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.
Highlights
Cryptococcosis is an infection of global importance with significant attributable mortality
central nervous system (CNS) cryptococcosis is typically associated with HIV infection [1] but in higher-income countries it is increasingly recognized in patients without HIV/AIDS [3,4,5,6,7]
Immune status, geography and environmental exposure likely all contribute to risk of cryptococcosis since the incidence in Australia’s aboriginal population is 10.4/million/year even correcting for place of residence; the commonest molecular genotype was VGI and mortality ranged between 0–15% [7]
Summary
Cryptococcosis is an infection of global importance with significant attributable mortality. Studies have demonstrated important differences in epidemiology, risk factors for infection, clinical complications and approaches to therapy between HIV-infected and non-HIV-infected patients, and within subgroups of the latter [3,7]. This article focuses on CNS cryptococcosis in non-HIV-infected patients including key insights into infection caused by C. gattii. A key message is that HIV-negative patients may require a longer duration of induction, and total, therapy, depending on both host and pathogen factors. More recently described risks include the use of newer biologicals and recreational intravenous drug use
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