The effects of rheum officinale on the progression of feline chronic kidney disease.

Master of ScienceDepartment of Clinical SciencesGregory F. GrauerChronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. The purpose of this study was to investigate the effects of Chinese rhubarb (Rheum officinale) supplementation on the progression of feline CKD. Cats with stable IRIS stage II or III CKD and without certain comorbidities were included in the study. Cats were randomly divided into 3 treatment groups and administered Chinese rhubarb extract (Group 1, Rubenal®, Vetoquinol, Forth Worth, TX; 75 mg tablet by mouth every 12 h), benazepril as a positive control (Group 2, 0.5 mg/kg by mouth every 24 h), or both (Group 3). Cats were fed a commercial renal specific diet and enteric phosphate binder as appropriate. Body weight, laboratory data, and blood pressure were recorded every 3 months. Variables between groups at enrollment and within groups over visits were compared with ANOVA and repeated measures ANOVA, respectively. A treatment by visit interaction term was included in all repeated measures models. Significance was set at p ≤ 0.05. Except for body weight there was no significant differences between treatment groups at enrollment. There was no significant change in body weight, hematocrit (Hct), UPC, serum creatinine, or systemic blood pressure over time as compared to baseline within any group. There was no significant difference between groups over time in regards to change in body weight, Hct, UPC, serum creatinine, or systemic blood pressure. The treatment by time interaction was non-significant in all models. Based on easily measured clinical parameters, this study failed to detect a significant difference in cats administered a Chinese rhubarb supplement, benazepril, or both

Antigenemia without antigenuria in a cat with histoplasmosis

Case summary Based on demonstration of the yeast phase of Histoplasma capsulatum on fine-needle aspirate cytology of the kidney, a 5-year-old cat was diagnosed with histoplasmosis. Urine and serum were tested for antigen via a Histoplasma antigen enzyme immunoassay. At the time of diagnosis, and on multiple occasions during antifungal treatment, antigenemia was detected without antigenuria. The cat was treated with standard therapy and achieved clinical remission. Relevance and novel information Diagnosis is most commonly made by finding the yeast phase of H capsulatum via cytology of fluid samples or cytology or histopathology of infected tissues. In certain cases this may require invasive tests. Recently, a non-invasive test, a Histoplasma antigen enzyme immunoassay, has been shown to be a sensitive test for supporting the diagnosis of histoplasmosis in cats. Urine has been considered the biologic specimen of choice for antigen testing and there is a paucity of information concerning the use of other specimens such as serum. The case herein reports a cat with antigenemia without antigenuria. These findings suggest that further research is necessary to better understand the ideal biologic sample or combination of samples as it pertains to antigen testing in cats. It also suggests that to maximize sensitivity both urine and serum may need to be tested in cats with suspected histoplasmosis

Reduced susceptibility to fluconazole in a cat with histoplasmosis

Case summary An 11-year-old neutered male domestic longhair cat was diagnosed with histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph node size initially decreased with fluconazole therapy (11.8 mg/kg PO q12h); however, after 13 months of continuous fluconazole therapy, lymphadenomegaly worsened and samples were collected for culture and antifungal susceptibility. The Histoplasma capsulatum isolate had a very high fluconazole minimum inhibitory concentration (MIC) of 64 µg/ml and an itraconazole MIC of 0.06 µg/ml. The owner declined a change to itraconazole and, ultimately, the cat developed neurologic signs and was euthanized. Owing to the initial response to fluconazole followed by treatment failure and high MIC value, acquired fluconazole resistance was suspected. Clinical breakpoints for fluconazole for the dimorphic fungi are not available to define true antifungal resistance. Relevance and novel information This is the first published report of reduced susceptibility to fluconazole in a cat being treated for histoplasmosis. Fluconazole failure and increases in MIC between pretreatment and long-term treatment isolates are known to occur in humans with histoplasmosis. Practitioners should be aware of this possibility when treating cats with fluconazole (particularly in cases with long-term [>1 year] fluconazole therapy or in cases with disease recrudescence)

Tracing histoplasmosis genomic epidemiology and species occurrence across the USA.

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

Clinical utility of an immunoglobulin A‐based serological panel for the diagnosis of chronic enteropathy in dogs

Abstract 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

Clinical utility of an immunoglobulin A‐based serological panel for the diagnosis of chronic enteropathy in dogs

BackgroundA 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.ObjectivesTo 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.AnimalsFifty-five dogs with primary intestinal disease.MethodsSerum 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.ResultsTwenty-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 importanceThe 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

Evaluation of serum 25‐hydroxyvitamin D, C‐reactive protein, and haptoglobin as biomarkers in dogs newly diagnosed with histoplasmosis

Abstract 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

Tracing histoplasmosis genomic epidemiology and species occurrence across the USA

Histoplasmosis 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.</p