Background: With the limited options available for therapy to treat invasive fungal infections (IFI), radioimmunotherapy (RIT) can potentially offer an effective alternative treatment. Microorganism-specific monoclonal antibodies have shown promising results in the experimental treatment of fungal, bacterial, and viral infections, including our recent and encouraging results from treating mice infected with Blastomyces dermatitidis with 213Bi-labeled antibody 400-2 to (1→3)-β-glucan. In this work, we performed a safety study of 213Bi-400-2 antibody in healthy dogs as a prelude for a clinical trial in companion dogs with acquired invasive fungal infections and later on in human patients with IFI. Methods: Three female beagle dogs (≈6.1 kg body weight) were treated intravenously with 155.3, 142.5, or 133.2 MBq of 213Bi-400-2 given as three subfractions over an 8 h period. RBC, WBC, platelet, and blood serum biochemistry parameters were measured periodically for 6 months post injection. Results: No significant acute or long-term side effects were observed after RIT injections; only a few parameters were mildly and transiently outside reference change value limits, and a transient atypical morphology was observed in the circulating lymphocyte population of two dogs. Conclusions: These results demonstrate the safety of systemic 213Bi-400-2 administration in dogs and provide encouragement to pursue evaluation of RIT of IFI in companion dogs.

BACKGROUND: To better understand clinical and epidemiologic patterns of blastomycosis, we report on a large series of blastomycosis in Indiana.
METHODS: All microbiologically and histopathologically confirmed cases of blastomycosis from four hospitals serving Central Indiana from 1985 to 2014 were identified. Available data were collected. Data on population estimates, annual precipitation, and construction in Indiana were evaluated for correlations with incidence rates of blastomycosis.
RESULTS: A total of 114 patients were identified. The mean age was 44.4 years; 27% had diabetes mellitus, and 16% were immunosuppressed. Most presented with pneumonia (90%); 48% had extrapulmonary disease (CNS involvement in 9%), and 15% developed ARDS. Cultures, cytopathology, and histopathology were positive in 86%, 27%, and 85% of the sample, respectively, and fungal antigen was positive in 76%. Amphotericin B was administered in 49%, and 87% received an azole. Total mortality was 12%. Immunosuppression (OR = 3.0), diabetes mellitus (OR = 2.9), and multilobar pneumonia (OR = 2.9) were associated with increased likelihood of ICU admission. There was a significant increase in incidence over time in Marion County. There was no correlation with amount of precipitation, but the rise in incidence coincided with a 2005 state initiative to expand Indiana\'s highway infrastructure.
CONCLUSIONS: The incidence of blastomycosis in Central Indiana may be on the rise. Physicians in endemic areas should be aware of the potentially fulminant consequences of the disease.

OBJECTIVE: Blastomycosis osteomyelitis is a well-known but infrequently encountered complication of infection with the dimorphic mold, Blastomyces dermatitidis. Oftentimes, the diagnosis is unsuspected, resulting in a delay in making the diagnosis. The role of intraoperative consultation in making a rapid diagnosis has not been discussed previously.
METHODS: Retrospective chart review of clinicopathologic information was conducted from all cases of blastomycosis osteomyelitis and arthritis diagnosed at Rush University Medical Center between 2000 and 2010.
RESULTS: Fourteen cases of blastomycosis osteomyelitis and/or arthritis were identified, 12 of which clinically and radiologically presented as a bone tumor. The disease most commonly affected the lower extremities, particularly around the knee joint. Septic arthritis generally occurred secondary to osteomyelitis of the adjacent bone. Frozen section was performed in 10 cases, all of which were correctly diagnosed as granulomatous osteomyelitis. Two cases were culture negative, one of which showed many budding yeast forms typical of B dermatitidis on histology.
CONCLUSIONS: Blastomycosis osteomyelitis should be considered in the differential diagnosis of bone tumor, particularly when there is history of residence or travel in endemic areas. This disease can be correctly identified at frozen section, thus offering rapid diagnosis. There is an excellent correlation between morphologic and microbiologic studies.

OBJECTIVE: A review of the clinical presentation, diagnosis, treatment and outcomes of 30 solid organ transplant recipients (SOTRs) with histoplasmosis or blastomycosis from 3 Midwestern academic medical centers.
BACKGROUND: The endemic fungal pathogens, Histoplasma capsulatum and Blastomyces dermatitidis, may cause severe infection in SOTRs. In this report, we describe the clinical presentation, diagnosis, treatment, and outcomes of these endemic fungal infections (EFIs) among SOTRs at 3 academic transplant centers.
METHODS: A retrospective review was conducted of SOTRs with histoplasmosis or blastomycosis from 3 Midwestern medical centers in the United States. Data collected included demographics, immunosuppression, clinical presentation, method of diagnosis, antifungal treatment, response to therapy, and patient and graft survival.
RESULTS: Between 1996 and 2008, 30 transplant recipients with histoplasmosis or blastomycosis were identified, giving a cumulative incidence of infection of 0.50% (30/5989); 73% of the study patients were renal transplant recipients, and the median time to disease onset after transplantation was 10.5 months. The lungs were the most common site of infection (83%), and 60% had disseminated disease. Urine antigen testing was positive in all patients in whom it was performed (23/23). Initial antifungal therapy consisted of amphotericin B in 70%, and 87% received azoles, typically itraconazole (83%). Two patients developed relapsed infection and 7 patients had graft failure after EFI. Overall mortality was 30%, with an attributable mortality of 13%.
CONCLUSIONS: As in several previous single-center studies, the incidence of post-transplant histoplasmosis and blastomycosis was <1%, but often resulted in disseminated infection. In this cohort, EFI was associated with a high rate of allograft loss and overall mortality.

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A 17-year-old male presented to a local hospital with symptoms of pneumonia and a hacking cough productive of yellow sputum. Direct examination of a bronchial lavage sample revealed organisms morphologically consistent with Blastomyces dermatitidis, which was confirmed by culture. The patient was placed on intravenous antifungal therapy and his condition improved dramatically.
OBJECTIVE: to describe the gross and microscopic morphologies of both yeast and mold forms of B. dermatitidis; to identify B. dermatitidis given patient history, and microscopic and colony morphology; to describe the symptoms of primary pulmonary infections caused by B. dermatitidis, and to name additional tissues typically affected by the systemic pathogen.

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Fungal pathogens have emerged as a public health menace owing to the expanding population of vulnerable patients and a heightened exposure to fungi in our environment, particularly for the systemic dimorphic fungi that inhabit soil worldwide. A better understanding of these invaders and their pathogenic mechanisms is badly needed to further research into therapeutic options. Advances in the molecular tools available for genetic manipulation of Blastomyces dermatitidis have enhanced our ability to study this poorly understood dimorphic fungal pathogen. Recent refinements in gene-transfer techniques, new selection markers, reliable reporter fusions and successes in gene targeting have shed light upon the importance of the mycelium-to-yeast transition and the crucial and complex role the BAD1 adhesin plays in pathogenesis.