ABSTRACT
OBJECTIVE: To evaluate temporal changes in serum C-reactive protein (CRP) and haptoglobin (Hp) concentrations in dogs with pulmonary coccidioidomycosis and assess their utility to detect remission. METHODS: 31 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021 were included in a retrospective cohort study that utilized archived serum. Serum was originally obtained at diagnosis and once every 3 months after antifungal administration until either remission or 12 months. Time points were designated as baseline (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). Serum CRP and Hp were measured at a reference laboratory with ELISA assays. RESULTS: Median serum CRP and Hp concentrations decreased from T0 (CRP, 56 mg/L; Hp, 716.1 mg/dL) to T1 (CRP, 3.3 mg/L; Hp, 240.5 mg/dL); subsequent decreases were not significant. Eighteen (60%) and 16 (53%) of 30 dogs had normal serum CRP and Hp concentrations at T1, respectively. Absolute serum CRP (AUC, 0.58; 95% CI, 0.45 to 0.72) and Hp (AUC, 0.65; 95% CI, 0.52 to 0.78) were poor detectors of remission. However, the percentage change in Hp from T0 to T1 (AUC, 0.90; 95% CI, 0.74 to 1.0) was an excellent predictor of remission within 12 months. CONCLUSIONS: Serum CRP and Hp concentrations decrease in the first 3 months of antifungal treatment in dogs with pulmonary coccidioidomycosis, and the percentage change of Hp may help predict dogs that will achieve remission within 12 months of treatment. CLINICAL RELEVANCE: Serum CRP and Hp may be useful adjunctive biomarkers to monitor treatment response in dogs with pulmonary coccidioidomycosis.
Subject(s)
Antifungal Agents , C-Reactive Protein , Coccidioidomycosis , Dog Diseases , Haptoglobins , Lung Diseases, Fungal , Animals , Dogs , Dog Diseases/drug therapy , Dog Diseases/blood , Coccidioidomycosis/veterinary , Coccidioidomycosis/drug therapy , Coccidioidomycosis/blood , Haptoglobins/analysis , Haptoglobins/metabolism , C-Reactive Protein/analysis , Retrospective Studies , Male , Female , Antifungal Agents/therapeutic use , Lung Diseases, Fungal/veterinary , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/blood , Cohort Studies , Biomarkers/bloodABSTRACT
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 sona 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 sona 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 (sona) 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 sona 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.
Subject(s)
Antibodies, Fungal , Coccidioides , Coccidioidomycosis , Dog Diseases , Immunodiffusion , Animals , Dogs , Dog Diseases/immunology , Dog Diseases/microbiology , Dog Diseases/diagnosis , Coccidioidomycosis/veterinary , Coccidioidomycosis/diagnosis , Coccidioidomycosis/immunology , Antibodies, Fungal/blood , Antibodies, Fungal/immunology , Immunodiffusion/veterinary , Immunodiffusion/methods , Coccidioides/immunology , Sensitivity and Specificity , Point-of-Care Systems , Immunoglobulin G/blood , Immunoglobulin G/immunologyABSTRACT
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 RecipientsABSTRACT
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).
Subject(s)
Cat Diseases , Coccidioidomycosis , Invasive Fungal Infections , Cats , Animals , Antifungal Agents/therapeutic use , Invasive Fungal Infections/veterinary , Itraconazole , Terbinafine , Coccidioidomycosis/veterinary , Cat Diseases/drug therapyABSTRACT
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.
Subject(s)
Cat Diseases , Coccidioidomycosis , Dermatomycoses , Histoplasmosis , Invasive Fungal Infections , Cats , Animals , Invasive Fungal Infections/veterinary , Antifungal Agents/therapeutic use , Coccidioidomycosis/veterinary , Dermatomycoses/veterinary , Histoplasmosis/veterinary , Cat Diseases/diagnosis , Cat Diseases/drug therapyABSTRACT
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.
Subject(s)
Coccidioidomycosis , Otters , Animals , Coccidioidomycosis/veterinary , Otters/microbiology , Polymerase Chain Reaction/veterinary , Hematologic Tests/veterinary , California/epidemiologyABSTRACT
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/veterinaryABSTRACT
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 StatesABSTRACT
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 GABSTRACT
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 , CoccidioidesABSTRACT
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/veterinaryABSTRACT
OBJECTIVE: To determine associations between antibody serologic tests and tracheobronchial lymphadenopathy (TBL) in dogs with pulmonary coccidioidomycosis and identify variables associated with time to resolution of TBL. ANIMALS: 32 client owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. METHODS: Prospective cohort study. Thoracic radiographs and anti-Coccidioides spp antibody serology were performed at baseline and once every 3 months until remission or for a maximum of 12 months. Radiographic tracheobronchial lymph node height, length, and area were measured and recorded as ratios via comparison with the length of the T4 vertebral body (LT4) and length of the manubrium. Severity of TBL was also subjectively categorized as mild, moderate, or severe. RESULTS: Tracheobronchial lymphadenopathy was identified in 81% (26/32; 95% CI, 64% to 93%) of dogs. There was no relevant association between TBL presence or severity and antibody serology results. Tracheobronchial lymphadenopathy resolved in 72% (n = 18) of dogs at the 3-month evaluation. The median time to resolution of TBL after initiation of fluconazole was 96 days (range, 72 to 386 days). Univariate analysis identified increasing TBL severity (hazard ratio, 0.40; 95% CI, 0.19 to 0.84; P = .02) and length:LT4 ratio (hazard ratio, 0.41; 95% CI, 0.20 to 0.82; P = .01) as variables associated with reduced probability of resolution of TBL. CLINICAL RELEVANCE: Antibody serologic test results are not clinically useful to predict TBL presence or severity in dogs with pulmonary coccidioidomycosis, and larger tracheobronchial lymph nodes are more likely to take longer to resolve. Resolution of TBL occurs in most dogs within 3 to 6 months after fluconazole administration.
Subject(s)
Coccidioidomycosis , Dog Diseases , Lymphadenopathy , Humans , Dogs , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Fluconazole/therapeutic use , Prospective Studies , Coccidioides , Lymphadenopathy/veterinary , Dog Diseases/pathologyABSTRACT
BACKGROUND: 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.
Subject(s)
Coccidioidomycosis , Humans , Dogs , Animals , Coccidioidomycosis/veterinary , Coccidioidomycosis/pathology , Prospective Studies , Vitamin D , C-Reactive Protein/analysis , Immunoglobulin GABSTRACT
A 7-year-old, male neutered, Miniature Australian Shepherd from Arizona was presented for evaluation of a 3-month history of progressive cough. Thoracic radiographs revealed a focal alveolar pulmonary pattern and suspected tracheobronchial lymph node enlargement. Serum anti-Coccidioides spp. IgM/IgG antibodies were not detected by agar gel immunodiffusion performed by 2 different reference commercial veterinary laboratories approximately 3.5 and 3.75 months after respiratory tract signs were first noted. The dog failed to respond to empiric therapy with a cough suppressant and various antibiotics. Tracheobronchoscopy and bronchoalveolar lavage (BAL) were subsequently performed and cytological examination of the BAL fluid identified marked neutrophilic inflammation characterized by mildly degenerate neutrophils and no infectious organisms. Bacterial cultures were negative but fungal cultures revealed growth of Coccidioides spp. Clinical signs improved shortly after initiation of fluconazole administration and the dog achieved long-term sustained clinical remission. Here, we provide a description of a dog with pulmonary coccidioidomycosis diagnosed with fungal culture of BAL fluid. Airway sampling with cytological examination and fungal culture should be considered in dogs with persistent respiratory related clinical signs, negative antibody serology, and that have lived in or traveled to endemic areas.
Subject(s)
Coccidioidomycosis , Dogs , Male , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Coccidioidomycosis/veterinary , Australia , Coccidioides , Inflammation/veterinary , Immunoglobulin M/therapeutic use , Bronchoalveolar Lavage/veterinaryABSTRACT
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 , RadiographyABSTRACT
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.
Subject(s)
Coccidioidomycosis , Horse Diseases , Horses , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/epidemiology , Coccidioidomycosis/veterinary , Lung/pathology , Granuloma/veterinary , California/epidemiology , Horse Diseases/pathologyABSTRACT
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.
Subject(s)
Coccidioidomycosis , Dog Diseases , Dogs , Animals , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Fluconazole/therapeutic use , Retrospective Studies , Lethargy/veterinary , Dog Diseases/diagnosisABSTRACT
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.
Subject(s)
Coccidioidomycosis , Dog Diseases , Animals , Central Nervous System , Coccidioides , Coccidioidomycosis/diagnosis , Coccidioidomycosis/veterinary , Dog Diseases/diagnosis , Dogs , Prospective Studies , Retrospective StudiesABSTRACT
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.
Subject(s)
Coccidioidomycosis , Fungal Vaccines , Animals , Coccidioidomycosis/prevention & control , Coccidioidomycosis/veterinary , Dogs , Lung , Spores, Fungal , Vaccination , Vaccines, AttenuatedABSTRACT
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.