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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 -
MBio Aug 2021The development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell-mediated immune responses. Here, we asked...
The development of effective vaccines against fungal infections requires the induction of protective, pathogen-specific cell-mediated immune responses. Here, we asked whether combination adjuvants based on delta inulin (Advax) formulated with Toll-like receptor (TLR) agonists could improve vaccine protection mediated by a fungal recombinant protein, Bl-Eng2 (i.e., endoglucanase 2), which itself harbors an immunodominant antigen and dectin-2 agonist/adjuvant. We found that Bl-Eng2 formulated with Advax3 containing TLR9 agonist or Advax8 containing TLR4 agonist provided the best protection against pulmonary infection with Blastomyces dermatitidis, being more effective than complete Freund's adjuvant or Adjuplex. Advax3 was most efficient in inducing gamma interferon (IFN-γ)- and interleukin-17 (IL-17)-producing antigen-specific T cells that migrated to the lung upon Blastomyces dermatitidis infection. Mechanistic studies revealed Bl-Eng2/Advax3 protection was tempered by neutralization of IL-17 and particularly IFN-γ. Likewise, greater numbers of lung-resident T cells producing IFN-γ, IL-17, or both IFN-γ and IL-17 correlated with fewer fungi recovered from lung. Protection was maintained after depletion of CD4 T cells, partially reduced by depletion of CD8 T cells, and completely eliminated after depletion of both CD4 and CD8 T cells. We conclude that Bl-Eng2 formulated with Advax3 is promising for eliciting vaccine-induced antifungal immunity, through a previously uncharacterized mechanism involving CD8 and also CD4 T cells producing IFN-γ and/or IL-17. Although no licensed vaccine exists as yet against any fungal disease, these findings indicate the importance of adjuvant selection for the development of effective fungal vaccines. Fungal disease remains a challenging clinical and public health problem. Despite medical advances, invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immunocompetent and -deficient hosts, with worldwide mortality rates ranking 7th, even ahead of tuberculosis. The development of safe, effective vaccines remains a major hurdle for fungi. Critical barriers to progress include the lack of defined fungal antigens and suitable adjuvants. Our research is significant in identifying adjuvant combinations that elicit optimal vaccine-induced protection when formulated with a recombinant protective antigen and uncovering the mechanistic bases of the underlaying vaccine protection, which will foster the strategic development of antifungal vaccines.
Topics: Adjuvants, Immunologic; Animals; Blastomyces; Blastomycosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Fungal Vaccines; Immunity, Cellular; Interferon-gamma; Inulin; Male; Mice; Mice, Inbred C57BL; Mycoses; Vaccines, Synthetic
PubMed: 34399628
DOI: 10.1128/mBio.02018-21 -
Journal of Clinical Microbiology Sep 2021Laboratory diagnosis of blastomycosis relies on a combination of methods, including antigen detection. We assessed the performance of analyte-specific reagents from...
Laboratory diagnosis of blastomycosis relies on a combination of methods, including antigen detection. We assessed the performance of analyte-specific reagents from Gotham Biotech (Portland, ME) for quantitative detection of Blastomyces dermatitidis galactomannan (GM) in urine using an enzyme immunoassay (EIA) compared to the quantitative EIA from MiraVista Diagnostics (Indianapolis, IN). Residual urine from 232 unique patients previously tested by the MiraVista assay was evaluated using the Gotham EIA, which showed 97.4% (74/76), 100% (156/156), and 99.1% (230/232) positive, negative, and overall agreement, respectively. Correlation between the quantitative B. dermatitidis antigen levels by the Gotham and MiraVista EIAs was low ( = 0.20). Medical records were available for 36 of the 232 patients, among whom four had confirmed blastomycosis and both the Gotham and MiraVista EIAs were positive. Nine of these patients had histoplasmosis, and the Gotham and MiraVista EIAs yielded negative results in 44.4% (4/9) and 22.2% (2/9) of cases, respectively. Both assays were negative in the remaining 23 patients. After laboratory implementation of the Gotham EIA, chart reviews were performed on the first 50 unique patients (51 samples) tested by the assay in our hospital. Among these, 3/50 (6%) samples were positive by the Gotham EIA, including two samples from a patient with culture-confirmed blastomycosis and one from a patient with histoplasmosis (also positive by the MiraVista EIA). All remaining patients were negative by the Gotham EIA and had alternative diagnoses. Our findings show comparable performance between the Gotham and MiraVista quantitative EIAs for detection of B. dermatitidis GM in urine.
Topics: Antigens, Fungal; Blastomyces; Blastomycosis; Humans; Immunoenzyme Techniques; Sensitivity and Specificity
PubMed: 34346719
DOI: 10.1128/JCM.01444-21 -
Journal of the American Veterinary... Jun 2019
Topics: Animals; Blastomyces; Blastomycosis; Dog Diseases; Dogs; Fatal Outcome; Male
PubMed: 31067183
DOI: 10.2460/javma.254.11.1287 -
Public Health Reports (Washington, D.C.... 1996THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of... (Review)
Review
THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight ( < or = 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium marneffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents; and research focused on the understanding, prevention, and control of fungal infections.
Topics: Humans; Immunocompromised Host; Mycoses; Opportunistic Infections; Public Health; Risk Factors; United States
PubMed: 8643813
DOI: No ID Found -
Cureus Feb 2022Blastomycosis is a systemic mycosis endemic to the Midwestern and South Central United States. Infection is caused by inhaling spores of () that inhabit soil. Acute...
Blastomycosis is a systemic mycosis endemic to the Midwestern and South Central United States. Infection is caused by inhaling spores of () that inhabit soil. Acute respiratory distress syndrome (ARDS) is a rare complication of pulmonary blastomycosis with a significantly high mortality rate. We present a case of blastomycosis associated with severe ARDS treated with traditional prone position ventilation (PPV) and neurally adjusted ventilator assist (NAVA) along with antifungal therapy, steroids, and supportive care in a rural setting with no access to extracorporeal membrane oxygenation (ECMO). This case demonstrates that traditional therapies such as prone position ventilation can help patients with blastomycosis-associated ARDS especially in rural settings where advanced therapies such as ECMO are lacking. The use of NAVA in blastomycosis-associated ARDS needs further research.
PubMed: 35308721
DOI: 10.7759/cureus.22207 -
Current Protocols in Microbiology Dec 2020Dimorphic fungi in the genera Blastomyces, Histoplasma, Coccidioides, and Paracoccidioides are important human pathogens that affect human health in many countries...
Dimorphic fungi in the genera Blastomyces, Histoplasma, Coccidioides, and Paracoccidioides are important human pathogens that affect human health in many countries throughout the world. Understanding the biology of these fungi is important for the development of effective treatments and vaccines. Gene editing is a critically important tool for research into these organisms. In recent years, gene targeting approaches employing RNA-guided DNA nucleases, such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9), have exploded in popularity. Here, we provide a detailed description of the steps involved in applying CRISPR/Cas9 technology to dimorphic fungi, with Blastomyces dermatitidis in particular as our model fungal pathogen. We discuss the design and construction of single guide RNA and Cas9-expressing targeting vectors (including multiplexed vectors) as well as introduction of these plasmids into Blastomyces using Agrobacterium-mediated transformation. Finally, we cover the outcomes that may be expected in terms of gene-editing efficiency and types of gene alterations produced. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Construction of CRISPR/Cas9 targeting vectors Support Protocol 1: Choosing protospacers in the target gene Basic Protocol 2: Agrobacterium-mediated transformation of Blastomyces Support Protocol 2: Preparation of electrocompetent Agrobacterium Support Protocol 3: Preparation and recovery of Blastomyces frozen stocks.
Topics: Agrobacterium; Base Sequence; Blastomyces; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Coculture Techniques; Fungi; Gene Editing; Gene Targeting; Microbiological Techniques; Polymerase Chain Reaction; RNA, Guide, CRISPR-Cas Systems
PubMed: 33315302
DOI: 10.1002/cpmc.132 -
Cureus Aug 2021Blastomycosis is a fungal infection caused by . While blastomycosis can cause systemic infection affecting multiple organs, localized blastomycosis of the breast is...
Blastomycosis is a fungal infection caused by . While blastomycosis can cause systemic infection affecting multiple organs, localized blastomycosis of the breast is uncommon. Here, we report the case of a 50-year-old female with a localized left breast growth which started as a nodule and later ulcerated extensively. Although her clinical picture raised concerns for breast malignancy, workup revealed cutaneous blastomycosis with superimposed methicillin-susceptible and infection. Interestingly, there was no evidence of pulmonary disease on CT chest imaging. She was treated with Amphotericin B for seven days and discharged on oral Itraconazole for nine months. Additionally, she received amoxicillin-clavulanate for her bacterial superinfection. On the six-month follow-up, the patient showed significant improvement. Blastomycosis can mimic several diseases including malignancy, pyoderma gangrenosum, and mycobacterial and bacterial infections leading to delayed diagnosis and treatment.
PubMed: 34540497
DOI: 10.7759/cureus.17276 -
MMWR. Morbidity and Mortality Weekly... Jul 1996Blastomycosis is a disease of humans and animals caused by inhalation of airborne spores from Blastomyces dermatitidis, a dimorphic fungus found in soil. The spectrum of...
Blastomycosis is a disease of humans and animals caused by inhalation of airborne spores from Blastomyces dermatitidis, a dimorphic fungus found in soil. The spectrum of clinical manifestations of blastomycosis includes acute pulmonary disease, subacute and chronic pulmonary disease (most common presentations), and disseminated extrapulmonary disease (cutaneous manifestations are most common, followed by involvement of the bone, the genitourinary tract, and central nervous system). Although the disease is not nationally notifiable, it was designated a reportable condition in Wisconsin in 1984 following two large outbreaks. This report summarizes information about cases of blastomycosis reported in Wisconsin during 1986-1995 and highlights the importance of surveillance for blastomycosis in areas with endemic disease.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blastomycosis; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Male; Middle Aged; Wisconsin
PubMed: 8676851
DOI: No ID Found -
International Journal of Infectious... Jul 2020Diagnosing pulmonary blastomycosis (PB) requires the detection of Blastomyces dermatitidis in pulmonary secretions or tissue, which can be achieved via bronchoscopic...
OBJECTIVES
Diagnosing pulmonary blastomycosis (PB) requires the detection of Blastomyces dermatitidis in pulmonary secretions or tissue, which can be achieved via bronchoscopic procedures like bronchoalveolar lavage (BAL) or brush and transbronchial biopsy (TBBx). This descriptive study retrieved the data of PB that was diagnosed by bronchoscopy to define which bronchoscopic procedure produced the highest yield.
METHODS
Retrospectively, all patients diagnosed with PB via bronchoscopic approach were identified. Non-invasive BAL was referred to when performed first in the order of bronchoscopic procedures, and invasive BAL was used when it was performed after other bronchoscopic procedures.
RESULTS
A total of 111 patients were included in the study. BAL produced the highest yield of all bronchoscopic procedures (>87%), regardless if it was performed first in order (non-invasive, 87.3%) or not (invasive BAL, 89.6%) (p = 0.43). Performing bronchoscopy and BAL earlier in the course of the disease resulted in a significantly better diagnostic yield.
CONCLUSIONS
BAL is probably enough to diagnose PB. Also, it had the best yield when performed earlier, regardless of whether it was performed first in order or not. BAL culture had a better yield in detecting Blastomyces dermatitidis over fungal stain and cytology.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blastomycosis; Bronchoalveolar Lavage; Bronchoscopy; Female; Humans; Male; Middle Aged; Retrospective Studies; Young Adult
PubMed: 32371194
DOI: 10.1016/j.ijid.2020.04.077