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1.
Med Mycol ; 62(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38061838

ABSTRACT

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.


There are several diagnostic methodologies available in coccidioidomycosis. Direct comparisons of these methods are limited. Prior studies have not compared quantitative immunodiffusion to complement fixation testing. Our results show these tests are highly concordant.


Subject(s)
Coccidioides , Coccidioidomycosis , Animals , Complement Fixation Tests/veterinary , Antibodies, Fungal , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Immunodiffusion/veterinary
2.
Med Mycol ; 62(3)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38425102

ABSTRACT

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.


Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.


Subject(s)
Coccidioidomycosis , Kidney Transplantation , Humans , Fluconazole/adverse effects , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Antifungal Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/veterinary , Retrospective Studies , Transplant Recipients
3.
Med Mycol ; 62(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38148116

ABSTRACT

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.


Subject(s)
Coccidioidomycosis , Dog Diseases , Animals , Dogs , Coccidioides , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Coccidioidomycosis/microbiology , Dog Diseases/epidemiology , Dog Diseases/microbiology , Models, Animal , Southwestern United States
4.
Med Mycol ; 61(11)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37863836

ABSTRACT

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.


Cutaneous Coccidioidomycosis (CC) is defined as a fungal infection of the skin and/or subcutaneous tissues caused by the Coccidioides fungus. CC has been classified into primary CC which is caused by direct inoculation of the fungal organism into the skin, reactive CC defined as delayed hypersensitivity reaction, and disseminated CC which involves multiple organs infection. CC infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. Untreated CC can lead to worsening of local infection and the risk of dissemination to other organs. Coccidioidomycosis may be incorrectly diagnosed, and patients are more likely to receive unnecessary antibacterial drugs, laboratory tests, imaging, and invasive procedures, all of which could contribute to unnecessary costs and additional adverse health consequences. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8­16 weeks) in our study with 75% cases initially misdiagnosed. There is a need for collaboration between doctors and researchers across multiple counties within the Central Valley of California to develop strategies for diagnosing and treating CC and raising awareness in the community about the elevated risk of this infection for prevention and early detection.


Subject(s)
Coccidioidomycosis , Male , Humans , Female , Adult , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Delayed Diagnosis/veterinary , Cellulitis/veterinary , Retrospective Studies , California/epidemiology , Coccidioides
5.
Med Mycol ; 61(10)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37804176

ABSTRACT

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 role of antifungal susceptibility in the management of coccidioidomycosis remains unknown. This report presents cases of complex coccidioidomycosis where clinicians elected to conduct antifungal susceptibility testing as part of the treatment approach.


Subject(s)
Antifungal Agents , Coccidioidomycosis , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Coccidioides , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary
6.
Med Mycol ; 61(11)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37935009

ABSTRACT

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.


This study aimed to determine the prevalence of exposure to coccidioidomycosis, the cause of Valley Fever in both humans and animals, among military working dogs (MWDs)located in endemic regions of the United States. The data will be used to guide efforts to study MWDs as sentinels for human disease.


Subject(s)
Coccidioides , Coccidioidomycosis , United States/epidemiology , Humans , Animals , Dogs , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Coccidioidomycosis/microbiology , Working Dogs , Arizona/epidemiology , Immunoglobulin G
7.
Med Mycol ; 60(10)2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36166843

ABSTRACT

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.


Coccidioidomycosis (CM), also known as San Joaquin Valley Fever, causes a variety of symptoms including pneumonia. This historical study investigates CM of the lungs in American soldiers with CM in the 1950s, prior to modern antifungals, to better understand the natural history.


Subject(s)
Coccidioidomycosis , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Antifungal Agents/therapeutic use , Retrospective Studies , Radiography
8.
Med Mycol ; 58(3): 328-332, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31212311

ABSTRACT

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 sona 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 sona 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 sona 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.


Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Immunoenzyme Techniques , Point-of-Care Systems , Animals , Antibodies, Fungal/blood , Chromatography, Affinity , Coccidioides , Coccidioidomycosis/diagnosis , Dog Diseases/microbiology , Dogs , Immunoglobulin G/blood , Immunoglobulin M/blood
9.
Emerg Infect Dis ; 25(1): 123-125, 2019 01.
Article in English | MEDLINE | ID: mdl-30561305

ABSTRACT

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.


Subject(s)
Coccidioides/physiology , Coccidioidomycosis/veterinary , Dog Diseases/transmission , Horse Diseases/transmission , Animals , Coccidioides/isolation & purification , Coccidioidomycosis/diagnosis , Coccidioidomycosis/microbiology , Coccidioidomycosis/transmission , Dog Diseases/diagnosis , Dog Diseases/microbiology , Dogs , Female , Horse Diseases/diagnosis , Horse Diseases/microbiology , Horses , Humans , Male , Washington
10.
Med Mycol ; 57(Supplement_1): S16-S20, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30690603

ABSTRACT

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.


Subject(s)
Coccidioides/growth & development , Coccidioides/physiology , Coccidioidomycosis/veterinary , Disease Reservoirs/microbiology , Mammals/microbiology , Animals , Coccidioides/genetics , Ecology , Genome, Fungal , Granuloma/microbiology , Humans , Hyphae/physiology , Mice , Phylogeny , Spores, Fungal
11.
Med Mycol ; 57(7): 800-806, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-30649403

ABSTRACT

The diagnosis of coccidioidomycosis (CM) in dogs is typically based on clinical presentation, serology, and (less frequently) spherule identification. Agar gel immunodiffusion (AGID) is the most commonly employed serological method, but AGID is slow (requiring up to a week for titer). A Coccidioides antigen enzyme immunoassay (EIA) is also available; however, sensitivity is low in CM dogs. An antibody EIA was developed to detect canine immunoglobulin G (IgG) reacting to Coccidioides antigens. Serum was evaluated from dogs with pathology proven CM and/or AGID positive CM, as well as dogs with histoplasmosis, blastomycosis, non-fungal infections, or healthy dogs. A standard curve was used to convert optical density (OD) values into EIA units (EU). Serum and urine samples from CM dogs were also tested in the antigen EIA. Sensitivity and specificity for IgG were 89.2% and 97.2%, respectively, upon evaluation of dogs with proven or probable CM and control dogs. Cross-reactivity was observed in 7.7% and in 6.4% of dogs with histoplasmosis or blastomycosis, respectively. The antigen EIA alone was insensitive (33.8%). Combined IgG and antigen testing increased sensitivity to 93.2%, as three dogs were IgG-negative but had detectable serum or urine antigen. In 22 dogs with proven CM, sensitivity was statistically similar for antibody EIA and AGID (86% and 73%; P = .487). The MiraVista® canine Coccidioides antibody IgG EIA may aid in the diagnosis of CM by improving turnaround time with comparable sensitivity to AGID. Serial or concurrent testing by antibody and antigen EIAs may be beneficial when screening dogs for CM.


Subject(s)
Antibodies, Fungal/blood , Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Immunoenzyme Techniques/methods , Immunoglobulin G/blood , Animals , Antigens, Fungal/immunology , Blastomycosis , Coccidioides/immunology , Coccidioidomycosis/diagnosis , Cross Reactions , Dog Diseases/immunology , Dog Diseases/microbiology , Dogs , Histoplasmosis , Immunoglobulin M , Sensitivity and Specificity
12.
Med Mycol ; 57(Supplement_1): S67-S75, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30690600

ABSTRACT

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.


Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/microbiology , Dogs/microbiology , Meningoencephalitis/drug therapy , Animals , Anticonvulsants/therapeutic use , Antifungal Agents/economics , Antifungal Agents/therapeutic use , Brain/diagnostic imaging , Coccidioides/drug effects , Coccidioidomycosis/drug therapy , Cough , Dog Diseases/drug therapy , Female , Fever , Glucocorticoids/therapeutic use , Magnetic Resonance Imaging , Male , Meningoencephalitis/diagnosis , Meningoencephalitis/microbiology , Seizures
13.
J Am Anim Hosp Assoc ; 55(5): 238-242, 2019.
Article in English | MEDLINE | ID: mdl-31433229

ABSTRACT

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.


Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Serologic Tests/veterinary , Animals , Coccidioidomycosis/blood , Coccidioidomycosis/diagnosis , Coccidioidomycosis/pathology , Dog Diseases/blood , Dogs , Female , Male , Sensitivity and Specificity
14.
Vet Radiol Ultrasound ; 60(1): 47-55, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30260537

ABSTRACT

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.


Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Magnetic Resonance Imaging/veterinary , Skull/diagnostic imaging , Animals , Arizona , Coccidioides/isolation & purification , Coccidioidomycosis/diagnosis , Coccidioidomycosis/diagnostic imaging , Coccidioidomycosis/microbiology , Dog Diseases/diagnostic imaging , Dog Diseases/microbiology , Dogs , Female , Male , Retrospective Studies , Skull/microbiology
15.
Vet Pathol ; 55(6): 905-915, 2018 11.
Article in English | MEDLINE | ID: mdl-30071801

ABSTRACT

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.


Subject(s)
Coccidioidomycosis/veterinary , Primate Diseases/pathology , Animals , Coccidioidomycosis/microbiology , Coccidioidomycosis/pathology , Female , Lung/pathology , Macaca/microbiology , Male , Microscopy, Electron/veterinary , Pan troglodytes/microbiology , Papio/microbiology , Polymerase Chain Reaction/veterinary , Primate Diseases/microbiology
16.
Article in English | MEDLINE | ID: mdl-28289027

ABSTRACT

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.


Subject(s)
14-alpha Demethylase Inhibitors/therapeutic use , Antifungal Agents/therapeutic use , Coccidioides/drug effects , Coccidioidomycosis/drug therapy , Coccidioidomycosis/veterinary , Dog Diseases/drug therapy , Pyridines/therapeutic use , Tetrazoles/therapeutic use , Animals , Antifungal Agents/pharmacokinetics , Coccidioidomycosis/microbiology , Disease Models, Animal , Dog Diseases/microbiology , Dogs , Female , Male , Pyridines/pharmacokinetics , Sterol 14-Demethylase/metabolism , Tetrazoles/pharmacokinetics
17.
Mycopathologia ; 181(1-2): 151-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26419685

ABSTRACT

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.


Subject(s)
Biopsy , Coccidioides/isolation & purification , Coccidioidomycosis/veterinary , Neoplasms/veterinary , Animals , Coccidioides/genetics , Coccidioidomycosis/diagnosis , Coccidioidomycosis/pathology , Diagnosis, Differential , Dogs , Neoplasms/diagnosis , Neoplasms/pathology , Pathology, Molecular , Polymerase Chain Reaction
18.
Vet Dermatol ; 27(5): 346-e87, 2016 10.
Article in English | MEDLINE | ID: mdl-27397725

ABSTRACT

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.


Subject(s)
Antifungal Agents/pharmacology , Cat Diseases/microbiology , Coccidioidomycosis/veterinary , Dog Diseases/microbiology , Animals , Arizona/epidemiology , Cat Diseases/drug therapy , Cat Diseases/pathology , Cats , Coccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Coccidioidomycosis/pathology , Dog Diseases/drug therapy , Dog Diseases/pathology , Dogs , Female , Male , Retrospective Studies
19.
Vet Radiol Ultrasound ; 56(5): 520-30, 2015.
Article in English | MEDLINE | ID: mdl-25857572

ABSTRACT

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.


Subject(s)
Cat Diseases/pathology , Central Nervous System Infections/veterinary , Coccidioidomycosis/veterinary , Dog Diseases/pathology , Granuloma/veterinary , Magnetic Resonance Imaging/veterinary , Animals , Cat Diseases/microbiology , Cat Diseases/therapy , Cats , Central Nervous System Infections/microbiology , Central Nervous System Infections/pathology , Central Nervous System Infections/therapy , Coccidioides/physiology , Coccidioidomycosis/microbiology , Coccidioidomycosis/pathology , Coccidioidomycosis/therapy , Cross-Sectional Studies , Dog Diseases/microbiology , Dog Diseases/therapy , Dogs , Female , Granuloma/microbiology , Granuloma/pathology , Granuloma/therapy , Male , Retrospective Studies
20.
Med Mycol ; 52(2): 156-66, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24577001

ABSTRACT

Coccidioidomycosis (CM) is a mycotic disease that affects mammals, including humans. Official data relative to CM in Mexico has not been collected since 1995, thus its prevalence remains unknown. The objectives of this study were to identify the predominant Coccidioides species in Mexico, infer their current geographical distribution and explore the correlation between species and clinical presentation. We collected 154 strains, which were cultured, inactivated, and processed for DNA extraction. Nine microsatellite loci, the Ag2/PRA gene and Umeyama Region were amplified from each isolate. To infer the current geographical distribution of Coccidioides spp. and to establish a correlation between genotype and clinical presentation, we evaluated genetic population structure under the following grouping criteria: putative origin and clinical presentation records. Microsatellite analysis showed that 82% of the isolates corresponded to C. posadasii and 18% were C. immitis. The species identification results obtained using Umeyama region, Ag2/PRA, and microsatellites of five of the isolates were inconsistent with the data collected for the remaining isolates. C. posadasii strains were found primarily in the northeastern region and C. immitis in the northwestern region. However, there was no relationship between clinical presentation and Coccidioides species. The molecular markers used in this study proved to have a high power of resolution to identify the Coccidioides species recovered in culture. While we found C. posadasii to be the most abundant species in Mexico, more detailed clinical records are needed in order to obtain more accurate information about the infections in specific geographical locations.


Subject(s)
Coccidioides/classification , Coccidioides/genetics , Coccidioidomycosis/epidemiology , Coccidioidomycosis/microbiology , Endemic Diseases , Animals , Coccidioides/isolation & purification , Coccidioidomycosis/pathology , Coccidioidomycosis/veterinary , DNA, Fungal/genetics , Dog Diseases/microbiology , Dogs , Environmental Microbiology , Genotype , Humans , Mexico/epidemiology , Microsatellite Repeats , Molecular Typing , Mycological Typing Techniques , Phylogeography , Topography, Medical
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