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Re-estimation of the burden of serious fungal diseases in Uganda.

BACKGROUND: It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the availability of local data. OBJECTIVE: We sought to update the 2015 publication on the incidence and prevalence of serious fungal diseases in Uganda. METHODS: Using the Leading International Fungal Education methodology, we reviewed published data on fungal diseases and drivers of fungal diseases in Uganda. Regional or global data were used where there were no Ugandan data. RESULTS: With a population of ~45 million, w

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… Cryptococcosis Cryptococcosis, predominantly caused by Cryptococcus neoformans , a WHO critical priority pathogen, 5 accounts for 15–20% of AIDS-related deaths annually, with a disproportionate effect on PLWH in East, Central, Southern, and West Africa. 76 In Africa, our recent systematic review has … Cryptococcosis data, the most studied fungal disease in Uganda, are mainly derived from prospective clinical studies which may not translate into a good epidemiological estimate. …

Discovery of new fungal jumonji H3K27 demethylase inhibitors for the treatment of Cryptococcus neoformans and Candida auris infections.

Invasive fungal infections have become a serious public health problem. To tackle the challenges of limited efficacy in antifungal therapy and severe drug resistance, antifungal drugs with new mechanisms of action are urgently needed. Our previous study identified JIB-04 to be an inhibitor of fungal histone demethylase (HDM). To promote target validation and inhibitor design, herein a series of new JIB-04 derivatives were designed and synthesized. After the establishment of structure-activity relationship, compound A4 was identified to possess potent antifungal activity against Cryptococcus ne

Central Nervous System-Infecting Pathogens Escherichia coli and Cryptococcus neoformans Exploit the Host Pdlim2 for Intracellular Traversal and Exocytosis in the Blood-Brain Barrier.

Microbial penetration of the blood-brain barrier, a prerequisite for the development of central nervous system (CNS) infection, involves microbial invasion, intracellular traversal, and exocytosis. Microbial invasion of the blood-brain barrier has been investigated, but the molecular basis for microbial traversal and exit from the blood-brain barrier remains unknown. We performed transcriptome analysis of human brain microvascular endothelial cells (HBMEC) infected with Escherichia coli and Cryptococcus neoformans, representative bacterial and fungal pathogens common in CNS infections. Among t

Cryptococcus albidus Fungemia in an Immunosuppressed Child: Case Report and Systematic Literature Review.

Cryptococcus albidus, synonymous with Naganishia albida, rarely causes opportunistic infection in immunocompromised individuals. Its clinical features, particularly in children, are not well defined. Here, we report a case of C albidus fungemia in an immunosuppressed child; we also present results of a systematic review, for which we searched PubMed, Embase, and Web of Science using the keywords "cryptococcus" and "albidus." Our goal was to describe the spectrum of disease, diagnostic approaches, therapies, and outcomes. We identified 20 cases of invasive infection, only 2 of which involved ch

Production of IL-17A at Innate Immune Phase Leads to Decreased Th1 Immune Response and Attenuated Host Defense against Infection with Cryptococcus deneoformans.

IL-17A is a proinflammatory cytokine produced by many types of innate immune cells and Th17 cells and is involved in the elimination of extracellularly growing microorganisms, yet the role of this cytokine in the host defense against intracellularly growing microorganisms is not well known. Cryptococcus deneoformans is an opportunistic intracellular growth fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. In the current study, we analyzed the role of IL-17A in the host defense against C. deneoformans infection. IL-17A was quickly produ

Multicenter Cryptococcal Antigen Screening of HIV-Infected Patients in Iran.

Early diagnosis and targeted preemptive antifungal treatment are crucial in reducing cryptococcal meningitis (CM)-related mortality in individuals living with human immunodeficiency virus (HIV). The present study was performed to determine cryptococcal antigenemia and outcomes among HIV-infected patients in Iran. This multicenter prospective study was conducted between October 2016 and December 2018. For the purpose of the study, blood samples were randomly collected from 177 profoundly immunosuppressed (CD4+ counts < 200 cells/µL) HIV-positive individuals in six major cities of Iran. The pati

Environmental distribution of Cryptococcus species and some other yeast-like fungi in India.

A study of environmental distribution revealed the occurrence of Cryptococcus neoformans and C. gattii in 9% and 3%, respectively, of 611 samples investigated. C. neoformans showed the highest isolation frequency from tree trunk hollows in Delhi (31%), whereas C. gattii occurred in 12% of the samples in Delhi and 5% in Rajasthan. In addition, Cryptococcus laurentii (=Papiliotrema laurentii), C. rajasthanensis (=Papiliotrema rajasthanensis), C. podzolicus (=Saitozyma podzolica) and C. flavescens (=Papiliotrema flavescens) occurred in 0.5% each. The recovery of C. flavescens and C. podzolicus wa

Peritoneal Dialysis-Related Peritonitis: Atypical and Resistant Organisms.

Peritoneal dialysis (PD)-related peritonitis remains to be one of the most frequent and serious complications of PD. In this study, existing literature has been reviewed on PD peritonitis caused by atypical organisms and antibiotic resistant organisms and their impact on patient outcomes. Although uncommon, delay in recognition of PD peritonitis caused by atypical organisms can lead to poor patient outcomes if there is a delay in diagnosis and implementation of appropriate treatment. There is also a large difference in prevalence of antibiotic-resistant infections across the world with variabl

[Prevalence and factors associated with cryptococcal antigenemia in HIV-infected patients in Cotonou/Benin].

OBJECTIVE: Determine the prevalence of cryptococcal antigenemia and associated factors in HIV-infected patients in Cotonou in order to introduce systematic screening in national guidelines. PATIENTS AND METHODS: This is a cross-sectional, descriptive and analytical study conducted from June to September 2015 in four outpatient treatment centers with adult patients infected with HIV, receiving or not antiretroviral treatment with a number of CD4≤200cell/μL and who have given their informed consent to participate in the study. For each enrolled patient, after signing the informed consent form,

Cryptococcal osteomyelitis: a report of 5 cases and a review of the recent literature.

Cryptococcus neoformans is a fungal pathogen associated with advanced HIV disease and other disorders associated with immune dysfunction. The pulmonary and the central nervous system are the most common manifestations of the disease. Localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. Herein, we present five cases of Cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. We also identified 84 additional cases of isolated cryptococcal osteomyelitis in the literature. Using these data, we have made some general recommendations regarding a

A two-gene balance regulates Salmonella typhimurium tolerance in the nematode Caenorhabditis elegans.

Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediated by the reciprocal activity of lys-7 and the tyrosine kinase abl-1. Together this i

Invasion of Cryptococcus neoformans into human brain microvascular endothelial cells is mediated through the lipid rafts-endocytic pathway via the dual specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3).

Cryptococcus neoformans is a neurotropic fungal pathogen, which provokes the onset of devastating meningoencephalitis. We used human brain microvascular endothelial cells (HBMEC) as the in vitro model to investigate how C. neoformans traverses across the blood-brain barrier. In this study, we present several lines of evidence indicating that C. neoformans invasion is mediated through the endocytic pathway via lipid rafts. Human CD44 molecules from lipid rafts can directly interact with hyaluronic acid, the C. neoformans ligand. Bikunin, which perturbs CD44 function in the lipid raft, can block

Cryptococcus gattii meningoencephalitis in an immunocompetent person 13 months after exposure.

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 pati

Identification of Cryptococcus gattii by use of L-canavanine glycine bromothymol blue medium and DNA sequencing.

Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi. Cryptococcus neoformans is ecologically widespread and affects primarily immunocompromised patients, while C. gattii is traditionally found in tropical climates and has been reported to cause disease in immunocompetent patients. l-Canavanine glycine bromothymol blue (CGB) agar can be used to differentiate C. neoformans and C. gattii, but there are few reports of its performance in routine clinical practice. Growth of C. gattii on CGB agar produces a blue color, indicating the assimilation of glycine, while C.

Simultaneous identification of molecular and mating types within the Cryptococcus species complex by PCR-RFLP analysis.

The Cryptococcus species complex consists of two species, Cryptococcus neoformans and Cryptococcus gattii, which cause systemic infections in both immunocompromised and immunocompetent patients. Both species have a bipolar mating system, with mating type (MAT) alpha being predominant in clinical and environmental isolates. The strains of the Cryptococcus species complex have been divided into eight major molecular types, which show differences in epidemiology, biology and pathogenicity. In this study, two PCR-RFLP analyses, based on the CAP1 and GEF1 genes, which are both located at the MAT lo

The effect of corticosteroids on visual loss in Cryptococcus neoformans var. gattii meningitis.

In Papua New Guinea visual loss is a frequent sequal to Cryptococcus neoformans var. gattii meningitis in immunocompetent patients. We have previously postulated that visual loss may occur as a result of the immunological response to infection around the optic nerve. This retrospective study set out to explore the effect of corticosteroids on visual outcome. Sixteen patients received varying doses of corticosteroid (mainly 100-250 mg of hydrocortisone daily for the prevention of febrile reactions to amphotericin) and 10 received anticryptococcal therapy alone. Visual deterioration occurred les

Melanin, melanin "ghosts," and melanin composition in Cryptococcus neoformans.

Melanin synthesis is associated with virulence for the pathogenic fungus Cryptococcus neoformans. Exposure of nonmelanized C. neoformans 4067 cells to 4 M guanidinium isothiocyanate followed by 6 M HCl at 100 degrees C resulted in complete solubilization of cellular structures. However, exposure of melanized C. neoformans 24067 to the same conditions produced a suspension of black particles. Analysis of black particles with transmission and scanning electron microscopy revealed cell "ghosts" with electron-dense walls. Electron spin resonance (ESR) spectroscopy of suspensions of black particles

Retinal vascular nonperfusion and retinal neovascularization as a consequence of cytomegalovirus retinitis and cryptococcal choroiditis.

BACKGROUND: Cytomegalovirus retinitis and cryptococcal choroiditis are opportunistic infections in patients with acquired immune deficiency syndrome. These infections are associated with a retinal vasculitis and vascular attenuation. METHODS: We present a case of retinal vascular nonperfusion and retinal neovascularization in a patient with acquired immune deficiency syndrome. RESULTS: Retinal vascular nonperfusion and retinal neovascularization were confirmed by fluorescein angiography. CONCLUSIONS: This is the first reported case of retinal neovascularization in a patient with acquired im