First oral fungicide on its way?
 An intriguing story came to our attention this month in TheScientist.com. Amphotericin B is one of the oldest drugs available to clinicians for the treatment of Aspergillus infections. First identified in 1955 it is one of the few fungicides available i.e. those that are capable of killing the infecting fungus rather than just stopping it growing.
Unfortunately amphotericin is very poorly soluble in water so must be dissolved using relatively toxic substances, and cannot be taken by mouth as it will not dissolve in the stomach and absorb into the bloodstream of a patient very efficiently.
As a result amphotericin and current derivatives (see treatment section) are available as drugs to be given intravenously and partly as a result of that and partly because of the toxicity of the drug it must be administered in hospital under constant surveillance. This can be unpleasant for the patient, limits the dose that can be given to any particular patient and is an expensive process involving a lot of time from medical staff.
Kishor Wasan, a pharmacologist at the University of British Columbia, has rather luckily (as presented in the aformentioned story) developed a new variant of amphotericin that can be given in orally in animal experiments and successfully eliminate Aspergillus fumigatus infection. Currently in 'preclinical trials' this new drug (in competition with another oral amphotericin drug currently in clinical trials) has the potential to offer clinicians a new weapon with which to treat aspergillosis.
This Month
 Several new features this month, ranging from technical to medical. We have started to make parts of our content available for browsing on mobile phones and similar small screen devices. These small platforms are getting more popular and are going to be useful for applications such as quick reference in the clinic or while travelling, so we will make diagnosis, treatment, case histories, articles and patient information available, but to begin with we have made our blog available for this format. To get the 'pared down' content browse your mobile to http://mippin.com/aspergillusblog
On an educational theme we now host the learning material for a major course in medical mycology run by Dr Paul Bowyer at Wythenshawe Hospital, Manchester, UK entitled 'Medical Mycology Workshop: Molecular Diagnostics Tutorial' - complete with animated guides.
Latest News and Articles
There have been 69 additions (10 reviews) to the articles section. Readers should also note that it is now possible to read the abstract of each article simply by clicking in the Abstract link appearing alongside each article. We have picked out a few of the highlights here:
Conidiation color mutants of Aspergillus fumigatus are highly pathogenic to the heterologous insect host Galleria mellonella
The use of the greater wax moth as an in vivo model system for the investigation of virulence of Aspergillus fumigatus. Melanin mutants of A. fumigatus are tested and found to have enhanced insect mortality, as did various conidial colour mutants. This is the opposite of the result seen in mammalian tests where melanin mutanst have reduced virulence.
Comments suggest that colour mutants of Aspergillus could be used in the wild to control pest insect growth.
A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus
Stressed fungi rely on the UPR to support growth and virulence. Disruption of the UPR via mutating the hacA gene successfully showed that Aspergillus fumigatus cannot grow at elevated temperatures without this pathway, cannot infect mice and rendered the fungus sensitive to antifungal drugs. This pathway is therefore a useful target for future antifungal drugs.
The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: a 10-year analysis at a single institution at Japan.
An extensive study describing the clinical features of invasive fungal infections for 334 patients from 1997 to 2006. Infection rate, site of infection, risk factors and mortality rates are all covered.
Mould eradication and asthma
The author argues that peak expiratory flow is too insensitive as a measure of the effiectiveness of removing sources of mould from the patients environment. Changes in patient medication (as observed in Burr et.al) are important endpoints. The author argues that endpoints must be both relevant and sensitive.
Reviews
Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis - a review.
CF patients are prone to infection due to having partially defective immune systems and the likelyhood of undergoing prolonged antibiotic and steroid treatments :- all of these factors increase the risk of infection.
This review suggests the several consequences of filamentous fungal infection to the health of this group of people.
Secondary metabolism: regulation and role in fungal biology
One of several review articles on fungal biology uploaded this month. Other subjects include; role of reactive oxygen species in cellular differentiation, RNA interference, Fungal adaption to the mammalian host and how fungi cope and adapt to ionising radiation.
Treatment
We have a complete rewrite and update of the protocol for Chronic Invasive Pulmonary Aspergillosis by Prof David Denning (Registration required).
Diagnosis
Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis
An extensive review that concludes that a single PCR-negative result is sufficient to exclude a diagnosis of proven or probably invasive pulmonary infection (IPA) whereas two positive tests are required to confirm the diagnosis.
A standard test is needed as there is still a lack of homogeniety of the methods used.
Conferences & Workshops
Research Skills Training Workshop FUNGI AS A CLINICAL PROBLEM on 30th March - 3rd April 2009 at Aberdeen University, UK.
NB to find out about workshops go to the Conferences search page and select 'Workshop' for the Abbreviation.
Genomes
Aspergillus oryzae has been added to the list of species we have searchable genome information for.
Species Database
We have the original papers of 184 asexual forms, 36 sexual forms and 27 previous names located in the Species Database. You can see them all listed if you tick the box entitled 'Species for which the original paper is available' and then click 'Search' (NOT 'List all species').
Aspergillus and Penicillium Polyphasic identification - This is an interactive key for the identification of Aspergillus and Penicillium species. Free registration required.
Images
3  Images of subacute IPA in rhematoid nodules of the lung. in a patient with rheumatoid arthritis. Histology sections stained with H&E.
Varying fields from a case of rheumatoid disease complicated by Aspergillus infection.
At the margin there are pallisaded histiocytes, as seen in a rheumatoid nodule, with
abundant Aspergillus in the cavity
Registration is required (no charge) to view images.
Research
Infectious Diseases Society of America/Education & Research Foundation (IDSA ERF) Joint Research Awards Deadline Feb 13th 2009.
Blog
Running at roughly 4000 accesses per month the Aspergillus Blog has been an outstanding success since its inception in March 2008, doubling in use every two to three months.
Patients
We run a highly active support group and Question & Answer bulletin boards for all patients and their relatives.
Technical Tips
Our discussion group (email and/or website) designed to promote discussion on technical issues for laboratory workers.
Searching the website
There is now a third facility to search for information on Aspergillus. Covering all the information in the Aspergillus Website and including a series of websites we feel contain useful information NOT currently available on the Aspergillus Website, the Aspergillus World search engine contains large amounts of focussed information from all over the world. If you can suggest more (particularly keen to access information on industrial applications) then let us know at admin@aspergillus.org.uk.
RSS
Download our updates and articles automatically every time we add to those pages- no need to wait for the next newsletter. 40 000 pages accesses per month. Use RSS.
What is RSS and how do I use it? Get help here.
Thanks for reading!
Visit our website again soon.
The Aspergillus Team.
Contact us/Feedback |
Blog
RSS
