Fungal Infection Trust
October 2016
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12th Annual Fungal Update (Bart's Hospital, London)
 
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Highlights of this month...

Antifungal Stewardship and Emerging Fungal Threats

As the Journal of Antimicrobial Chemotherapy celebrates 40 years of publication it has published an edition highlighting the need for better management of antifungal drugs. Based on discussions held at the Steering Comittee of the Continuing Antifungal Research and Education (CARE) Programme in Madrid, November 2015 there are eight articles/reviews written under to all-encompassing title "Antifungal stewardship: existing framework and future perspectives"
 
This open access edition is introduced by Prof Malcolm Richardson with the following beginning:
 
"The aim of antimicrobial stewardship is to preserve the future effectiveness of antimicrobial agents and to improve patient outcomes. Antifungal stewardship shares this aim but has features and challenges specific to the management of invasive fungal diseases (IFDs). These include high case-fatality rates, high drug costs and the development of antifungal resistance."
 
"The key issues discussed focus on questions such as: What tools can be used to guide antifungal stewardship? What is the current treatment landscape for diseases such as aspergillosis, candidosis and cryptococcosis? Have stewardship programmes been designed for the not-so-common fungal infections such as fusariosis or mucormycosis? How can surveillance and diagnostics be used to optimize antifungal management strategies?"
 
Talks include: The current treatment landscape: the need for antifungal stewardship programmes (Munoz et.al); The current management landscape: aspergillosis (Maertens et.al.); The role of the multidisciplinary team in antifungal stewardship (Agrawal et.al.); Conclusion and future perspectives on antifungal stewardship (Aquado et.al.)

In the same month the Royal Society of London has published reviews and research articles for a discussion meeting issue entitled ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. Introduced by Fisher, Gow and Gurr the issue centres around why fungal pathogens seems to be causing more disease than in the past and on a wide range of living organisms, and what we can do to tackle this emerging threat on plants and animals worldwide. Amongst 17 publications are:
 
News
In a newsletter that already highlights the impact that fungi have on deaths from AIDS worldwide (Denning, above), it seems appropriate to show some balance and point out the new paper in the articles section (Aspernigrins) that demonstrates two new secondary metabolites isolated from Aspergillus niger that have activity against infection of cells with HIV and are thus potential candidates to treat people with AIDS.
NB for this and many hundreds more secondary metabolites produced by Aspergillus refer to our Mycotoxin/Metabolites section containing details of over 800 secondary metabolites.
 
The Fungal Infection Trust have celebrated their 25th anniversary by holding the Great Big Fungal Spore Balloon Race on Saturday 29th October. So far (24 hrs) six 'spores' have crossed the pennine hills and been picked up in Yorkshire.
 
The antifungal interaction webpages and APP's for smartphone have been updated with 33 changes since the last update and new versions of the APP's will be available in a few weeks. Users should note that this is a listing of all those interactions that are on record and anticipated and NOT all possible interactions. If a medication does not appear in our listings there is a small chance it may still interact with an antifungal drug so you should proceed with caution, especially for the newer antifungal drugs.

Featured Website Section
The new Biodeterioration section complements our existing Geo-microbiology section as it covers the broad subject area of man-made objects that can and are deteriorated by microrganisms and in particular Aspergillus.
 
Man-made objects vary from the mundane such as paper deterioration that most of us will be aware of to the surprising observations that glass and metals can also be subject to attack from fungi, even in extreme environments such as the International Space Station.
 
Interestingly there is a small literature on the growth of Aspergillus in liquid fuels such as diesel and aircraft fuel where many of us probably assumed such liquids to be self-sterilising. There is a hazard to aircraft engines if contamination is not rigorously removed.
 
Perhaps most worryingly Aspergillus is able to grow and degrade the concrete used to house nuclear reactors and nuclear waste, over time potentially releasing radioactive material into the atmosphere. Studies have show Aspergillus niger attacking the concrete housing of the damaged Chernobyl reactors.
 
More positively, also in this section are examples of how Aspergillus and other fungi can be useful. They can degrade man made substances polluting our environment (Bioremediation). Fungi can be used for polluted land reclaimation, detoxifying metallic and radioactive pollutants, even removing cyanide from wastewater.

Articles
Clinical implications of microbial biofilms in chronic rhinosinusitis and orbital cellulitis.
19% of isolates from 70 clinical samples grew fungi with Aspergillus flavus the most common fungi. All (100%) of the isolates from sinus grew A. flavus, 9 out of 64 cellulitis isolates produced fungi, four of which were A. flavus. Half of the A. flavus isolates produced biofilm.
Biofilm producing strains of A.flavus were resistant to Amphotericin and so likely to fail to respond to antifungal treatment in the clinic.
 
Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome.
Destroyed lung syndrome is an uncommon (11% of patients with TB in some publications) consequence of TB and results in a large scale fibrosing of one lung, usually the left. The authors of this paper suggest that it may also be a rare feature of patients with chronic pulmonary aspergillosis (CPA) and the authors demonstrate many similarities.
 
Aspernigrins with anti-HIV-1 activities from the marine-derived fungus Aspergillus niger SCSIO Jcsw6F30.
Two new metabolites, aspernigrins C and D, together with six known compounds, were isolated from the marine-derived fungus Aspergillus niger SCSIO Jcsw6F30. All the isolated compounds were evaluated for their inhibitory activities against infection with HIV-1 SF162 in TZM-bl cells. Malformin C showed the strongest anti-HIV-1 activity with IC50 of 1.4±0.06μM, meanwhile aspernigrin C also exhibited potent activity with IC50 of 4.7±0.4μM.
 
Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia.
Chest computed tomography (CT) findings of nodules, ground glass opacities, and consolidations are often interpreted as representing invasive fungal infection in individuals with febrile neutropenia. We assessed whether these CT findings were present in asymptomatic individuals with acute myeloid leukemia (AML) at low risk of invasive fungal disease.
Conclusion: Chest CT may result in over-diagnosis of invasive fungal disease in individuals with febrile neutropenia if interpreted without correlation to the patients' clinical status.
Reviews
The purpose of this paper is to review the important recent advances made in how innate immune cells, microbes, and the environment contribute to the expression of allergic disease, emphasizing the allergen-related signals that drive allergic responses.
 
The last few years have seen crucial advances in how innate immune cells contribute to allergy and asthma. Simultaneously with these advances, important progress has been made in our understanding of how the environment, and especially pathogenic organisms, such as bacteria, viruses, helminths, and especially fungi derived from the natural and built environments, either promote or inhibit allergic inflammation and disease.
 
Fungal cell membrane - promising drug target for antifungal therapy.
Current antifungal armory includes very few effective drugs like Amphotericin B, new generation azoles including voriconazole and posaconazole, echinocandins like caspofungin, micafungin, to name a few. Azole class of antifungals which target fungal cell membrane are first choice of treatment for many years because of their effectiveness.
As fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during last few years.  This review focuses on cell membrane as antifungal target with emphasis on membrane biogenesis, structure and function of cell membrane, cell membrane inhibitors, screening assays, recent advances and future prospects.
Veterinary
Aspergillus otitis in small animals - a retrospective study of 17 cases.
Aspergillus spp. are saprophytic opportunistic fungal organisms and are a common cause of otomycosis in humans. Although there have been case reports of Aspergillus otitis externa in dogs, to the best of the authors' knowledge, this is the first retrospective case series describing Aspergillus otitis in dogs and cats.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
The Gorgas Course in Clinical Tropical Medicine, Universidad Peruana, Peru Jan 30 - March 31 2017/div>
 
CBS Course Fungal Biodiversity 2017, Utrecht, Uppsalalaan 8, The Netherlands Feb 6-17 2017
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Patients & carers
We have simplified the blogging facility on the Patients website (www.nacpatients.org.uk) to try to encourage more people to add their own content - writing about event that tell us more about living with aspergillosis or any other relevant material. Write your own blog by registering with the website and then after logging in go to the blogging page at www.nacpatients.org.uk/blog and click on 'Create new blog entry' at the top of the page. Then just start typing, upload pictures, add other media. The only limit is your imagination!
 
The Patient & Carers meeting in October was headlined by a presentation from our Outpatients Parenteral Antimicrobial Therapy team (OPAT). As some antifungal medications can be difficult to take and need a daily hospital visit for some i.e. those people needing intravenous delivery, we run a service that allows many to have that treatment as an outpatient and even in their own homes in some cases. This allows our patients to spend less time living in the hospital and more time in their more familiar homes environment and thus has many advantages. The advantages are not limited to the patient - thousands of bed days are being freed up by this service allowing better use of our beds and saving a lot of NHS funding to boot.
 
Aspergillosis Community (National Aspergillosis Centre) normally meets on the first friday of each 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.

If you want a text reminder when each meeting is approaching (UK only) then send us an email at admin@aspergillus.org.uk.
 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR