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14 pages, 1717 KiB

Open AccessArticle

Cryptococcosis in Colombia: Compilation and Analysis of Data from Laboratory-Based Surveillance

by Patricia Escandón, Jairo Lizarazo, Clara Inés Agudelo and Elizabeth Castañeda

J. Fungi 2018, 4(1), 32; https://doi.org/10.3390/jof4010032 - 01 Mar 2018

Cited by 29 | Viewed by 5074

The passive and voluntary surveillance of cryptococcosis in Colombia since 1997 has seen an increasing participating rate, revealing its importance to both in immunosuppressed and immunocompetent people. The present work details the national data gathered in 1997–2016, through a retrospective analysis of the [...] Read more.

The passive and voluntary surveillance of cryptococcosis in Colombia since 1997 has seen an increasing participating rate, revealing its importance to both in immunosuppressed and immunocompetent people. The present work details the national data gathered in 1997–2016, through a retrospective analysis of the information collected in the survey. From a total of 1974 cases reported, an overall incidence of 0.23 cases per 100,000 people was found. This incidence rose to 1.1 cases per 1000 people in the Acquired Immunodeficiency Syndrome (AIDS) population. Cryptococcosis was most common in male young adults (26–40 years), with a male:female ratio of 3.9:1 in the general population and 5.4:1 in Human Immunodeficiency Virus (HIV) patients. Culture was the most common form of diagnosis in 96.3% of cases, recovering C. neoformans species in 87.5% and C. gattii in 3.1% of samples. VNI was the most prevalent (96.1%) molecular type, while VGII predominated in C. gattii isolates (54.3%). Early mortality was reported as the outcome in 47.5% of patients. Cryptococcosis remains an important opportunistic disease in Colombia and is gaining status as a primary pathogen in apparently immunocompetent patients. Our findings show the importance of including cryptococcosis as a notifiable disease, which will allow for improving opportune diagnosis and treatment, resulting in better patient outcomes. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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13 pages, 1823 KiB

Open AccessArticle

Differences in Sirtuin Regulation in Response to Calorie Restriction in Cryptococcus neoformans

by Tejas Bouklas, Lindsey Masone and Bettina C. Fries

J. Fungi 2018, 4(1), 26; https://doi.org/10.3390/jof4010026 - 18 Feb 2018

Cited by 5 | Viewed by 3574

Abstract

Cryptococcus neoformans successfully replicates in low glucose in infected patients. In the serotype A strain, H99, growth in this condition prolongs lifespan regulated by SIR2, and can be modulated with SIR2-specific drugs. Previous studies show that lifespan modulation of a cryptococcal population affects [...] Read more.

Cryptococcus neoformans successfully replicates in low glucose in infected patients. In the serotype A strain, H99, growth in this condition prolongs lifespan regulated by SIR2, and can be modulated with SIR2-specific drugs. Previous studies show that lifespan modulation of a cryptococcal population affects its sensitivity to antifungals, and survival in an infection model. Sirtuins and their role in longevity are conserved among fungi; however, the effect of glucose starvation is not confirmed even in Saccharomyces cerevisiae. Lifespan analysis of C. neoformans strains in low glucose showed that 37.5% exhibited pro-longevity, and lifespan of a serotype D strain, RC2, was shortened. Transcriptome comparison of H99 and RC2 under calorie restriction demonstrated differences, confirmed by real-time PCR showing that SIR2, TOR1, SCH9, and PKA1 expression correlated with lifespan response to calorie restriction. As expected, RC2-sir2Δ cells exhibited a shortened lifespan, which was reconstituted. However, shortened lifespan from calorie restriction was independent of SIR2. In contrast to H99 but consistent with altered SIR2 regulation, SIR2-specific drugs did not affect outcome of RC2 infection. These data suggest that SIR2 regulation and response to calorie restriction varies in C. neoformans, which should be considered when Sirtuins are investigated as potential therapy targets for fungal infections. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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Review

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11 pages, 297 KiB

Open AccessReview

An Overview of Sex Bias in C. neoformans Infections

by Tiffany E. Guess, Joseph A. Rosen and Erin E. McClelland

J. Fungi 2018, 4(2), 49; https://doi.org/10.3390/jof4020049 - 18 Apr 2018

Cited by 22 | Viewed by 4702

Abstract

Cryptococcosis, a fungal disease arising from the etiologic agent Cryptococcus neoformans, sickens a quarter of a million people annually, resulting in over 180,000 deaths. Interestingly, males are affected by cryptococcosis more frequently than females, a phenomenon observed for more than a half [...] Read more.

Cryptococcosis, a fungal disease arising from the etiologic agent Cryptococcus neoformans, sickens a quarter of a million people annually, resulting in over 180,000 deaths. Interestingly, males are affected by cryptococcosis more frequently than females, a phenomenon observed for more than a half century. This disparity is seen in both HIV⁻ (~3M:1F) and HIV⁺ (~8M:2F) populations of cryptococcal patients. In humans, male sex is considered a pre-disposing risk factor for cryptococcosis and males suffering from the disease have more severe symptoms and poorer outcomes. There are numerous observational, clinical and epidemiological studies documenting the male disadvantage in C. neoformans but with no further explanation of cause or mechanism. Despite being commonly acknowledged, little primary research has been conducted elucidating the reasons for these differences. The research that has been conducted, however, suggests sex hormones are a likely cause. Given that the sex difference is both prevalent and accepted by many researchers in the field, it is surprising that more is not known. This review highlights the data regarding differences in sexual dimorphism in C. neoformans infections and suggests future directions to close the research gap in this area. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

8 pages, 215 KiB

Open AccessReview

Interactions of Cryptococcus with Dendritic Cells

by Karen L. Wozniak

J. Fungi 2018, 4(1), 36; https://doi.org/10.3390/jof4010036 - 15 Mar 2018

Cited by 14 | Viewed by 3649

Abstract

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host [...] Read more.

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

22 pages, 2784 KiB

Open AccessReview

Innate Immunity against Cryptococcus, from Recognition to Elimination

by Althea Campuzano and Floyd L. Wormley, Jr.

J. Fungi 2018, 4(1), 33; https://doi.org/10.3390/jof4010033 - 07 Mar 2018

Cited by 51 | Viewed by 9706

Abstract

Cryptococcus species, the etiological agents of cryptococcosis, are encapsulated fungal yeasts that predominantly cause disease in immunocompromised individuals, and are responsible for 15% of AIDS-related deaths worldwide. Exposure follows the inhalation of the yeast into the lung alveoli, making it incumbent upon the [...] Read more.

Cryptococcus species, the etiological agents of cryptococcosis, are encapsulated fungal yeasts that predominantly cause disease in immunocompromised individuals, and are responsible for 15% of AIDS-related deaths worldwide. Exposure follows the inhalation of the yeast into the lung alveoli, making it incumbent upon the pattern recognition receptors (PRRs) of pulmonary phagocytes to recognize highly conserved pathogen-associated molecular patterns (PAMPS) of fungi. The main challenges impeding the ability of pulmonary phagocytes to effectively recognize Cryptococcus include the presence of the yeast’s large polysaccharide capsule, as well as other cryptococcal virulence factors that mask fungal PAMPs and help Cryptococcus evade detection and subsequent activation of the immune system. This review will highlight key phagocyte cell populations and the arsenal of PRRs present on these cells, such as the Toll-like receptors (TLRs), C-type lectin receptors, NOD-like receptors (NLRs), and soluble receptors. Additionally, we will highlight critical cryptococcal PAMPs involved in the recognition of Cryptococcus. The question remains as to which PRR–ligand interaction is necessary for the recognition, phagocytosis, and subsequent killing of Cryptococcus. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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17 pages, 753 KiB

Open AccessReview

Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans

by Steven T. Denham and Jessica C. S. Brown

J. Fungi 2018, 4(1), 25; https://doi.org/10.3390/jof4010025 - 17 Feb 2018

Cited by 42 | Viewed by 9907

Abstract

Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading [...] Read more.

Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape. We focus on fungal factors that allow C. neoformans to disseminate from the lungs via intracellular and extracellular routes. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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3412 KiB

Open AccessReview

Neuro-Immune Mechanisms of Anti-Cryptococcal Protection

by Rebecca A. Drummond

J. Fungi 2018, 4(1), 4; https://doi.org/10.3390/jof4010004 - 25 Dec 2017

Cited by 11 | Viewed by 5077

Abstract

Cryptococcal meningitis (CM) is a life-threatening fungal disease affecting both immunosuppressed and immunocompetent people. The main causative agent of CM is Cryptococcus neoformans, a basidiomycete fungus prevalent in the environment. Our understanding of the immune mechanisms controlling C. neoformans growth within the [...] Read more.

Cryptococcal meningitis (CM) is a life-threatening fungal disease affecting both immunosuppressed and immunocompetent people. The main causative agent of CM is Cryptococcus neoformans, a basidiomycete fungus prevalent in the environment. Our understanding of the immune mechanisms controlling C. neoformans growth within the central nervous system (CNS) is poor. However, there have been several recent advances in the field of neuroimmunology regarding how cells resident within the CNS, such as microglia and neurons, can participate in immune surveillance and control of infection. In this mini-review, the cells of the CNS are discussed with reference to what is currently known about how they control C. neoformans infection. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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2442 KiB

Open AccessReview

HIV-Associated Cryptococcal Disease in Resource-Limited Settings: A Case for “Prevention Is Better Than Cure”?

by Rita O. Oladele, Felix Bongomin, Sara Gago and David W. Denning

J. Fungi 2017, 3(4), 67; https://doi.org/10.3390/jof3040067 - 02 Dec 2017

Cited by 27 | Viewed by 7856

Abstract

Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in [...] Read more.

Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan Africa. Furthermore, 75% of the estimated 181,100 deaths associated with cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays have revolutionised the diagnosis of this deadly opportunistic infection. The theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic meningitis and death has been conclusively proven. Thus, cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has been demonstrated as a cost-effective strategy with survival benefits and has been incorporated into HIV national guidelines in several countries. However, this is yet to be implemented in a number of other high HIV burden countries. Flucytosine-based combination therapy during the induction phase is associated with improved survival, faster cerebrospinal fluid sterilisation and fewer relapses. Flucytosine, however, is unavailable in many parts of the world. Studies are ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis, proactive antifungal therapy with concurrent management of raised intracranial pressure creates the potential to markedly reduce mortality associated with this disease. Full article

(This article belongs to the Special Issue Cryptococcus and Cryptococcosis)

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