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      Cryptococcosis

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          Abstract

          Cryptococcosis is an infectious disease caused by the encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii. Once a relatively uncommon cause of human disease, cryptococcal infection can develop in apparently immunocompetent hosts and has emerged as an important opportunistic infection in humans over the past several decades as immunocompromised populations expand in the setting of HIV/AIDS, organ transplantation, malignancies, and treatment for other conditions. Clinical manifestations are myriad but pulmonary and central nervous system (CNS) infections are the most common. Improvements in diagnostic testing and standardized approaches to antifungal therapy, when available, have made considerable impact in the management of this infection. While the widespread use of highly active antiretroviral therapy (HAART) has improved the outcome of cryptococcosis in many HIV-infected patients, cryptococcosis remains an entity of considerable morbidity and mortality in many parts of the world, and restoration of host immunity can present management challenges that require individualized management. As immunocompromised populations continue to expand, it is likely that cryptococcosis will remain an important opportunistic fungal infection of humans requiring ongoing investigation.

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          Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

          Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
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            Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis

            The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19−/−) and IL-17R–deficient (IL-17RA−/−) mice experienced severe OPC, whereas Th1-deficient (IL-12p35−/−) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19−/− and IL-17RA−/−, but not IL-12−/−, mice, and TCR-αβ cells were more important than TCR-γδ cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and β defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.
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              Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.

              Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.
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                Author and article information

                Contributors
                +12109164355 , +1210916-0388 , drhospenthal@gmail.com
                +12105674132 , +1210567-4076 , mrinaldi@satx.rr.com
                eileen.maziarz@dm.duke.edu
                perfe001@mc.duke.edu
                Journal
                978-3-319-13090-3
                10.1007/978-3-319-13090-3
                Diagnosis and Treatment of Fungal Infections
                Diagnosis and Treatment of Fungal Infections
                978-3-319-13089-7
                978-3-319-13090-3
                24 November 2014
                2015
                : 175-193
                Affiliations
                [2 ]GRID grid.267309.9, ISNI 0000000106295880, University Of Texas Health Science Cente, ; San Antonio, Texas USA
                [3 ]GRID grid.215352.2, ISNI 0000000121845633, University of Texas, San Antonio Health Science Center, ; San Antonio, Texas USA
                GRID grid.189509.c, ISNI 0000000100241216, Department of Medicine, Division of Infectious Diseases, , Duke University Medical Center, ; PO Box 102359, 27710 Durham, NC USA
                Article
                15
                10.1007/978-3-319-13090-3_15
                7122569
                9b149559-8851-43c1-9a36-239e1089f1fa
                © Springer International Publishing Switzerland 2015

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                © Springer International Publishing Switzerland 2015

                cryptococcosis,cryptococcus neoformans,cryptococcus gattii,cryptococcal meningitis,opportunistic mycoses,hiv/aids,solid organ transplantation (sot),central nervous system (cns) infection,immune reconstitution inflammatory syndrome (iris)

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