Open label clinical trial of orally administered molnupiravir as a first-line treatment for naturally occurring effusive feline infectious peritonitis.

BACKGROUND: Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed. OBJECTIVE: To evaluate the efficacy of PO molnupiravir (MPV; EIDD-2801) to treat effusive FIP. ANIMALS: Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS-441524. METHODS: A single-center, prospective, open-label longitudinal, non-inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10-15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS-441524. RESULTS: Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non-survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non-inferior to historic control cats treated with PO GS-441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, -9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS-441524. CONCLUSIONS AND CLINICAL IMPORTANCE: Molnupiravir is an effective antiviral treatment for effusive FIP.

Epithelial hypoxia maintains colonization resistance against Candida albicans.

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.

Diagnosis and classification of portosystemic shunts: a machine learning retrospective case-control study.

Diagnosis of portosystemic shunts (PSS) in dogs often requires multiple diagnostic tests, and available clinicopathologic tests have limitations in sensitivity and specificity. The objective of this study was to train and validate a machine learning model (MLM) that can accurately predict the presence of a PSS utilizing routinely collected demographic data and clinicopathologic features. Dogs diagnosed with PSS or control dogs tested for PSS but had the condition ruled out (non-PSS) were identified. Dogs were included if a complete blood count and serum chemistry panel were available from PSS diagnostic testing. Dogs with a PSS were subcategorized as having a single intrahepatic PSS, a single extrahepatic PSS, or multiple extrahepatic PSS. An extreme gradient boosting (XGboost) MLM was trained with data from 70% of the cases, and MLM performance was determined on the test set, comprising the remaining 30% of the case data. Two MLMs were created. The first was designed to predict the presence of any PSS (PSS MLM), and the second to predict the PSS subcategory (PSS SubCat MLM). The trained PSS MLM had a sensitivity of 94.3% (95% CI 90.1-96.8%) and specificity of 90.5% (95% CI 85.32-94.0%) for dogs in the test set. The area under the receiver operator characteristic curve (AUC) was 0.976 (95% CI; 0.964-0.989). The mean corpuscular hemoglobin, lymphocyte count, and serum globulin concentration were most important in prediction classification. The PSS SubCat MLM had an accuracy of 85.7% in determining the subtype of PSS of dogs in the test set, with variable sensitivity and specificity depending on PSS subtype. These MLMs have a high accuracy for diagnosing PSS; however, the prediction of PSS subclassification is less accurate. The MLMs can be used as a screening tool to increase or decrease the index of suspicion for PSS before confirmatory diagnostics such as advanced imaging are pursued.

Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Correction: Cook et al. An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats. Viruses 2022, 14, 2429.

In the original publication [...].

Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Survey of Bacterial Isolates and Their Antimicrobial Susceptibility Patterns from Dogs with Infective Endocarditis.

Infective endocarditis (IE) is a potentially fatal disease in dogs. Limited information exists regarding the characterization of bacterial isolates from dogs with IE. The objective of this study was to describe bacterial isolates associated with IE and their antimicrobial susceptibility patterns. A retrospective analysis of dogs with IE and bacterial isolates was performed, and antimicrobial susceptibility was interpreted using current veterinary cut points where available. The susceptibility rate was assessed for association with survival and previous antimicrobial administration. Fifty-one bacterial isolates were identified from 45 dogs, and 33 had antimicrobial susceptibility performed. Staphylococcus spp. (14/51; 27.5%) was the most common organism. Antimicrobials with the lowest susceptibility rate were ampicillin (19/26; 73%), doxycycline (16/22; 73%), and enrofloxacin (22/29; 76%) with 12/33 (36%) of isolates exhibiting multidrug resistance (MDR). Individual antimicrobial resistances and the MDR rate were not associated with a difference in survival rate. Bacterial isolates from dogs that had received fluoroquinolone antimicrobials in the month before diagnosis had a higher rate of non-intrinsic fluoroquinolones resistance (5/8;62.5%) compared to those that did not receive fluoroquinolones (2/21; 9.5%) (p = 0.03). Antimicrobial resistance and MDR phenotype were common in this study. Culture and antimicrobial susceptibility testing should be pursued in dogs with IE to help guide antimicrobial therapy.

Efficacy of Oral Remdesivir Compared to GS-441524 for Treatment of Cats with Naturally Occurring Effusive Feline Infectious Peritonitis: A Blinded, Non-Inferiority Study.

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5-15 mg/kg) compared to orally administered remdesivir (25-30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; -13.5-57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

Etiology and effusion characteristics in 29 cats and 60 dogs with pyothorax (2010-2020).

BACKGROUND: Pyothorax, an accumulation of inflammatory fluid in the pleural space, is often caused by foreign body inhalation in dogs, whereas the etiology in cats can be more difficult to discern. OBJECTIVE: Compare clinical, microbiologic findings, and etiology in cats and dogs with pyothorax. ANIMALS: Twenty-nine cats and 60 dogs. METHODS: Medical records of cats and dogs diagnosed with pyothorax from 2010 to 2020 were reviewed. Clinical findings, fluid analysis, and microbiologic results were retrieved. RESULTS: Antimicrobials had been administered to equal proportions of cats and dogs before fluid sampling (45% and 47%). Groups did not differ in age or total protein concentration or percentage neutrophils in pleural fluid, but effusion cell count was significantly higher in cats than in dogs (P = .01). Neutrophils containing intracellular bacteria were identified in more cats (27/29, 93%) than dogs (44/60, 73%; P = .05). Penetrating damage to the thorax was implicated as the cause of pyothorax in equal percentages of cats (76%) and dogs (75%). Etiology could not be determined in 2 cats and 1 dog. Cats had higher numbers of bacterial isolates per patient (median, 3) than dogs (median, 1; P = .01) and anaerobes were isolated more often in cats (23/29, 73%) than in dogs (27/60, 45%; P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Pyothorax had similar etiologies in cats and dogs. Cats had higher fluid cell counts, higher numbers of bacterial isolates identified per patient, and intracellular bacteria detected more commonly than did dogs.

Characteristics of Extended-Spectrum ß-Lactamase Producing Enterobacterales Isolated from Dogs and Cats, 2011-2021.

The rising prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales is a significant threat to animal and human health. This study aims to describe the clinical features, antimicrobial susceptibility patterns, and genotypic features of infections associated with ESBL-producing Enterobacterales in dogs and cats seen at a tertiary referral veterinary teaching hospital. Enterobacterales isolated from dogs and cats that underwent ESBL testing during the study period were identified using a search of the hospital antimicrobial susceptibility test software database. Medical records of confirmed ESBL isolates were reviewed, and the source of infection, clinical findings, and antimicrobial susceptibility were recorded. Genomic DNA from bacterial isolates was evaluated for antimicrobial resistance genes with whole genome sequencing. Thirty ESBL-producing isolates were identified based on phenotypic testing (twenty-nine from dogs, one from a cat); twenty-six were Escherichia coli and the remainder were Klebsiella spp. Bacterial cystitis was the most commonly identified (8/30, 27%) clinical problem associated with infection. Resistance to three or more antimicrobial classes was identified in 90% (27/30) of isolates, and all isolates were susceptible to imipenem. Over 70% of isolates were susceptible to piperacillin-tazobactam, amikacin, and cefoxitin. BlaCTX-M-15 was the most common ESBL gene identified, present in 13/22 (59%) isolate genomes. A wide range of clinical infections were identified. Piperacillin-tazobactam and amikacin may be alternatives to carbapenem therapy. Further, larger-scale studies are needed.

Evaluation of Leptospira infection and exposure in free-roaming cat populations in northern California and southern Texas.

OBJECTIVES: Leptospirosis is a re-emergent zoonotic bacterial disease associated with renal and hepatic injury. In free-roaming cats in some regions, a high prevalence of Leptospira antibodies has been identified, and pathogenic leptospires have been detected in renal tissue, indicating that they may play a role in Leptospira epidemiology. The objective of this study was to determine the prevalence of Leptospira seroreactivity and urinary shedding of Leptospira DNA in free-roaming cats from northern California and southern Texas. A secondary objective was to compare the results of a point-of-care (POC) assay, designed to detect Leptospira antibodies, with the results of the microscopic agglutination test (MAT) when applied to serum samples from feral cats. METHODS: Specimens were obtained from free-roaming cats from northern California (n = 52; 2020) and southern Texas (n = 75; 2017). Leptospira quantitative PCR was performed on blood and urine specimens from Californian cats. Serum samples from Californian and Texan cats were subjected to MAT to categorize them as Leptospira antibody-positive or antibody-negative. The performance of the POC assay was assessed using the MAT as the gold standard. RESULTS: Leptospira DNA was not detected in the blood or urine of any cats tested. The results of the MAT were positive in 17.3% (n = 9) of Californian cats and 10.7% (n = 8) of Texan cats (P = 0.3). The median MAT titer was 1:100 (range 1:100-1:200) in Californian cats and 1:200 (range 1:100-1:800) in Texan cats. The POC assay was negative in all specimens. CONCLUSIONS AND RELEVANCE: Free-roaming cats in California and Texas are exposed to Leptospira species and may have the potential to act as sentinel hosts. No cats had evidence of current infection, as determined using PCR on blood and urine specimens. The POC test did not reliably detect anti-Leptospira antibodies in these cats. The role of cats in the maintenance or shedding of pathogenic leptospires requires further investigation.

Retrospective evaluation of fresh platelet concentrate administration in dogs: Patient characteristics, outcomes, and transfusion practices in 189 transfusion episodes (2008-2019).

OBJECTIVE: To describe patient characteristics, underlying disease processes, clinical outcomes, transfusion dose and type (therapeutic or prophylactic), platelet count changes, and adverse events associated with platelet concentrate (PC) administration in dogs. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: A total of 149 dogs, representing 189 PC transfusion episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In this population, 39 of 149 dogs (26.2%) were diagnosed with primary immune-mediated thrombocytopenia, 22 of 149 (14.8%) had decreased bone marrow production, 12 of 149 (8.0%) received PC during a massive transfusion, 3 of 149 (2.0%) had congenital thrombocytopathia, 59 of 149 (39.6%) had severe thrombocytopenia of other causes, and 14 of 149 (9.4%) underwent transfusion for miscellaneous causes without a documented severe thrombocytopenia. In 117 of 149 dogs (78.5%), >1 site of hemorrhage was noted. The most common sites of hemorrhage were the gastrointestinal (GI) tract in 89 of 149 (59.7%) and the skin in 78 of 149 (52.3%). Overall survival to discharge was 59.1% (88/149). The median PC dose was 0.8 units per 10 kg of body weight per transfusion episode (range: 0.2-6.7). Of 189 episodes, 29 of 189 (15.7%) were prophylactic, and 158 of 189 (83.6%) were therapeutic. For 99 of 189 transfusion episodes, paired pre- and postplatelet counts were available within 24 hours. The median platelet count change was 5.0 × 109 /L (5000/µL; range: -115 × 109 /L to 158 × 109 /L [-115,000 to 158,000/µL]); the posttransfusion platelet count was significantly higher than pretransfusion (P < 0.0001). The increase in platelet count after transfusion was greater in the prophylactic group than the therapeutic group (P = 0.0167). Transfusion reactions were suspected during 2 of 168 episodes (1.2%). CONCLUSIONS: Immune-mediated thrombocytopenia was the most common disease process that resulted in PC transfusion. PC was more frequently administered to animals with active hemorrhage rather than prophylactically, and most dogs had evidence of hemorrhage in multiple organ systems, particularly the GI tract and skin. PC transfusions typically appeared safe, and the median platelet count increased after transfusion.

Characterization of clinicopathologic and abdominal ultrasound findings in dogs with glucocorticoid deficient hypoadrenocorticism.

BACKGROUND: Clinical findings of glucocorticoid-deficient hypoadrenocorticism (GDH) can overlap with other diseases, presenting a diagnostic challenge. OBJECTIVES: Describe clinicopathologic and ultrasonographic features of dogs with GDH and those suspected of having GDH that had the disease ruled out. ANIMALS: Six hundred twenty-three dogs. METHODS: Records from dogs with suspected GDH between 2003 and 2018 were reviewed. Dogs with hyperkalemia or hyponatremia were excluded. Dogs were categorized as controls when the resting serum cortisol or post-ACTH cortisol concentration were > 2 µg/dL. Clinicopathologic and ultrasonographic features were compared between groups. The optimal cut-point, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated for individual features used to detect GDH. RESULTS: Dogs were categorized as GDH (n = 29) or controls (n = 594). Lymphocyte count (>1750 cells/L; sensitivity, 96.6%; 95% confidence interval [CI], 82.8%-99.8%; specificity, 60.3%; 95% CI, 56.3%-64.1%; AUC, 0.828; 95% CI, 0.762-0.894) and albumin/globulin ratio (<1.081; sensitivity, 86.2%; 95% CI, 69.4%-94.5%; specificity, 78.8%; 95% CI, 75.3%-81.9%; AUC, 0.886; 95% CI, 0.827-0.944) had the highest discriminatory power between groups. Left adrenal gland width <0.39 cm was 80% (95% CI, 58.4%-91.9%) sensitive and 82.4% (95% CI, 74.2-88.4) specific for GDH. Serum cobalamin concentrations and ultrasonographic abnormalities of the GI tract were not different between groups. CONCLUSION AND CLINICAL IMPORTANCE: No single variable could be used to confidently rule out GDH and obviate the need for cortisol testing in dogs with a clinical presentation consistent with GDH.

An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats.

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and ß-D-N4-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg/kg, GS-441524 and RDV at 25 mg/kg, and intravenously administered RDV at 7 mg/kg achieves plasma levels greater than the established corresponding EC50 values, which are sustained over 24 h for GS-441514 and RDV.

Evaluation of a machine learning tool to screen for hypoadrenocorticism in dogs presenting to a teaching hospital.

BACKGROUND: Dogs with hypoadrenocorticism (HA) have clinical signs and clinicopathologic abnormalities that can be mistaken as other diseases. In dogs with a differential diagnosis of HA, a machine learning model (MLM) has been validated to discriminate between HA and other diseases. This MLM has not been evaluated as a screening tool for a broader group of dogs. HYPOTHESIS: An MLM can accurately screen dogs for HA. ANIMALS: Dogs (n = 1025) examined at a veterinary hospital. METHODS: Dogs that presented to a tertiary referral hospital that had a CBC and serum chemistry panel were enrolled. A trained MLM was applied to clinicopathologic data and in dogs that were MLM positive for HA, diagnosis was confirmed by measurement of serum cortisol. RESULTS: Twelve dogs were MLM positive for HA and had further cortisol testing. Five had HA confirmed (true positive), 4 of which were treated for mineralocorticoid and glucocorticoid deficiency, and 1 was treated for glucocorticoid deficiency alone. Three MLM positive dogs had baseline cortisol ≤2 µg/dL but were euthanized or administered glucocorticoid treatment without confirming the diagnosis with an ACTH-stimulation test (classified as "undetermined"), and in 4, HA was ruled out (false positives). The positive likelihood ratio of the MLM was 145 to 254. All dogs diagnosed with HA by attending clinicians tested positive by the MLM. CONCLUSIONS AND CLINICAL IMPORTANCE: This MLM can robustly predict HA status when indiscriminately screening all dogs with blood work. In this group of dogs with a low prevalence of HA, the false positive rates were clinically acceptable.

Use of machine-learning algorithms to aid in the early detection of leptospirosis in dogs.

Leptospirosis is a life-threatening, zoonotic disease with various clinical presentations, including renal injury, hepatic injury, pancreatitis, and pulmonary hemorrhage. With prompt recognition of the disease and treatment, 90% of infected dogs have a positive outcome. Therefore, rapid, early diagnosis of leptospirosis is crucial. Testing for Leptospira-specific serum antibodies using the microscopic agglutination test (MAT) lacks sensitivity early in the disease process, and diagnosis can take >2 wk because of the need to demonstrate a rise in titer. We applied machine-learning algorithms to clinical variables from the first day of hospitalization to create machine-learning prediction models (MLMs). The models incorporated patient signalment, clinicopathologic data (CBC, serum chemistry profile, and urinalysis = blood work [BW] model), with or without a MAT titer obtained at patient intake (=BW + MAT model). The models were trained with data from 91 dogs with confirmed leptospirosis and 322 dogs without leptospirosis. Once trained, the models were tested with a cohort of dogs not included in the model training (9 leptospirosis-positive and 44 leptospirosis-negative dogs), and performance was assessed. Both models predicted leptospirosis in the test set with 100% sensitivity (95% CI: 70.1-100%). Specificity was 90.9% (95% CI: 78.8-96.4%) and 93.2% (95% CI: 81.8-97.7%) for the BW and BW + MAT models, respectively. Our MLMs outperformed traditional acute serologic screening and can provide accurate early screening for the probable diagnosis of leptospirosis in dogs.

Role of Diagnostics in Epidemiology, Management, Surveillance, and Control of Leptospirosis.

A One Health approach to the epidemiology, management, surveillance, and control of leptospirosis relies on accessible and accurate diagnostics that can be applied to humans and companion animals and livestock. Diagnosis should be multifaceted and take into account exposure risk, clinical presentation, and multiple direct and/or indirect diagnostic approaches. Methods of direct detection of Leptospira spp. include culture, histopathology and immunostaining of tissues or clinical specimens, and nucleic acid amplification tests (NAATs). Indirect serologic methods to detect leptospiral antibodies include the microscopic agglutination test (MAT), the enzyme-linked immunosorbent assay (ELISA), and lateral flow methods. Rapid diagnostics that can be applied at the point-of-care; NAAT and lateral flow serologic tests are essential for management of acute infection and control of outbreaks. Culture is essential to an understanding of regional knowledge of circulating strains, and we discuss recent improvements in methods for cultivation, genomic sequencing, and serotyping. We review the limitations of NAATs, MAT, and other diagnostic approaches in the context of our expanding understanding of the diversity of pathogenic Leptospira spp. Novel approaches are needed, such as loop mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches to leptospiral nucleic acid detection.

Sex Differences in Susceptibility to Coccidioidomycosis.

To assess sex-specific differences in coccidioidomycosis, a retrospective analysis of human patients, nonhuman primates, and veterinary patients (including the neutered status of the animal) was performed. We found higher rates of infection and severity in males. This observed increased infection risk suggests deeper biological underpinnings than solely occupational/exposure risks.

Outcome and prognostic factors in infective endocarditis in dogs: 113 cases (2005-2020).

BACKGROUND: Factors associated with outcome in dogs diagnosed with infective endocarditis (IE) are not well characterized. OBJECTIVES: Evaluate outcome and prognostic factors in dogs with IE. ANIMALS: One hundred and thirteen dogs with IE. METHODS: Medical records for dogs that fulfilled the modified Duke criteria between 2005 and 2020 were retrospectively reviewed. Signalment, preexisting conditions, clinicopathologic findings, treatment regimen, and outcomes were recorded. Univariate logistic regression was performed to identify categorical factors associated with mortality, and then multivariate analysis was performed. RESULTS: Dogs were categorized as survivors (n = 47), non-survivors (n = 57), or lost to follow-up (n = 9). Survival to discharge and at 1 month was documented in 79 (70%) of 113 and 56 (54%) of 104 dogs, respectively, with median survival time (MST) of 72 days. Risk factors associated with mortality included development of congestive heart failure (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.4-97.8), thromboembolic events (OR, 5.7; 95% CI, 2.3-14.4), and acute kidney injury (OR, 6.2; 95% CI, 2.0-18.8). Administration of antithrombotic medications was associated with survival (OR, 0.35; 95% CI, 0.13-0.97). Dogs that were not treated with antithrombotics had MST of 92 days, whereas dogs treated with antithrombotics did not reach MST during the study period. The heart valves involved and etiologic agent identified did not correlate with outcome. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with IE that had thromboembolic events, acute kidney injury, or congestive heart failure had higher risk of mortality. Administration of antithrombotics was associated with prolonged survival time.

Disseminated Rasamsonia argillacea species complex infections in 8 dogs.

BACKGROUND: Clinical features, treatment, and outcome of opportunistic infections with Rasamsonia spp., a nonpigmented filamentous mold, are not well documented in dogs. OBJECTIVES: Describe clinical, radiographic, pathologic features, and outcome of dogs with disseminated Rasamsonia species complex infections. ANIMALS: Eight client-owned dogs. METHODS: Retrospective case series. Medical records were reviewed to describe signalment, history, clinicopathologic and imaging findings, microbiologic and immunologic results, cyto- and histopathologic diagnoses, treatment, and outcome. RESULTS: Presenting complaints were nonspecific with anorexia (n = 5) and back pain (n = 4) most common. Five dogs were German Shepherd dogs. Six dogs had multifocal discospondylitis and 2 had pleural effusion. Six dogs had Rasamsonia piperina and 2 had Rasamsonia argillacea infections with isolates identified using DNA sequencing. Rasamsonia spp. were isolated by urine culture in 5 of 7 dogs. Five of 6 dogs had positive serum Aspergillus galactomannan antigen enzyme immunoassay (EIA) results. Median survival time was 82 days, and 317 days for dogs that survived to discharge. Four died during initial hospitalization (median survival, 6 days). All isolates had low minimum effective concentrations (MECs) to echinocandins with variable minimum inhibitory concentrations (MICs) for azole antifungal drugs. CONCLUSIONS AND CLINICAL IMPORTANCE: Rasamsonia spp. infections in dogs are associated with multisystemic disease involving the vertebral column, central nervous system, kidneys, spleen, lymph nodes, lungs, and heart. The infection shares clinical features with other systemic mold infections and can be misidentified when using phenotypical microbiologic methods. Molecular techniques are required to identify the organism and guide appropriate antifungal treatment.