- Cryptococcal pleuritis with pleural effusion as the only clinical presentation in a patient with hepatic cirrhosis: A case report and literature review. [Journal Article]
- MMedicine (Baltimore) 2019; 98(28):e16354
- CONCLUSIONS: Similar cases in cryptococcal pleuritis patients with pleural effusion as the only clinical presentation in the literature are also reviewed. Through literature review, we recommend that pleural effusion cryptococcal antigen test should be used to diagnose cryptococcal pleuritis to reduce misdiagnosis. The early administration of antifungal drug with activity to Cryptococcus seemed beneficial in preventing dissemination of cryptococcosis.
- Repurposing the thrombopoietin receptor agonist eltrombopag as an anticryptococcal agent. [Journal Article]
- MMMed Mycol 2019 Jul 12
- In this study, a Food and Drug Administration (FDA)-approved drug with previously unreported antifungal activity was investigated for suitability for use as an anticryptococcal agent. First, we scree…
In this study, a Food and Drug Administration (FDA)-approved drug with previously unreported antifungal activity was investigated for suitability for use as an anticryptococcal agent. First, we screened a compound library of 1018 FDA-approved drugs against Cryptococcus neoformans. Of 52 drugs possessing anti-Cryptococcus activity, eltrombopag was chosen due to its novel activity. The susceptibility of Cryptococcus against eltrombopag was then studied by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), while the synergy of eltrombopag with other drugs was tested by fractional inhibitory concentration index (FICI). Eltrombopag had a limited spectrum of antifungal activity against C. neoformans/C. gattii species complex (MICs of 0.125 mg/l), Candida glabrata (MIC, 0.25 mg/l), and Trichophyton rubrum (MIC, 0.5 mg/l). Eltrombopag affected cryptococcal virulence factors, including capsule and biofilm formation, melanin production, and growth ability at 37°C. Further, RNA sequencing and deletion mutant library screening experiments revealed that genes involved in the calcineurin pathway, lipid biosynthesis, membrane component, and transporter genes were associated with eltrombopag. In addition, eltrombopag showed synergism with the calcineurin inhibitor FK506 (FICI < 0.5) against Cryptococcus species. In conclusion, eltrombopag exhibited excellent antifungal activity against Cryptococcus species potentially via a mode of action which interferes with virulence factors and the calcineurin pathway, indicating that eltrombopag might be usefully repurposed as an antifungal agent for treating cryptococcosis.
- Case Report: Cryptococcal meningitis in an apparently immunocompetent patient in Nepal - challenges in diagnosis and treatment. [Case Reports]
- WOWellcome Open Res 2019; 4:55
- A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for…
A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for Cryptococcus in the CSF helped in making the diagnosis of cryptococcal meningitis in our patient who was apparently immunocompetent. Treatment with liposomal amphotericin B could not be started on time due to financial constraints. The patient had a stroke and further deteriorated. Liposomal amphotericin B is stocked by the government of Nepal for free supply to patients with visceral leishmaniasis, but the policy does not allow the drug to be dispensed for other infections. The family members of our patient acquired the drug within a few days from a government center using their political connections and following administering the treatment the patient improved. This case demonstrates the utility of considering cryptococcal meningitis as a differential diagnosis, and including tests for Cryptococcus when dealing with immunocompetent patients presenting with meningitis. It also demonstrates the effects of the sociopolitical situation on health care delivery in low- and middle-income countries (LMICs) such as Nepal.
- A Mimic of Hepatic Encephalopathy: Two Cases of Cryptococcal Meningitis in North America. [Case Reports]
- JCJ Clin Transl Hepatol 2019 Jun 28; 7(2):191-193
- In the non-human immunodeficiency virus infected population, cryptococcosis occurs primarily in people who are functionally immunosuppressed, including patients who have undergone solid organ transpl…
In the non-human immunodeficiency virus infected population, cryptococcosis occurs primarily in people who are functionally immunosuppressed, including patients who have undergone solid organ transplantation requiring immunosuppressive medications, are on corticosteroids, or have renal failure or cirrhosis. Cryptococcal meningitis poses a particular challenge in the setting of cirrhosis because its clinical presentation can mimic hepatic encephalopathy. Here, we describe two patients with decompensated cirrhosis, both with a known history of hepatic encephalopathy who had lumbar punctures and were found to have cryptococcal meningitis. The first patient had a subacute fluctuating change in mental status, while the second patient had progressive subacute headaches, gait disturbance, and hearing loss. Both patients were treated with amphotericin B and flucytosine induction, but only the second survived to maintenance therapy. These cases demonstrate the importance of having a high index of suspicion for cryptococcal meningitis in cirrhosis and having a low threshold for performing a lumbar puncture when altered mental status or other neurologic complaints are not fully explained by hepatic encephalopathy. We also provide a brief review of the pathobiology of cryptococcal infection in cirrhosis and highlight the challenges in therapy.
- Pulmonary cryptococcosis characteristics in immunocompetent patients-A twenty-year clinical retrospective analysis in China. [Journal Article]
- MMycoses 2019 Jul 09
- CONCLUSIONS: Gender and alcohol drinking could be PC risk factors of concern in patients without severe immunodeficiency. No significant difference occurred in symptoms or radiographic characteristics between patients with different levels of immune status. The unique radiographic non-air pathway distribution in the lung may be the feature of Cryptococcus invasion that may enhance accurate diagnosis. This article is protected by copyright. All rights reserved.
- Isolation, identification and screening of yeasts towards their ability to assimilate biodiesel-derived crude glycerol: microbial production of polyols, endopolysaccharides and lipid. [Journal Article]
- JAJ Appl Microbiol 2019 Jul 09
- CONCLUSIONS: Newly isolated, food-derived and non-previously studied yeast isolates converted biodiesel-derived glycerol into several added-value metabolites.Alternative ways of crude glycerol valorization through yeast fermentations were provided and added-value compounds were synthesized. This article is protected by copyright. All rights reserved.
- Molecular docking and pharmacokinetic evaluation of natural compounds as targeted inhibitors against Crz1 protein in Rhizoctonia solani. [Journal Article]
- BBioinformation 2019; 15(4):277-286
- Crz1p regulates Calcineurin, a serine-threonine-specific protein phosphatase, in Rhizoctonia solani. It has attracted consideration as a novel target of antifungal therapy based on studies in numerou…
Crz1p regulates Calcineurin, a serine-threonine-specific protein phosphatase, in Rhizoctonia solani. It has attracted consideration as a novel target of antifungal therapy based on studies in numerous pathogenic fungi, including, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. To investigate whether Calcineurin can be a useful target for the treatment of Crz1 protein in R. solani causing wet root rot in Chickpea. The work presented here reports the in-silico studies of Crz1 protein against natural compounds. This study Comprises of quantitative structure-toxicity relationship (QSTR) and quantitative structure-activity relationship (QSAR). All compounds showed high binding energy for Crz1 protein through molecular docking. Further, a pharmacokinetic study revealed that these compounds had minimal side effects. Biological activity spectrum prediction of these compounds showed potential antifungal properties by showing significant interaction with Crz1. Hence, these compounds can be used for the prevention and treatment of wet root rot in Chickpea.
- Advanced HIV: diagnosis, treatment, and prevention. [Review]
- LHLancet HIV 2019 Jul 05
- Substantial progress has been made this century in bringing millions of people living with HIV into care, but progress for early HIV diagnosis has stalled. Individuals first diagnosed with advanced H…
Substantial progress has been made this century in bringing millions of people living with HIV into care, but progress for early HIV diagnosis has stalled. Individuals first diagnosed with advanced HIV have higher rates of mortality than those diagnosed at an earlier stage even after starting antiretroviral therapy (ART), resulting in substantial costs to health systems. Diagnosis of these individuals is hindered because many patients are asymptomatic, despite being severely immunosuppressed. Baseline CD4 counts and screening for opportunistic infections, such as tuberculosis and cryptococcus, is crucial because of the high mortality associated with these co-infections. Individuals with advanced HIV should have rapid ART initiation (except when found to have symptoms, signs, or a diagnosis of cryptococcal meningitis) and those in treatment failure should switch treatment. Overcoming barriers to testing and adherence through the development of differentiated care models and providing psychosocial support will be key in reaching populations at high risk of presenting with advanced HIV.
- Complementary Use of Microscopic Techniques and Fluorescence Reading in Studying Cryptococcus-Amoeba Interactions. [Journal Article]
- JVJ Vis Exp 2019 Jun 22; (148)
- To simulate Cryptococcus infection, amoeba, which is the natural predator of cryptococcal cells in the environment, can be used as a model for macrophages. This predatory organism, similar to macroph…
To simulate Cryptococcus infection, amoeba, which is the natural predator of cryptococcal cells in the environment, can be used as a model for macrophages. This predatory organism, similar to macrophages, employs phagocytosis to kill internalized cells. With the aid of a confocal laser-scanning microscope, images depicting interactive moments between cryptococcal cells and amoeba are captured. The resolution power of the electron microscope also helps to reveal the ultrastructural detail of cryptococcal cells when trapped inside the amoeba food vacuole. Since phagocytosis is a continuous process, quantitative data is then integrated in the analysis to explain what happens at the timepoint when an image is captured. To be specific, relative fluorescence units are read in order to quantify the efficiency of amoeba in internalizing cryptococcal cells. For this purpose, cryptococcal cells are stained with a dye that makes them fluoresce once trapped inside the acidic environment of the food vacuole. When used together, information gathered through such techniques can provide critical information to help draw conclusions on the behavior and fate of cells when internalized by amoeba and, possibly, by other phagocytic cells.
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- Candida species isolated from pigeon (Columbia livia) droppings may express virulence factors and resistance to azoles. [Journal Article]
- VMVet Microbiol 2019 May 29; 235:43-52
- Even though it is widely known that Cryptococcus spp. may transmit cryptococcosis trough aerosol formed when dried birds (mainly pigeons) droppings are dispersed and become airborne, little is known …
Even though it is widely known that Cryptococcus spp. may transmit cryptococcosis trough aerosol formed when dried birds (mainly pigeons) droppings are dispersed and become airborne, little is known about the role of these birds in harboring other pathogenic yeasts in their gastrointestinal tract, feathers and beaks, specifically because these animals often stay and reproduce close or even above air conditioner units. Here we evaluated the prevalence of pathogenic yeasts isolated from pigeon droppings collected in the outside area of a University Hospital in Brazil. We also aimed to investigate the pathogenic potential and antifungal susceptibility of Candida species of medical interest isolated from these samples. Therefore, we performed the evaluation of virulence factors attributes expression in vitro, including the ability to adhere to human buccal epithelial cells and biofilm formation and to produce lytic enzymes, such as phospholipases, proteinases and hemolysins. Antifungal susceptibility testing against fluconazole, itraconazole, amphotericin and micafungin was also performed. The Candida genus was the most prevalent in our study, with several medically important species being isolated. Of note, these strains were able to express several virulence factors in vitro, clearly showing their pathogenic potential. Our study was able to demonstrate that Candida spp. isolated from pigeon droppings may express virulence factors in the same manner of clinical isolates, suggesting a pathogenic potential for these yeasts. The fact these strains were collected from the outside area of a tertiary hospital may be of interest, because they may be a source of infection, specifically to immunocompromised hosts.