Fungal Infection Trust
December 2015

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Highlights of this month...

Chronic Pulmonary Aspergillosis Guidelines Published

First mentioned at the European Respiratory Society (ERS) Conference in Amsterdam late in September, the first guidelines (drawn up in conjunction the ERS and ESCMID) for Chronic Pulmonary Aspergillosis have now been published.
The article in the treatment section of the Aspergillus Website that looks at aspergillosis in the context of neutropenia has been extensively updated by Isabel Rodriguez Goncer, MD, adding a considerable amount of content and 120 new references from 2004 onwards.
Patients & carers: Many thanks to the people who contributed to our survey on the potential benefits of isavuconazole. Your views have been collated and a report forwarded to the regulatory body who asked us to carry out the work (SMC).
Amongst several very good points made it emerged that patients and carers view the potential benefits as worthwhile but care must be taken to ensure both doctors and patients are aware of several side effects that are common amongst people with chronic aspergillosis when taking voriconazole but are not likely to have been noticed in the tested group of (acute aspergillosis) patients.
The value of getting the opinions of patients and carers was well illustrated by this work, as was the willingness of patients & carers to participate - we had 34 reponses in 10 days. 
Whether use of high-dose steroids in acute-stage allergic bronchopulmonary aspergillosis (ABPA) is associated with superior outcomes has not been known. The authors compare the efficacy and safety of two glucocorticoid protocols in ABPA.Treatment-naive ABPA subjects randomly received either high-dose or medium-dose oral prednisolone.
Conclusions: Cumulative glucocorticoid dose and side-effects were significantly higher in the high-dose group.Medium-dose oral glucocorticoids are as effective and safer than high-dose in treatment of ABPA.
The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, the authors hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.
Conclusions: CF-ABPA patients were likelier to have elevated specific IgE to A. fumigatus and were less frequently co-infected with Staphylococcus aureus. Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.
Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin.
To reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, the authors created a "genetic dereplication" strain in which they deleted eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total). This strain allowed them to discover a novel compound that they designate aspercryptin and to propose a biosynthetic pathway for the compound.
Subtherapeutic Posaconazole Exposure and Treatment Outcome in Patients With Invasive Fungal Disease.
Posaconazole exposure is insufficient in more than 40% of patients at risk of or with invasive fungal disease when taking oral solution and posaconazole exposure is positively correlated with a successful treatment outcome. Therapeutic drug monitoring of posaconazole can detect underexposure and can be helpful in treatment optimization.
Mammalian hormones have been demonstrated to have stimulatory or inhibitory effects on growth for organisms such as Candida albicans, Paracoccidioides brasiliensis, Saccharomyces cerevisiae, Rhizopus nigricans, Aspergillus fumigatus, Coccidioides, and dermatophytic fungi.
A number of fungi have been shown to have specific binding proteins for corticosteroid, estrogen and progesterone that are stereo-specific and high affinity. In some instances, the interactions of a mammalian hormone with the organism, in vivo, affects pathogenesis.
Genome expression profiles of C. albicans in the presence of estradiol or progesterone, and S. cerevisiae with progesterone, indicate major up-regulation of various drug resistance pumps, like CDR1, and CDR2, can affect antifungal susceptibility.
Azole antifungal interactions occur with fungal hormone binding proteins. Azoles also can block mammalian steroidogenesis. The finding of interactions of mammalian hormones with fungi and subsequent functional responses by the fungi, suggest that hormonal interactions with fungal systems has been conserved throughout evolution and have an important role in fungal pathogenesis, as well as in the overall biology of the organisms.
Immunotherapy of Fungal Infections
For several decades, intense basic research efforts have been directed at development of fungal immunotherapies. Nevertheless, this approach suffers from a severe bench-bedside disconnect owing to several reasons: the chemical and biological peculiarities of the fungal antigens, the complexities of host-pathogen interactions, an under-appreciation of the fungal disease landscape, the requirement of considerable financial investment to bring these therapies to clinical use, as well as practical problems associated with immunizations. In this general, non-exhaustive review, we summarize the features of ongoing research efforts directed towards devising safe and effective immunotherapeutic options for mycotic diseases, encompassing work on antifungal vaccines, adoptive cell transfers, cytokines, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), and other agents.
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
State-of-the-art infection models to study molecular mechanisms of human fungal infections: FEBS advanced practical course February 14, 2016, Jena, Germany
Course of Medical Mycology of the Institut Pasteur will be held in Paris, 21 March-15 April, 2016. The course will be taught in English and is aimed to microbiologists (MDs, PhDs and veterinarians) with previous practice in a medical mycology laboratory
Few effective treatments for disseminated Aspergillus infections in dogs are available. Posaconazole has potent and broad-spectrum activity against Aspergillus spp., but its use has not yet been sufficiently evaluated in dogs.
The aim of this study was to determine the safety and efficacy of posaconazole for the treatment of naturally occurring disseminated Aspergillus infections in dogs.
Prospective, nonrandomized, noncontrolled study with posaconazole administered to dogs at dosage of 5 mg/kg PO q12h. 
The treatment response for dogs with disseminated disease while receiving posaconazole was defined as clinical remission (n = 4) and clinical improvement (n = 6). There was a high rate of relapse during treatment or after cessation of treatment in both groups, and most dogs died or were euthanized due to progressive disease. 
Posaconazole appears to be safe and well-tolerated for treatment of disseminated Aspergillus infections in dogs. Long-term survival >1 year is possible with prolonged treatment, but relapse is common.
Contribute to clinical data on rare infections:

Patients & carers
If you participated in our survey on isavuconazole ealier thos month, take a look at the top of this email for news on the results and thank you for helping!
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.

Dedicated newsletter available at the Patients Website 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR