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J. Fungi, Volume 2, Issue 3 (September 2016) – 6 articles

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Open AccessReview
Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence
J. Fungi 2016, 2(3), 25; https://doi.org/10.3390/jof2030025 - 08 Sep 2016
Cited by 3 | Viewed by 1699 | Correction
Abstract
Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the [...] Read more.
Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the environment, an invasive fungal infection (IFI) is a rare outcome that is often reserved for those patients who are immunocompromised. Given the potential for significant morbidity and mortality within this patient population from IFI due to Aspergillus spp., along with the rise in the use of therapies that confer immunosuppression, there is an increasing need for appropriate initial clinical suspicion leading to accurate diagnosis and effective treatment. Voriconazole remains the first line agent for therapy; however, the use of polyenes, novel triazole agents, or voriconazole in combination with an echinocandin may also be utilized. Consideration as to which particular agent and for what duration should be made in the individual context for each patient based upon underlying immunosuppression, comorbidities, and overall tolerance of therapy. Full article
(This article belongs to the Special Issue Aspergillus fumigatus: From Diagnosis to Therapy)
Open AccessReview
Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery
J. Fungi 2016, 2(3), 24; https://doi.org/10.3390/jof2030024 - 06 Sep 2016
Cited by 5 | Viewed by 2412
Abstract
Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique [...] Read more.
Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP). We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P) and pyrophosphate (PP) groups covalently attached at different positions. This review focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans; (2) the identification of PP-IP5 (IP7) as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3) why IPK enzymes represent suitable candidates for drug development. Full article
(This article belongs to the Special Issue Novel Antifungal Drug Discovery)
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Open AccessReview
PCR Technology for Detection of Invasive Aspergillosis
J. Fungi 2016, 2(3), 23; https://doi.org/10.3390/jof2030023 - 11 Aug 2016
Cited by 2 | Viewed by 1591
Abstract
The application of molecular technologies to aid diagnosis and management of infectious diseases has had a major impact and many assays are in routine use. Diagnosis of aspergillosis has lagged behind. Lack of standardization and limited commercial interest have meant that PCR was [...] Read more.
The application of molecular technologies to aid diagnosis and management of infectious diseases has had a major impact and many assays are in routine use. Diagnosis of aspergillosis has lagged behind. Lack of standardization and limited commercial interest have meant that PCR was not included in consensus diagnostic criteria for invasive fungal disease. In the last ten years careful evaluation and validation by the Aspergillus European PCR initiative with the development of standardized extraction, amplification and detection protocols for various specimen types, has provided the opportunity for clinical utility to be investigated. PCR has the potential to not only exclude a diagnosis of invasive aspergillosis but in combination with antigen testing may offer an approach for the early diagnosis and treatment of invasive aspergillosis in high-risk populations, with the added benefit of detection of genetic markers associated with antifungal resistance. Full article
(This article belongs to the Special Issue Aspergillus fumigatus: From Diagnosis to Therapy)
Open AccessCorrection
Correction: Kwon-Chung, K.J. et al. Is Cryptococcus gattii a Primary Pathogen? J. Fungi 2015, 1, 154–167
J. Fungi 2016, 2(3), 20; https://doi.org/10.3390/jof2030020 - 05 Jul 2016
Viewed by 1300
Abstract
The authors of the published paper [1] would like to correct Table 1.[...] Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
Open AccessReview
Galactomannan and 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Aspergillosis
J. Fungi 2016, 2(3), 22; https://doi.org/10.3390/jof2030022 - 04 Jul 2016
Cited by 12 | Viewed by 2713
Abstract
Invasive aspergillosis (IA) is a severe complication among hematopoietic stem cell transplant recipients or patients with hematological malignancies and neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed in other populations, such as solid-organ transplant recipients, patients with solid tumors or auto-immune diseases, [...] Read more.
Invasive aspergillosis (IA) is a severe complication among hematopoietic stem cell transplant recipients or patients with hematological malignancies and neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed in other populations, such as solid-organ transplant recipients, patients with solid tumors or auto-immune diseases, and among intensive care unit patients. Frequent delay in diagnosis is associated with high mortality rates. Cultures from clinical specimens remain sterile in many cases and the diagnosis of IA often only relies on non-specific radiological signs in the presence of host risk factors. Tests for detection of galactomannan- (GM) and 1,3-β-d-glucan (BDG) are useful adjunctive tools for the early diagnosis of IA and may have a role in monitoring response to therapy. However, the sensitivity and specificity of these fungal biomarkers are not optimal and variations between patient populations are observed. This review discusses the role and interpretation of GM and BDG testing for the diagnosis of IA in different clinical samples (serum, bronchoalveolar lavage fluid, cerebrospinal fluid) and different groups of patients (onco-hematological patients, solid-organ transplant recipients, other patients at risk of IA). Full article
(This article belongs to the Special Issue Aspergillus fumigatus: From Diagnosis to Therapy)
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Open AccessReview
Triazole Resistance in Aspergillus spp.: A Worldwide Problem?
J. Fungi 2016, 2(3), 21; https://doi.org/10.3390/jof2030021 - 04 Jul 2016
Cited by 34 | Viewed by 2862
Abstract
Since the first description of an azole-resistant A. fumigatus strain in 1997, there has been an increasing number of papers describing the emergence of azole resistance. Firstly reported in the USA and soon after in Europe, it has now been described worldwide, challenging [...] Read more.
Since the first description of an azole-resistant A. fumigatus strain in 1997, there has been an increasing number of papers describing the emergence of azole resistance. Firstly reported in the USA and soon after in Europe, it has now been described worldwide, challenging the management of human aspergillosis. The main mechanism of resistance is the modification of the azole target enzyme: 14-α sterol demethylase, encoded by the cyp51A gene; although recently, other resistance mechanisms have also been implicated. In addition, a shift in the epidemiology has been noted with other Aspergillus species (mostly azole resistant) increasingly being reported as causative agents of human disease. This paper reviews the current situation of Aspergillus azole resistance and its implications in the clinical setting. Full article
(This article belongs to the Special Issue Aspergillus fumigatus: From Diagnosis to Therapy)
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