by nuclear scintigraphy, UPC or packed cell volume was seen in cats treated with MSCs. Individual changes in GFR were 12%, 8%, 8%, 2%, -13% and -67% in treated cats compared with 16%, 36% and 0% in placebo-treated cats. While administration of MSC culture expanded from cryopreserved adipose was not associated with adverse effects, significant improvement in renal function was not observed immediately after administration. Long-term follow-up is necessary to determine whether MSC administration affects disease progression in cats with CKD.

The nutritional management of feline chronic kidney disease

Chronic kidney disease (CKD) is a frequent disease seen in older cats and while it is a progressive condition, the veterinary practice team can play a key role in delaying the inevitable. Dietary modifications are key to slowing the progression of renal disease and alleviating its metabolic consequences. There are four main objectives of nutritional management. These are: a) provide sufficient energy to maintain a good body condition; b) alleviate the clinical manifestations of uraemia; c) minimise fluid, electrolyte and acid-base disturbances; and d) slow disease progression. This article reviews the nutritional concepts employed in the management of CKD, and demonstrates why a renal diet should be implemented early in the disease to maximise both its benefits and acceptance by the feline patient.

Feline disease with trend of human zoonosis in Thailand

Feline disease is usually an important concern in veterinarian medical practice. There are many feline diseases and some have trends to transmit to human. As cat is an important human pet, it is no doubt that zoonosis is important consideration in veterinarian medicine. Here, the author briefly reviews and discusses on the important feline diseases that pose chance for human zoonosis in Thailand, a tropical Southeast Asian country.

The use of glucocorticoids in marmoset wasting syndrome.

BackgroundMarmoset wasting syndrome (MWS) is one of the leading causes of morbidity and mortality in captive marmosets, and thus far no reliable treatment has been found. Glucocorticoids are used widely to treat inflammatory conditions of the GI tract such as human and feline inflammatory bowel disease, which, such as MWS, are histologically characterized by chronic lymphoplasmacytic inflammation in the intestines. Budesonide is a glucocorticoid with few reported side effects due to the majority of it being metabolized into inactive compounds by the liver before entering the systemic circulation.MethodEleven marmosets presented with antemortem signs consistent with MWS and were treated with oral prednisone or budesonide for 8 weeks.ResultsThe marmosets in our study demonstrated a significant increase in both weight and albumin levels (relative to pre-treatment values) after glucocorticoid therapy.ConclusionsGlucocorticoids are an effective therapy to ameliorate the clinical signs associated with MWS with minimal side effects.

Advances of Echocardiography in Equines Practice - A Review

Echocardiography has become routinely procedure used in the diagnosis, management, and follow-up of patients with any suspected or known heart diseases. It is one of the most widely used diagnostic modality in cardiology. It can provide a wealth of helpful information, including the size and shape of the heart, pumping capacity, and the location and extent of any tissue damage of heart. An Echocardiogram on other hand gives physician’s estimates of heart function such as a calculation of the cardiac output, ejection fraction, and diastolic function. It also helps to evaluate cardiac defects such as, atrial septal defects, AV valve stenoses, coronary artery defects, occult DCM, coronary artery disease, feline heartworm disease, persistent left cranial vena cava, canine hypertrophic cardiomyopathy and feline diastolic dysfunction may be identified. This Review details principle, uses, technique, types and limitations of Echocardiography in equines.

Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate.

Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. Data from a nine-sample combined plasma exogenous creatinine-iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5-98.2%; specificity 60-91.3%) or borderline (sensitivity 91.1-96%; specificity 76.5-81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

Disease facts: feline periodontal disease

Periodontal disease is common in feline patients. It is often more challenging for owners to perform oral homecare in cats than dogs, and difficulty in examination of the mouth makes the role of the veterinary team essential. Regular oral examination is important, every six months being recommended for ‘healthy’ mouths, while an examination every three months is recommended where pathology is noted. This article will outline the aetiology, pathogenesis, staging and treatment options for feline periodontal disease.

Feline dental radiography and radiology: A primer.

Information crucial to the diagnosis and treatment of feline oral diseases can be ascertained using dental radiography and the inclusion of this technology has been shown to be the best way to improve a dental practice. Becoming familar with the techniques required for dental radiology and radiography can, therefore, be greatly beneficial. Novices to dental radiography may need some time to adjust and become comfortable with the techniques. If using dental radiographic film, the generally recommended 'E' or 'F' speeds may be frustrating at first, due to their more specific exposure and image development requirements. Although interpreting dental radiographs is similar to interpreting a standard bony radiograph, there are pathologic states that are unique to the oral cavity and several normal anatomic structures that may mimic pathologic changes. Determining which teeth have been imaged also requires a firm knowledge of oral anatomy as well as the architecture of dental films/digital systems. This article draws on a range of dental radiography and radiology resources, and the benefit of the author's own experience, to review the basics of taking and interpreting intraoral dental radiographs. A simplified method for positioning the tubehead is explained and classic examples of some common oral pathologies are provided.

Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded, placebo-controlled clinical trial.

Maropitant is commonly used for acute vomiting. A pharmacokinetic and toxicity study in cats indicated that longer term usage appears safe. The aim of this study was to assess the efficacy of maropitant for management of chronic vomiting and inappetence associated with feline chronic kidney disease (CKD). Forty-one cats with stable International Renal Interest Society Stage II or III CKD, no known concurrent illness, and a complaint of chronic vomiting and inappetence attributed to CKD were enrolled in a randomized, placebo-controlled, blinded clinical study. A complete blood count, serum biochemistry, urinalysis, urine culture, T4 and blood pressure were required for entry. Maropitant was administered at a dose of 4 mg orally (median 1.1 mg/kg, range 0.6-2.9 mg/kg) daily for 2 weeks. Owners kept daily logs of vomiting incidence, appetite and activity scores. Physical examination, weight, body condition score and serum biochemistry were performed before and after the trial period. Mann-Whitney statistics were used to compare treatment groups. Thirty-three cats successfully completed the trial: 21 cats received the drug (nine Stage II cats, 12 Stage III cats) and 12 cats received placebo (seven Stage II cats, five Stage III cats). There was a statistically significant decrease in vomiting in cats with CKD that received maropitant (P <0.01). Cats that received maropitant did not have statistically significant differences in appetite scores, activity scores, weight or serum creatinine compared with placebo. Maropitant was demonstrated to palliate vomiting associated with CKD, and may be helpful in the nutritional management of cats with CKD.

Multi-centered investigation of a point-of-care NT-proBNP ELISA assay to detect moderate to severe occult (pre-clinical) feline heart disease in cats referred for cardiac evaluation

ObjectiveTo prospectively evaluate the diagnostic accuracy of a point-of-care (POC) N-terminal pro-B-type natriuretic peptide (NT-proBNP) ELISA to assess the likelihood of moderate to severe occult heart disease (OcHD) in a clinical population of cats suspected to have heart disease. AnimalsOne hundred and forty-six asymptomatic client-owned cats with a heart murmur, gallop rhythm, arrhythmia, or cardiomegaly. MethodsPhysical examination, blood pressure measurement and echocardiography were performed prospectively. Point-of-care ELISA was visually assessed as either positive or negative by a reader blinded to the echocardiographic results. ResultsForty-three healthy cats, 50 mild OcHD, 31 moderate OcHD, 6 severe OcHD, and 16 cats equivocal for OcHD were examined. Cats with OcHD included 65 with hypertrophic cardiomyopathy, 6 with restrictive or unclassified cardiomyopathy, 1 with arrhythmogenic right ventricular cardiomyopathy, and 15 with non-cardiomyopathic forms of heart disease. Point-of-care ELISA differentiated cats with moderate or severe OcHD with sensitivity/specificity of 83.8%/82.6% and overall accuracy of 82.9%. Positive POC ELISA increased likelihood of moderate or severe OcHD by a factor of 4.8 vs. those that tested negative. Point-of-care ELISA differentiated cats with moderate or severe cardiomyopathic OcHD with sensitivity/specificity of 88.6%/81.3% and overall accuracy of 83.2%. ConclusionIn a select sample of cats referred for cardiac evaluation, positive POC NT-proBNP ELISA increases likelihood of moderate to severe OcHD while negative POC NT-proBNP ELISA result excludes moderate to severe OcHD.

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

The GM2 gangliosidoses, Tay–Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were largely normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated SD patients and those in future clinical trials.

Development of targeted therapies for Parkinson's disease and related synucleinopathies

Therapeutic efforts in neurodegenerative diseases have been very challenging, particularly due to a lack of validated and mechanism-based therapeutic targets and biomarkers. The basic idea underlying the novel therapeutic approaches reviewed here is that by exploring the molecular basis of neurodegeneration in a rare lysosomal disease such as Gaucher's disease (GD), new molecular targets will be identified for therapeutic development in common synucleinopathies. Accumulation of α-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies, suggesting that improved clearance of α-synuclein may be of therapeutic benefit. To achieve this goal, it is important to identify specific mechanisms and targets involved in the clearance of α-synuclein. Recent discovery of clinical, genetic, and pathological linkage between GD and PD offers a unique opportunity to examine lysosomal glucocerebrosidase, an enzyme mutated in GD, for development of targeted therapies in synucleinopathies. While modulation of glucocerebrosidase and glycolipid metabolism offers a viable approach to treating disorders associated with synuclein accumulation, the compounds described to date either lack the ability to penetrate the CNS or have off-target effects that may counteract or limit their capabilities to mediate the desired pharmacological action. However, recent emergence of selective inhibitors of glycosphingolipid biosynthesis and noninhibitory pharmacological chaperones of glycosphingolipid processing enzymes that gain access to the CNS provide a novel approach that may overcome some of the limitations of compounds reported to date. These new strategies may allow for development of targeted treatments for synucleinopathies that affect both children and adults.

Annotated features of domestic cat - Felis catus genome.

BackgroundDomestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors.FindingsHere we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), bisulfite sequencing of Boris, a male cat from St. Petersburg (Russia), and light 30× sequencing of Sylvester, a European wildcat progenitor of cat domestication. The annotation includes 21,865 protein-coding genes identified by a comparative approach, 217 loci of endogenous retrovirus-like elements, repetitive elements which comprise about 55.7% of the whole genome, 99,494 new SNVs, 8,355 new indels, 743,326 evolutionary constrained elements, and 3,182 microRNA homologues. The methylation sites study shows that 10.5% of cat genome cytosines are methylated. An assisted assembly of a European wildcat, Felis silvestris silvestris, was performed; variants between F. silvestris and F. catus genomes were derived and compared to F. catus.ConclusionsThe presented genome annotation extends beyond earlier ones by closing gaps of sequence that were unavoidable with previous low-coverage shotgun genome sequencing. The assembly and its annotation offer an important resource for connecting the rich veterinary and natural history of cats to genome discovery.

Feline chronic kidney disease is associated with upregulation of transglutaminase 2: a collagen cross-linking enzyme.

Chronic kidney disease is a major cause of morbidity and mortality in cats. Transglutaminase 2 (TG2) is a calcium-dependent enzyme proposed to mediate tubulointerstitial fibrosis in the kidney by cross-linking collagen fibrils. Postmortem kidney tissue was obtained from primary renal azotemic (n = 10) and nonazotemic (n = 5) cats (14 domestic short hair, 1 Burmese; aged 9-23.7 years). Extracellular matrix protein deposition was determined by Masson's trichrome staining and collagen immunofluorescence. Total kidney transglutaminase (TG) enzyme activity and TG2 protein were measured in tissue homogenates by putrescine incorporation and Western blotting. Extracellular TG enzyme activity and TG2 protein were determined in situ by immunofluorescence, quantified by multiphase image analysis. Results were compared using the unpaired Student's t-test with Welch's correction. Elevated plasma creatinine, urea, and phosphate concentrations were associated with tubulointerstitial fibrosis but not glomerular fibrosis. Kidney homogenates from azotemic cats showed a 3-fold higher total TG enzyme activity and TG2 protein compared with kidneys from nonazotemic cats. Immunofluorescent studies performed in situ confirmed a 3-fold higher extracellular TG enzyme activity and TG2 protein in cats with azotemia. Tubulointerstitial TG2 showed a positive linear correlation with both renal function and tubulointerstitial fibrosis. In conclusion, for cats with azotemia, both filtration failure and tubulointerstitial fibrosis were associated with the upregulation of TG2, a collagen cross-linking enzyme and the major isoform of transglutaminase in the kidney. TG2 may provide a new therapeutic target for drugs designed to slow the progression of feline chronic kidney disease.