October 2019
  Research highlight
 
Anti-fungal activity of a novel triazole, PC1244, against emerging azole-resistant Aspergillus fumigatus and other species of Aspergillus (Colley et al., 2019)
 
Patients affected by azole-resistant strains of Aspergillus may fail treatment with currently-available antifungals, but a new triazole shows promise: PC1244 was specifically designed to be inhaled and persist at high concentrations in the lungs for a long time.
Colley et al. showed that PC1244 was comparable to posaconazole in vitro against a selection of azole-resistant strains of Aspergillus fumigatus and other Aspergillus species. They went on to show that PC1244 was considerably more potent than posaconazole, when both were administered intranasally in an in vivo neutropenic mouse model.
  • Against an azole-susceptible strain of Aspergillus, PC1244 was 6- to 15-fold more potent than posaconazole at reducing the amount of fungus in the lungs and the amount of galactomannan antigen in the bloodstream.
  • PC1244 was 15- to 27-fold more potent than posaconazole against an itraconazole-resistant strain of Aspergillus.
A related inhaled triazole, PC945, is currently in several phase 2 trials for patients with underlying lung conditions (e.g. CF, lung transplant, asthma). Approval of more inhaled antifungals could potentially mean fewer side effects for aspergillosis patients as well as less development of antifungal resistance. There is also some data suggesting that inhaled and systemic antifungals could be given at the same time to produce a synergistic effect.
 
  News and notices
 
There are lots of conferences taking place in November, these can be found in our conferences and event calendar.
 
Now is the time to consider submitting abstracts or registering to attend the conferences below:
 
The British Thoratic Society Winter Meeting, 4-6 December 2019.  The deadline for abstract submission has passed but registration is still open.
 
12th Asia-Pacific Microscopy Conference, 3-7 February 2020. Abstract submission has closed but registration is still open.
 
Fungal Biodiversity 2020, 10-14 February 2020. This course provides a concise overview of the biodiversity of organisms representing the Kingdom Fungi and registration is now open! 
 
15th European Conference on Fungal Genetics, 17-20 February 2020. The deadline for abstract submission has passed. Registration is now open. Registration closes at midnight on February 5 2020.
 
9th Advances Against Aspergillosis and Mucormycosis, 27-29 February 2020. Abstract submission is open until 15 November 2019. Registration is now open with standard fees of £385 available until 12 January 2020.
 
Mycology 2020, 13-14 March 2020. The closing date for oral abstracts is midnight 8 February 2020. Poster abstracts close at midnight 24 February 2020. Registration is now open.
 
The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, 22-25 March 2020. Abstract submission deadlines for nurses is November 5 2019. For Physicians, Data Management, Quality Management and Statisticians the abstract submission deadline is December 15.
 
The 30th European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), 18-21 April 2020. Abstracts can be submitted from 2 October to 27 November 2019.
 
  Research articles
 
Clinical experience with new formulation SUBA®-itraconazole for prophylaxis in patients undergoing stem cell transplantation or treatment for haematological malignancies (Nield et al., 2019)
This study assesses the therapeutic drug concentrations, safety and tolerability of a standard prophylactic dose of SUper BioAvailability-itraconazole (SUBA®-itraconazole). SUBA®-itraconazole achieved rapid therapeutic trough concentrations, was associated with low rates of IFI and was well tolerated in the study population. The authors suggest that his formulation should be considered a realistic and safe first-line agent for the prevention of IFIs in those undergoing HSCT and intermediate/high-risk therapy for haematological malignancies.
 
Fungal biofilm morphology impacts hypoxia fitness and disease progression. (Kowalski et al., 2019)
Microbial populations form intricate macroscopic colonies with diverse morphologies whose functions remain to be fully understood. This study describes a notable effect of oxygen tension on the macroscopic and biofilm morphotypes of the human fungal pathogen Aspergillus fumigatus. It also describes the host response to infection in terms of disease progression in a murine model. The authors conclude that filamentous fungal biofilm morphology affects fungal-host interactions and should be taken into consideration when assessing virulence and host disease progression of an isolated strain.
 
Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity. (Ferreira D et al., 2019)
Invasive fungal infections (IFI) is a worldwide serious health problem and Amphotericin B (AmB) has been considered the drug of choice for IFI treatment. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. Some lines of evidence have shown that an extemporaneous lipid emulsion preparation of AmB (AmB/LE) was able to attenuate nephrotoxicity, presenting similar benefits at a lower cost. It is also known that reduced vitamin D levels hasten the progression of kidney disease. This study demonstrates that mice with a vitamin D deficiency experienced more kidney toxicity when given amphotericin B (lipid formulation). It may therefore be important to monitor and replenish low vitamin D levels in AmB treated patients.
 
  Veterinary articles
 
Isolation of Aspergillus caninus (Synonym: Phialosimplex caninus) from a canine Iliac lymph node (Kano et al., 2019).
This paper reports the first case of canine A. caninus infection in Japan. It describes presentation, in vitro susceptibility tests of the isolate and subsequent therapy.
 
  Reviews
 
Ibrexafungerp: A novel oral glucan synthase inhibitor (David et al., 2019)
Ibrexafungerp is a novel glucan synthase inhibitor currently undergoing phase II and phase III clinical trials. This compound has demonstrated in vitro activity against clinically important fungal pathogens including Candida spp. and Aspergillus spp. It is able to retain activity against many echinocandin-resistant strains of Candida due to differential avidity for the target site compared to echinocandins. In vivo animal models have demonstrated efficacy in murine models of invasive candidiasis, aspergillosis, and pneumocystis. Due to high bioavailability, it can be administered both orally and intravenously. A favorable drug interaction and tolerability profile is observed with this compound. This review summarizes existing data that have either been published or presented at international symposia.
 
National trends in incidence, prevalence and disability-adjusted life years of invasive aspergillosis in Iran: a systematic review and meta-analysis (Tavakoli et al., 2019)
This review provides an overview of the epidemiology, prevalence, incidence, clinical manifestations, underlying diseases, survivals, treatments, outcomes, and societal impact through disability-adjusted life years (DALYs) of IA in Iran. It is the first paper published with analyses DALY and other related statistics for invasive aspergillosis.
 
Amyloidosis secondary to chronic pulmonary aspergillosis: Case report and a systematic review of literature (Patel et al., 2019)
This case report highlights an uncommon complication (secondary amyloidosis) of CPA. The index case presented primarily with features of the nephrotic syndrome that masked the clinical features of CPA.
 
  Patients and carers
 
Patient meeting
This month’s patient meeting was delivered by Dr Caroline Baxter on 'why do azole antifungal drugs cause peripheral neuropathy'. This was followed by a talk from Dr Graham Atherton on 'monitoring air pollution'. The whole meeting is available to watch online so why not make a cup of tea and take a look.
 
Manchester Rare Disease Showcase
Following last month’s successful trip to Cambridge for RareSummit19, hosted by the Cambridge Rare Disease Network, the team stayed a little closer to home this month and took part in the Manchester Rare Disease Showcase on 8th October. The event was held at the Bridgewater Hall in central Manchester and was Findacure’s biggest and best event in their showcase series yet. Graham, Chris and Helen from the National Aspergillosis Centre (pictured below) joined over 100 other delegates who came to discover the fantastic work taking place in North West England's thriving rare disease community. We were able to share patient stories with a poster and handouts from the Aspergillosis Trust, and spread the word about Aspergillus, the conditions it causes and the work that the National Aspergillosis Centre does to support people who live with Aspergillosis.
 
National Aspergillosis Centre at the Manchester Rare Disease Showcase
Meetings and support
 
We host a weekly video phone call with around 4-8 patients and a member of NAC staff each week. You can use a computer or mobile device to join the video call by downloading the Zoom software by following this link: https://zoom.us/j/243782379. This meeting runs from 11:00-12:00 BST every Thursday.
 
To receive a text reminder when each meeting is approaching send us your mobile phone number (NB this doesn't operate in the US) to admin@aspergillus.org.uk.
 
Our meetings for the aspergillosis community occur on the first Friday of each month at the Altounyan Suite, North West Lung Centre, Manchester at 12.30pm BST. If you can't make it in person you are welcome to watch on Facebook. We broadcast live (this is limited to UK patients only) and post the recording so you can watch it in your own time. (Facebook Broadcast) 
 
Join our Facebook Groups
  • Our Aspergillosis Support Facebook Group has over 2000 members and is a safe place to meet and talk to other people with aspergillosis. We have a public group and a private group.
  • We also have a Facebook group for carers, friends and family of someone who is affected by the disease - join here
  • To find our regional and international groups, search the following terms within Facebook: 'aspergillosis'; 'aspergillus'; 'ABPA'
 
Jobs
Clinical networks
Conferences
 
 
 
 
(5-8 November, Manila, Philippines)
 
6-9 November, Basel, Switzerland
 
6-9 November, Dubai
 
7-8 November, Chicago, USA
 
13-15 November, Argentina
 
 
See more groups and societies
 
 
Visit our sites
 
(MFIG)
(MRCM)
(free online microscopy course)
(fungal education for clinicians)
 
 
     
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR
 
 
 
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