Cryptococcal meningitis

Bicanic, Tihana; Harrison, Thomas S.

doi:10.1093/bmb/ldh043

Cited by 329 publications

(359 citation statements)

References 68 publications

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“…Clinical observations have revealed that patients infected with C. gattii have a higher rate of hydrocephalus requiring shunting [18]. The mechanism is hypothesized to be the obstruction of CSF outflow by to a large burden of yeasts and polysaccharide plugging the arachnoid granulations.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

et al. 2009

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A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalization.

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Section: Discussionmentioning

confidence: 99%

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

et al. 2009

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“…1 CM has become the leading cause of community-acquired meningitis (ahead of tuberculous and bacterial meningitis), and if not treated correctly, has a significant mortality. 2 In 2009, the global incidence of CM ranged from 0.04-12% per year among persons living with human immunodeficiency virus (HIV)/AIDS. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases, range 144 000-1.3 million).…”

Section: Introductionmentioning

confidence: 99%

A medical audit of the management of cryptococcal meningitis in HIV-positive patients in the Cape Winelands (East) district, Western Cape

Pressentin¹,

Conradie

Mash

2012

South African Family Practice

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. 8 The key concerns were management of CMassociated raised intracranial pressure (ICP), general CM management uncertainties, and follow-up challenges regarding ART and long-term fluconazole adherence. The key recommendations included addressing resource needs (manometers), paying attention to the diagnosis and management of raised ICP, and addressing the need to develop a local CM treatment guideline. AbstractBackground: Cryptococcal meningitis (CM) has become the most common type of community-acquired meningitis. CM has a poor outcome if the initial in-hospital treatment does not adhere to standard guidelines. The aim of this audit was to improve the quality of the care of human immunodeficiency virus (HIV) positive patients with CM in the Cape Winelands District.Method: Following an initial audit in 2008, the researchers and a new audit team introduced interventions, and planned a second audit cycle. The folders of 25 HIV-positive adults (admitted to three district hospitals, one regional hospital, and one tuberculosis hospital) were audited.Results: Spinal manometry was performed more consistently in the regional hospital, than in the district hospitals. Reasons for failing to reach the 14-day amphotericin B target were in-patient deaths, drug stock problems, and renal impairment. The renal monitoring of amphotericin B treatment was suboptimal. The quality of care at district hospitals appeared to be comparable to that found at the regional hospital. The in-patient referral for antiretroviral treatment (ART) counselling was better in the district hospital setting. However, both levels of care had difficulty in achieving the four-week target between the onset of amphotericin B and onset of ART. Conclusion:Deficiencies in the quality of care remained. Between the prior and current audit cycles, there was no consistent improvement in care at the regional hospital. An integrated care pathway document has been developed, and adopted as policy in the Cape Winelands district. Its impact on the quality of care will be evaluated by a dedicated audit team in the future.Peer reviewed.

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“…The pathogenic fungus Cryptococcus neoformans is one of two species of cryptococci commonly associated with infection in humans (2,6). Unifying characteristics of the pathogenic cryptococci include the production of a polysaccharide capsule, the ability to form melanin pigments through the activity of the multicopper oxidase laccase, and the ability to adapt to and thrive at mammalian host temperature.…”

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confidence: 99%

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

et al. 2011

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Adaptation to host temperature is a prerequisite for any pathogen capable of causing deep infection in humans. Our previous studies demonstrated that a Cryptococcus neoformans ccr4⌬ mutant lacking the major deadenylase involved in regulated mRNA decay was defective in host temperature adaptation and therefore virulence. In this study, the ccr4⌬ mutant was found to exhibit characteristics of chronic unfolded-protein response (UPR) engagement in both the gene expression profile and phenotype. We demonstrate that host temperature adaptation in C. neoformans is accompanied by transient induction of the endoplasmic reticulum (ER) stress response and that Ccr4-dependent posttranscriptional gene regulation contributes to resolution of ER stress during host temperature adaptation.The pathogenic fungus Cryptococcus neoformans is one of two species of cryptococci commonly associated with infection in humans (2, 6). Unifying characteristics of the pathogenic cryptococci include the production of a polysaccharide capsule, the ability to form melanin pigments through the activity of the multicopper oxidase laccase, and the ability to adapt to and thrive at mammalian host temperature. Adaptation of C. neoformans to the host temperature is accompanied by major changes in gene expression as measured by microarray analysis and serial analysis of gene expression (SAGE) (5,19,29). This modulation of gene expression likely requires alterations in mRNA synthesis rates through activation of transcriptional transactivators and repressors, as well as alterations in chromatin structure. In addition to mRNA synthesis, our previous studies of a C. neoformans ccr4⌬ mutant lacking the major mRNA deadenylase involved in regulated mRNA turnover suggest a role for posttranscriptional regulation of gene expression in C. neoformans host temperature adaptation (24).Destabilization of specific transcripts in response to stress is highly conserved. In the model yeast Saccharomyces cerevisiae, deletion of CCR4 results in stabilization of transcripts encoding distinct functional classes (ribosome biogenesis, translation initiation, and tRNA synthesis) in response to temperature stress (13). In mammalian cells, subsets of transcripts were destabilized in response to heat shock, and induction of endoplasmic reticulum (ER) stress by treatment with tunicamycin or potentiation of ER calcium release by thapsigargin treatment triggered destabilization of a subset of mRNAs in which are included several transcripts encoding ribosomal proteins (8). This suggests that in response to heat shock and ER stress, distinct pools of transcripts representing specific cellular processes are targeted for degradation.The conserved ER stress response involves engagement of the unfolded-protein response (UPR) and the ER-associated degradation (ERAD) pathway (18). The UPR serves to retool the ER for enhanced protein folding, and ERAD serves to remove unfolded proteins from the ER lumen and shunt them into a degradative pathway. Microarray analyses performed in S. cerevisiae ...

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Cryptococcal meningitis

Cited by 329 publications

References 68 publications

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

A medical audit of the management of cryptococcal meningitis in HIV-positive patients in the Cape Winelands (East) district, Western Cape

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

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