Fungal Infection Trust
August 2015
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Highlights of this month...
 Frisvad & Larsen (2015) have written a detailed review of the diversity of metabolite production by Aspergillus species and the specificity of metabilite production within species. Remarkably varieties within a species maintain their 'metabolite profile', differences arising when particular metabolite clusters are still present, but silenced.
 
Extrolites appear to have evolved because of ecological challenges rather than being inherited from ancestral species, at least when comparing the species in the different sections of Aspergillus. Within the Aspergillus sections, secondary metabolite pathways seem to inherit from ancestral species, but the profiles of these secondary metabolites are shaped by the biotic and abiotic environment. We hypothesize that many new and unique section-specific small molecule extrolites in each of the Aspergillus will be discovered.
 
Svahn et. al  (2014) carried out experiments on a toxin produced by Aspergillus fumigatus (gliotoxin) that is known to enhance pathogenicity as it inhibits components of the immune system in mice, allowing a fungal infection to proceed. They discovered that the presence of cellular components of the bacteria Escherichia coli and Staphylococcus aureus induced the production of gliotoxin by A. fumigatus.
 
Arturo Casadevall writes in Helio Infectious Disease News of the co-evolution of warm blooded mammals alongside fungi. He warns of the importance of remaining vigilant and active in our age-old battle against fungal infection - even after many million years they carry as potent a threat as ever, perhaps more so with the arrival of global warming..
Articles
Dekio et. al. (2015) investigated the performance and the clinical impact of histologic examination of infected tissue in patients with suspected invasive fungal infection (IFI) at a tertiary pediatric center. Tissue was obtained from deep subcutaneous tissue, visceral organs, or the sinonasal cavity. Communication of histology results prompted changes in antifungal therapy 64% of the time. This included initiation of antifungal therapy in 13 patients who were not previously receiving therapy. Fifteen (42%) patients underwent surgical excision within 48 hours of histologic diagnosis. CONCLUSIONS: Histology can provide rapid, accurate, and clinically actionable information to clinicians caring for children with IFI.
 
Deciphering chemokine properties by a hybrid agent-based model of Aspergillus fumigatus infection in human alveoli.
In the lung, Aspergillus fumigatus is able to quickly adapt to the humid environment and, if not removed within a time frame of 4-8 h, the pathogen may cause damage by germination and invasive growth. Applying a to-scale agent-based model of human alveoli to simulate early A. fumigatus infection under physiological conditions, Pollmächer & Figge (2015) recently demonstrated that alveolar macrophages require chemotactic cues to accomplish the task of pathogen detection within the aforementioned time frame. 
Performing simulations for more than a million virtual infection scenarios, the authors find that the ratio of secretion rate to the diffusion coefficient is the main indicator for the success of pathogen detection.
 
PURPOSE: 1. To assess the efficacy of omalizumab therapy in improving sinonasal outcomes in refractory allergic fungal rhinosinusitis (AFRS) patients with moderate or severe asthma. 2. To determine if omalizumab therapy reduces the usage of corticosteroids or antifungal therapy in AFRS patients.
CONCLUSION: Gan et. al. (2015) state that Omalizumab therapy can be considered as a potential adjunct for the treatment for patients with refractory AFRS with moderate or severe asthma. However, larger prospective studies to confirm the findings of this study will be required.
Reviews
Relevance of EORTC Criteria for the Diagnosis of Invasive Aspergillosis in HIV-Infected Patients, and Survival Trends Over a 20-Year Period in France.
Before the advent of combination antiretroviral therapy (cART), roughly 50% of cases of invasive aspergillosis (IA) associated with human immunodeficiency virus (HIV) infection involved individuals without classical predisposing host factors, and the median survival time was <4 months after diagnosis. Denis et. al. (2015) examined if the situation evolved over time using the revised European Organisation for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC) definition and analyzed survival trends after diagnosis over 20 years.
In the cART era, EORTC criteria, developed for use in hematology/oncology, applied to only half the cases diagnosed among HIV-infected patients. A rapid diagnosis of IA is paramount to improve survival. For patients who do not fulfill the EORTC definition, the authors suggest that the addition of "HIV infected with a CD4 count <100 cells/µL" to the EORTC host criteria be validated.
 
Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings.
Franquet et. al. (2015) Conclusions: The radiologist plays a major role in the diagnosis of pulmonary Aspergillus infection. When radiographic findings are subtle or equivocal, CT frequently allows identification of the disease process. Although imaging findings in various types of pulmonary aspergillosis may be nonspecific, in the appropriate clinical setting, familiarity with the thin-section CT findings may suggest and even help establish the specific diagnosis.
 
Major bioactive metabolites from marine fungi: A Review.
The marine fungi particularly those associated with marine alga, sponge, invertebrates, and sediments appear to be a rich source for secondary metabolites, possessing antibiotic, antiviral, antifungal activities. Besides, a few growth stimulant properties which may be useful in studies on wound healing, carcinogenic properties, and in the study of cancers are reported. Recent investigations on marine filamentous fungi looking for biologically active secondary metabolites indicate the tremendous potential of them as a source of new medicines. Hasan et. al. (2015) review about some important bioactive metabolites reported from marine fungal strains which are antibacterial, antitumour and antinflammatory in action.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar(NB we have discontinued use of the Google calendar).
 
Paediatric Mycology - Postgraduate training 12th - 13th October, Lisbon, Portugal
 
CBS Course Medical Mycology (China) October 17-25, Shanghai, China.

The Second International Veterinary Mycology Course (ISHAM) October 26-30, Turin, Italy
Veterinary
The aim of this study was to describe the pharmacokinetics and bioavailability of itraconazole (ITR) oral solution in healthy cats.
CONCLUSIONS AND RELEVANCE:
The disposition of ITR oral solution in cats is characterised by a long terminal half-life, a short peak time and moderate bioavailability.
Attention!
Nominate fungal (incl. non-pathogenic) genomes for sequencing at the Joint Genome Institute (JGI) here
 
Contribute to clinical data on rare infections:

Patients & carers
Aspergillosis Community (National Aspergillosis Centre) meets on the first friday of every month at the Altounyan Suite, North West Lung Centre, Manchester at 1.30pm BST/GMT. If you can't make it in person, you are welcome to listen in to our live broadcast.

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Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR