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      Current and New Perspectives in the Diagnosis of Blastomycosis and Histoplasmosis

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          Abstract

          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 Histoplasma capsulatum 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.

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          Most cited references81

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          Loop-mediated isothermal amplification of DNA.

          T. Notomi (2000)
          We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.
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            Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

            Abstract Background Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. Methods To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups’ findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. Results There is no change in the classifications of “proven,” “probable,” and “possible” IFD, although the definition of “probable” has been expanded and the scope of the category “possible” has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. Conclusions These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
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              Histoplasmosis: a Clinical and Laboratory Update

              Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.
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                Author and article information

                Journal
                J Fungi (Basel)
                J Fungi (Basel)
                jof
                Journal of Fungi
                MDPI
                2309-608X
                29 December 2020
                January 2021
                : 7
                : 1
                : 12
                Affiliations
                Infectious Diseases Section, Veterans Affairs Ann Arbor Healthcare System, University of Michigan Medical School, Ann Arbor, MI 48105, USA; ckauff@ 123456med.umich.edu
                Author notes
                [* ]Correspondence: linderk@ 123456med.umich.edu
                Author information
                https://orcid.org/0000-0001-5352-4738
                Article
                jof-07-00012
                10.3390/jof7010012
                7823406
                33383637
                2c1024d5-467e-49a6-8ce6-2b5d3936eae8
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 December 2020
                : 24 December 2020
                Categories
                Review

                blastomycosis,blastomyces dermatitidis,histoplasmosis,histoplasma capsulatum,antigen detection

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