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Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients

1
Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2145, Australia
2
Westmead Institute for Medical Research, Westmead, Sydney 2145, Australia
3
Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital and the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2145, Australia
*
Author to whom correspondence should be addressed.
J. Fungi 2019, 5(3), 71; https://doi.org/10.3390/jof5030071
Received: 12 June 2019 / Revised: 22 July 2019 / Accepted: 29 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Fungal Infections of the Central Nervous System)
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PDF [312 KB, uploaded 2 August 2019]

Abstract

Central nervous system (CNS) cryptococcosis in non-HIV infected patients affects solid organ transplant (SOT) recipients, patients with malignancy, rheumatic disorders, other immunosuppressive conditions and immunocompetent hosts. More recently described risks include the use of newer biologicals and recreational intravenous drug use. Disease is caused by Cryptococcus neoformans and Cryptococcus gattii species complex; C. gattii is endemic in several geographic regions and has caused outbreaks in North America. Major virulence determinants are the polysaccharide capsule, melanin and several ‘invasins’. Cryptococcal plb1, laccase and urease are essential for dissemination from lung to CNS and crossing the blood–brain barrier. Meningo-encephalitis is common but intracerebral infection or hydrocephalus also occur, and are relatively frequent in C. gattii infection. Complications include neurologic deficits, raised intracranial pressure (ICP) and disseminated disease. Diagnosis relies on culture, phenotypic identification methods, and cryptococcal antigen detection. Molecular methods can assist. Preferred induction antifungal therapy is a lipid amphotericin B formulation (amphotericin B deoxycholate may be used in non-transplant patients) plus 5-flucytosine for 2–6 weeks depending on host type followed by consolidation/maintenance therapy with fluconazole for 12 months or longer. Control of raised ICP is essential. Clinicians should be vigilant for immune reconstitution inflammatory syndrome. View Full-Text
Keywords: Cryptococcosis; Cryptococcus neoformans; Cryptococcus gattii; central nervous system; meningo-encephalitis; cerebral infection; HIV-negative patients; epidemiology; antifungal therapy Cryptococcosis; Cryptococcus neoformans; Cryptococcus gattii; central nervous system; meningo-encephalitis; cerebral infection; HIV-negative patients; epidemiology; antifungal therapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Beardsley, J.; Sorrell, T.C.; Chen, S. .-A. Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients. J. Fungi 2019, 5, 71.

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