Aspergillus Newsletter
January 2014

New source for potential antifungal drug

A recent paper in Nature Communications has described the first use in vivo of synthetic cationic small molecules that exhibit antimicrobial target specificity and low toxicity compared with amphotericin. Once dispersed in aqueous solution the particles self assemble and integrate into microbial cell membranes, disrupting membrane integrity.
 
In vitro and in vivo demonstrations of biocompatibility and antifungal activity are reported and illustrated, the latter using a mouse model for fungal keratitis that shows good antifungal activity (against Candida) and better condition of the cornea post treatment compared with amphotericin.
 
Good disruption of Candida biofilm was demonstrated.
 
This paper shows clear improvement over earlier versions for this type of drug, in particular the very low degree of toxicity against mammalian cells.
News
The Aspergillus Website is changing. Viewers may have noticed that the appearance of parts of the webite has changed recently. The Patients section have migrated to a new structure already but it is impossible to change the main website all in one go so we have elected to change on section at a time. Within the last few days the new library section (articles, books, theses) has been launched with improved navigation, searching and cross linking of content. This process should be complete by the middle of this year. Registered users in the old website will be valid in the new website.
 
Following their inaugural launch in London, November 2013 with the support of Rupert Everett and Katie Melua GAFFI is hosting a second launch, this time in Delhi, India at the Indian Council for Medical Research (ICMR).
 
India probably has the largest burden of fungal disease in the world. Dr V M Katoch, Secretary, Department of Health Research & Director General, ICMR, Dr Rashmi Arora, Deputy Director, ICMR and GAFFI Advisor Professor Arunaloke Chakrabarti, explained to the high profile audience both the global and country specific-issues and potential for great health improvements.
 
Better diagnostic capability, affordable, high quality antifungal medicines and better medical training are the 3 avenues to a healthier population. Prof NK Ganguly (formerly Director General, ICMR) contributed to making the case for massive improvement in human health to combat fungal diseases. Physicians from chest diseases, AIDS, ophthalmologists and numerous other specialities attended.
 
Fungal infections kill at least 1,350,000 patients with or following AIDS, cancer, TB and asthma as well as causing untold misery and blindness to tens of millions more worldwide. Yet its symptoms are mostly hidden and occur as a consequence of other health problems, and the tragedy is that many of the best drugs have been available for almost 50 years.
Articles
 
NOTE access to all articles now requires registration
 
Micafungin inhibits 1,3-β-d-glucan synthase and interferes with fungal cell wall synthesis. Clinically, micafungin has been shown to be efficacious for the treatment of invasive fungal infections. However, little is known about the immunomodulatory activity of micafungin in these infections. Together, these findings suggest that the therapeutic efficacy of micafungin in aspergillosis is orchestrated by the activation of innate immune receptors affecting the inflammatory/anti-inflammatory balance during infection.
 
BACKGROUND: Caspofungin is an echinocandin class antifungal medication that is commonly used empirically in immunocompromised patients at high risk for invasive fungal disease.
CONCLUSION: Clinicians must remain aware that breakthrough fungal infections by species not covered by particular antifungals, including caspofungin, do occur and may have poor outcomes.
 
SIGNIFICANCE: The authors were "unable to show a beneficial effect of 3 months of treatment with voriconazole in patients with moderate-to-severe asthma who were IgE sensitized to A fumigatus on either the rate of severe exacerbations, quality of life, or other markers of asthma control."
 
Neosartorya fischeri NRRL 181 isolate secretes a defensin-like antifungal protein (NFAP) which has a remarkable antifungal effect against ascomycetous filamentous fungi. These data indicated that P. pastoris KM71H can produce the NFAP in an antifungally active folded state. Our results provide a base for further research, e.g., investigation the connection between the protein structure and the antifungal activity using site directed mutagenesis.
Reviews/Overviews
Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection.
 
For many years there has been a great interest in nonculture-based techniques such as the detection of galactomannan, β -D-glucan, and DNA by PCR-based methods in the treatment of invasive aspergillosis. There is a current interest in applying these tests to monitor the effectiveness of therapy after diagnosis and predict clinical outcomes. The search for improved markers for the early and sensitive diagnosis of IA continues to be a challenge.
Damp & Health
Indoor Environment Professionals
Join our LinkedIn group on Damp Building and Human Health.
 
Living in a damp home?
Please check out our LinkedIn group: Is my damp home making me ill? and read our new website pages
Conference Deadlines
45th Union World Conference on Lung Health (Barcelona, Spain - Oct 28 - Nov 1) - Abstract submission deadline is January 16th
 
International Symposium on HIV & Emerging Infectious Diseases (Marseille, France - May 21-23) - Abstract submission deadline is January 20th.
 
IUMS XIV International Congress of Mycology (Montreal, Canada - July 27 - Aug 1) - Abstract submission deadline is January 30th.
 
May 15-19) - Abstract submission deadline is February 1st.
Courses
Bringing PK and PD in Fungal Infections into the Clinic July 4-6 2014, Nijmegen, The Netherlands. For more information check website in January 2014.
 
Online course, Start approximately July 2014
Mechanisms in Fungal Infections is a blended, e-learning resource with CME content developed by an expert, multidisciplinary group of specialists.

The content on this Web site is intended for oncologists, hematologists, and infectious disease specialists who treat transplant patients and other patient populations at risk for developing fungal infections.
 
Allergy Academy, King's College, London. Online resources for allergy education. Intended for all audiences including doctors & patients.
Veterinary
 
A 3-year-old neutered male mixed-breed dog was presented with inappetence and respiratory distress. Thoracic radiography revealed a right-sided pneumothorax. Following stabilization, thoracic computed tomography found 1 large and many small pulmonary blebs in the right caudal lung lobe. The dog underwent a right lateral thoracotomy, identifying numerous emphysematous regions in the right middle lung lobe, and a right middle lung lobectomy was performed. Histopathologic examination of the resected lung lobe revealed severe, diffuse bronchopneumonia with necrotizing pleuritis and the presence of fungal organisms strongly suggestive of Aspergillus sp. Surgical removal of the affected lung lobe and continued medical treatment with itraconazole resolved the dog's clinical signs.
Attention Clinicians & Scientists
Case Histories Database 212 aspergillosis cases already recorded and you can add yours too.
 
Information on mycetoma on the WHO List of Neglected Tropical Diseases can be found here, and see also the media briefing of the Mycetoma Consortium here.
 
 
The Joint Genome Institute (JGI) welcomes nominations of genomes to be sequences in its Community Sequencing Program. For procedures how to submit a proposal, see here. The current fungal program can be found here.
 
You may like to contribute to the following collaborative groups who are collecting clinical data on these rare infections:
 
Fungiscope is a global rare fungal infection registry, a working group of ISHAM.
 
International Pediatric Fungal Network (PFN) collating information on treatment of pediatric patients
 
AspICU2 is a web-based multicentre observational survey to assess the burden of aspergillosis and other fungi in critically ill patients.
Patients
 
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Also of interest...
Jobs:
 
European Academy of Allergy and Clinical Immunology (EAACI) RESEARCH FELLOWSHIPS 2014
 
European Academy of Allergy and Clinical Immunology (EAACI) Clinical Fellowships 2014

Clinical Research Fellow at the National Aspergillosis Centre, Manchester, UK
 
Clinical Microbiologist at Changi General Hospital, Singapore
 
Molecular Pathologist at Changi General Hospital, Singapore
Conferences:
 
Courses:
 
Books:

 
 
Human Fungal Pathogens (The Mycota) by Kurzai, Oliver (29 Nov 2013)
 
 
Radiology Illustrated: Chest Radiology by Lee, Kyung Soo, Han, Joungho, Chung, Man Pyo and Jeong, Yeon Joo (29 Nov 2013)
Theses:
 
Optimization of Antifungal Prophylaxis in Haematological High-Risk Patients by Vehreschild, Maria J. G. T. 2013 Universitat zu Koln.
 
 
Anti-Group B Streptococci monoclonal antibodies protect against invasive Aspergillosis  by Wharton, Rebekah E. 2013. The University of Alabama at Birmingham.
Clinical Trials (35 Recruiting):
 
Research Grants:
 
Lab protocols:
 
Networking:
 
News blog:
 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR, UK,www.fungalinfectiontrust.org.uk