Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients

Beardsley, Justin; Sorrell, Tania C.; Chen, Sharon C.‐A.

doi:10.3390/jof5030071

Cited by 76 publications

(83 citation statements)

References 135 publications

(252 reference statements)

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“…In addition, laccase activity differs not only between species but also at the cellular location where it is quantified. Perhaps higher melanin production and lower capsule thickness are important factors that favor the dissemination and survival of C. neoformans in the central nervous system, unlike C. gattii, which is strongly associated with pulmonary cryptococcosis (43).…”

Section: Discussionmentioning

confidence: 99%

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

Sousa

Júnior

Frazão

et al. 2020

Preprint

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Cryptococcus spp. are important human pathogens responsible for about 180,000 deaths per year. Studying their virulence attributes can lead to better cryptococcosis prevention and treatment. In this work, we systematically investigated virulence attributes of Cryptococcus spp. clinical isolates and correlated them with patient data. We collected 66 C. neoformans and 19 C. gattii isolates from Brazilian patients and analyzed multiple phenotypes related with their capsule, production of laccase, melanin and extracellular vesicles. We also tested their virulence in Galleria mellonella and ability to evade macrophage LC3-associated phagocytosis (LAP). All phenotypes analyzed varied widely among the isolates, but C. neoformans isolates tended to melanize faster and more intensely and produce thinner capsules in comparison with C. gattii. We also observed correlations that match previous studies, such as that between secreted laccase – but not total melanin production – and disease outcome in patients. The most striking results, though, came from our measurements of Cryptococcus colony melanization kinetics, which followed a sigmoidal curve for most isolates. Faster melanization correlated positively with LAP evasion, virulence in G. mellonella and worse prognosis in humans. These results suggest that the speed of melanization, more than the total amount of melanin Cryptococcus spp. produces, is crucial for virulence.Graphical abstract

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Section: Discussionmentioning

confidence: 99%

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

Sousa

Júnior

Frazão

et al. 2020

Preprint

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“…Cryptococcus neoformans is the etiological agent of the cryptococcosis, a systemic mycosis with dissemination to central nervous system causing meningoencephalitis and primarily affecting immunocompromised patients such as HIV-positive patients (Maziarz and Perfect, 2016;Rajasingham et al, 2017;Beardsley et al, 2019).…”

Section: Cryptococcus Neoformansmentioning

confidence: 99%

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

et al. 2020

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The fungal cell wall is located outside the plasma membrane and is the cell compartment that mediates all the relationships of the cell with the environment. It protects the contents of the cell, gives rigidity and defines the cellular structure. The cell wall is a skeleton with high plasticity that protects the cell from different stresses, among which osmotic changes stand out. The cell wall allows interaction with the external environment since some of its proteins are adhesins and receptors. Since, some components have a high immunogenic capacity, certain wall components can drive the host's immune response to promote fungus growth and dissemination. The cell wall is a characteristic structure of fungi and is composed mainly of glucans, chitin and glycoproteins. As the components of the fungal cell wall are not present in humans, this structure is an excellent target for antifungal therapy. In this article, we review recent data on the composition and synthesis, influence of the components of the cell wall in fungi-host interaction and the role as a target for the next generation of antifungal drugs in yeasts (Candida and Cryptococcus) and filamentous fungi (Aspergillus).

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“…Cryptococcal meningitis (CM) is one of the most common clinical presentations of cryptococcosis, which accounts for more than 1 million cases and 625 000 deaths per year [1]. Elevated intracranial pressure (ICP) is the most common complication of CM, and can cause impaired mental status, neurological deterioration, and severe disability [2][3].…”

Section: Introductionmentioning

confidence: 99%

Triple therapy combined with ventriculoperitoneal shunts can improve neurological function and shorten hospitalization time in non-HIV cryptococcal meningitis patients with increased intracranial pressure

Liu

Deng

et al. 2020

Preprint

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Background: Raised intracranial pressure (ICP) and insufficient antifungal regimens, are the two main factors result to unsatisfactory outcomes in non-HIV cryptococcal meningitis (CM) patients. In this study, we try to discuss that whether triple therapy of amphotericin B (AmB), fluconazole (Flu), 5flucytosine (5-FC) plus ventriculoperitoneal shunts (VPS) is superior to AmB, 5-FC, Flu plus intermittent lumbar puncture in induction therapy in non-HIV CM patients with increased ICP. Methods:We reviewed 66 clinical records from non-HIV CM patients with increased ICP. The demographic and clinical characteristics, BMRC staging, cerebrospinal fluid profiles (CSF), brain magnetic resonance imaging, treatment, and outcomes of these individuals were retrospectively analyzed. All non-HIV CM patients with increased ICP (≥ 25 cmH2O) were divided into two groups, including 27 patients treated with triple antifungal agents and 39 patients treated with the same triple therapy plus VPS.Results: Triple therapy plus VPS group had a significantly higher frequency of satisfactory outcomes.More patients in triple therapy plus VPS group have CSF sterilization at 10 weeks follow-up. And patients in triple therapy plus VPS group present with lower CSF opening pressure, less CSF cryptococci count and CSF culture positive, and lower BMRC staging scores one week after VPS.Patients in triple therapy plus VPS group got the improvement in neurological function circumstances evaluated by comparing the BMRC staging before and after VPS. Triple therapy plus VPS group patients had shorter hospital stay. Conclusion:Triple antifungal agents combined with VPS can effectively reduce ICP, have faster rate of clearance of Cryptococcus, improve nerve function, shorten hospitalization time and get better outcomes in non-HIV CM patients with increased ICP. Our study indicated that triple therapy plus early VPS is maybe the optimal treatment for non-HIV CM patients with increased ICP. BackgroundCryptococcal meningitis (CM) is one of the most common clinical presentations of cryptococcosis, which accounts for more than 1 million cases and 625 000 deaths per year [1]. Elevated intracranial pressure (ICP) is the most common complication of CM, and can cause impaired mental status, neurological deterioration, and severe disability [2-3].The Infectious Diseases Society of America (IDSA) recommended the induction therapy of 4 amphotericin B (AmB) (0.7-1.0 mg/kg per day) combining with 5-flucytosine (5-FC) (100 mg/kg per day) for at least 4 weeks as the preferred regimen for non-HIV-infected and non-transplant patients with CM [4]. However, AmB and 5-FC may often cause severe toxic effects so that CM patients can't endure the recommended dosages of antifungal drugs. In addition, increased ICP (≥ 25 cm H2O) is frequent with CM, and is associated with reduced short-term survival and impaired treatment response [5]. Raised ICP and only moderately effective antifungal regimens, which frequently take more than 4-6 weeks to sterilize cerebrospinal fluid (CSF), are two ...

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Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients

Cited by 76 publications

References 135 publications

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

Triple therapy combined with ventriculoperitoneal shunts can improve neurological function and shorten hospitalization time in non-HIV cryptococcal meningitis patients with increased intracranial pressure

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