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https://www.readbyqxmd.com/read/29891599/-in-vitro-and-in-vivo-evaluation-of-apx001a-apx001-and-other-gwt1-inhibitors-against-cryptococcus
#1
Karen Joy Shaw, Wiley A Schell, Jonathan Covel, Gisele Duboc, C Giamberardino, Mili Kapoor, Molly Moloney, Quinlyn A Soltow, Jennifer L Tenor, Dena L Toffaletti, Michael Trzoss, Peter Webb, John R Perfect
Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans , is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated the in vitro and in vivo activity of several compounds including APX001A and its prodrug APX001, currently in clinical development for invasive fungal infections. These compounds target the conserved Gwt1 enzyme that is required for the localization of glycosylphosphatidyl inositol (GPI)-anchored cell wall mannoproteins in fungi...
June 11, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29866070/undiagnosed-cryptococcus-gattii-meningitis-leading-to-subsequent-ventriculoperitoneal-shunt-infection-in-a-patient-with-symptoms-of-normal-pressure-hydrocephalus-case-report-and-literature-review
#2
Wutthiseth Dhitinanmuang, Piriyaporn Chongtrakool, Anupop Jitmuang
BACKGROUND: Cryptococcus gattii is known to be an etiologic agent of human cryptococcosis, particularly in immunocompetent persons. C. gattii infection usually involves the central nervous system, the respiratory tract, or may be disseminated. Here we report an atypical manifestation of C. gattii infection in a patient who had C. gattii meningitis complicating the ventriculoperitoneal (VP) shunt infection and concurrent infected intraabdominal VP shunt pseudocyst. CASE PRESENTATION: A 66-year-old Thai female was initially diagnosed with normal pressure hydrocephalus (NPH) and underwent programmable VP shunt placement...
June 4, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29863700/-cerebral-cryptococcosys-with-depressive-disorder
#3
M S Artemieva, I I Yurovskaya, A N Gavrik, A A Lukashenko, I E Danilin
A case of cerebral cryptococcosis is described. Cryptococcus neoformans is the most pathogenic in humans. It often affects lungs, skin, muscles and tissues of the Central Nervous System (CNS). In case of CNS involvement, the main clinically diagnosed form of the disease is cryptococcal meningitis. The authors describe a patient with non-specific symptoms of anxiety-depressive disorder and further development of neurological symptoms and behavioral deviations.
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29785613/neuroinfections-caused-by-fungi
#4
REVIEW
Katarzyna Góralska, Joanna Blaszkowska, Magdalena Dzikowiec
BACKGROUND: Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. METHODS: One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections"...
May 21, 2018: Infection
https://www.readbyqxmd.com/read/29780913/cryptococcal-choroiditis-in-advanced-aids-with-clinicopathologic-correlation
#5
Christopher M Aderman, Ian R Gorovoy, Daniel L Chao, Michele M Bloomer, Anthony Obeid, Jay M Stewart
Purpose: To describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS). Observations: The patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29780795/a-novel-de-novo-mutation-in-the-cd40-ligand-gene-in-a-patient-with-a-mild-x-linked-hyper-igm-phenotype-initially-diagnosed-as-cvid-new-aspects-of-old-diseases
#6
Tábata T França, Luiz F B Leite, Tiago A Maximo, Christiane G Lambert, Nuria B Zurro, Wilma C N Forte, Antonio Condino-Neto
Mutations in the CD40 ligand (CD40L) gene ( CD40LG ) lead to X-linked hyper-IgM syndrome (X-HIGM), which is a primary immunodeficiency (PID) characterized by decreased serum levels of IgG and IgA and normal or elevated IgM levels. Although most X-HIGM patients become symptomatic during the first or second year of life, during which they exhibit recurrent infections, some patients exhibit mild phenotypes, which are usually associated with hypomorphic mutations that do not abrogate protein expression or function...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29749873/fatal-cryptococcal-meningitis-in-an-aids-patient-complicated-with-immune-reconstitution-syndrome-refractory-to-prolonged-amphotericin-b-treatment
#7
Thilinie D Bandaranayake, Onyema E Ogbuagu, Amit Mahajan, Alexander O Vortmeyer, Merceditas S Villanueva
Cryptococcus neoformans is a ubiquitous encapsulated environmental yeast that can cause severe central nervous system disease, primarily in immune compromised hosts. In patients with AIDS, the spectrum of cryptococcal central nervous system disease includes meningitis, cystic lesions, and mass-like cryptococcomas. We report a fatal case of meningitis and cerebritis caused by C. neoformans in an AIDS patient refractory to multiple courses of liposomal amphotericin B despite immune recovery with antiretroviral therapy...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29742198/peeling-the-onion-the-outer-layers-of-cryptococcus-neoformans
#8
Daniel P Agustinho, Liza C Miller, Lucy X Li, Tamara L Doering
Cryptococcus neoformans is an opportunistic fungal pathogen that is ubiquitous in the environment. It causes a deadly meningitis that is responsible for over 180,000 deaths worldwide each year, including 15% of all AIDS-related deaths. The high mortality rates for this infection, even with treatment, suggest a need for improved therapy. Unique characteristics of C. neoformans may suggest directions for drug discovery. These include features of three structures that surround the cell: the plasma membrane, the cell wall around it, and the outermost polysaccharide capsule...
2018: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29740519/repurposing-drugs-to-fast-track-therapeutic-agents-for-the-treatment-of-cryptococcosis
#9
Megan Truong, Leigh G Monahan, Dee A Carter, Ian G Charles
Many infectious diseases disproportionately affect people in the developing world. Cryptococcal meningitis is one of the most common mycoses in HIV-AIDS patients, with the highest burden of disease in sub-Saharan Africa. Current best treatment regimens still result in unacceptably high mortality rates, and more effective antifungal agents are needed urgently. Drug development is hampered by the difficulty of developing effective antifungal agents that are not also toxic to human cells, and by a reluctance among pharmaceutical companies to invest in drugs that cannot guarantee a high financial return...
2018: PeerJ
https://www.readbyqxmd.com/read/29738314/treatment-of-cryptococcosis-in-non-hiv-immunocompromised-patients
#10
Andrés F Henao-Martínez, Daniel B Chastain, Carlos Franco-Paredes
PURPOSE OF REVIEW: Cryptococcosis has become a common opportunistic infection among non-HIV immunocompromised hosts. Recent reports have shown the incidence of Cryptococcosis among HIV-negative immunocompromised patients reaches close to half of the overall cases reported in the USA. Management of this infection in this population carries unique challenges. We aim to review relevant and recent research findings to develop treatment recommendations for this type of population. RECENT FINDINGS: Most of the recommendations for the management of non-HIV immunocompromised host are extrapolated from HIV studies...
May 5, 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29737452/comparison-of-clinical-features-and-prognostic-factors-of-cryptococcal-meningitis-caused-by-cryptococcus-neoformans-in-patients-with-and-without-pulmonary-nodules
#11
Wenhao Cao, Cui Jian, Huojun Zhang, Shuyun Xu
Whether the clinical features of cryptococcal meningitis (CM) patients vary with the coexistence of pulmonary nodules is not clear. This study aimed to compare the clinical features of CM in patients with and without pulmonary nodules detected by chest computed tomography (CT). The medical records of CM patients hospitalized in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2010, to December 31, 2016, were retrospectively reviewed. Baseline demographics, laboratory and radiographic findings, clinical managements, and outcomes were analyzed...
May 8, 2018: Mycopathologia
https://www.readbyqxmd.com/read/29716538/ventriculoperitoneal-shunts-in-non-hiv-cryptococcal-meningitis
#12
Jia Liu, Zhuo-Lin Chen, Min Li, Chuan Chen, Huan Yi, Li Xu, Feng Tan, Fu-Hua Peng
BACKGROUND: Persistent and uncontrollable intracranial hypertension (ICH) and difficulty in reducing Cryptococcus count are severe problems in cryptococcal meningitis (CM) patients. The therapeutic effects of ventriculoperitoneal shunts (VPS) in non-HIV CM patients are not fully known, and the procedure is somewhat unusual. Here, our study offers a review to investigate the role of VPS in non-HIV CM. METHODS: We retrospectively collected data on 23 non-HIV CM patients with and without ventriculomegaly from 2010 to 2016...
May 1, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29710329/chronic-meningitis-investigated-via-metagenomic-next-generation-sequencing
#13
Michael R Wilson, Brian D O'Donovan, Jeffrey M Gelfand, Hannah A Sample, Felicia C Chow, John P Betjemann, Maulik P Shah, Megan B Richie, Mark P Gorman, Rula A Hajj-Ali, Leonard H Calabrese, Kelsey C Zorn, Eric D Chow, John E Greenlee, Jonathan H Blum, Gary Green, Lillian M Khan, Debarko Banerji, Charles Langelier, Chloe Bryson-Cahn, Whitney Harrington, Jairam R Lingappa, Niraj M Shanbhag, Ari J Green, Bruce J Brew, Ariane Soldatos, Luke Strnad, Sarah B Doernberg, Cheryl A Jay, Vanja Douglas, S Andrew Josephson, Joseph L DeRisi
Importance: Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed. Objective: To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious...
April 16, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29704215/population-pharmacokinetic-modeling-to-describe-the-total-plasma-and-free-brain-levels-of-fluconazole-in-healthy-and-cryptococcus-neoformans-infected-rats-how-does-the-infection-impact-the-drug-s-levels-on-biophase
#14
Izabel Almeida Alves, Keli Jaqueline Staudt, Fernando Olinto Carreño, Graziela de Araujo Lock, Carolina de Miranda Silva, Stela Maris Kuze Rates, Teresa Dalla Costa, Bibiana Verlindo De Araujo
PURPOSE: The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats. METHOD: The infection was induced by the administration of 100 μL of inoculum (1.105  CFU) through the tail vein. Free drug in the brain was assessed by microdialisys (μD). Blood and μD samples were collected at pre-determined time points up to 12 h after intravenous administration of FLC (20 mg/kg) to healthy and infected rats...
April 27, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29678697/intracranial-cryptococcoma-clinicopathologic-correlation-and-surgical-outcome-a-single-institution-experience
#15
Alok Uppar, A R Prabhu Raj, Subhas Konar, Sandeep Kandregula, Dhaval Shukla, Sampath Somanna, B Indira Devi, Yasha C, Nagarathna Chandrashekar
OBJECTIVE: To describe clinical characteristics of patients with intracranial cryptococcoma, clinicopathologic findings, and outcomes after surgery. MATERIALS AND METHODS: Clinical data were collected from hospital case records, and pathologic confirmation was done by a neuropathologist. Clinical details, imaging features, and treatment modalities were evaluated and correlated with outcomes based on regular follow-up. RESULTS: This case series included 5 cases of histology- and culture-proven intracranial cryptococcoma...
April 17, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29668826/variability-in-innate-host-immune-responses-to-cryptococcosis
#16
REVIEW
Mariam Garelnabi, Robin C May
Cryptococcosis is an invasive fungal disease caused by Cryptococcus neoformans and the closely related species C. gattii. The severe form of the disease, cryptococcal meningitis (CM), is rapidly fatal without treatment. Although typically a disease of immunocompromised (especially HIV-positive) individuals, there is growing awareness of cryptococcal disease amongst non-immunocompromised patients. Whilst substantial progress has been made in understanding the pathogenicity of C. neoformans in HIV patients, prospective data on cryptococcosis outside the context of HIV remains lacking...
2018: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29663539/cryptococcal-infections-over-a-15-year-period-at-a-tertiary-facility-impact-of-guideline-management
#17
Ian Gassiep, Joel Douglas, Theophilus I Emeto, Katherine Crawley, Elliott G Playford
BACKGROUND: Cryptococcosis is an invasive fungal infection caused primarily by Cryptococcus neoformans and Cryptococcus gattii species, presenting predominantly as meningoencephalitis. The aim of this study is to assess all cryptococcal infections managed at our facility from 2001-2015 to determine incidence, risk factors, and comparison of outcomes prior to and following introduction of the 2010 Infectious Disease Society of America (IDSA) guidelines. METHODS: Retrospective analysis of all patients diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015...
April 17, 2018: Mycoses
https://www.readbyqxmd.com/read/29630156/ulcerative-cellulitis-of-the-arm-a-case-of-primary-cutaneous-cryptococcosis
#18
G P Henderson, Sean Dreyer
Cutaneous cryptococcosis is usually secondary to the hematogenous dissemination of pulmonary or meningeal Cryptococcus neoformans. Primary cutaneous cryptococcosis (PCC) is a rare form of the infection, typically caused by direct inoculation from trauma to the skin [1]. Most cases of PCC present as a localized cellulitis, abscess, nodule, or ulceration. Herein, we present a case of a rapidly spreading cellulitis characterized by bullae and ulceration, caused by direct inoculation from a fall.
February 15, 2018: Dermatology Online Journal
https://www.readbyqxmd.com/read/29619316/pulmonary-cryptococcal-infection-presenting-with-multiple-lung-nodules
#19
Thilini L Basnayake, Aijye Lim, Bart J Currie
Pulmonary infections from the environmental fungus Cryptococcus gattii ( C. gattii ) are notable for cryptococcomas, which are usually solitary and can be very large. As with infections with Cryptococcus neoformans (C. neoformans) patients can have concomitant cryptococcal meningitis; however, unlike for C. neoformans, infections with C. gattii often occur in immunocompetent patients. The highest published incidence of C. gattii infection has been in the Indigenous Australian population of Arnhem Land in the tropical north of the country...
2018: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29596441/quantifying-donor-to-donor-variation-in-macrophage-responses-to-the-human-fungal-pathogen-cryptococcus-neoformans
#20
Mariam Garelnabi, Leanne M Taylor-Smith, Ewa Bielska, Rebecca A Hall, Daniel Stones, Robin C May
Cryptococcosis remains the leading cause of fungal meningitis worldwide, caused primarily by the pathogen Cryptococcus neoformans. Symptomatic cryptococcal infections typically affect immunocompromised patients. However, environmental exposure to cryptococcal spores is ubiquitous and most healthy individuals are thought to harbor infections from early childhood onwards that are either resolved, or become latent. Since macrophages are a key host cell for cryptococcal infection, we sought to quantify the extent of individual variation in this early phagocyte response within a small cohort of healthy volunteers with no reported immunocompromising conditions...
2018: PloS One
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