Sample records for blastomyces

  1. Blastomyces gilchristii as Cause of Fatal Acute Respiratory Distress Syndrome. (United States)

    Dalcin, Daniel; Rothstein, Aaron; Spinato, Joanna; Escott, Nicholas; Kus, Julianne V


    Since the 2013 description of Blastomyces gilchristii, research describing the virulence or clinical outcome of B. gilchristii infection has been lacking. We report molecular evidence of B. gilchristii as an etiologic agent of fatal acute respiratory distress syndrome. B. gilchristii infection was confirmed by PCR and sequence analysis.

  2. Phylogeographic Analysis of Blastomyces dermatitidis and Blastomyces gilchristii Reveals an Association with North American Freshwater Drainage Basins.

    Directory of Open Access Journals (Sweden)

    Lisa R McTaggart

    Full Text Available 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

  3. Coccidioides, cryptococcus, or blastomyces? A diagnostic dilemma encountered during frozen section evaluation. (United States)

    McClain, Colt M; Van Horn, Gerald T; Chappell, James D; Stratton, Charles W


    Intraoperative consultation via frozen section is an important part of modern day surgical pathology. Recognizing fungi in tissues on frozen and permanent sections is not always a simple task, and correctly identifying the agent can be a significant challenge, even for experienced microscopists. We present a case of a 17-year-old boy with chronic osteomyelitis involving the right proximal ulna. During an irrigation and debridement operation, a frozen section was sent to surgical pathology for evaluation. A limited patient history coupled with sparse organisms present in the frozen section led to the diagnosis of fungal osteomyelitis, favor Coccidioides . Follow-up permanent sections with special staining and successful fungal culture clarified the causal agent to be Blastomyces dermatitidis . The role of frozen sections is not to perfectly speciate the fungal pathogen but to describe the morphology and infectious process and provide a differential diagnosis of the candidate fungi. The importance of intraoperative culture in infectious cases cannot be understated, and it is the responsibility of pathologists to inform surgeons that tissue is needed for culture. A brief overview of Blastomyces , including histopathologic features and key microscopic differences from Coccidioides and Cryptococcus , is discussed.

  4. Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis.

    Directory of Open Access Journals (Sweden)

    Amber J Marty


    Full Text Available In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours, gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C and during the phase transition to mold (22°C. This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

  5. Interleukin 1 enhances vaccine-induced antifungal T-helper 17 cells and resistance against Blastomyces dermatitidis infection. (United States)

    Wüthrich, Marcel; LeBert, Vanessa; Galles, Kevin; Hu-Li, Jane; Ben-Sasson, Shlomo Z; Paul, William E; Klein, Bruce S


    Vaccine-induced T-helper 17 (Th17) cells are necessary and sufficient to protect against fungal infection. Although live fungal vaccines are efficient in driving protective Th17 responses and immunity, attenuated fungi may not be safe for human use. Heat-inactivated formulations and subunit vaccines are safer but less potent and require adjuvant to increase their efficacy. Here, we show that interleukin 1 (IL-1) enhances the capacity of weak vaccines to induce protection against lethal Blastomyces dermatitidis infection in mice and is far more effective than lipopolysaccharide. While IL-1 enhanced expansion and differentiation of fungus-specific T cells by direct action on those cells, cooperation with non-T cells expressing IL-1R1 was necessary to maximize protection. Mechanistically, IL-17 receptor signaling was required for the enhanced protection induced by IL-1. Thus, IL-1 enhances the efficacy of safe but inefficient vaccines against systemic fungal infection in part by increasing the expansion of CD4(+) T cells, allowing their entry into the lungs, and inducing their differentiation to protective Th17 cells.

  6. The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis. (United States)

    Wang, Huafeng; Li, Mengyi; Lerksuthirat, Tassanee; Klein, Bruce; Wüthrich, Marcel


    C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRγ as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen Blastomyces dermatitidis. MCL(-/-) mice showed impaired vaccine resistance against B. dermatitidis infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes in vitro. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with B. dermatitidis.

  7. Isolation, purification, and radiolabeling of a novel 120-kD surface protein on Blastomyces dermatitidis yeasts to detect antibody in infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Klein, B.S.; Jones, J.M.


    No well-defined Blastomyces-specific antigens are currently available. We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting to identify immunologically active molecules in the cell wall of B. dermatitidis. A major immunoreactive 120-kD protein (WI-1) was present in all five strains studied and comprised 5% of the protein in the cell wall extract obtained after freezing and thawing yeast cells. WI-1 was recognized by serum from all 10 patients with blastomycosis but by none of those from 5 patients with histoplasmosis. It was purified by electroelution, radiolabeled with 125I, and incorporated into a radioimmunoassay (RIA) for serodiagnosis of blastomycosis. Antibody to WI-1 was detected in 58 (85%) of 68 patients with blastomycosis (geometric mean titer, 1:2,981), in two (3%) of 73 patients with histoplasmosis, coccidioidomycosis, sporotrichosis, or candidiasis (titers, 1:86 and 1:91) and in none of 44 healthy persons. WI-1 was shown to be a surface molecule abundant on B. dermatitidis yeasts that were indirectly stained with serum from a rabbit immunized with WI-1. Approximately 0.93 pg of WI-1 or 4.7 x 10(6) WI-1 molecules were found on the surface of an individual yeast using an antigen-inhibition RIA; none was found on Histoplasma capsulatum or Candida albicans yeasts. We conclude that WI-1 is a novel, immunologically active surface molecule on the invasive form of B. dermatitidis and that WI-1 can be used to reliably detect antibody and study the immunopathogenesis of blastomycosis.

  8. Blastomyces dermatitidis prostatic and testicular infection in eight dogs (1992-2005). (United States)

    Totten, Amy Kaye; Ridgway, Marcella D; Sauberli, Debra S


    This was a retrospective case study of eight dogs diagnosed with prostatic or testicular B. dermatitidis infection. Signalment, clinical presentation, diagnostic procedures, and treatment options were evaluated. Review of medical records of dogs diagnosed with blastomycosis at the University of Illinois Veterinary Teaching Hospital from 1992 to 2005 yielded four dogs with prostatic blastomycosis (PB) and four dogs with testicular blastomycosis (TB). Three of the four dogs with PB and all four dogs with TB had evidence of urogenital disease. Three dogs with PB had an elevated body temperature and all had systemic disease. All dogs with TB had a normal body temperature, and three had systemic disease and one had clinical signs limited to testicular disease. Cytology or histopathology was used to diagnose PB or TB. Treatment included itraconazole or fluconazole with or without nonsteroidal anti-inflammatory drugs. PB and TB are infrequently recognized and may be under diagnosed due to failure to specifically evaluate these tissues. PB or TB should be considered in the evaluation and staging of male dogs with blastomycosis. Male dogs with urogenital signs should be evaluated via prostatic or testicular cytology or histopathology since proper identification and management of PB or TB may improve overall treatment success.

  9. Cutaneous blastomycosis and dermatophytic pseudomycetoma in a Persian cat from Bangkok, Thailand. (United States)

    Duangkaew, Lerpen; Larsuprom, Lawan; Kasondorkbua, Chaiyan; Chen, Charles; Chindamporn, Ariya


    This is a case report of concurrent of blastomycosis and pseudomycetoma in a 3 year-old Persian cat from Bangkok, Thailand. Histopathology from antemortem and postmortem samples revealed blastomycosis and dermatophyte pseudomycetoma. The PCR analysis of the formalin-embedded tissue of antemortem sample confirmed that blastomycosis was caused by Blastomyces dermatitidis. Dermatophyte infection was caused by Microsporum canis. According to the author's knowledge, this is the first case of Blastomyces dermatitidis and dermatophyte pseudomycetoma in South-East Asia.

  10. Successful Treatment of Osseous Blastomycosis without Pulmonary or Disseminated Disease and Review of the Literature (United States)

    Day, Shandra R.; Weiss, David B.; Hazen, Kevin C.; Moore, Christopher C.


    Blastomycosis commonly occurs following inhalation of Blastomyces dermatitidis conidia causing a pulmonary infection and can disseminate to extrapulmonary sites. Osseous involvement primarily results from hematogenous spread but in rare cases direct inoculation can occur. We describe a case of osseous blastomycosis without pulmonary or disseminated disease successfully treated with posaconazole. PMID:24703876

  11. Carpal intra-articular blastomycosis in a Labrador retriever


    Woods, Katharine S.; Barry, Maureen; Richardson, Danielle


    A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.

  12. A multiplex quantitative real-time polymerase chain reaction panel for detecting neurologic pathogens in dogs with meningoencephalitis


    Han, Jae-Ik; Chang, Dong-Woo; Na, Ki-Jeong


    Meningoencephalitis (ME) is a common inflammatory disorder of the central nervous system in dogs. Clinically, ME has both infectious and non-infectious causes. In the present study, a multiplex quantitative real-time polymerase chain reaction (mqPCR) panel was optimized for the detection of eight canine neurologic pathogens (Blastomyces dermatitidis, Cryptococcus spp., Neospora caninum, Borrelia burgdorferi, Bartonella spp., Toxoplasma gondii, Ehrlichia canis, and canine distemper virus [CDV]...

  13. A multiplex quantitative real-time polymerase chain reaction panel for detecting neurologic pathogens in dogs with meningoencephalitis. (United States)

    Han, Jae-Ik; Chang, Dong-Woo; Na, Ki-Jeong


    Meningoencephalitis (ME) is a common inflammatory disorder of the central nervous system in dogs. Clinically, ME has both infectious and non-infectious causes. In the present study, a multiplex quantitative real-time polymerase chain reaction (mqPCR) panel was optimized for the detection of eight canine neurologic pathogens (Blastomyces dermatitidis, Cryptococcus spp., Neospora caninum, Borrelia burgdorferi, Bartonella spp., Toxoplasma gondii, Ehrlichia canis, and canine distemper virus [CDV]). The mqPCR panel was subsequently applied to 53 cerebrospinal fluid (CSF) samples collected from dogs with ME. The analytic sensitivity (i.e., limit of detection, expressed as molecules per 1 mL of recombinant vector) was 3.8 for CDV, 3.7 for Ehrlichia canis, 3.7 for Bartonella spp., 3.8 for Borrelia burgdorferi, 3.7 for Blastomyces dermatitidis, 3.7 for Cryptococcus spp., 38 for Neospora caninum, and 3.7 for Toxoplasma gondii. Among the tested CSF samples, seven (15%) were positive for the following pathogens in decreasing order of frequency: Cryptococcus spp. (3/7), Blastomyces dermatitidis (2/7), and Borrelia burgdorferi (2/7). In summary, use of an mqPCR panel with high analytic sensitivity as an initial screen for infectious agents in dogs with ME could facilitate the selection of early treatment strategies and improve outcomes.

  14. Blastomycosis presenting as solitary nodule: A rare presentation

    Directory of Open Access Journals (Sweden)

    Ashish Dhamija


    Full Text Available Blastomycosis is a chronic granulomatous and suppurative mycosis, caused by Blastomyces dermatitidis, which in the great majority of cases presents as a primary pulmonary disease. Primary cutaneous blastomycosis is very rare. We present a 57-year-old female patient with a solitary, slowly progressive nodule over upper lip of 2½ months duration. Initially, differential diagnosis of cutaneous leishmaniasis, pyoderma and deep mycoses were entertained. Slit smear preparation was suspicious of deep mycotic infection which was subsequently confirmed by biopsy and culture.

  15. [Bacteriologic and serologic diagnosis of enteral infections]. (United States)

    Ringelmann, R


    Infections of the gastrointestinal tract still are numerous, ranging on the second place after infections of the respiratory tract. Some of them show quite severe or prolonged course. In contrast to other infections, especially those of the urinary tract, laboratory diagnostic of enteritis is only scarcely ordered. During the last ten years new methods and knowledge of etiologic germs like Campylobacter, Yersinia, various types of E. coli, Clostridium difficile, Rotavirus, Adenovirus, Giardia, Blastomyces and Cryptosporidia have been accumulated. A better etiologic diagnosis of these infections should enable the clinician to start a more precise and therefore more effective therapy.

  16. Associação da rifampicina à anfotericina B no tratamento da paracoccidioidomicose: resultados em três pacientes tratados Association of Amphotericin B and Rifampicin in the treatment of paracoccidioidomycosis. Report of efficacy in three cases

    Directory of Open Access Journals (Sweden)

    Bodo Wanke


    Full Text Available Trabalhos experimentais demonstraram que a anfotericina B, desorganizando funcionalmente a membrana celular fúngica, permite a penetração da rifampicina no citoplasma e sua conseqüente ação contra Histoplasma capsulatum, Blastomyces dermatitidis e Candida albicans. Com metade das doses habituais' de anfotericina B associada à rifampicina conseguem-se melhores resultados do que com a anfotericina B isoladamente em doses plenas. Os Autores discutem as possíveis aplicações desta associação no tratamento da paracoccidioidomi-cose e apresentam 3 casos desta micose em que a inatividade clínica e micológica só foi obtida após o emprego combinado destas drogas.Experimental data have shown that low concentration of amphotericin B disrupts of the fungal cellular membranes, enhancing entrance of rifampicin into citoplasm, where it acts specifically as an antifungal agent against Histoplasma capsulatum, Blastomyces dermatitidis and Candida albicans. Amphotericin B in half dosage combined with rifampicin is more effective than when used alone in full dosage. The Authors discuss the possible indications of this association in the therapy of paracoccidioidomycosis, and report its efficacy in three cases of this disease only controlled after its use.

  17. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis. (United States)

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S


    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  18. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi


    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  19. Lymphocyte transformation in presumed ocular histoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Ganley, J.P.; Nemo, G.J.; Comstock, G.W.; Brody, J.A.


    Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

  20. Episodic syncope caused by ventricular flutter in a tiger (Panthera tigris). (United States)

    DeLillo, Daniel M; Jesty, Sophy A; Souza, Marcy J


    A captive, 9-yr-old castrated male tiger (Panthera tigris) from an exotic cat sanctuary and rescue facility was observed to have three collapsing episodes within a 2-wk interval prior to being examined by veterinarians. No improvement in clinical signs was noted after empiric treatment with phenobarbital. During a more complete workup for epilepsy, ventricular flutter was observed on electrocardiogram (ECG). The arrhythmia resolved with a single intravenous bolus of lidocaine. Cardiac structure and function were unremarkable on echocardiogram and cardiac troponin I levels were within normal limits for domestic felids. No significant abnormalities were noted on abdominal ultrasound. Complete blood count and biochemistry panel were unremarkable, and heartworm antigen and Blastomyces urine antigen enzyme-linked immunosorbent assays were negative. Antiarrhythmic treatment with sotalol was initiated. On follow-up ECG performed 1 mo later, no significant arrhythmias were noted, and clinical signs have completely resolved.

  1. Isolation of Aureimonas altamirensis, a Brucella canis-like bacterium, from an edematous canine testicle. (United States)

    Reilly, Thomas J; Calcutt, Michael J; Wennerdahl, Laura A; Williams, Fred; Evans, Tim J; Ganjam, Irene K; Bowman, Jesse W; Fales, William H


    Microbiological and histological analysis of a sample from a swollen testicle of a 2-year-old Border Collie dog revealed a mixed infection of the fungus Blastomyces dermatitidis and the Gram-negative bacterium Aureimonas altamirensis. When subjected to an automated microbial identification system, the latter isolate was provisionally identified as Psychrobacter phenylpyruvicus, but the organism shared several biochemical features with Brucella canis and exhibited agglutination, albeit weakly, with anti-B. canis antiserum. Unequivocal identification of the organism was only achieved by 16S ribosomal RNA gene sequencing, ultimately establishing the identity as A. altamirensis. Since its first description in 2006, this organism has been isolated infrequently from human clinical samples, but, to the authors' knowledge, has not been reported from a veterinary clinical sample. While of unknown clinical significance with respect to the pathology observed for the polymicrobial infection described herein, it highlights the critical importance to unambiguously identify the microbe for diagnostic, epidemiological, infection control, and public health purposes.

  2. In vitro and in vivo studies of ambruticin (W7783): new class of antifungal antibiotics. (United States)

    Ringel, S M


    Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 mug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 mug/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 mug/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.

  3. Probable Pulmonary Blastomycosis in a Wild Coyote (Canis latrans

    Directory of Open Access Journals (Sweden)

    Luis E. Rodríguez-Tovar


    Full Text Available A female coyote (Canis latrans was fatally injured by a vehicle on a road in San Luis Potosi, Mexico. Because of deteriorating clinical signs, the animal was euthanized. Postmortem examination of the lungs showed numerous small multifocal white nodules (0.5–1 cm diameter disseminated throughout. Histopathologic examination revealed multifocal coalescing granulomas with abundant macrophages, numerous neutrophils, fibroblasts, plasma cells, and lymphocytes. Abundant intracellular and extracellular thick-walled, refractile, spherical yeasts (10–15 μm were observed within the granulomas. The yeasts were intensely PAS-positive, with granular protoplasm. Broad-based single budding yeasts were occasionally present. Based on the microscopic findings of the pulmonary lesions and the morphological features of the organism, a diagnosis of chronic pyogranulomatous pneumonia caused by Blastomyces dermatitidis was made. To our knowledge, the case described herein is the first report of pulmonary blastomycosis in a wild coyote.

  4. Pulmonary blastomycosis in a professional diver: An occupational risk

    Directory of Open Access Journals (Sweden)

    Ryan R Kroll


    Full Text Available In certain parts of the United States and Canada, and northern Ontario in particular, the dimorphic fungus Blastomyces dermatitidis is endemic and can cause infection in exposed individuals. The site of infection is usually pulmonary, causing respiratory and constitutional symptoms, but can also affect other sites in the body. Symptom severity can vary substantially from no symptoms to fatal acute respiratory distress syndrome. The present report describes a 27-year-old professional diver who had recently worked in northern Ontario, who developed symptoms of pneumonia and exhibited atypical findings on chest imaging. He was diagnosed with blastomycosis based on histopathological findings and fungal culture, and was treated with amphotericin B and itraconazole in accordance with treatment guidelines. While outdoor occupations in endemic areas increase the risk of infection, there is no literature specifically identifying professional diving as an occupational risk for blastomycosis.

  5. Fungal osteomyelitis and septic arthritis. (United States)

    Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T


    Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.

  6. Studies on the physiological bases of morphogenesis in fungi; the respiratory metabolism of dimorphic pathogenic fungi. (United States)



    The interconversions of mycelial and yeast-like forms (M right harpoon over left harpoon Y) in Blastomyces dermatitidis and in Blastomyces brasiliensis are characterized as examples of thermal dimorphism since the phenomena are apparently dependent only on the temperature of incubation of these two species. The change in morphology consequent upon Y --> M conversion is considered to result from the selective inhibition of cell division, without the simultaneous inhibition of growth. Such selective inhibition is viewed in a wider context as an example of the differential operation of the physicochemical apparatus of the cell in the control of form development by an organism. To analyze this differential operation, which is here dependent only on temperature, we have studied the effect of temperature on oxygen consumption by each of the dimorphic forms. In the absence of external substrate the yeast forms consume 5 to 6 times more oxygen per unit dry weight than do the M forms.The Y forms exhibit an exogenous oxidation of acetate and of glucose, as well as an oxidative assimilation of these substrates, whereas the M forms exhibit no exogenous metabolism in either a resting or starved condition. A study of the effect of a wide range of temperatures on oxygen consumption by the M forms indicates the operation of two rate-limiting processes: (a) one with an activation energy of 13,250 calories/gm. molecule over the range 5-30 degrees , and (b) reversible enzyme inactivation; the latter process assuming importance in the higher temperature range. On abrupt, large changes in temperature the balance between these two rate-limiting reactions (which it is suggested characterizes the steady state) is apparently disrupted as a result of a lag in the assumption of a rate of reversible enzyme inactivation characteristic of the new temperature. This disruption of balance is evidenced in overshoot phenomena. The effect of an analogous disruption of balance, and of increasing

  7. Development of a slide agglutination assay for detection of blastomycosis. (United States)

    Hatch, Wayne O; Scalarone, Gene M


    Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitides, which is endemic to eastern regions of the USA, is commonly misdiagnosed as a viral or bacterial infection and therefore treated improperly. Over the years, many immunodiagnostic assays to aid in the diagnosis of blastomycosis have been developed; however, a reliable assay for use in local clinics still remains elusive. Procedures for a slide agglutination assay for detection of antibody in serum from rabbits immunized with B. dermatitidis were evaluated with antigenic preparations from B. dermatitidis adsorbed to polystyrene microparticles. Yeast-phase lysates from five isolates of B. dermatitides: namely ER-593 (Eagle River, WI, USA), ER-598 (Eagle River, WI, USA), 48938 (India), B5896 (Mt. Iron, MN, USA), and T-58 (TN, USA) were evaluated for their sensitivity and specificity. Sensitivities of the lysates ranged from 29% to 83% whereas specificities ranged from 13% to 100%. Lysate ER-593 provided the most promising results with a sensitivity of 82% and specificity of 100%. This study provides suggests that a simple rapid slide agglutination assay for detecting blastomycosis may be used for screening patients with suspected B. dermatitidis infection.

  8. Fungal Infections in Some Economically Important Freshwater Fishes

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal*, Uzma Sheikh and Rabia Mughal


    Full Text Available Aim of this study was to investigate fungal infections in four species of carps including goldfish, Carassius (C. auratus L.; silver carp, Hypophthalmichthys (H. molitrix Richardsons; rahu, Labeo (L. rohita Hamilton and Ctenopharyngodon (C. idella Valenciennes. Nine specimens of each species were studied for the presence of fungal infections. Infected fishes showed clinical signs such as fungal growth on skin, fins, eyes, eroded fins and scales, hemorrhages on body surface and abdominal distension. The specimens from infected organs of fish were inoculated on each, malt extract, Sabouraud dextrose and potato dextrose agars. The fungal colonies of white, black, green, grey and brown colors were observed in the agar plates. Slides were prepared and stained with 0.05% Trypan blue in lactophenol. C. auratus showed the highest infection rate (44.4% followed by H. molitrix and L. rohita (11.1% each. Five fungal species viz. Aspergillus (33.3%, Penicillium (22.2%, Alternaria (27.7%, Blastomyces spp (11.1% and Rhizopus (5.5% were isolated. Posterior part of the fish had significantly (P=0.05 higher (62.5% infection as compared to anterior part (37.5%. The caudal fin with 31.25% infection was the single most affected area. This study showed that most of the fungi isolated from fishes are considered as normal mycoflora, yet many fungi can cause natural infections in ponds and aquarium.

  9. Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians

    Directory of Open Access Journals (Sweden)

    Codifava Margherita


    Full Text Available Abstract Background Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable. Case presentation We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe. Conclusions Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.

  10. Molecular cloning, characterization and differential expression of DRK1 in Sporothrix schenckii. (United States)

    Hou, Binbin; Zhang, Zhenying; Zheng, Fangliang; Liu, Xiaoming


    The dimorphism of Sporothrix schenckii (S. schenckii) reflects a developmental switch in morphology and lifestyle that is necessary for virulence. DRK1, a hybrid histidine kinase, functions as a global regulator of dimorphism and virulence in Blastomyces dermatitidis (B. dermatitidis) and Histoplasma capsulatum (H. capsulatum). The partial cDNA sequence of DRK1 of S. schenckii, designated SsDRK1, was obtained using degenerate primers based on the conserved domain of the DRK1 of other fungi. The complete cDNA sequence of SsDRK1 was obtained by 5' and 3' RACE. The full-length cDNA is 4743 bp in size and has an open reading frame (ORF) of 4071 bp, encoding 1356 amino acid residues. The predicted molecular mass of SsDRK1 is 147.3 kDa with an estimated theoretical isoelectric point of 5.46. The deduced amino acid sequence of SsDRK1 shows 65% identity to that of B. dermatitidis. The SsDRK1 was predicted to be a soluble histidine kinase and to contain three parts: sensor domain, linker domain and functional domain. Quantitative real-time RT-PCR revealed that SsDRK1 was more highly expressed in the yeast stage compared with that in the mycelial stage, which indicated that the SsDRK1 may be involved in the dimorphic switch in S. schenckii.

  11. Dimorphic fungal osteoarticular infections. (United States)

    Rammaert, B; Gamaletsou, M N; Zeller, V; Elie, C; Prinapori, R; Taj-Aldeen, S J; Roilides, E; Kontoyiannis, D P; Brause, B; Sipsas, N V; Walsh, T J; Lortholary, O


    The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.

  12. Could Histoplasma capsulatum Be Related to Healthcare-Associated Infections?

    Directory of Open Access Journals (Sweden)

    Laura Elena Carreto-Binaghi


    Full Text Available 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.

  13. Diversity of endophytic fungal community of cacao (Theobroma cacao L. and biological control of Crinipellis perniciosa, causal agent of Witches' Broom Disease

    Directory of Open Access Journals (Sweden)


    Full Text Available The basidiomycete fungus Crinipellis perniciosa (Stahel Singer is the causal agent of Witches' Broom Disease of Cacao (Theobroma cacao L. which is the main factor limiting cacao production in the Americas. Pod losses of up to 90% are experienced in affected areas as evidenced by the 50% drop in production in Bahia province, Brazil following the arrival of the C. perniciosa in the area in 1989. The disease has proven particularly difficult to control and many farmers in affected areas have given up cacao cultivation. In order to evaluate the potential of endophytes as a biological control agent of this phytopathogen, the endophytic fungal community of resistant and susceptible cacao plants as well as affected branches was studied between 2001 and 2002. The fungal community was identified by morphological traits and rDNA sequencing as belonging to the genera Acremonium, Blastomyces, Botryosphaeria, Cladosporium, Colletotrichum, Cordyceps, Diaporthe, Fusarium, Geotrichum, Gibberella, Gliocladium, Lasiodiplodia, Monilochoetes, Nectria, Pestalotiopsis, Phomopsis, Pleurotus, Pseudofusarium, Rhizopycnis, Syncephalastrum, Trichoderma, Verticillium and Xylaria. These fungi were evaluated both in vitro and in vivo by their ability to inhibit C. perniciosa. Among these, some were identified as potential antagonists, but only one fungus (Gliocladium catenulatum reduced the incidence of Witches' Broom Disease in cacao seedlings to 70%.

  14. Posaconazole: An Update of Its Clinical Use

    Directory of Open Access Journals (Sweden)

    Simon Leung


    Full Text Available Posaconazole (PCZ is a relatively new addition to the azole antifungals. It has fungicidal activities against Aspergillus fumigatus, Blastomyces dermatitidis, selected Candida species, Crytopcoccus neoformans, and Trichosporon. PCZ also has fungistatic activities against Candida, Coccidioides, selected Fusarium spp., Histoplasma, Scedosporium and Zygomycetes. In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against A. fumigatus, C. glabrata and C. neoformans. 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.

  15. Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity. (United States)

    Sterkel, Alana K; Lorenzini, Jenna L; Fites, J Scott; Subramanian Vignesh, Kavitha; Sullivan, Thomas D; Wuthrich, Marcel; Brandhorst, Tristan; Hernandez-Santos, Nydiaris; Deepe, George S; Klein, Bruce S


    Systemic fungal infections trigger marked immune-regulatory disturbances, but the mechanisms are poorly understood. We report that the pathogenic yeast of Blastomyces dermatitidis elaborates dipeptidyl-peptidase IVA (DppIVA), a close mimic of the mammalian ectopeptidase CD26, which modulates critical aspects of hematopoiesis. We show that, like the mammalian enzyme, fungal DppIVA cleaved C-C chemokines and GM-CSF. Yeast producing DppIVA crippled the recruitment and differentiation of monocytes and prevented phagocyte activation and ROS production. Silencing fungal DppIVA gene expression curtailed virulence and restored recruitment of CCR2(+) monocytes, generation of TipDC, and phagocyte killing of yeast. Pharmacological blockade of DppIVA restored leukocyte effector functions and stemmed infection, while addition of recombinant DppIVA to gene-silenced yeast enabled them to evade leukocyte defense. Thus, fungal DppIVA mediates immune-regulatory disturbances that underlie invasive fungal disease. These findings reveal a form of molecular piracy by a broadly conserved aminopeptidase during disease pathogenesis.

  16. Structure and function of a fungal adhesin that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function.

    Directory of Open Access Journals (Sweden)

    T Tristan Brandhorst

    Full Text Available Blastomyces adhesin-1 (BAD-1 is a 120-kD surface protein on B. dermatitidis yeast. We show here that BAD-1 contains 41 tandem repeats and that deleting even half of them impairs fungal pathogenicity. According to NMR, the repeats form tightly folded 17-amino acid loops constrained by a disulfide bond linking conserved cysteines. Each loop contains a highly conserved WxxWxxW motif found in thrombospondin-1 (TSP-1 type 1 heparin-binding repeats. BAD-1 binds heparin specifically and saturably, and is competitively inhibited by soluble heparin, but not related glycosaminoglycans. According to SPR analysis, the affinity of BAD-1 for heparin is 33 nM±14 nM. Putative heparin-binding motifs are found both at the N-terminus and within each tandem repeat loop. Like TSP-1, BAD-1 blocks activation of T cells in a manner requiring the heparan sulfate-modified surface molecule CD47, and impairs effector functions. The tandem repeats of BAD-1 thus confer pathogenicity, harbor motifs that bind heparin, and suppress T-cell activation via a CD47-dependent mechanism, mimicking mammalian TSP-1.

  17. 河北省张家口地区育龄期妇女阴道炎病原体分布、耐药性特征及危险因素分析%Analysis of pathogenic bacteria, drug resistance and risk factors in patients with vaginitis in Zhangjiakou area

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate characteristics of pathogen distribution and drug resistance,and to analyze risk factors of the infection in patients with vaginitis in Zhangjiakou area.Methods Vaginal secretion specimen from 368 patients with vaginitis were collected and then processed by germiculture,identification and drug sensitivity tests.Risk factors of infection were identified among age,marriage history,first sexual intercourse age,education,childbearing history,abortion history,contraception,householding et al by single factor x2 analysis and Logistic regression analysis.Results Blastomyces albicans,ureaplasma urealyticum,escherichia coli,enterococcus faecalis and gardner vaginal bacteria listed top 5 of composition of infection rate in patients with vaginitis.Blastomyces albicans was sensitive to multiple antifungal agent; escherichia coli and gardner vaginal bacteria were resistant to multiple antibiotics but sensitive to imipenem;ureaplasma urealyticum was resistant to multiple antibiotics but sensitive to josamycin and clarithromycin;enterococcus faecalis was strongly resisted to SMZ and erythromycin.Age ranging from 31 ~40y,application of IUD,positive abortion history and first sex intercourse before 23y were identified as risk factors for infection in patients with vaginitis.Conclusion Infection characteristics and risk factors could be utilized as indicators in considering treatment programs for patients with vaginitis.%目的 探讨张家口地区育龄期妇女阴道炎病原体分布、耐药性特征,并对其危险因素进行分析.方法 收集368例阴道炎患者阴道分泌物进行病原体培养与鉴定,并进行药敏试验;采用单因素x2检验及Logistic回归分析在年龄、婚否、初交年龄、文化、生育史、流产史、避孕方式、家庭居住地等因素中确定阴道炎病原体感染的危险因素.结果 阴道炎患者病原体感染率前五位分别为白色念珠菌、解脲支原体、大肠埃希菌、粪

  18. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Som Gowda Nanjappa

    Full Text Available Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+ T-cell help, vaccine-induced CD8(+ T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+ T cells (Tc17 cells have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+ T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  19. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. (United States)

    Nanjappa, Som Gowda; Heninger, Erika; Wüthrich, Marcel; Gasper, David Joseph; Klein, Bruce S


    Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+) T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  20. Evaluation of the detection of melanin by the Fontana-Masson silver stain in tissue with a wide range of organisms including Cryptococcus. (United States)

    Bishop, Justin A; Nelson, Ann Marie; Merz, William G; Askin, Frederic B; Riedel, Stefan


    It is not uncommon for surgical pathologists to encounter yeast and yeast-like organisms in tissue sections, and correct identification is imperative for guiding therapy. The Fontana-Masson silver stain for detecting melanin has been accepted as a relatively specific stain for diagnosing cryptococcosis in tissue based on few studies with limited numbers of organisms. This study was designed to test the value of the Fontana-Masson silver by investigating a large collection of tissues with infections that may mimic cryptococcosis. Cases of cryptococcosis and other infections that can morphologically mimic it were identified in the pathology archives of The Johns Hopkins Hospital and The Armed Forces Institute of Pathology. Overall, Fontana-Masson silver was positive in 25 (56%) of 45 cases, including infections caused by Cryptococcus neoformans (9/9), Coccidioides immitis (7/7), Blastomyces dermatitidis (4/10), Paracoccidioides brasiliensis (2/2), Lacazia loboi (1/1), and Rhinosporidium seeberi (1/1). The percentage of organisms staining varied widely, from less than 1% to 100%. Fontana-Masson silver was negative in all infections caused by Histoplasma capsulatum (n = 10), Histoplasma duboisii (n = 1), Sporothrix schenckii (n = 1), and the alga genus Prototheca (n = 2). Fontana-Masson silver was 100% sensitive for cryptococcosis. The specificity was low, however, with 5 of 9 noncryptococcal species being positive in some cases. These results need to be confirmed and extended to other isolates and species but it is clear that many organisms in the morphological differential diagnosis of cryptococcosis can be Fontana-Masson silver stain positive. Accordingly, results of the Fontana-Masson silver stain, especially a positive, should be interpreted cautiously and only in the context of the organism's morphological features and host factors.

  1. Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses (United States)

    Thompson, George R.; Rendon, Adrian; Ribeiro dos Santos, Rodrigo; Queiroz-Telles, Flavio; Ostrosky-Zeichner, Luis; Azie, Nkechi; Maher, Rochelle; Lee, Misun; Kovanda, Laura; Engelhardt, Marc; Vazquez, Jose A.; Cornely, Oliver A.; Perfect, John R.


    Background. Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV. Methods. The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed. Results. Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2–331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events. Conclusions. ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents. Clinical Trials Registration. NCT00634049. PMID:27169478

  2. Blastomycosis in Quebec (1981–90: Report of 23 Cases and Review of Published Cases from Quebec

    Directory of Open Access Journals (Sweden)

    G St-Germain


    Full Text Available Twenty-three cases of blastomycosis were reported in a survey conducted in the province of Quebec from 1981–90. Thirteen patients resided south of the St Lawrence River and the other 10, north. Two small geographical clusters were apparent in and around the cities of Sherbrooke and Quebec. The male to female ratio was 1.6:1 and the median age was 47 years (range 26 to 77. Lung involvement was observed in 19 cases and was the only site involved in 11. Cutaneous manifestations were reported in 11 cases while bone infection (three cases and central nervous system (CNS infections were also noted. Diagnosis was confirmed by culture in 21 cases and by histopathology in two cases. Of the 21 culture-positive cases, 12 strains of Blastomyces dermatitidis were isolated from lungs, nine from skin, and one each from bone and brain. Serodiagnostic tests by immunodiffusion or complement fixation were positive for only one of the 10 patients known to have been tested. Ten patients were treated with amphotericin B, 11 with ketoconazole, one with fluconazole and eight underwent surgery. While amphotericin B was used in eight of the 10 earliest treated cases, ketoconazole was administered in 10 of the 13 more recent cases. Of the patients for whom follow-up data have been obtained, 21 are reported cured (one of whom was not treated and one patient died of another cause. This survey confirms that blastomycosis is a rare disease in this endemic area and that patterns of therapy are changing.

  3. Pulmonary Blastomycosis in Vilas County, Wisconsin: Weather, Exposures and Symptoms

    Directory of Open Access Journals (Sweden)

    Dennis J. Baumgardner


    Full Text Available Purpose: Blastomycosis is a serious fungal infection contracted by inhalation of Blastomyces spores from the environment. Case occurrence in dogs in Vilas County, Wisconsin, has been associated with antecedent weather. We aimed to explore the effects of weather on the occurrence of human pulmonary blastomycosis in this area, and update exposure factors and symptoms since last published reports. Methods: Mandatory case reports were reviewed. Chi-square test was used for categorical data of exposures, comparing 1979–1996 (n=101 versus 1997–June 2013 (n=95. Linear regression was used to model local weather data (available 1990–2013; n=126; Southern Oscillation Index (SOI, North Atlantic Oscillation Index (NAOI, and Wisconsin River water discharge (WRD from the adjacent county (all available for 1984–2013; n=174; and case counts of known onset by warm (April–September and cold (October–March 6-month periods. Results: Distribution of pulmonary blastomycosis cases did not vary by season. Environmental exposures for the 1997–June 2013 group (mean age 45, 59% male were: residence(76%, excavation (42% and gardening (31%, all similar to the 1979–1996 group. Fishing (23% vs. 37%; P=0.09 and hunting (15% vs. 26%; P=0.13 exposures were less common in 1997–June 2013, but not significantly different. Overall, 69% of cases recalled some prior soil-disturbing activities. Considering the 6-month warm/cold periods, 19% of variation is explained by a direct relationship with total precipitation from two periods prior (P=0.005. There was no association of case occurrence with SOI, NAOI or WRD. Estimated annual incidence of blastomycosis for 1997–June 2013 was 27/100,000 compared with 44/100,000 for 1984–1996. Several symptoms were significantly less frequent in 2002–June 2013 compared to earlier years. Conclusions: As with dogs, human pulmonary blastomycosis occurrence is partially determined by antecedent precipitation. It is unclear if

  4. 侵袭性真菌病的非培养实验室诊断方法%Non-cultural methods for the laboratory diagnosis of invasive fungal diseases

    Institute of Scientific and Technical Information of China (English)

    杨启文; 徐英春


    侵袭性真菌病的非培养实验室检测方法主要包括真菌抗原检测、真菌抗体血清学检测以及分子生物学检测。真菌抗原检测包括(1,3)-β-D-葡聚糖检测、半乳甘露聚糖检测、隐球菌荚膜多糖抗原检测以及念珠菌甘露聚糖抗原检测等。不同的抗原用于诊断不同的真菌感染。抗真菌抗体的血清学检测主要包括荚膜组织胞浆菌、粗球孢子菌/副球孢子菌以及皮炎芽生菌的相应血清抗体的检测。分子生物学检测则包括非扩增的核酸检测技术、核酸扩增检测技术、直接测序以及基质辅助激光解吸电离飞行时间质谱( MALDI-TOF MS)技术。尽管分子生物学检测的方法尚未标准化,但其是未来侵袭性真菌病非培养检测的重要发展方向。(中华检验医学杂志,2014,37:721-724)%Non-cultural laboratory diagnostic methods include fungal antigen detection, anti-fungal antibody detection and molecular methods. Fungal antigen detection aim at ( 1, 3 )-β-D-glucan, galactomannan, cryptococcal capsular polysaccharide antigen and candida mannan antigen.Different antigen is used to diagnose different fungal infection.Antifungal antibody include antibody against Histoplasma capsulatum, Coccidioides immitis/Paracoccidiodes and Blastomyces dermatitidis.Molecular methods include non-amplification nucleic acid detection, nucleic acid amplification test, direct sequencing and matrix-assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF MS ) technology.Even though molecular methods are limited because of no standardization, the future of its usage is promising.

  5. Comparative genomics allowed the identification of drug targets against human fungal pathogens

    Directory of Open Access Journals (Sweden)

    Martins Natalia F


    Full Text Available Abstract Background The prevalence of invasive fungal infections (IFIs has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases. Results In silico analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for Candida albicans or Aspergillus fumigatus and other 2 genes (kre2 and erg6 relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (C. albicans, A. fumigatus, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Paracoccidioides lutzii, Coccidioides immitis, Cryptococcus neoformans and Histoplasma capsulatum. Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for α-1,2-mannosyltransferase and erg6 that encodes for Δ(24-sterol C-methyltransferase. Conclusions Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of

  6. 细菌或真菌对UF-1000i尿沉渣分析仪红细胞检测的影响%Influence of different bacteria or fungi on the determination of urinary sediments by UF-1000i urinary sediment analyzer

    Institute of Scientific and Technical Information of China (English)

    郑沁; 赵儒; 黄茜; 熊明; 粟军


    目的 探讨不同浓度不同种类细菌或真菌对UF-1000i尿沉渣分析仪(简称UF-1000i)红细胞(RBC)测定结果的影响,以对泌尿系统疾病诊断、评估提供更可靠的实验室依据.方法 健康体检者尿液标本制作成混合尿基质,将不同浓度泌尿系统感染常见细菌和真菌菌液加入制备混合尿基质,用UF-1000i检测各种浓度菌尿RBC.收集各种RBC浓度梯度病理血尿标本,加入白念珠菌菌液,调整真菌终浓度后用UF-1000i检测各种浓度菌尿RBC.每份标本同时进行显微镜镜检.结果 泌尿系统感染常见革兰阴性杆菌(大肠埃希菌、铜绿假单胞菌、肺炎克雷伯菌)、革兰阳性球菌(金黄色葡萄球菌)和低浓度的白念珠菌(<106/mL)对UF-1000i RBC测定结果无明显影响.粪肠球菌制备菌尿中,细菌浓度为109/mL时UF-1000i检测结果显示尿RBC假阳性.白念珠菌制备菌尿中,真菌浓度从106/mL开始UF-1000i检测结果显示尿RBC假阳性.真菌浓度增至108/mL时,导致血尿标本RBC定量结果显著假性增高 (P=0.006).结论 UF-1000i具有独立的双检测通道,在很大程度上减少了细菌对尿RBC检测的干扰.但并不能有效避免高浓度真菌对RBC检测结果的影响,易造成尿RBC检测假阳性结果而影响实验室检测质量,需进行显微镜镜检校正以保证检验结果的准确性.%Objective To study the influence of different bacteria or fungi with different levels on the determination of urinary red blood cell(RBC) count by UF-1000i urinary sediment analyzer (UF-l000i) ,so as to provide more reliable laboratory evidence in the diagnosis and follow-up of urinary tract diseases. Methods The urine RBC counts were analyzed by UF-l000i from urine mixture specimens and hematuria specimens with Blastomyces albicans,in parallel with manual microscopy respectively. Results The Granmegative bacilli ( Escherichia coli,Klebsiella,pneumonia and Pseudomonas aeruginosa) and Gram-positive cocci

  7. Analysis of related factors on urinary tract infection with diabetes%糖尿病并发尿路感染相关因素分析

    Institute of Scientific and Technical Information of China (English)



    Objective To analyze the related factors of urinary tract infection with diabetes. Methods Ret-rospective studies were conducted in 350 diabetes cases who were in hospital from 2008.01.01 to 2008.12.31 in en-docrine department of our hospital. Results The primary pathogen was Gram-negative bacteria(84.9%),The major one was Eachefichia coil (59.7%), the followed one was Enterococcus faecalis (11.2%). The Bacillus cloacae、Staphylococcus epidemidis、Klebsiella pneumoniae、Bacillus aerogenes、Bacillus proteus、Blastomyces albicans also were the pathogens which caused the urinary tract infection. The influence of infection:the higher was the incidence of female patients;The older was the diabetes patients,the higher was the incidence of urinary tract infection;The longer course of diabetes,the higher was the incidence of urinary tract infection; Complicated by the ketosis patients were higher in the incidence of urinary tract infection;The hyperglycosemia patients were higher than the multisystem pa-tients;the patients with nervous bladder were higher than the patients without. Conclusion Diabetes patients who suffered from urinary tract infection are more in old lady,long course、hyperglycosemia and with urgent or chronicity complication.%目的 探讨糖尿病并发尿路感染的相关因素.方法 回顾性分析350例糖尿病患者临床资料.结果 350例糖尿病患者中,并发尿路感染73例,占20.9%,女性186例患者中尿路感染者54例(29.0%),高于男性糖尿病患者164例中尿路感染者19例(11.6%)(χ2=16.08,P<0.01);空腹血糖<11.1 mmol/L,尿路感染者31例(17.4%),空腹血糖≥11.1 mmol/L,尿路感染者42例(24.4%),餐后2 h血糖<16.7 mmol/L,尿路感染者28例(15.4%),餐后2 h血糖≥16.7 mmol/L,尿路感染者45例(26.8%),血糖越高,尿路感染的发生率也越高(χ2=2.60、6.88,P<0.01);病程≥5年的糖尿病患者183例中并发尿路感染者48例(26.2%),高于病程<5年的糖尿病患者167

  8. 复方蛇床子灌注液对奶牛乳房炎6种主要致病菌的抑杀作用%The inhibition activity of compound Fructus cnidii perfusate on six main pathogens of cow mastitis

    Institute of Scientific and Technical Information of China (English)

    刘翠艳; 唐亮; 韩春杨; 章孝荣; 赵宏坤


    Objective To confirm the inhibitory effect of Fufang Shechuangzi (compound Fructus cnidii) perfusate on pathogenic bacteria of cow mastitis Method Fufang Shechuangzi perfusate was used as a subject drug. Six pathogenic bacteria (Staphylococcusaureus, Escherichia coli, Streptococcus agalactiae, Streptococcus dysgalactiae, Blastomyces albicans and Candida tropicalis) caused cow mastitis were used as experimental strains. The inhibition activities of Fufang Shechuangzi perfusate in vitro were evaluated by the agar plate diffusion method measuring inhibition zone and the solid medium of drug measuring the minimal inhibitory concentration. Result Fufang Shechuangzi perfusate showed better inhibitory activity to these six bacteria. The concentration of 0. 1 g/mL Fufang Shechuangzi perfusate had strong inhibitory activity to Streptococcus agalactiae and Staphylococcus aureus ( MIC value 0. 0015 g/mL) and the sizes of inhibition zone were 33 mm and 28 mm, respectively. Conclusion Fufang Shechuangzi perfusate has strong inhibition activities on six main pathogens of cow mastitis with extensive antibacterial spectrum, and the concentration of the drugs is positively correlated with the inhibition effects.%目的 通过实验证明复方蛇床子灌注液对奶牛乳房炎病原菌的抑杀作用.方法 复方蛇床子灌注液为受试药物,6种引起奶牛乳房炎的常见病原菌(金黄色葡萄球菌、大肠埃希菌、无乳链球菌、停乳链球菌、白色念珠菌和热带假丝酵母菌)为实验菌株,采用测定抑菌圈的琼脂平板扩散法和测定最小抑菌浓度(MIC)的药物固体培养基法来评价复方蛇床子灌注液的体外抗菌活性.结果 复方蛇床子灌注液对6种供试菌株均有较好的抑菌作用,其中0.1 g/mL的原药液对无乳链球菌和金黄色葡萄球菌表现了强大的抑制作用(MIC值达0.0015 g/mL).抑菌圈直径分别高达33mm和28 mm.结论 复方蛇床子灌注液对奶牛乳房炎6种主要致病菌

  9. Phamacodynamic Studies of Jingdekang Spray%净得康喷雾剂的抗菌、止痒、抗炎作用研究

    Institute of Scientific and Technical Information of China (English)

    刘元; 韦焕英; 黄凤娇


    Objective: To observe the mainly pharmacological effects of Jingdekang Spray. Method:Pharmacological effects of Jingdekang Spray on in vitro antibacterial action. The rat model of vaginitis infected with blastomyces albicans or baeteria were established,then the rats were randomly divided into four groups( 10 in each)and two groups were treated with Jingdekang Spray 2.0 g · kg - 1 and 0. 5 g· kg - 1 ( 1 mL· kg - 1 ), one group was treated with Fuyanping capsule 0. 5 g· kg - 1, and the last group was treated with distilled water. The therapeutic effects of Jingdekang Spray on vaginosis rats were observed. The cavia cobaya model of topical pruritus caused by histamine phosphate was used to observe the relieving itching effect of Jingdekang Spray, which were divided as mentioned above. The mouse model of ear swelling induced by croton oil was used to study the antiinfiammatory effect of Jingdekang Spray, which were randomly divided into four groups, 10 rats in each group, and two groups of the extender of croton oil in mouse's ear were treated with Jingdekang Spray 10.0, 2. 5 g· kg-1. Result: Jingdekang Spray could inhibit the growth of bacteria which caused vagina infection;restrain the bacterial and mycotic vaginitis evident. The inhibitory rate for bacterial vaginitis was 82.6%. The curative ratio of mycotica vaginitis was 90%.The spray could restrain the pruritus of cavy by histamine phosphate obviously,the inhibitory rate was 51.2%. The inhibitory rate of extender of croton oil in mouse's ear was 15.8%. Conclusion :Jingdekang Spray has effects of antibacterial, relieve itching and anti-inflammation.%目的:观察净得康喷雾剂的主要药效学作用.方法:采用体外抗菌;细菌致大鼠阴道炎模型、霉菌致大鼠阴道炎模型,取造模成功的大鼠随机分为4组,每组10只.其中2个组分别阴道给予净得康喷雾剂生药2.0,0.5g·kg-1(给药体积为1 mL·kg-1);1个组阴道给予妇炎平胶囊0.5 g·kg-1;余1组为模