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Journal of Fungi (Basel, Switzerland) Jan 2023Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. is the species responsible for most infections in North America and is... (Review)
Review
Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.
PubMed: 36675937
DOI: 10.3390/jof9010117 -
PloS One 2016Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their...
Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their natural habitat is in the environment, little is known about their specific ecologic niche(s). Here, we analyzed 25 microsatellite loci from 169 strains collected from various regions throughout their known endemic range in North America, representing the largest and most geographically diverse collection of isolates studied to date. Genetic analysis of multilocus microsatellite data divided the strains into four populations of B. dermatitidis and four populations of B. gilchristii. B. dermatitidis isolates were recovered from areas throughout North America, while the B. gilchristii strains were restricted to Canada and some northern US states. Furthermore, the populations of both species were associated with major freshwater drainage basins. The four B. dermatitidis populations were partitioned among (1) the Nelson River drainage basin, (2) the St. Lawrence River and northeast Atlantic Ocean Seaboard drainage basins, (3) the Mississippi River System drainage basin, and (4) the Gulf of Mexico Seaboard and southeast Atlantic Ocean Seaboard drainage basins. A similar partitioning of the B. gilchristii populations was observed among the more northerly drainage basins only. These associations suggest that the ecologic niche where the sexual reproduction, growth, and dispersal of B. dermatitidis and B. gilchristii occur is intimately linked to freshwater systems. For most populations, sexual reproduction was rare enough to produce significant linkage disequilibrium among loci but frequent enough that mating-type idiomorphic ratios were not skewed from 1:1. Furthermore, the evolutionary divergence of B. dermatitidis and B. gilchristii was estimated at 1.9 MYA during the Pleistocene epoch. We suggest that repeated glaciations during the Pleistocene period and resulting biotic refugia may have provided the impetus for speciation as theorized for other species associated with temperate freshwater systems.
Topics: Aquatic Organisms; Blastomyces; Blastomycosis; Canada; DNA, Fungal; Ecosystem; Genetic Loci; Genetic Speciation; Genetic Variation; Humans; Lakes; Linkage Disequilibrium; Microsatellite Repeats; Multilocus Sequence Typing; Phylogeny; Phylogeography; Rivers; United States
PubMed: 27428521
DOI: 10.1371/journal.pone.0159396 -
The New England Journal of Medicine Feb 2017
Topics: Adult; Blastomyces; Blastomycosis; Fingers; Hemoptysis; Humans; Lung; Male; Osteomyelitis; Sputum; Tomography, X-Ray Computed
PubMed: 28177861
DOI: 10.1056/NEJMicm1606811 -
Applied and Environmental Microbiology Mar 2021Outbreaks of blastomycosis, caused by the fungus , occur in endemic areas of the United States and Canada but the geographic range of blastomycosis is expanding....
Outbreaks of blastomycosis, caused by the fungus , occur in endemic areas of the United States and Canada but the geographic range of blastomycosis is expanding. Previous studies inferred the location of through epidemiologic data associated with outbreaks because culture of from the environment is often unsuccessful. In this study, we used a culture-independent, PCR-based method to identify DNA in environmental samples using the BAD1 promoter region. We tested 250 environmental samples collected in Minnesota, either associated with blastomycosis outbreaks or environmental samples collected from high- and low-endemic regions to determine basal prevalence of in the environment. We identified a fifth BAD1 promoter haplotype of prevalent in Minnesota. Ecological niche analysis identified latitude, longitude, elevation, and site classification as environmental parameters associated with the presence of Using this analysis, a Random Forest model predicted presence in basal environmental samples with 75% accuracy. These data support use of culture-independent, PCR-based environmental sampling to track spread into new regions and to characterize the unknown environmental niche. Upon inhalation of spores from the fungus from the environment, humans and animals can develop the disease blastomycosis. Based on disease epidemiology, is known to be endemic in the United States and Canada around the Great Lakes and in the Ohio and Mississippi River Valleys but is starting to emerge in other areas. is extremely difficult to culture from the environment so little is known about the environmental reservoirs for this pathogen. We used a culture-independent PCR-based assay to identify the presence of DNA in soil samples from Minnesota. By combining molecular data with ecological niche modeling, we were able to predict the presence of in environmental samples with 75% accuracy and to define characteristics of the environmental niche. Importantly, we showed the effectiveness of using a PCR-based assay to identify in environmental samples.
PubMed: 33355116
DOI: 10.1128/AEM.01922-20 -
Virulence Dec 2019This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, , , and . In response to... (Review)
Review
This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, , , and . In response to temperature, undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for and related thermally dimorphic fungi is essential for virulence. In the yeast phase, upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release. yeast also secrete dipeptidyl-peptidase IVA (DPPIVA), a serine protease that blunts the action of cytokines released from host immune cells. transcriptional profiling of yeast has uncovered genes such as and involved in zinc scavenging that contribute to virulence during murine pulmonary infection. The discovery and characterization of genes important for virulence has led to advances at the bedside regarding novel diagnostics, vaccine development, and new targets for drug discovery.
Topics: Adaptation, Physiological; Animals; Blastomyces; Blastomycosis; Fungal Proteins; Humans; Hyphae; Mice; Temperature; Transcriptional Activation; Virulence; Virulence Factors
PubMed: 29532714
DOI: 10.1080/21505594.2018.1449506 -
Journal of Fungi (Basel, Switzerland) Dec 2020The diagnosis of blastomycosis and histoplasmosis can be difficult for clinicians who rarely see infections caused by these environmentally restricted dimorphic fungi.... (Review)
Review
The diagnosis of blastomycosis and histoplasmosis can be difficult for clinicians who rarely see infections caused by these environmentally restricted dimorphic fungi. Historically, the diagnosis of blastomycosis has been established by culture and sometimes by histopathologic identification. Currently, antigen detection in urine and serum has been shown to aid in the rapid diagnosis of blastomycosis, and newer antibody assays are likely to contribute to our diagnostic capability in the near future. The gold standard for the diagnosis of histoplasmosis has been culture of the organism from involved tissues, aided in some patients by histopathological verification of the typical yeast forms in tissues. Antigen detection has contributed greatly to the ability of clinicians to rapidly establish the diagnosis of histoplasmosis, especially in severely ill and immunocompromised patients, and antibody testing for provides important adjunctive diagnostic capability for several forms of both acute and chronic histoplasmosis. For both of these endemic mycoses, novel molecular tests are under active investigation, but remain available in only a few reference laboratories. In this review, we provide a synopsis of diagnostic test options that aid in establishing whether a patient has blastomycosis or histoplasmosis.
PubMed: 33383637
DOI: 10.3390/jof7010012 -
Journal of Clinical Microbiology Feb 2021Blastomycosis due to and is a significant cause of respiratory mycoses in North America with occasional reported outbreaks. We developed a highly sensitive, specific,...
Development of a Duplex Real-Time PCR Assay for the Differentiation of Blastomyces dermatitidis and and a Retrospective Analysis of Culture and Primary Specimens from Blastomycosis Cases from New York (2005 to 2019).
Blastomycosis due to and is a significant cause of respiratory mycoses in North America with occasional reported outbreaks. We developed a highly sensitive, specific, and reproducible TaqMan duplex real-time PCR assay for the differentiation of and The new assay permitted retrospective analysis of cultures (2005 to 2019) and primary clinical specimens from blastomycosis cases (2013 to 2019) from New York patients. We identified as the predominant pathogen in 38 cases of blastomycosis, while was a minor pathogen involved in five cases; these findings expand understanding of blastomycosis in New York. The duplex real-time PCR assay could be implemented in reference and public health laboratories to further understand the ecology and epidemiology of blastomycosis due to and .
Topics: Blastomyces; Blastomycosis; Humans; New York; North America; Real-Time Polymerase Chain Reaction; Retrospective Studies
PubMed: 33298609
DOI: 10.1128/JCM.02078-20 -
Pharmacy (Basel, Switzerland) Oct 2015Posaconazole (PCZ) is a relatively new addition to the azole antifungals. It has fungicidal activities against , , selected species, , and . PCZ also has fungistatic... (Review)
Review
Posaconazole (PCZ) is a relatively new addition to the azole antifungals. It has fungicidal activities against , , selected species, , and . PCZ also has fungistatic activities against , , selected spp., , and In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against , and . The absorption of PCZ suspension is enhanced when given with food, nutritional supplements, and carbonated beverages. Oral administration of PCZ in divided doses also increases its bioavailability. PCZ has a large volume of distribution and is highly protein bound (>95%). The main elimination route of PCZ is fecal. PCZ is an inhibitor of the CYP3A4 enzyme; therefore, monitoring for drug-drug interactions is warranted with other CYP3A4 substrates/inhibitors/inducers. The most common adverse effects include headache, fatigue, nausea, vomiting and elevated hepatic enzymes. PCZ, with its unique antifungal activities, expands the azole class of antifungal agents. Because of its limit in formulation, PCZ oral suspension is recommended in immunocompromised patients with functional gastrointestinaltracts who fail conventional antifungal therapies or who are suspected to have a breakthrough fungal infection. However, a delayed-release tablet formulation and intravenous (IV) injection became available in 2014, expanding the use of PCZ in other patient populations, including individuals who are unable to take oral formulations.
PubMed: 28975914
DOI: 10.3390/pharmacy3040210 -
BioMed Research International 2015Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the... (Review)
Review
Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the risk for HAI, particularly the use of medical devices; patients with severe cuts, wounds, and burns; stays in the intensive care unit, surgery, and hospital reconstruction works. Several fungal HAI are caused by Candida spp., usually from an endogenous source; however, cross-transmission via the hands of healthcare workers or contaminated devices can occur. Although other medically important fungi, such as Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum, have never been considered nosocomial pathogens, there are some factors that point out the pros and cons for this possibility. Among these fungi, H. capsulatum infection has been linked to different medical devices and surgery implants. The filamentous form of H. capsulatum may be present in hospital settings, as this fungus adapts to different types of climates and has great dispersion ability. Although conventional pathogen identification techniques have never identified H. capsulatum in the hospital environment, molecular biology procedures could be useful in this setting. More research on H. capsulatum as a HAI etiologic agent is needed, since it causes a severe and often fatal disease in immunocompromised patients.
Topics: Blastomyces; Candida; Cross Infection; Equipment and Supplies; Histoplasma; Humans; Paracoccidioides
PubMed: 26106622
DOI: 10.1155/2015/982429 -
Clinical Infectious Diseases : An... Jan 2019Blastomyces helicus (formerly Emmonsia helica) is a dimorphic fungus first isolated from a man with fungal encephalitis in Alberta, Canada. The geographic range,... (Review)
Review
BACKGROUND
Blastomyces helicus (formerly Emmonsia helica) is a dimorphic fungus first isolated from a man with fungal encephalitis in Alberta, Canada. The geographic range, epidemiology, and clinical features of disease are unknown.
METHODS
We reviewed human and veterinary isolates of B. helicus identified among Blastomyces and Emmonsia isolates at the University of Alberta Microfungus Collection and Herbarium, University of Texas Health San Antonio's Fungus Testing Laboratory, and Associated Regional and University Pathologists Laboratories. Isolates were selected based on low Blastomyces dermatitidis DNA probe values and/or atypical morphology. Species identification was confirmed for most isolates by DNA sequence analysis of the internal transcribed spacer with or without D1/D2 ribosomal RNA regions. Epidemiological and clinical data were analyzed.
RESULTS
We identified isolates from 10 human and 5 veterinary cases of B. helicus infection; all were referred from western regions of Canada and the United States. Isolates remained sterile in culture, producing neither conidia nor sexual spores in the mycelial phase, but often producing coiled hyphae. Isolates were most frequently cultured from blood and bronchoalveolar lavage in humans and lungs in animals. Most infected persons were immunocompromised. Histopathological findings included pleomorphic, small or variably sized yeast-like cells, with single or multiple budding, sometimes proliferating to form short, branching, hyphal-like elements. Disease carried a high case-fatality rate.
CONCLUSIONS
Blastomyces helicus causes fatal pulmonary and systemic disease in humans and companion animals. It differs from B. dermatitidis in morphological presentation in culture and in histopathology, by primarily affecting immunocompromised persons, and in a geographic range that includes western regions of North America.
Topics: Animals; Blastomyces; Canada; Communicable Diseases, Emerging; Humans; Lung Diseases, Fungal; Mycoses; United States
PubMed: 29878145
DOI: 10.1093/cid/ciy483