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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.

Objective: To compare 2 point-of-care lateral flow assays (LFAs) with immunodiffusion (ID) IgG results for anti-coccidioidal antibody detection in dogs with coccidioidomycosis. A further aim was to compare the quantifiable output of 1 of the LFAs to ID antibody titers., Sample: Serum banked from 73 client-owned dogs diagnosed with pulmonary or disseminated coccidioidomycosis., Methods: ID was used to determine antibody presence and titer against a coccidioidal antigen preparation. All sera were subsequently tested on an LFA based on recombinant chitinase 1 (CTS1) and the commercially available sōna LFA. LFA results were analyzed and compared to ID IgG results and clinical diagnosis., Results: All assays showed similar sensitivities in detecting anti-coccidioidal antibodies (83.6% to 89.0%). When compared with ID IgG, the CTS1 LFA had a positive percent agreement of 100%, while the sōna LFA had a positive percent agreement of 91.4%. Since the CTS1 LFA is semiquantitative, we were able to compare test line densities with ID titers and found a strong correlation between the 2 assays (Spearman ρ = 0.82)., Clinical Relevance: This is the first side-by-side evaluation of a commercially available LFA (sōna) and a newer more rapid anti-CTS1 antibody LFA using serum from dogs with coccidioidomycosis. Both LFAs tested have similar sensitivity to ID IgG results. The CTS1 LFA can be read after 10 minutes and is semiquantitative, while the sōna LFA is read after 30 minutes, and the results are subject to interpretation. Accurate and fast detection of anti-coccidioidal antibodies allows clinicians to initiate appropriate treatment without diagnostic delay.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Coccidioidomycosis is a potentially fatal fungal disease of humans and animals that follows inhalation of Coccidioides spp. arthroconidia in the environment. The disease in dogs resembles that in people, and because dogs may be at increased risk of exposure due to their proximity to the ground and digging behavior, they are valuable models for the disease in humans. Dogs have been sentinels for identification of new regions of endemicity in Washington and Texas. Canine serosurveillance has also been used to predict variables associated with environmental presence of Coccidioides spp. Expansion of the endemic region of coccidioidomycosis with climate change-along with predicted population increases and increased development in the southwest United States-may result in 45.4 million additional people at risk of infection by 2090. Here we provide an overview of the value of dogs as sentinels for the disease and encourage the routine reporting of coccidioidomycosis cases in dogs to public health agencies. We also highlight the value of dogs as naturally occurring models for studying novel treatment options and preventatives, such as a novel live avirulent coccidioidomycosis vaccine., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The incidence of coccidioidomycosis continues to increase. The diagnosis frequently relies on non-invasive diagnostic testing with immunodiffusion and complement fixation (CF) testing the current gold standard. A direct comparison of quantitative immunodiffusion and CF for IgG antibodies has not been previously reported. In a comparison of 368 samples, there was close concordance observed (360/368 = 97.8%) (P-value < .001). These tests can be considerably interchangeable in the reference laboratory setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Clinical Relevance: Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured., Aim: In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs., Evidence Base: Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from 'preclinical' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology., Abbreviations for Antifungal Drugs: AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole)., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A southern sea otter (Enhydra lutris nereis) stranded dead in central California, USA, with a distended pericardial sac containing thousands of free-floating proteinaceous masses. Serology, fungal culture, PCR, and sequencing confirmed the etiology of this novel lesion as Coccidioides immitis. Range expansion of this zoonotic pathogen is predicted with climate change., (© Wildlife Disease Association 2024.)

Clinical Relevance: In contrast to superficial fungal infections, such as dermatophytosis, invasive fungal infections (IFIs) are characterised by penetration of tissues by fungal elements. Disease can spread locally within a region or can disseminate haematogenously or via the lymphatics. The environment is the most common reservoir of infection. Since fungal spores are airborne, indoor cats are also susceptible to IFIs. Some environmental fungi are ubiquitous and present globally, while others are endemic or hyperendemic within specific geographic regions. Zoonotic pathogens include Microsporum canis, Sporothrix schenckii and Sporothrix brasiliensis., Aim: In the first of a two-part article series, the approach to the investigation of feline IFIs and oomycoses is reviewed. As well as tips for diagnosis, and information on the ecological niche and distribution of fungal pathogens, the review covers clinical presentation of the most common IFIs, including cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis, phaeohyphomycosis, aspergillosis and dermatophytic pseudomycetoma, as well as the oomycoses pythiosis, lagenidiosis and paralagenidiosis. In Part 2, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties and adverse effects of antifungal drugs are reviewed, and the treatment and prognosis for specific IFIs and oomycoses are discussed., Evidence Base: The review draws on published evidence and the authors' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive and three (1.1%) were equivocally IgM-positive. The IgG-positive samples were from Arizona (2 [prevalence 8.0%]) and California (4 [3.7%]). These data will guide future efforts to study MWDs as sentinels for human coccidioidomycosis., (Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology 2023.)

Cutaneous Coccidioidomycosis (CC) infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022 using the ICD9 and ICD10 codes for coccidioidomycosis and CC. We identified 40 patients with CC during the study period. The mean age of the study population was 43 years (with standard deviation of 14.08). Among these, 60% were men and 40% women. The appearance of the lesions varied from ulcers, plaques, nodules, blisters, cellulitis, and abscesses. The most common site of CC lesions was in the lower extremities (42.5%), followed by upper extremities (30%), chest and abdomen, head and neck (25% each). Only 22.5% of the 40 cases were diagnosed as CC and 15% were diagnosed as erythema nodosum. Rest were diagnosed initially as bacterial cellulitis in 37.5%, tinea in 7.5%, and others in 12.5%. There was resolution of the cutaneous lesions in all patients with antifungal treatment. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8-16 weeks) in our study with 75% cases initially misdiagnosed. Comprehensive knowledge about the manifestations and evaluation of CC among primary care providers and emergency room physicians is essential to prevent delays in diagnosis and treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The clinical utility of Coccidioides species antifungal susceptibility testing (AST) remains unclear. This study describes the clinical course of eight patients with severe or chronic coccidioidomycosis and subsequent Coccidioides AST. We present the clinical manifestations, antifungal treatment regimens, and clinical outcomes for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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.

Background: Clinicopathologic variables predictive of disseminated coccidioidomycosis are known in humans but have not been explored in dogs. Serum 25-hydroxyvitamin (OH)D correlates with severity of disease of various etiologies in dogs but its role in coccidioidomycosis is unknown., Objective: Determine whether serum 25(OH)D concentrations are different in dogs with coccidioidomycosis compared with healthy controls and if clinicopathologic variables are associated with extent of disease., Animals: Thirty-five dogs with coccidioidomycosis (pulmonary, n = 13; disseminated, n = 15; uncharacterized, n = 7), and 25 healthy control dogs., Methods: Prospective cohort study. Serum 25(OH)D and C-reactive protein (CRP) concentrations were measured with modified-HPLC and a commercial ELISA kit, respectively., Results: There was no difference in 25(OH)D concentrations between dogs with coccidioidomycosis (median, interquartile range [IQR]; 31.9 ng/mL, 23.3-49.2) and controls (29.5 ng/mL, 25.6-40.8, P = .73). Serum 25(OH)D concentration was lower in dogs with coccidioidomycosis and IgG titers ≥1:32 than dogs with titers below this cut-off (P = .02). Dogs with IgG titers ≥1:32 were more likely to have disseminated disease (OR, 7.5; 95% CI: 1.1-68; P = .03). Serum CRP concentrations were higher in dogs with IgG titers ≥1:16 (median, IQR; 4474.8 ng/mL, 2885.8-8236.1) than in those below this cut-off (151.2 ng/mL, 30.4-2907.3; P = .02). There was a significant inverse association between serum 25(OH)D and CRP at 25(OH)D concentrations ≤33 ng/mL., Conclusion and Clinical Importance: Serum 25(OH)D concentration was lower for dogs with IgG titers ≥1:32, indicating a potential association between semi-quantitative titers and 25(OH)D concentrations in dogs with coccidioidomycosis. IgG titers ≥1:32 yielded higher odds of disseminated disease, but was inadequate as a standalone test to determine form of disease., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii . We searched the records of the California Animal Health and Food Safety Laboratory from 1990 through 2020 for cases of coccidioidomycosis in horses. The selection criteria for these cases were: 1) live-born horses submitted for autopsy, and 2) a diagnosis of coccidioidomycosis was established, regardless of cause of death. During that time, 19,054 horses were received, and 26 cases (0.14%) of coccidioidomycosis were diagnosed in horses, of which 19 (73%) cases had pneumonia and/or pleuritis with or without lesions in other organs, and 7 (27%) cases had lesions only in organs other than the lungs (nasal mucosa, spleen, thoracic lymph nodes, heart, pericardial sac, liver, kidney, mediastinum, and/or mesentery). Pneumonia was diagnosed as the cause of death in 1,838 (9.64%) of the horses received; Coccidioides spp. was the cause of pneumonia in 19 (1.0%) of these animals. Horses have been reported to have low susceptibility to coccidioidomycosis, and the severity and chronicity of the disease can be variable. Lesions in our cases consisted of multifocal-to-coalescing pyogranulomas with intralesional fungal spherules. Coccidioidomycosis must be considered a differential diagnosis in cases of persistent cough, chronic weight loss, fever, and cases with a travel history to, or living in, a region considered endemic for coccidioidomycosis. Coccidioides spp. infection should also be considered when pyogranulomatous inflammation is found within lung, spleen, nasal mucosa, and lymph nodes of horses.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955 to 1958, followed through 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiographs. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9 cm (IQR: 2-2.9-4-4.9 cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19 cm (Interquartile range [IQR] 1-1.9-2-2.9 cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objective: To characterize the clinical course and therapeutic response in dogs with coccidioidomycosis treated with fluconazole., Animals: 49 client-owned dogs with coccidioidomycosis that were treated with fluconazole and had ≥ 2 follow-up examinations., Procedures: Medical records were retrospectively searched to identify dogs in which coccidioidomycosis was diagnosed between January 2015 and May 2020. Data recorded from each dog included signalment, clinical signs, diagnostic test results, and treatment., Results: Dogs were treated with fluconazole at a median initial dosage of 19.7 mg/kg/d. Median treatment duration was 298.5 days, with 26 of the 49 dogs completing treatment during the study period. Respiratory signs, lethargy, and hyporexia were the most common clinical signs. Frequency of lethargy decreased after 30 days, whereas frequency of hyporexia and respiratory signs decreased after 90 days. Median IgG titer at diagnosis was 1:32 and was significantly decreased, compared with baseline titer, at all recheck intervals after 90 days. Hyperglobulinemia, monocytosis, and neutrophilia were the most common clinicopathologic abnormalities. Hyperglobulinemia resolved within 30 days, neutrophilia resolved within 90 days, and monocytosis resolved after 180 days., Clinical Relevance: Improvements in clinical signs, titers, and clinicopathologic abnormalities were observed after initiation of treatment with fluconazole. Improvement began as early as the first 3 months of treatment, but some variables did not resolve until after 6 to 9 months of treatment. This information provides clinical guidance and describes expectations when prescribing fluconazole to treat coccidioidomycosis in dogs.

Coccidioidomycosis is a significant health problem of dogs and humans in endemic regions, especially California and Arizona in the U.S. Both species would greatly benefit from a vaccine to prevent this disease. A live avirulent vaccine candidate, Δcps1, was tested for tolerability and efficacy to prevent pulmonary coccidioidomycosis in a canine challenge model. Vaccine injection-site reactions were transient and there were no systemic effects observed. Six of seven vaccine sites tested and all draining lymph nodes were sterile post-vaccination. Following infection with Coccidioides posadasii, strain Silveira, arthroconidia into the lungs, dogs given primary and booster vaccinations had significantly reduced lung fungal burdens (P = 0.0003) and composite disease scores (P = 0.0002) compared to unvaccinated dogs. Dogs vaccinated once had fungal burdens intermediate between those given two doses or none, but disease scores were not significantly different from unvaccinated (P = 0.675). Δcps1 was well-tolerated in the dogs and it afforded a high level of protection when given as prime and boost. These results drive the Δcps1 vaccine toward a licensed veterinary vaccine and support continued development of this vaccine to prevent coccidioidomycosis in humans., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [John N Galgiani reports financial support was provided by National Institutes of Health. Edward Robb reports financial support and equipment, drugs, or supplies were provided by Anivive Life Sciences, LLC. Edward Robb reports a relationship with Anivive Lifesciences, LLC that includes: employment.. Lisa Shubitz has patent #Fungal lmmunogens and Related Materials and Methods WO2014164843-A1 issued to Arizona Board of Regents. Marc Orbach has patent #Fungal lmmunogens and Related Materials and Methods WO2014164843-A1 issued to Arizona Board of Regents.]., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To evaluate the utility of enzyme immunoassays (EIAs) for the detection of Coccidioides antigen and antibody in CSF in the diagnosis of CNS coccidioidomycosis in dogs., Animals: 51 dogs evaluated for CNS disease in a single specialty center in Tucson in 2016., Procedures: Excess CSF after routine analysis was banked after collection from dogs presented to the neurology service. Samples were tested by EIA for presence of Coccidioides antigen and antibody. Clinical data were collected from medical records retrospectively., Results: 22 dogs were diagnosed with CNS coccidioidomycosis (CCM) or another neurologic disease (non-CCM). These groups of dogs overlapped in the presenting complaints, MRI results, and routine CSF analysis results. Four dogs, all with CCM, had positive antigen EIA results. With clinical diagnosis used as the reference standard, CSF antigen testing had low sensitivity (20%) but high specificity (100%) for diagnosis of CCM. Ten dogs with CCM and 4 dogs with other diagnoses had antibody detected in CSF by EIA. Sensitivity of CSF antibody testing was 46%, specificity was 86%, and positive and negative predictive values for the study population were 71% and 68%, respectively., Clinical Relevance: Diagnosis of CNS coccidioidomycosis in dogs in an endemic region was hampered by overlap of clinical signs with other neurologic disorders and the low sensitivity of confirmatory diagnostics. The evaluated Coccidioides-specific EIAs performed on CSF can aid in the diagnosis. A prospective study is warranted to corroborate and refine these preliminary findings.

Background: The majority of dogs with coccidioidomycosis recover with administration of fluconazole or itraconazole, although some cases are refractory or the dogs do not tolerate administration of these medications., Objectives: The objective was to describe the treatment outcomes and therapeutic monitoring of 8 dogs with refractory coccidioidomycosis treated with posaconazole., Animals: Eight dogs with refractory coccidioidomycosis., Methods: Retrospective case series. Medical records from Veterinary Specialty Center of Tucson were searched to identify dogs with refractory coccidioidomycosis that were treated with posaconazole. Clinical information and the results of monitoring trough serum posaconazole concentrations were retrieved., Results: Eight dogs with refractory coccidioidomycosis were treated with 2.5 to 10 mg/kg per day of posaconazole. Six of 8 dogs recovered or developed clinical remission while administered posaconazole. Thirteen serum concentrations from 8 dogs tested were >1 μg/mL (range, 1.52 to >6 μg/mL) and the drug was well-tolerated by 7 dogs. One dog required dosage reductions and treatment was ultimately discontinued because of hepatotoxicosis., Conclusions and Clinical Importance: Posaconazole should be considered as a treatment option for dogs with refractory coccidioidomycosis. Monitoring of indicators of liver function or injury along with therapeutic drug monitoring is recommended to tailor dosage in the event of hepatic toxicosis., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Knowledge of the clinical and magnetic resonance imaging (MRI) features of intracranial Coccidioides infection in dogs is essential for prompt diagnosis to limit disease-associated morbidity and death., Objectives: To describe the MRI appearance of intracranial coccidioidomycosis in dogs, identify associated clinical and clinicopathologic findings, and report outcomes of medical treatment., Animals: Forty-five client-owned dogs with presumed intracranial Coccidioides infection., Methods: Retrospective case series. Medical records and images were reviewed. Clinical history, examination findings, serology, imaging characteristics, treatment, and outcome were recorded. Included cases had an abnormal brain MRI and positive Coccidioides serology by agar-gel-immunodiffusion (AGID)., Results: Median age was 7-years. Generalized tonic-clonic seizures were the most common presenting sign (25/45). Two lesion categories were identified: a granulomatous form with 1 or more distinct, intra-axial, contrast-enhancing foci (37/45), and a second variation with diffuse, bilateral, symmetrical lesions of the caudate nuclei and frontal lobes (8/45). Serum IgG titers ranged from 1 : 1 to ≥ 1 : 256; 2 dogs had positive IgM titers at 1 : 2. All dogs with follow-up serology (34/45) had a reduction in titer. Mean duration of follow-up was 22.4 ± 20.5 months (median 16 months). Six dogs were lost to follow-up <1-year after diagnosis (median 9 months). Five dogs were clinically well but had yet to be followed for >1-year. Of the remaining 34 dogs, 28 (82%) were alive ≥ 1-year after diagnosis. Thirteen of these dogs had follow-up times ≥ 2-years., Conclusions and Clinical Importance: The prognosis for intracranial Coccidioides infection is generally more favorable with medical treatment than in earlier reports., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A 3-mo-old male llama was examined because of a 4-wk history of lethargy and ill thrift. Clinical examination revealed subcutaneous masses in the left prescapular and right inguinal regions, mild ataxia, a slight head tilt to the right, and right ear droop. The cria died before clinical workup was complete. At autopsy, there was generalized lymphadenomegaly, a hepatic nodule, a midbrain mass causing rostral compression of the cerebellum, and internal hydrocephalus. Microscopic findings included pyogranulomatous lymphadenitis, meningoencephalitis, hepatitis, and bronchopneumonia. Intralesional fungal spherules, most consistent with Coccidioides spp., were identified in the lymph nodes, lung, and brain. Fungal culture, single-nucleotide variation genotyping real-time PCR, and DNA sequencing confirmed Coccidioides posadasii . The dam of the cria was native to Arizona and had been moved to Missouri ~2.5 y previously. Agar gel immunodiffusion assay of the herd revealed that only the dam was positive for Coccidioides spp.; 6 herdmates were negative. Computed tomography of the dam revealed multiple nodules within the lungs and liver, which were presumed to be an active coccidioidomycosis infection. This case of systemic coccidioidomycosis in a llama native to Missouri was presumably acquired by vertical transmission from the dam.

Background: Point-of-care (POC) Coccidioides antibody assays may provide veterinarians with rapid and accurate diagnostic information., Objectives: To determine the agreement of a POC lateral flow assay (LFA), sona Coccidioides (IMMY, Norman, Oklahoma) with the current diagnostic standard, the immunodiffusion assay (agar gel immunodiffusion [AGID]; Coccidioidomycosis Serology Laboratory, University of California, Davis, California)., Animals: Forty-eight sera specimens from 48 dogs., Methods: Sera specimens were collected from client-owned dogs that had a clinical suspicion for coccidioidomycosis. Animals were classified as Coccidioides antibody-positive (n = 36) based on a positive AGID or Coccidioides antibody-negative (n = 12) based on a negative AGID. The performance of the LFA assay was determined by comparing results to AGID results., Results: The LFA assay demonstrated agreement in 32 of 36 Coccidioides antibody-positive specimens and 12 of 12 Coccidioides antibody-negative specimens, resulting in a positive percentage agreement of 88.9% (95% confidence interval [CI], 74.7-95.6%) and negative percentage agreement of 100% (95% CI, 75.8-100%) as compared to AGID. A receiver operator characteristic curve was constructed, and the area under the curve was 0.944 (CI, 0.880-1.000)., Conclusion and Clinical Importance: This LFA is a rapid alternative to the traditional AGID. The LFA provides excellent predictive value for positive results. Positive agreement was lower in dogs with low AGID titers; therefore, confirmatory testing is recommended if a high index of suspicion exists., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Coccidioidomycosis in dogs can range from mild respiratory disease or vague, chronic malaise to acute, severe life-threatening illness. The diagnosis of coccidioidomycosis in dogs is based on clinical presentation and serology. Spherule identification is not typical because of low numbers of organisms in specimens, and the invasive nature of sampling tissues and lungs. Conventional serological assays require samples to be submitted to a reference laboratory and results take several days to one week. The sōna Coccidioides Antibody Lateral Flow Assay (LFA) (IMMY Diagnostics) is a rapid, bench-side test used for detection of Coccidioides antibodies that is available and FDA-cleared for use in humans but has not been evaluated in dogs. The goal of this study was to compare the LFA to conventional agar gel immunodiffusion (AGID). Paired serum samples were collected for screening by the LFA and submitted to a commercial reference laboratory for AGID screen and titer. Of 56 paired serum samples analyzed, 30 were positive and 26 were negative on the sōna Coccidioides antibody LFA. The overall percentage agreement plus 95% confidence interval (CI) was 87.5% (76.20-93.99). Positive percent agreement was 89.7% (73.38-96.65) and negative percent agreement was 85.2% (67.25-94.36). The kappa coefficient to assess agreement was 0.749 (95% CI, 0.576-0.923), which is interpreted as good agreement between the tests (>70%). The sōna Coccidioides antibody LFA provided rapid, point-of-care results with a high level of agreement to standard AGID serology in dogs clinically suspected to have coccidioidomycosis, and may aid in diagnosis of coccidioidomycosis in dogs., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: The goal of this study was to describe the clinical presentation, diagnosis and treatment of coccidioidomycosis in cats residing in a region endemic for Coccidioides species., Methods: A retrospective review of records was performed at both primary and tertiary care veterinary practices in Tucson and Phoenix, Arizona, USA. Data collected included signalment, clinical signs, physical examination findings, diagnostic test results, treatment and outcome., Results: Fifty-one feline cases were identified from six veterinary hospitals. Cats presented with clinical signs and laboratory abnormalities similar to what has been seen in dogs, including respiratory illness (n = 20/51), neutrophilia (n = 24/31), monocytosis (n = 17/31) and hyperglobulinemia (n = 16/30). However, cats at diagnosis were typically significantly ill, with 31/51 having disseminated infection, most commonly to the skin (n = 22). Additionally, 43/44 cats that had serum antibody tests performed were positive, and median titer at diagnosis was 1:32 (range 1:4 to ⩾1:256). Serum antibody titers were significantly reduced ( P ⩽0.001) in cats that responded to treatment compared with cats that did not clinically improve. Forty of 46 cats that were treated with oral fluconazole responded and did not require additional therapy. Fourteen cats developed recurrent disease and all but one had antifungal therapy successfully reinstituted., Conclusions and Relevance: Coccidioidomycosis is a disease of concern for cats residing in the regions endemic for Coccidioides species. Disease is most often disseminated at the time of diagnosis, possibly due to delays in presentation for care and recognition of the infection. Suspicion of disease, serum chemistries, blood cell counts, presence of antibody and imaging aid in the diagnosis of coccidioidomycosis in cats. Serum antibody reduction during treatment frequently correlated with an adequate response to medication. Consideration of coccidioidomycosis as a cause of illness will lead to earlier diagnosis and potentially better treatment outcomes in cats.

Coccidioides immitis is an emerging fungal pathogen in Washington State (WA). While the geographical boundaries of C. immitis in WA have not been well characterized, human infections have resulted from exposure in the south-central region of the state. Since 2010, only one dog has been identified as a probable locally acquired animal case, despite pilot canine serological surveys from south-central WA revealing a 9.8% seroprevalence. On the suspicion that clinical animal cases may be underdiagnosed and/or underreported, we assessed WA veterinarians' knowledge, attitudes and practices regarding coccidioidomycosis. All veterinarians with active licenses in WA were invited to complete a self-administered, web-based survey from November 2018 to January 2019. Four hundred and twenty-five of 2,211 (19.2%) veterinarians returned the survey and were eligible for inclusion in the final analysis. Nearly, all respondents (98.8%) had heard of coccidioidomycosis, but only 31.5% and 25.6% knew that locally acquired animal and human cases, respectively, had been reported in WA. Only half (52.6%) of participants knew that the disease was reportable. Fewer than 20% of respondents reported confidence that their knowledge of coccidioidomycosis was up to date, and 76.9% "never" or "rarely" considered the risk of disease in their patients. A statistically significant predictor of a high knowledge score (≥70%), however, included practicing in endemic counties where the Washington State Department of Health had previously delivered outreach and education services. While the results suggest some success with these activities, it is clear that information on the emergence of coccidioidomycosis is not adequately reaching veterinary practitioners in WA. The data support that more frequent CE opportunities, and dissemination of public health communications through veterinary-specific modalities, would help fill the knowledge gap. In turn, improved diagnosis and reporting of animal cases would assist in our overall understanding the epidemiology of coccidioidomycosis in WA., (© 2019 Blackwell Verlag GmbH.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Coccidioidomycosis, or Valley Fever, is a fungal infection caused by Coccidioides spp., soil-living fungi endemic to the southwest region of the United States. The infection can cause various diseases including respiratory, neurologic, cardiac, dermatologic, and ocular disease as well as osteomyelitis in dogs and many other mammals. Obtaining a definitive diagnosis can be challenging. Serology is commonly used as a screening diagnostic test for disease, but both false-negative and false-positive results have been reported. Fifty-two cases of coccidioidomycosis diagnosed via histopathology were retrospectively evaluated. The sensitivity of serology in the study population was determined to be 87% for immunoglobulin G and 46% for immunoglobulin M. The cases were evaluated for an association between negative serology results and anatomic location of disease, but these variables were found to be independent. This study reports the sensitivity of serology for canine coccidioidomycosis and highlights the importance of using multiple diagnostic tests for definitive diagnosis of infection.

Coccidioidomycosis is a predominantly respiratory infection of animals and humans caused by soil-dwelling fungi. Long known to be endemic to North American deserts, locally acquired human cases first emerged in Washington State in 2010. To inform development of an environmental niche map, we conducted an ecological cross-sectional study of the association between soil and climactic variables and canine seroprevalence in Washington State, at the zip code tabulation area level. Soil predictors included soil texture (per cent sand, silt and clay), pH, electrical conductivity and water storage capacity; climactic predictors included mean annual air temperature and liquid precipitation. Clustering was evaluated with Moran's I, and four modelling approaches were adopted a priori: two models without any smoothing (logistic regression and quasi-logistic regression) and two smoothing models (non-spatial and spatial smoothing). No evidence was found for clustering, and both smoothing models resulted in marked attenuation of all coefficients. Temperature was found to have a positive effect in the non-smoothing models (prevalence odds ratio, logistic model: 1.70, 95% confidence interval 1.02, 2.84). While no other significant associations were found, there was suggestive evidence of a positive effect for pH. Despite the limitations inherent to the ecological and cross-sectional nature of these data, these findings provide insight for the development of an environmental niche map in Washington State and demonstrate the utility of using data from an animal sentinel to predict human disease risk., (© 2019 Blackwell Verlag GmbH.)

Over 18 mo, adult female pigtailed macaques ( Macaca nemestrina ) housed at a breeding facility in Arizona were monitored every 6 mo for alopecia. The study period coincided with the movement of a majority of animals from primarily outdoor housing to continuous indoor housing and a corresponding decrease in available space. These changes were made due to the newly recognized prevalence of coccidioidomycosis at this site. The effects of pregnancy status, changes in outdoor access or space, and administration of fluconazole for the treatment of coccidioidomycosis on alopecia were explored. In this group of pigtailed macaques pregnancy did not appear to affect alopecia, in contrast to findings from a closely related species, rhesus macaques. Fluconazole administration increased alopecia in older animals but not in the youngest age group. Conversely, the effects of limited outdoor access or decreased space on increasing alopecia were greatest in the youngest group of animals.

An anonymous web-based survey of alpaca owners was used to learn more about the clinical presentation, diagnosis, and treatment of coccidioidomycosis in alpacas in the United States. Thirty-seven owners, with 1,117 alpacas, completed the survey. Over 4% of alpacas included in the study were diagnosed with coccidioidomycosis between 2005 and 2016 (5 post mortem, 46 clinically). Immunodiffusion titers ranged from 1:4 to ≥1:256 in sick animals. Alpacas residing in Arizona counties with a high incidence of human disease were 5.8 times more likely to contract coccidioidomycosis than animals residing in other areas of the state. Treatment was reported in 23 alpacas, and 78% of those animals died or were euthanized. Necropsy records from a veterinary diagnostic laboratory in Tucson, AZ were reviewed to estimate the severity of disease in this species. Nine cases identified for review died of disseminated coccidioidomycosis; the disease was extensive in most animals, with the lungs, lymph nodes, and liver the most frequently affected. Alpacas appear to be highly susceptible to severe illness as a result of infection by Coccidioides spp., frequently resulting in death. More research is needed to better understand the epidemiology, clinical signs, and treatment protocols for coccidioidomycosis in alpacas., (© 2018 Blackwell Verlag GmbH.)

Canine coccidioidomycosis, a systemic fungal infection endemic to arid and semiarid regions of North, Central, and South America, is commonly diagnosed in dogs living in or traveling through lower Sonoran life zones in the states of California and Arizona. Canine and human cases have geographic overlap. Similarities between clinical coccidioidomycosis in dogs and humans include asymptomatic infection, primary respiratory disease and disseminated disease. Differences include a high rate of dissemination in dogs, differences in predilection of dissemination sites, and a granulomatous or diffuse meningoencephalopathic form in the canine central nervous system (CNS) without the obstructive component seen in humans. Dogs presenting with CNS coccidioidomycosis most commonly experience seizures. Prior disease history and serology are unreliable indicators of CNS coccidioidomycosis. Magnetic resonance imaging (MRI) is advantageous for diagnosis of CNS coccidioidomycosis in dogs. Long-term administration of antifungal medication is promoted for treatment of both primary and disseminated coccidioidomycosis in dogs. Supportive treatment addressing pain, fever, inappetance, coughing, and other clinical signs improves patient care. Glucocorticoids and or anticonvulsants are also recommended for canine disseminated CNS disease. Protracted treatment times, lack of owner compliance, failure of the disease to respond to the first antifungal drug selected, and high cost are challenges of successfully treating dogs.

The prevailing hypothesis concerning the ecology of Coccidioides immitis and C. posadasii is that these human pathogenic fungi are soil fungi endemic to hot, dry, salty regions of the New World and that humans and the local, small-mammal fauna are only accidental hosts. Here we advance an alternative hypothesis that Coccidioides spp. live in small mammals as endozoans, which are kept inactive but alive in host granulomas and which transform into spore-producing hyphae when the mammal dies. The endozoan hypothesis incorporates results from comparative genomic analyses of Coccidioides spp. and related taxa that have shown a reduction in gene families associated with deconstruction of plant cell walls and an increase in those associated with digestion of animal protein, consistent with an evolutionary shift in substrate from plants to animals. If true, the endozoan hypothesis requires that models of the prevalence of human coccidioidomycosis account not only for direct effects of climate and soil parameters on the growth and reproduction of Coccidioides spp. but also consider indirect effects on these fungi that come from the plants that support the growth and reproduction of the small mammals that, in turn, support these endozoic fungi.

We report 5 cases of coccidioidomycosis in animals that were acquired within Washington, USA, and provide further evidence for the environmental endemicity of Coccidioides immitis within the state. Veterinarians should consider coccidioidomycosis in animals with compatible clinical signs that reside in, or have traveled to, south central Washington.

The neurological examination findings, clinical pathology (including Coccidioides immitis IgG/IgM serology) and magnetic resonance imaging (MRI) findings in 13 dogs with a novel form of intracranial coccidioidomycosis are described in a retrospective case series, with long-term clinical resolution documented in 11/13 dogs (84.6% of cases) with oral fluconazole therapy. The medical records of the Veterinary Neurological Center in Phoenix, Arizona from the years 2000 to 2017 were utilized to search for dogs with appropriate inclusion criteria. Magnetic resonance imaging findings were highly consistent across all cases and characteristically demonstrated bilaterally symmetric T2 hyperintensity throughout the frontal lobes, caudate nuclei, and rostral internal capsule, ±faint, wispy contrast enhancement on T1-postcontrast images. These findings were in stark contrast to previously reported MRI findings in dogs with intracranial coccidioidomycosis, which were typically characterized by a focal, strongly contrast enhancing granuloma and extensive vasogenic edema, typically unilateral. Schnauzer breeds represented eight of 13 (61.5%) cases, possibly suggesting a breed predilection. Three cases underwent repeat MRI after resolution of neurological signs and documentation of a decreased Coccidioides titer in response to fluconazole therapy. All demonstrated complete resolution of previously identified lesions, but with marked, severe atrophy of the caudate nuclei and frontal lobes bilaterally. Findings from this study document a variant appearance for intracranial coccidioidomycosis that, to the author's knowledge, has not been previously described in dogs. Authors propose that, although this variant demonstrates extensive pathological changes within the forebrain, the clinical outcome and response to treatment is favorable in a majority of cases., (© 2018 American College of Veterinary Radiology.)

Coccidioidomycosis in nonhuman primates has been sporadically reported in the literature. This study describes 22 cases of coccidioidomycosis in nonhuman primates within an endemic region, and 79 cases of coccidioidomycosis from the veterinary literature are also reviewed. The 22 cases included baboons ( n = 10), macaques ( n = 9), and chimpanzees ( n = 3). The majority died or were euthanized following episodes of dyspnea, lethargy, or neurologic and locomotion abnormalities. The lungs were most frequently involved followed by the vertebral column and abdominal organs. Microscopic examination revealed granulomatous inflammation accompanied by fungal spherules variably undergoing endosporulation. Baboons represented a large number of cases presented here and had a unique presentation with lesions in bone or thoracic organs, but none had both intrathoracic and extrathoracic lesions. Although noted in 3 cases in the literature, cutaneous infections were not observed among the 22 contemporaneous cases. Similarly, subclinical infections were only rarely observed (2 cases). This case series and review of the literature illustrates that coccidioidomycosis in nonhuman primates reflects human disease with a varied spectrum of presentations from localized lesions to disseminated disease.

Coccidioidomycosis is a fungal disease caused by either Coccidioides immitis or Coccidioides posadasii. Anecdotal evidence suggests that camelids are particularly susceptible to this disease and that a relatively large percentage of pneumonias in these animals are caused by Coccidioides spp. In a search of 21 y (1992-2013) of records from the California Animal Health and Food Safety Laboratory, we found 79 cases of coccidioidomycosis diagnosed in camelids; 66 (84%) had pneumonia and 13 (16%) had lesions only in organs other than the lungs. The organs most frequently affected were lung (84%) and liver (78%). Coccidioides spp. were the cause of pneumonia in 66 of 362 (18%) camelid cases during the study period. The lesions in affected organs were multifocal-to-coalescing pyogranulomas, which in most cases were visible grossly. Ten of the 12 formalin-fixed, paraffin-embedded lung samples tested by a universal Coccidioides spp. PCR assay were positive (4 C. immitis, 2 C. posadasii); the species could not be determined in 4 of the 10 cases positive by PCR. Coccidioidomycosis is an important cause of pneumonia in camelids in California, and can be caused by either C. immitis or C. posadasii.

Coccidioides spp. are saprophytic, dimorphic fungi that are endemic to arid climates, are capable of infecting many species, and result in diverse clinical presentations. An indoor-housed laboratory rhesus macaque presented with weight loss and decreased activity and appetite. During the diagnostic evaluation, a bronchiolar-alveolar pattern in the cranial lung lobes, consistent with bronchopneumonia, was noted on radiographs. Given the poor prognosis, the macaque was euthanized. Confirming the radiographic assessment, gross necropsy findings included multifocal to coalescing areas of consolidation in the right and left cranial lung lobes. Microscopically, the consolidated regions were consistent with a pyogranulomatous bronchopneumonia and contained round, nonbudding, fungal yeast structures considered to be morphologically consistent with Coccidioides immitis. Culture and colony morphology results were confirmed through additional diagnostic testing. Sequencing of the D1-D2 domain of the 28S large ribosomal subunit positively matched with a known sequence specific to C. immitis. Serology for Coccidioides spp. by both latex agglutination (IgM) and immunodiffusion (IgG) was positive. In this rhesus macaque, the concordant results from histology, culture, DNA sequencing, and serology were collectively used to confirm the diagnosis of coccidioidomycosis. This animal likely acquired a latent pulmonary infection with Coccidioides months prior to arrival, when housed outdoors in a Coccidioides-endemic area. The nonspecific clinical presentation in this macaque, coupled with the recent history of indoor housing and lag between clinical presentation and outdoor housing, can make similar diagnostic cases challenging and highlights the need for awareness regarding animal source when making an accurate diagnosis in an institutional laboratory setting.

Given the predisposition of dogs to coccidioidomycosis, identification of high-risk regions for coccidioidomycosis in dogs may improve early recognition of emerging human disease. We sought to identify risk factors for canine coccidioidomycosis and to produce a risk map for coccidioidomycosis occurrence. Forty-one dogs seen at the Veterinary Medical Teaching Hospital at the University of California, Davis, between 2005 and 2013 with coccidioidomycosis were identified together with a control population of 79 dogs. Owners were surveyed about potential risk factors including younger age, digging behaviour, and travel to Arizona or the California central valley. Risk factors were analysed using logistic regression analysis. Outcomes were used to generate a risk map for coccidioidomycosis in California. There was a significant correlation between the reported rate of coccidioidomycosis in humans and our risk map for canine coccidioidomycosis in California, supporting the idea of dogs as sentinels for emerging geographic areas for coccidioidomycosis in humans., (© 2016 Blackwell Verlag GmbH.)

Coccidioidomycosis can be a chronic, systemic fungal infection requiring long-term to lifetime medication. Thus, there is a need for improved antifungal agents with greater efficacy and reduced toxicity. VT-1161 has a low affinity for mammalian cytochromes and potently inhibits fungal CYP51 with proven efficacy in murine models of central nervous system (CNS) and respiratory coccidioidomycosis. Dogs experience coccidioidomycosis similar to humans and are a useful preclinical model for naturally occurring disease. Twenty-four client-owned dogs diagnosed with respiratory coccidioidomycosis based on radiography, serology, clinical signs, and clinicopathologic abnormalities were treated with a loading dose of VT-1161 for 14 days, followed by 46 days of a lower maintenance dose. Twelve dogs received a high dose (29 mg/kg loading, 6 mg/kg maintenance) and 12 received a low dose (10 mg/kg loading, 1.6 mg/kg maintenance). Response to treatment was assessed by calculating the reduction in disease scores at exit compared to disease scores at enrollment. Overall, 20 of 24 (83%) dogs had ≥50% reduction in enrollment disease scores at exit ( P < 0.001), with no difference between the high- and low-dose groups ( P = 0.66). Time-weighted average plasma concentrations for the high- and low-dose groups were 39 ± 5 μg/ml and 19 ± 2 μg/ml, respectively. In this open-label study, VT-1161 was efficacious for the treatment of respiratory coccidioidomycosis in naturally infected dogs. Combined with previously reported murine data, this finding supports the further development of VT-1161 for the treatment of coccidioidomycosis in humans., (Copyright © 2017 American Society for Microbiology.)

Coccidioides is a soil-dwelling fungus that causes coccidioidomycosis, a disease also known as Valley fever, which affects humans and a variety of animal species. Recent findings of Coccidioides in new, unexpected areas of the United States have demonstrated the need for a better understanding of its geographic distribution. Large serological studies on animals could provide important information on the geographic distribution of this pathogen. To facilitate such studies, we used protein A/G, a recombinant protein that binds IgG antibodies from a variety of mammalian species, to develop an enzyme immunoassay (EIA) that detects IgG antibodies against Coccidioides in a highly sensitive and high-throughput manner. We showed the potential of this assay to be adapted to multiple animal species by testing a collection of serum and/or plasma samples from dogs, mice, and humans with or without confirmed coccidioidomycosis. We then evaluated the performance of the assay in dogs, using sera from dogs residing in a highly endemic area, and found seropositivity rates significantly higher than those in dogs of non-endemic areas. We further evaluated the specificity of the assay in dogs infected with other fungal pathogens known to cross-react with Coccidioides. Finally, we used the assay to perform a cross-sectional serosurvey investigating dogs from Washington, a state in which infection with Coccidioides has recently been documented. In summary, we have developed a Coccidioides EIA for the detection of antibodies in canines that is more sensitive and has higher throughput than currently available methods, and by testing this assay in mice and humans, we have shown a proof of principle of its adaptability for other animal species.

Background: Coccidioidomycosis is a fungal disease caused by the dimorphic saprophytic fungus Coccidioides immitis or C. posadasii. Primary pulmonary infection can disseminate to cutaneous and subcutaneous tissues, or less commonly direct cutaneous inoculation may occur., Hypothesis/objectives: To characterize the historical, clinical, diagnostic and treatment findings in dogs and cats with cutaneous manifestation of coccidioidomycosis., Animals: Twenty three dogs and seventeen cats diagnosed between 2009 and 2015 in Arizona, USA., Methods: Retrospective review of medical records from dogs and cats from an endemic area with a confirmed diagnosis via histopathology, cytology and/or culture, and skin lesions., Results: Age of affected dogs ranged from 14 weeks to 13 years (median = 7 years), whereas cats ranged from 3 to 17 years (median = 9 years). Subcutaneous nodules were the most common lesions in both species. Lesions were distributed widely and not often found over sites of bone infection. In 75% of dogs and 54.5% of cats with cutaneous lesions there were clinical signs of systemic illness, supporting the diagnosis of cutaneous disseminated disease. Four dogs and four cats had localized lesions with no systemic illness, consistent with possible primary cutaneous infection. The most common mode of diagnosis was cytology identification in both species. Fluconazole was the most commonly prescribed antifungal drug., Conclusions and Clinical Importance: Coccidioidomycosis is the most common mycosis of dogs and cats in endemic regions and cutaneous signs of the disease may be an initial presenting complaint. This study identified a variety of cutaneous manifestations of the disease in dogs and cats and should be recognized by clinicians., (© 2016 ESVD and ACVD.)

Background: We observed evidence of protein-losing nephropathy in some dogs with coccidioidomycosis, suggestive of immune complex glomerulonephritis (ICGN). The goal of this study was to understand the prevalence of renal histopathologic lesions and proteinuria in dogs with coccidioidomycosis., Hypothesis: Biochemical and histopathological evidence of glomerular lesions is present in dogs with coccidioidomycosis., Animals: Hundred and fifty-six dogs with naturally occurring coccidioidomycosis., Methods: Retrospective case series. Clinical information and results of clinicopathologic testing were retrieved from the University of California, Davis Veterinary Medical Teaching Hospital (VMTH). Microscopic sections of renal tissue procured from necropsy of dogs with coccidioidomycosis were examined to evaluate the nature and distribution of lesions., Results: A total of 156 dogs with coccidioidomycosis were identified; 87 dogs had serum biochemistry and a urinalysis performed, 17 had urine protein:creatinine ratios (UPCs), and 24 had renal tissue available for histopathology. Eleven (13%) of the 87 dogs were azotemic, 55 (63%) were proteinuric (of which 14 [25%] had clinically relevant proteinuria defined as ≥3+ or ≥500 mg/dL), and 14 dogs had UPC ≥0.5 (range, 0.5-21.5, median 4.2). Thirteen (54%) of 24 dogs had renal histopathologic lesions suggestive of ICGN. Seven of these dogs had urinalyses performed; 5 (71%) had clinically relevant proteinuria as described above. Two dogs (33%) with normal glomeruli had granulomatous nephritis, 1 of which had intralesional Coccidioides spherules., Conclusions and Clinical Importance: Coccidioidomycosis should be considered as a possible contributor to glomerular disease in dogs. Whether similar lesions occur in other mammalian hosts, including humans, warrants further investigation., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Coccidioidomycosis is a respiratory fungal infection with occasional systemic dissemination. The disseminated coccidioidomycosis is considered a multifaceted disease. In medicine, disseminated coccidioidomycosis is included within a group of infectious diseases that have been referred as the great imitators. In many cases, malignancies are included in the presumptive diagnosis. In veterinary medicine, disseminated coccidioidomycosis is common in dogs. Nonetheless, despite of being a diagnostic dilemma, disseminated coccidioidomycosis is underestimated and frequently not included into differentials, even in endemic zones. Herein, we describe three cases of granulomatous inflammation caused by Coccidioides spp. which were masquerading malignancies in dogs (0.39 %). The presumptive diagnoses in these cases were osteosarcoma, lymphoma and neurofibroma, respectively. A PCR assay employing tissues in paraffin blocks resulted positive for C. posadasii in one of these cases. A comparative discussion on the ambiguous clinic-pathological presentation of disseminated coccidioidomycosis in dogs and humans is included.

Little published information is available to guide therapy for canine and feline patients with Coccidioides infections involving the central nervous system (CNS). The purpose of this cross-sectional retrospective study was to describe magnetic resonance imaging (MRI) features and outcome for a group of dogs and cats with solitary CNS Coccidiodes granulomas. Nine canine and two feline cases met inclusion criteria; four diagnosed and treated with surgery and fluconazole and seven diagnosed by serology or cytology and treated medically. Three cases had left Coccidioides endemic areas long before developing neurological disease. The MRI lesions shared many features with neoplastic masses. The extra-axial granulomas often had a lack of a distinct border between the mass and neural parenchyma. Four cases were extra-axial and seven were intra-axial, but distinguishing between extra-axial and intra-axial locations was sometimes challenging. The surgical cases had good outcomes and histology allowed definitive diagnosis. Medically managed patients also had generally good outcomes, with resolution of clinical signs in most cases. Findings indicated that distinction between neoplasia and focal Coccidioides granulomas based on MRI features is likely to be imprecise. Demonstration of the organism by cytology or histology is required for definitive diagnosis. The role of surgery for improving the outcome of brain or spinal coccidioidomycosis granulomas warrants further study., (© 2015 American College of Veterinary Radiology.)