ABSTRACT
This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8-58.2) kg and in 31 cats was 3.9 (2.4-6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (CSS ), and oral clearance in dogs were 14.2 (4.5-21.3) mg/kg/d, 26.8 (3.8-61.5) µg/mL, and 0.63 ml min-1 kg-1 , respectively, and in cats were 18.6 (8.2-40.0) mg/kg/d, 32.1 (1.9-103.5) µg/mL, and 0.61 ml min-1 kg-1 , respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median CSS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50-100 mg total daily dose in cats are recommended to achieve median CSS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on CSS (therapeutic drug monitoring) and treatment failure should be considered.
Subject(s)
Antifungal Agents/therapeutic use , Cat Diseases/drug therapy , Dog Diseases/drug therapy , Fluconazole/therapeutic use , Mycoses/veterinary , Administration, Oral , Animals , Antifungal Agents/pharmacokinetics , Cats , Dogs , Female , Fluconazole/pharmacokinetics , Male , Mycoses/drug therapyABSTRACT
The diagnosis of coccidioidomycosis (CM) in dogs is typically based on clinical presentation, serology, and (less frequently) spherule identification. Agar gel immunodiffusion (AGID) is the most commonly employed serological method, but AGID is slow (requiring up to a week for titer). A Coccidioides antigen enzyme immunoassay (EIA) is also available; however, sensitivity is low in CM dogs. An antibody EIA was developed to detect canine immunoglobulin G (IgG) reacting to Coccidioides antigens. Serum was evaluated from dogs with pathology proven CM and/or AGID positive CM, as well as dogs with histoplasmosis, blastomycosis, non-fungal infections, or healthy dogs. A standard curve was used to convert optical density (OD) values into EIA units (EU). Serum and urine samples from CM dogs were also tested in the antigen EIA. Sensitivity and specificity for IgG were 89.2% and 97.2%, respectively, upon evaluation of dogs with proven or probable CM and control dogs. Cross-reactivity was observed in 7.7% and in 6.4% of dogs with histoplasmosis or blastomycosis, respectively. The antigen EIA alone was insensitive (33.8%). Combined IgG and antigen testing increased sensitivity to 93.2%, as three dogs were IgG-negative but had detectable serum or urine antigen. In 22 dogs with proven CM, sensitivity was statistically similar for antibody EIA and AGID (86% and 73%; P = .487). The MiraVista® canine Coccidioides antibody IgG EIA may aid in the diagnosis of CM by improving turnaround time with comparable sensitivity to AGID. Serial or concurrent testing by antibody and antigen EIAs may be beneficial when screening dogs for CM.
Subject(s)
Antibodies, Fungal/blood , Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Immunoenzyme Techniques/methods , Immunoglobulin G/blood , Animals , Antigens, Fungal/immunology , Blastomycosis , Coccidioides/immunology , Coccidioidomycosis/diagnosis , Cross Reactions , Dog Diseases/immunology , Dog Diseases/microbiology , Dogs , Histoplasmosis , Immunoglobulin M , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To determine the sensitivity and specificity of a commercial whole blood real-time PCR assay (RT-PCR) for the diagnosis of histoplasmosis when compared to direct organism identification and/or urine antigen quantification by enzyme immunoassay (UA-EIA). A secondary objective was to compare the sensitivity and specificity of RT-PCR to anti-Histoplasma immunoglobulin G antibody detection by enzyme immunoassay (IgG-EIA) and IgG-EIA to UA-EIA. ANIMALS: Cats presented to the Kansas State University Veterinary Health Center from February through September of 2023 in which histoplasmosis was diagnosed or suspected. METHODS: From February through September of 2023, cats were tested by RT-PCR, IgG-EIA, and UA-EIA if histoplasmosis was diagnosed cytologically or was a differential diagnosis for the presenting clinical signs. Cats were excluded if all 3 tests were not submitted or if the diagnosis of histoplasmosis could not be excluded despite a negative UA-EIA result. Cats with cytologically or histologically confirmed histoplasmosis were designated as proven histoplasmosis cases, and cats with a positive UA-EIA result without cytological or histological confirmation were designated as probable histoplasmosis cases. RESULTS: 10 cats were diagnosed with either proven (n = 6) or probable (4) histoplasmosis, and 10 cats were considered true negatives. Whole blood RT-PCR results were negative in all 20 cats (sensitivity, 0%; 95% CI, 0% to 30.85%). The IgG-EIA was 90% sensitive (95% CI, 55.50% to 99.75%) and 70% specific (95% CI, 34.75% to 93.33%). The UA-EIA results were positive in all cats with proven histoplasmosis. CLINICAL RELEVANCE: This commercial RT-PCR is insensitive when used on whole blood collected in EDTA and should not be used to diagnose feline histoplasmosis. Further studies are required to determine whether alternate RT-PCR protocols for EDTA-collected whole blood could be useful for diagnosing histoplasmosis in cats.
Subject(s)
Cat Diseases , Histoplasmosis , Real-Time Polymerase Chain Reaction , Animals , Cats , Antigens, Fungal/blood , Antigens, Fungal/urine , Cat Diseases/diagnosis , Cat Diseases/blood , Cat Diseases/microbiology , Histoplasma/isolation & purification , Histoplasmosis/veterinary , Histoplasmosis/diagnosis , Histoplasmosis/blood , Immunoenzyme Techniques/veterinary , Immunoglobulin G/blood , Real-Time Polymerase Chain Reaction/veterinary , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To evaluate temporal changes in serum C-reactive protein (CRP) and haptoglobin (Hp) concentrations in dogs with pulmonary coccidioidomycosis and assess their utility to detect remission. METHODS: 31 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021 were included in a retrospective cohort study that utilized archived serum. Serum was originally obtained at diagnosis and once every 3 months after antifungal administration until either remission or 12 months. Time points were designated as baseline (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). Serum CRP and Hp were measured at a reference laboratory with ELISA assays. RESULTS: Median serum CRP and Hp concentrations decreased from T0 (CRP, 56 mg/L; Hp, 716.1 mg/dL) to T1 (CRP, 3.3 mg/L; Hp, 240.5 mg/dL); subsequent decreases were not significant. Eighteen (60%) and 16 (53%) of 30 dogs had normal serum CRP and Hp concentrations at T1, respectively. Absolute serum CRP (AUC, 0.58; 95% CI, 0.45 to 0.72) and Hp (AUC, 0.65; 95% CI, 0.52 to 0.78) were poor detectors of remission. However, the percentage change in Hp from T0 to T1 (AUC, 0.90; 95% CI, 0.74 to 1.0) was an excellent predictor of remission within 12 months. CONCLUSIONS: Serum CRP and Hp concentrations decrease in the first 3 months of antifungal treatment in dogs with pulmonary coccidioidomycosis, and the percentage change of Hp may help predict dogs that will achieve remission within 12 months of treatment. CLINICAL RELEVANCE: Serum CRP and Hp may be useful adjunctive biomarkers to monitor treatment response in dogs with pulmonary coccidioidomycosis.
Subject(s)
Antifungal Agents , C-Reactive Protein , Coccidioidomycosis , Dog Diseases , Haptoglobins , Lung Diseases, Fungal , Animals , Dogs , Dog Diseases/drug therapy , Dog Diseases/blood , Coccidioidomycosis/veterinary , Coccidioidomycosis/drug therapy , Coccidioidomycosis/blood , Haptoglobins/analysis , Haptoglobins/metabolism , C-Reactive Protein/analysis , Retrospective Studies , Male , Female , Antifungal Agents/therapeutic use , Lung Diseases, Fungal/veterinary , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/blood , Cohort Studies , Biomarkers/bloodABSTRACT
Invasive fungal infections (IFIs) are growing in importance in veterinary and human medicine. IFIs such as aspergillosis, blastomycosis, coccidioidomycosis and histoplasmosis remain challenging to treat in dogs. Isavuconazole is a novel antifungal medication that, when compared to currently used azoles, has an expanded spectrum of antifungal activity Rudramurthy (2011), Pfaller (2013), Spec (2018), has more predictable pharmacokinetics in humans Desai (2016), Cojutti (2021) and may cause fewer side effects such as liver and renal toxicity Maertens (2016), DiPippo (2018). The pharmacokinetic profile and safety of isavuconazole in dogs has not yet been characterized. The purpose of this study was to evaluate the pharmacokinetics of isavuconazole in healthy dogs that received a single dose of the prodrug isavuconazonium sulfate. Using full crossover design, six healthy beagle dogs received isavuconazonium sulfate at a mean (+/- SD) dose of 20.6 (+/- 2.8) mg/kg orally and 21.8 (+/- 4.2) mg/kg intravenously. Plasma was collected for batched pharmacokinetic analysis of prodrug and metabolite, isavuconazole, by ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The median (Q1-Q3) maximum isavuconazole peak plasma concentration was estimated at 3,876.5 (2,811.0-4,800.0) ng/mL following oral administration, with a median (Q1-Q3) peak level at 1.3 (1.0-2.0) hours. Following intravenous administration, the median (Q1-Q3) isavuconazole peak plasma concentration was estimated at 3,221.5 (2,241.5-3,609.0) ng/mL, with a median (Q1-Q3) peak level at 0.4 (0.3-0.6) hours. The median (Q1-Q3) half-life of isavuconazole was 9.4 (7.0-12.2) hours and 14.0 (8.1-21.7) hours for oral and intravenous routes, respectively. One dog received inadvertent subcutaneous drug administration without any apparent adverse effects. Another dog experienced an anaphylactic reaction following accidental rapid drug infusion. No other drug-related adverse events were observed. At dosages used in this study, healthy dogs achieved isavuconazole plasma levels comparable to human therapeutic targets, and when properly administered the drug was well-tolerated.
Subject(s)
Antifungal Agents , Nitriles , Pyridines , Triazoles , Animals , Dogs , Pyridines/pharmacokinetics , Pyridines/administration & dosage , Nitriles/pharmacokinetics , Triazoles/pharmacokinetics , Triazoles/administration & dosage , Antifungal Agents/pharmacokinetics , Male , Female , Administration, Oral , Prodrugs/pharmacokinetics , Cross-Over StudiesABSTRACT
OBJECTIVES: The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using blood serum and the urinary lateral flow assay (LFA), for the detection of Histoplasma capsulatum in cats with histoplasmosis. METHODS: Eight client-owned domestic cats diagnosed with histoplasmosis were selected based on cytological, histopathological, mycological, molecular or antigenic techniques. The blood serum of these animals was tested in a semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum. Urine samples were tested for H capsulatum antigen using LFA. RESULTS: Five cats were seropositive on IgG EIA (5/8, with diagnostic sensitivity equal to 62.5%; 95% confidence interval [CI] 24.5-91.5) and five cats were positive on H capsulatum antigen LFA (5/7, with diagnostic sensitivity equal to 71.4%; 95% CI 29.0-96.3). The combined diagnostic sensitivity when interpreted in parallel was 87.5% (7/8, 95% CI 47.3-99.7). The specificity for the anti-Histoplasma IgG EIA was 100% (95% CI 71.5-100) and for the H capsulatum antigen LFA it was also 100% (95% CI 71.5-100). CONCLUSIONS AND RELEVANCE: The semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum in blood serum and the urinary LFA for the detection of the same agent emerge as new minimally invasive diagnostic techniques that can assist in the approach to disseminated and pulmonary feline histoplasmosis, especially when both techniques are considered together.
Subject(s)
Cat Diseases , Histoplasma , Histoplasmosis , Sensitivity and Specificity , Cats , Animals , Histoplasmosis/veterinary , Histoplasmosis/diagnosis , Cat Diseases/diagnosis , Cat Diseases/microbiology , Histoplasma/isolation & purification , Histoplasma/immunology , Male , Female , Antibodies, Fungal/blood , Immunoenzyme Techniques/veterinary , Immunoglobulin G/bloodABSTRACT
OBJECTIVE: To evaluate selected gastrointestinal side effects of high-concentration buprenorphine (HCB) in healthy rabbits. ANIMALS: 10 healthy New Zealand White rabbits ranging in body weight between 3.0 and 3.8 kg. METHODS: Eight, 6-month-old, New Zealand White rabbits received a single injection of HCB SC (0.24 mg/kg). The rabbits were previously randomized to receive SC and oral saline as a control. Two rabbits received saline for the purpose of blinding the outcome assessors. Food and water consumption, fecal and urine production, and fecal pellet number were recorded for all rabbits before HCB administration and the 3 days postinjection. RESULTS: A clinically and statistically significant decrease in food and water consumption was observed in rabbits receiving an injection of HCB, compared to rabbits receiving saline. In the 24 hours after injection, HCB-treated rabbits consumed a median of 17 g of food (range, 0 to 82 g), while saline-treated rabbits consumed 122 g of food (31 to 181 g). Rabbits receiving HCB injections also produced significantly less feces both in terms of pellet numbers and overall quantity, along with decreased urine production. CLINICAL RELEVANCE: A single administration of HCB has a clinically significant impact on multiple physiological functions in healthy rabbits. Administration of this drug could potentially worsen clinical signs of anorexia and decrease defecation in healthy rabbits. The effects of HCB on diseased or painful rabbits are not yet known.
ABSTRACT
ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
Subject(s)
Histoplasmosis , Histoplasmosis/epidemiology , Histoplasma/genetics , Genotype , Genomics , TexasABSTRACT
Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment-associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non-associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.
Subject(s)
Cat Diseases , Dog Diseases , Purpura, Thrombocytopenic, Idiopathic , Dogs , Animals , Cats , Dog Diseases/diagnosis , Cat Diseases/diagnosis , Purpura, Thrombocytopenic, Idiopathic/veterinary , Purpura, Thrombocytopenic, Idiopathic/diagnosis , ConsensusABSTRACT
OBJECTIVE: To determine associations between antibody serologic tests and tracheobronchial lymphadenopathy (TBL) in dogs with pulmonary coccidioidomycosis and identify variables associated with time to resolution of TBL. ANIMALS: 32 client owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. METHODS: Prospective cohort study. Thoracic radiographs and anti-Coccidioides spp antibody serology were performed at baseline and once every 3 months until remission or for a maximum of 12 months. Radiographic tracheobronchial lymph node height, length, and area were measured and recorded as ratios via comparison with the length of the T4 vertebral body (LT4) and length of the manubrium. Severity of TBL was also subjectively categorized as mild, moderate, or severe. RESULTS: Tracheobronchial lymphadenopathy was identified in 81% (26/32; 95% CI, 64% to 93%) of dogs. There was no relevant association between TBL presence or severity and antibody serology results. Tracheobronchial lymphadenopathy resolved in 72% (n = 18) of dogs at the 3-month evaluation. The median time to resolution of TBL after initiation of fluconazole was 96 days (range, 72 to 386 days). Univariate analysis identified increasing TBL severity (hazard ratio, 0.40; 95% CI, 0.19 to 0.84; P = .02) and length:LT4 ratio (hazard ratio, 0.41; 95% CI, 0.20 to 0.82; P = .01) as variables associated with reduced probability of resolution of TBL. CLINICAL RELEVANCE: Antibody serologic test results are not clinically useful to predict TBL presence or severity in dogs with pulmonary coccidioidomycosis, and larger tracheobronchial lymph nodes are more likely to take longer to resolve. Resolution of TBL occurs in most dogs within 3 to 6 months after fluconazole administration.
Subject(s)
Coccidioidomycosis , Dog Diseases , Lymphadenopathy , Humans , Dogs , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Fluconazole/therapeutic use , Prospective Studies , Coccidioides , Lymphadenopathy/veterinary , Dog Diseases/pathologyABSTRACT
BACKGROUND: Histoplasma antigen and anti-Histoplasma antibody detection are used to support the diagnosis of histoplasmosis. There is a paucity of published data on antibody assays. OBJECTIVES: Our primary hypothesis was that anti-Histoplasma immunoglobulin G (IgG) antibody detection using enzyme immunoassay (EIA) will be more sensitive as compared to immunodiffusion (ID). ANIMALS: Thirty-seven cats and 22 dogs with proven or probable histoplasmosis; 157 negative control animals. METHODS: Residual stored sera were tested for anti-Histoplasma antibodies using EIA and ID. Results of urine antigen EIA were reviewed retrospectively. Diagnostic sensitivity was calculated for all three assays and compared between immunoglobulin G (IgG) EIA and ID. The diagnostic sensitivity of urine antigen EIA and IgG EIA, interpreted in parallel, was reported. RESULTS: Sensitivity of IgG EIA was 30/37 (81.1%; 95% confidence interval [CI], 68.5%-93.4%) in cats and 17/22 (77.3%; 95% CI, 59.8%-94.8%) in dogs. Diagnostic sensitivity of ID was 0/37 (0%; 95% CI, 0%-9.5%) in cats and 3/22 (13.6%; 95% CI, 0%-28.0%) in dogs. Immunoglobulin G EIA was positive in all animals (2 cats and 2 dogs) with histoplasmosis but without detectable antigen in urine. Diagnostic specificity of IgG EIA was 18/19 (94.7%; 95% CI, 74.0%-99.9%) in cats and 128/138 (92.8%; 95% CI, 87.1%-96.5%) in dogs. CONCLUSION AND CLINICAL IMPORTANCE: Antibody detection by EIA can be used to support the diagnosis of histoplasmosis in cats and dogs. Immunodiffusion has an unacceptably low diagnostic sensitivity and is not recommended.
Subject(s)
Cat Diseases , Dog Diseases , Histoplasmosis , Cats , Dogs , Animals , Histoplasma , Histoplasmosis/diagnosis , Histoplasmosis/veterinary , Retrospective Studies , Antigens, Fungal , Immunoglobulin G , Immunodiffusion/veterinary , Immunoenzyme Techniques , Sensitivity and Specificity , Cat Diseases/diagnosis , Cat Diseases/urine , Dog Diseases/diagnosisABSTRACT
BACKGROUND: Culture can be used for diagnosis and antifungal susceptibility testing in animals with fungal infections. Limited information is available regarding the diagnostic performance of culture and the susceptibility patterns of Histoplasma spp. isolates. HYPOTHESIS/OBJECTIVES: Describe the clinical utility of culture and the susceptibility patterns of Histoplasma spp. isolates causing histoplasmosis in cats and dogs. ANIMALS: Seventy-one client-owned animals, including 33 cats and 19 dogs with proven or probable histoplasmosis. METHODS: Culture was attempted from tissue or fluid samples. Diagnostic performance of culture, cytopathology, and antigen detection were compared with final diagnosis. Susceptibility to antifungal agents was determined for a subset (11 from dogs, 9 from cats) of culture isolates. RESULTS: Culture had a diagnostic sensitivity of 17/33 (52%; 95% confidence interval [CI], 34%-69%) and 15/19 (79%; 95% CI, 61%-97%) and specificity of 6/6 (100%; 95% CI, 54%-100%) and 10/10 (100%; 95% CI, 69%-100%) in cats and dogs, respectively. Culture was not positive in any animal in which cytopathology and antigen testing were negative. Target drug exposure (area under the concentration curve [AUC]/minimum inhibitory concentration [MIC] >25) should be easily achieved for all isolates for itraconazole, voriconazole, or posaconazole. Five of 20 (25%) isolates had fluconazole MIC ≥32 µg/mL and achieving target drug exposure is unlikely. CONCLUSIONS AND CLINICAL IMPORTANCE: Fungal culture did not improve diagnostic sensitivity when used with cytopathology and antigen detection. Susceptibility testing might help identify isolates for which fluconazole is less likely to be effective.
Subject(s)
Dog Diseases , Histoplasmosis , Cats , Dogs , Animals , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Histoplasmosis/diagnosis , Histoplasmosis/drug therapy , Histoplasmosis/veterinary , Fluconazole/pharmacology , Fluconazole/therapeutic use , Itraconazole/pharmacology , Itraconazole/therapeutic use , Histoplasma , Microbial Sensitivity Tests/veterinary , Dog Diseases/diagnosis , Dog Diseases/drug therapyABSTRACT
BACKGROUND: A panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders. OBJECTIVES: To evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases. ANIMALS: Fifty-five dogs with primary intestinal disease. METHODS: Serum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points. RESULTS: Twenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P = .99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.
Subject(s)
Dog Diseases , Inflammatory Bowel Diseases , Dogs , Animals , Immunoglobulin A , Escherichia coli , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/veterinary , Inflammatory Bowel Diseases/pathology , Intestines/pathologyABSTRACT
BACKGROUND: Serum 25-hydroxyvitamin (OH)D, C-reactive protein (CRP), and haptoglobin are useful biomarkers in various infectious diseases and inflammatory disorders in dogs, but their utility in histoplasmosis is unknown. OBJECTIVE: Determine if serum 25(OH)D, CRP, and haptoglobin concentrations are different in dogs with histoplasmosis compared to healthy controls and whether serum globulin, albumin, CRP, or haptoglobin are associated with 25(OH)D concentration. ANIMALS: Twenty-two client-owned dogs (histoplasmosis, n = 12; controls, n = 10). METHODS: Prospective case-control study. Dogs with histoplasmosis were categorized as pulmonary, disseminated, or gastrointestinal (GI) tract. Serum 25(OH)D was measured using modified high-performance liquid chromatography (HPLC). Serum CRP and haptoglobin were measured with ELISA assays. RESULTS: Dogs with histoplasmosis were grouped as disseminated (n = 8) and GI tract (n = 4). No dogs had pulmonary tract involvement alone. Dogs with histoplasmosis (median, interquartile range [IQR]; 11.6 ng/mL, 16.8) had lower serum 25(OH)D concentrations than controls (35.7 ng/mL, 17.6; P < .001). Serum CRP and haptoglobin concentrations were higher in dogs with histoplasmosis (CRP: median, IQR; 63.5 mg/L, 37.1 and haptoglobin: 459.7 mg/dL, 419.6) than controls (CRP: 1.9 mg/L, 2; P < .001 and haptoglobin: 85.5 mg/dL, 106.7; P = .003). Serum 25(OH)D concentration was positively associated with fold change in serum albumin concentration (ρ = 0.77; P < .001), and negatively associated with fold change in serum globulin (ρ = -0.61; P = .003) and CRP concentrations (ρ = -0.56; P = .01). CONCLUSION AND CLINICAL IMPORTANCE: Assay of serum 25(OH)D, CRP, and haptoglobin could have clinical value in dogs with histoplasmosis.
Subject(s)
Dog Diseases , Histoplasmosis , Animals , Dogs , C-Reactive Protein/analysis , Haptoglobins/analysis , Case-Control Studies , Histoplasmosis/diagnosis , Histoplasmosis/veterinary , Vitamin D , Biomarkers , Dog Diseases/diagnosisABSTRACT
OBJECTIVE: To describe the prevalence of ocular lesions in cats with newly diagnosed histoplasmosis. ANIMALS: 55 client-owned domestic cats. PROCEDURES: As part of this prospective case series, cats diagnosed with histoplasmosis between the years 2015 and 2020 underwent complete ophthalmic examinations by a board-certified veterinary ophthalmologist prior to the initiation of antifungal treatment. Histoplasmosis was diagnosed by consistent clinical findings and identification of Histoplasma yeast on pathology or by the use of a commercially available enzyme immunoassay to detect Histoplasma antigen in urine. RESULTS: Of the 55 cats, 45 (82%; 95% CI, 72% to 92%) had signs of active anterior, posterior, or panuveitis. The most common lesions were identified in the posterior portion of the globe and included chorioretinitis and partial retinal detachments (44/55 [80%; 95% CI, 69% to 90%] cats). CLINICAL RELEVANCE: Detailed ophthalmic examinations should be performed on all cats with diagnosed or suspected histoplasmosis, as ocular involvement and subsequent vision loss are common.
Subject(s)
Cat Diseases , Histoplasmosis , Animals , Antifungal Agents/therapeutic use , Cat Diseases/diagnosis , Cat Diseases/drug therapy , Cat Diseases/epidemiology , Cats , Face , Histoplasma , Histoplasmosis/diagnosis , Histoplasmosis/epidemiology , Histoplasmosis/veterinary , PrevalenceABSTRACT
OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 670/0.75 and 6% HES 130/0.4 dilution of canine whole blood on coagulation using dynamic viscoelastic coagulometry (DVC). ANIMALS: 56 healthy adult dogs. PROCEDURES: 2 blood samples were obtained from each dog and randomized to 1 of 7 groups-undiluted or 2 dilutions (1:3 or 1:10) of 3 different fluids: saline (0.9% NaCl) solution, 6% HES 670/0.75, or 6% HES 130/0.4. Dilutions were calculated to simulate approximately a 10- or 30-mL/kg body weight IV bolus of each fluid. DVC was performed on each sample. Coagulation parameters compared between groups included clot rate (CR), platelet function (PF), and activated clotting time. RESULTS: Dilution with saline solution did not significantly affect coagulation, while dilution with HES 670/0.75 and HES 130/0.4 caused a dose-dependent significant decrease in CR (1:3 HES 670/0.75, P = 0.007; 1:10 HES 670/0.75, P = 0.002; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0003) and PF (1:3 HES 670/0.75, P < 0.0001; 1:10 HES 670/0.75, P < 0.0001; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0015). CLINICAL RELEVANCE: Dilution of canine blood with HES 670/0.75 and HES 130/0.4, at clinically relevant doses (10 and 30 mL/kg), led to significant hypocoagulability beyond dilutional effect. This was, in part, due to impaired PF, which was significantly greater with HES 670/0.75. Further research using DVC to assess the effects of HES on coagulation in dogs, ideally with clinical conditions warranting HES administration, is needed.
Subject(s)
Blood Coagulation , Hydroxyethyl Starch Derivatives , Animals , Blood Coagulation Tests/veterinary , Blood Platelets , Dogs , Hydroxyethyl Starch Derivatives/pharmacology , Plasma Substitutes/pharmacology , Platelet Function Tests/veterinary , Thrombelastography/veterinaryABSTRACT
This is a retrospective case series consisting of five dogs diagnosed with schistosomiasis. The purpose of this article is to report the presence of naturally occurring canine schistosomiasis in Kansas and to provide clinical details regarding schistosomiasis. Medical records of dogs diagnosed with schistosomiasis from 2000 to 2009 were reviewed, and information extracted included signalment, history, clinical signs, diagnostic test results, treatment, and outcome. Affected dogs were primarily medium to large breed and young to middle aged. All dogs were considered outdoor dogs, with three having known access to surface water. Common clinical signs included gastrointestinal disease and signs associated with hypercalcemia. Fecal flotation was negative in all dogs in contrast to fecal saline sedimentation and fecal polymerase chain reaction, which were both positive in all dogs in which it was performed. All dogs treated specifically for schistosomiasis fully recovered. This article describes the first reported cases of canine schistosomiasis in the Midwest and the first reported case of intestinal intussusception secondary to schistosomiasis. Recognizing that canine schistosomiasis is present in Kansas and possibly other Midwestern states should prompt veterinarians to perform appropriate diagnostic investigation in suspect animals as the diagnosis is straight forward and relatively inexpensive.
Subject(s)
Dog Diseases/epidemiology , Schistosomiasis/veterinary , Animals , Anthelmintics/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/pathology , Dogs , Feces/parasitology , Female , Kansas/epidemiology , Male , Retrospective Studies , Schistosomiasis/epidemiologyABSTRACT
BACKGROUND: Commercially available, noninvasive testing options for histoplasmosis are limited outside of the United States. OBJECTIVES: To describe the diagnostic performance of a novel Histoplasma antigen enzyme immunoassay (IM EIA) for the diagnosis of histoplasmosis in dogs. ANIMALS: Twenty dogs with histoplasmosis, 79 dogs without histoplasmosis, and 11 unclassified dogs providing 202 urine samples. METHODS: This a prospective study using stored urine samples. Samples were analyzed with the IM EIA and with the commercially available Histoplasma antigen EIA (MV EIA). Dogs were classified based on final proven diagnosis and performance of the IM EIA was described and compared with the MiraVista enzyme immunoassay (MV EIA). RESULTS: The diagnostic sensitivity (DSe), specificity (DSp), and accuracy (DAc) of the IM EIA were 70% (51%-89%), 99% (97%-100%), and 93% (81%-100%), respectively. The DSe, DSp, and DAc for the MV EIA were 95% (85%-100%), 99% (97%-100%), and 98% (95%-100%), respectively. The area under the receiver operator characteristic curve was significantly smaller for IM EIA (0.87) as compared with MV EIA (0.97, P = .03). This was primarily due to 6 false negative IM EIA results, 4 from dogs with disease localized to the gastrointestinal tract. The MV EIA was positive in 5/6 of these dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The IM EIA might be useful for the diagnosis of disseminated histoplasmosis in dogs, but clinical usefulness will be limited in dogs with histoplasmosis localized to the GI tract.
Subject(s)
Antibodies, Monoclonal , Histoplasma , Animals , Antigens, Fungal , Dogs , Immunoenzyme Techniques , Prospective Studies , Sensitivity and SpecificityABSTRACT
CASE SUMMARY: This report describes a cat with a rare form of histoplasmosis: invasive rhinitis with adnexal involvement, mimicking disease more commonly caused by cryptococcosis or aspergillosis. This case is especially noteworthy as it was from an area where histoplasmosis is not enzootic. RELEVANCE AND NOVEL INFORMATION: Invasive fungal rhinitis causes significant morbidity in cats. Diagnostic investigation of more common pathogens includes detection of fungal antigen (Cryptococcus) or antifungal antibodies (Aspergillus). This case demonstrates that histoplasmosis can present as chronic nasal disease in cats. Histoplasma antigen testing provides a non-invasive diagnostic option. Moreover, this case serves as a reminder that histoplasmosis can affect cats anywhere, even in non-enzootic areas.
ABSTRACT
OBJECTIVE: To report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Twenty client-owned dogs presenting for elective ovariohysterectomy or castration. METHODS: The dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg(-1)) and hydromorphone (0.1 mg kg(-1)) i.m. approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg(-1)) i.v. to effect and in dogs in group 2 with diazepam (0.2 mg kg(-1)) i.v. followed by etomidate (2 mg kg(-1)) i.v. to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5-4%) and group 2 received a combination of fentanyl (0.8 microg kg(-1) minute(-1)) and midazolam (8.0 microg kg(-1) minute(-1)) i.v. plus sevoflurane (adjustable vaporizer setting 0.5-4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively. RESULTS: Baseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma. CONCLUSIONS AND CLINICAL RELEVANCE: There was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.