Search

Endemic mycoses represent a growing public health challenge in North America. We describe the epidemiology of 1,392 microbiology laboratory-confirmed cases of blastomycosis, histoplasmosis, and coccidioidomycosis in Ontario during 1990-2015. Blastomycosis was the most common infection (1,092 cases; incidence of 0.41 cases/100,000 population), followed by histoplasmosis (211 cases) and coccidioidomycosis (89 cases). Incidence of blastomycosis increased from 1995 to 2001 and has remained elevated, especially in the northwest region, incorporating several localized hotspots where disease incidence (10.9 cases/100,000 population) is 12.6 times greater than in any other region of the province. This retrospective study substantially increases the number of known endemic fungal infections reported in Canada, confirms Ontario as an important region of endemicity for blastomycosis and histoplasmosis, and provides an epidemiologic baseline for future disease surveillance. Clinicians should include blastomycosis and histoplasmosis in the differential diagnosis of antibiotic-refractory pneumonia in patients traveling to or residing in Ontario.

Dimorphic fungi cause several endemic mycoses which range from subclinical respiratory infections to life-threatening systemic disease. Pathogenic-phase cells of Histoplasma, Blastomyces, Paracoccidioides and Coccidioides escape elimination by the innate immune response with control ultimately requiring activation of cell-mediated immunity. Clinical management of disease relies primarily on antifungal compounds; however, dimorphic fungal pathogens create a number of challenges for antifungal drug therapy. In addition to the drug toxicity issues known for current antifungals, barriers to efficient drug treatment of dimorphic fungal infections include natural resistance to the echinocandins, residence of fungal cells within immune cells, the requirement for systemic delivery of drugs, prolonged treatment times, potential for latent infections, and lack of optimized standardized methodology for in vitro testing of drug susceptibilities. This review will highlight recent advances, current therapeutic options, and new compounds on the horizon for treating infections by dimorphic fungal pathogens.

Overview: Rare fungal infections, including those hitherto not reported in Europe, may occur sporadically in non-endemic areas, or imported cases may be seen., Infections: Blastomycosis is mainly seen in North America; no cases have been reported in Europe. Histoplasmosis, which is endemic in the eastern US, Central and South America, has been diagnosed in Japan and Europe. Coccidioidomycosis is endemic in the southwestern US, Central and South America; only one imported case has been reported in Europe. The primary mode of transmission is inhalation of conidia or spores from the environment., Disease Signs: Most feline cases present with a combination of clinical signs (mainly respiratory, along with skin, eye, central nervous system and bone). Lymphadenopathy and systemic signs may be present., Diagnosis: Diagnosis is based on fungal detection by cytology and/or histology. Commercial laboratories do not routinely perform fungal culture. Diagnosis of coccidioidomycosis, which is more difficult, may be supported by antibody detection., Treatment: Treatment consists of prolonged systemic antifungal therapy, with itraconazole as the first-choice agent for histoplasmosis and blastomycosis. The prognosis is good if owner compliance is adequate and adverse drug effects do not occur., Prevention: Cat owners travelling to endemic areas should be warned about these diseases. There is no zoonotic risk.

Aim: 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., (© 2011 John Wiley & Sons A/S.)

Blastomyces dermatitidis and Histoplasma capsulatum are dimorphic fungi that often cause self-limited respiratory infections. However, they may also cause severe disseminated disease, depending on the level of the exposure to the organism and the host immune status. In addition, patients with infections caused by these fungi may have very similar clinical presentations. Although microbiologic culture is a standard method for detecting these pathogens, their recovery may require days to weeks, and the manipulation of cultures presents a significant safety hazard to laboratory personnel. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect and differentiate B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens. Primers and fluorescence resonance energy transfer hybridization probes were designed to target the histidine kinase and glyceraldehyde-3-phosphate dehydrogenase genes of B. dermatitidis and H. capsulatum, respectively. The analytical sensitivity of the assay was determined to be 100 copies/μl for both fungi. From culture isolates, the assay demonstrated 100% specificity and 100% sensitivity for B. dermatitidis and 100% specificity and 94% sensitivity for H. capsulatum. Detection directly from 797 clinical specimens demonstrated specificities and sensitivities of 99% and 86% for B. dermatitidis and 100% and 73% for H. capsulatum compared with the results for culture. This real-time PCR assay provides a rapid method for the detection of B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens.

Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. This review gives a brief background of human diseases associated with these organisms and describes the development, details, and utility of murine models of blastomycosis, as well as coccidioidomycosis and histoplasmosis.

In 60% of the infections caused by Blastomyces dermatitidis and in 47% of the infections caused by Histoplasma capsulatum, some of the organisms are acid-fast in tissue sections. Treatment with 1N hydrochloric acid at 60 degrees C abolishes the acid-fastness of H capsulatum, which indicates that the acid-fastness may be related to mycolic acid. Organisms of B dermatitidis, however, remain acid-fast in 83% of the sections treated with acid. The presence of acid-fastness in small cells can aid in the differentiation of B dermatitidis and H capsulatum from Cryptococcus neoformans and Candida albicans, Persistent acid-fastness of organisms after treatment with heated acid helps identify B dermatitidis in tissue sections, especially when the strain is small or in other ways atypical.