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 Advances in the Detection of Aspergillus Developing Drug Resistance
Researchers at the University of Manchester and the National Aspergillosis Centre have developed a sophisticated method of identifying strains of Aspergillus that are likely to be resistant to many of the antifungal drugs currently available.
Traditionally testing is done by growing samples of the isolates under test and then treating them with ever increasing doses of antifungal - This procedure takes several days and cannot be carried out if nothing grows out of a clinical specimen - something that happens regularly (10-50% failure rate).
The research at the National Aspergillosis Centre uses rapid molecular techniques (PCR) to detect tiny amounts of DNA in clinical samples, whether or not the sample contains fungi that will grow out in culture, thus removing the requirement to grow out a sample prior to testing, saving many days.
Further use of the isolated DNA was made to amplify a gene (CYP51A and model) in which specific mutations are commonly present in resistant strains of Aspergillus. Analysis of the regions of the gene carrying the mutation(s) in those samples that failed to grow a viable culture of Aspergillus (and therefire would have been missed from the survey) estimates the frequency of resistant isolates in CPA at 50%, and in ABPA at 75%.
Going by these figures there is a clear need to identify resistance in patients with nonculturable Aspergillus infections.
Latest News and Articles
 The Fungal Research Trust is 20 years old this year and plan to celebrate with a meeting for researchers and patients at the Medical Society of London (close to Oxford Circus Underground Station) on the 18th June 2011. There will be a patients meeting in the afternoon but everyone is also welcome to attend the morning session when we will be able to listen to a series of research talks given by people who have had research funded by the FRT. Full program is available here.
Selected articles: (126 new articles added, 80 full articles)
AspICU2 is a multicenter web-based observational survey to assess the burden of Aspergillus and other fungi in critically ill patients. By registering now, you will enter the AspICU2 project community, and receive regular updates on the project.
Articles: There have been 125 additions to the Articles section (82 full papers), of which 16 are reviews and 87 pre-2000. We have picked out a few of the highlights here:
Comparative in vivo dose-dependent activity of caspofungin and
anidulafungin against echinocandin-susceptible and -resistant
Aspergillus fumigatus
Echinocandin antifungals (caspofungin, micafungin, anidulafungin) are distinct from the azole class of antifungals (itraconazole, posaconazole, voriconazole) and are the drug of choice for some invasive fungal diseases including invasive aspergillosis. Unlike the azole group resistance of Aspergillus to echinocandins remains very rare despite there being a mechanism to do so, mutation of the Fks gene.
This mutation is found occasionally in clinical samples of the fungus Candida so why not in Aspergillus?
This paper finds that mutation of Fks in Aspergillus renders it less able to infect the host, and the mutant Aspergillus was still attacked by two of the three echinocandin drugs albeit less well than non-mutant Aspergillus. Putting these two observations together might help explain why mutant Aspergillus has rarely been isolated in the clinic.
 Imaging findings in intracranial Aspergillus infection in immunocompetent patients
"Sinonasal disease with intracranial extension is the commonest
pattern of Aspergillus infection followed by intracranial mass lesions.
Hyperdense sinonasal disease with bone destruction and intracranial extension
on computed tomography, hypointense signal intensity of the lesions on T2W
magnetic resonance images, presence of areas of restricted diffusion, decreased
perfusion on perfusion-weighted imaging, and presence of hemorrhages are key
to the imaging diagnosis of fungal infection."
Guidelines for the Treatment of Invasive Fungal Disease by Aspergillus spp. and Other Fungi Issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). 2011 Update (in spanish).
The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organ transplant recipients, patients admitted to intensive care units, and children.
Cryptic Aspergillus nidulans antimicrobials
The search for new antifungal drugs is as important as it ever was as resistance to antifungals steadily increases in infecting isolates of Aspergillus. Interestingly one subject of much promise for the generation of new antifungals is fungi - in this case Aspergillus nidulans.
Genomic sequencing of A. nidulans reveals many genes that are not switched on under laboratory condition. Finding a way to activate these genes can lead to the expression of many antimicrobial and antifungal substances - in this case nine substances based on emodin that exhibit antimicrobial activity.
Reviews
Histopathologic diagnosis of fungal infections in the 21st century
As advanced molecular diagnostic techniques (e.g. PCR) start to gain acceptance it is worth remembering the unique appeal of making a slide from slices of a clinical specimen and viewing it under the microscope. This is a time honoured process and though it is slow compared with PCR it is the only way to get information about the host tissue being invaded, the morphological characteristics to the fungus as it invades and the reaction to infection of the host tissue. This review covers the strengths and limitations of this technique.
Aspergillus flavus
The fungus is found infecting agricultural crops and coating them with aflatoxin. It is also a potent animal and human pathogen, infecting both when the immune system of the host is compromised.
This review summarises recent advances in research in both of these contexts and how we may be able to control it better in the future
Historical Articles
13 additions since last month including:
Pseudotuberculosis by 'H' (1899)
A serological study of Aspergillus fumigatus by Bøe J, Hartmann O, Thjøtta T (1939)
Secondary Metabolites
A new secondary metabolite called oxylipin has been isolated from Aspergillus flavus
Laboratory Protocols
We are always looking for more for our collection - please send your suggestions here
Conferences - coming up
20th Anniversary Meeting of the Fungal Research Trust. Consisting of a series of talks designed to present some of the achievements of FRT funded research & a patients support meeting. Starting at 10am (2pm for the patients meeting) on 18th June 2011 at the Medical Society of London. More details soon. To book please email admin@aspergillus.org.uk
Call for abstracts: 5th Advances Against Aspergillosis 26-28 January 2012 Istanbul, Turkey -
Abstracts deadline September 27 2011.
Cellular and Molecular Fungal Biology Gordon Research Conference, June 17 - 22 2012, New Hampshire, USA.
Applications for this meeting must be submitted by May 20, 2012. Please apply early, as some meetings become oversubscribed (full) before this deadline.
FEMS 2011 26-30 June 2011, Geneva, Switzerland.
Many more here...
Notes & slides from the latest Aspergillosis Patients meeting at the National Aspergillosis Centre (NAC) are available to watch here.
The talk was given by Caroline Powell who runs the NHS Expert Patient Programme. The audience was split up into 3 groups (one online) and asked for their responses to the question 'What is the most difficult thing you experience about your chronic condition' Many different responses were discussed, recorded and responded to. If we get enough interest we will try to run a course at NAC and perhaps even online.
Helping the National Aspergillosis Centre carry out research. We have appointed our first patient advisers to a research project at the National Aspergillosis Centre. Elisabeth Kershaw and Derek Stewart will assist with suggestions for the drawing up of research projects that will be submitted for funding very shortly.
Aspergillus Association of America
 This US charity has has many similar aims to ourselves in the fight against aspergillosis and we are both hoping for closer collaboration in the future, but for now they are holding two fundraising 'events' that are well worth supporting:
- A one day, 192 mile bicycle journey from Derby Line, Vermont to Guilford, Vermont! Good luck Serena's husband!
- A fundraising cookbook consisting of many recipes donated by friends, costing $15 apiece
To offer support or buy a cookbook you should go to https://aspergillusassociation.org/Fundraising.html where you can offer payment via PayPal and if you are a US taxpayer it will be tax-deductible.
Himalayan 100 mile stage race
Lewis Fraser & Aaron McKevitt are to run one of the most demanding events in the world in aid of the Fungal Research Trust. The Himalayan Challenge (http://www.everestendurance.co.uk/) involves running 100 miles in 5 days at altitude and finishing 5000 feet higher than the start! This astonishing feat of endurance is in memory of Steph Smith who died tragically from an acute aspergillosis infection nearly 2 years ago.
Lewis was Steph's partner and his story has recently featured in our blog
Please donate in memory of Steph and in appreciation of this huge effort by Lewis & Aaron.
£1,884 donated already - many thanks to everyone who contributed.
Fungal Research Trust 20th Anniversary
The Fungal Research Trust are going to hold a second meeting for patients outside of Manchester in London on 18th June 2011. Full details. If you are interested in attending as a patient or carer suffering from aspergillosis please let us know Email
A patient volunteer is making & selling handmade cards for birthdays in aid of the Fungal Research Trust. 6 cards for £6 and 75% of that goes to the FRT. Order here.
Jobs
Ten jobs are currently being advertised:
- Nine MRC Clinical Research Training Fellowships in Clinical Pharmacology & Therapeutics, Universities of Liverpool and Manchester, UK. Closing date 31st May 2011
- Researcher, CBS Fungal Biodiversity Centre, Utrecht, The Netherlands. Closing date 15th June 2011
Advertise your vacancy free of charge on the Aspergillus Website here. *Optional donation to the Fungal Research Trust to cover costs incurred in providing this newsletter.
Courses and Workshops
We keep a listing of courses and workshops including 'one off' events and courses that repeat regularly. Course subjects are wide ranging and include medical mycology, lab ID, young scientists symposia and much more. Those coming up next are:
- NOT TOO LATE TO BOOK:- Aspergillosis: from Allergy to Invasive Disease, ESCMID Postgraduate Technical Workshop 25-26 May Manchester, UK Link
- Invasive Fungal Infections: Controversies and Lessons from Clinical Practice, ESCMID Postgraduate Education Course 23-24 June, St Petersburg, Russian Federation Link
- 10th ESCMID Summer School 2-9 July, Treviso, Italy Link
If you know of a course that should be added to this list please add it by contacting us here
Veterinary
In vivo confocal microscopy of equine fungal keratitis.
Describes in vivo corneal confocal microscopy of horses with fungal keratitis and correlate findings with clinical, histopathological, and microbiological evaluations of clinical cases and an ex vivo experimental equine fungal keratitis model.
NB Vets in the UK in need of assistance with acquiring antifungals please contact us here
Blog
- Airman's supreme challenge after tragic death of Steph By Hector Mackenzie
- Advances in the Detection of Aspergillus Developing Drug Resistance
- Pulmonary aspergillosis: an alternative diagnosis to lung cancer after a positive PET scan.
- Science, Engineering & Technology Student of the Year Awards 2011
- BEI extend their services to include Aspergillus
Latest Books
NB Use these links to support the Fungal Research Trust
Latest Theses
A novel reactor with two independently-driven impellers for gas-liquid processing by Arwyn John, University of Birmingham 2011 Link
The effect of 6-pentyl-2H-pyran-2-one on the prevention of spoilage and shelf-life extension of mangoes
by H-F Lai, Manchester Metropolitan University 2010 Link
NB Links to theses require library membership.
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