August 2019
  Research highlight
 
New Aspergillus fumigatus gene knock out library methodology published.
 
This paper describes a high throughput gene knockout method that combines a highly reproducible fusion PCR method to enable generation of gene replacement cassettes with a multi-well format transformation procedure. The process can be used to generate 96 null mutants within 5 days by a single person at a cost of less than £18 ($24) per mutant and is being employed in the authors’ laboratory at the University of Manchester, to generate a barcoded genome-wide knockout library in A. fumigatus. This library will be incredibly useful and will facilitate research into the molecular mechanisms that drive pathogenicity and drug resistance.
 
High‐throughput gene replacement in Aspergillus fumigatus (Zhao et al., 2019).
 
  News and notices
 
The Fungal Infection Trust are asking for feedback on their antifungal interactions app. If you use the app or database as a clinician or researcher please complete this survey and let FIT know of any improvements you’d like to see.
 
There are lots of conferences taking place in September including the 53rd Scientific Conference of the German-speaking Mycological Society in Mannheim, Germany; the 12th Global Infections Conference and the 11th Euro-Global Conference on Infectious Diseases.
 
Now is the time to consider submitting abstracts or registering to attend the conferences below:
 
12th Global Infections Conference, Singapore. Registration is open until 9th September – be quick!
 
Public Health England Annual Conference 2019. Registration is open. Bookings are subject to availability. In previous years the conference has been fully subscribed so book now to avoid disappointment.
 
GAIN2019, UK. Case study submission and registration now open.
 
11th Euro-Global Conference on Infectious Diseases, UK. It is still possible to submit an abstract. Registration is open until 23rd September.
 
30th Brazilian Congress of Microbiology, Maceió, Brazil. Abstract submission closed. Registration open.
 
6th International Conference on Mycology and Fungal Infections, Spain. Abstract submission now open. Registration open until 7th October.
 
2nd World Congress on COPD, Asthma and Lung Health, Spain. Abstract submission and registration are open.
 
9th Trends in Medical Mycology, Nice, France. Abstract submission is now closed. Registration is open, it is possible to register on-site.
 
4th International Conference on Innate Immune Memory, Nijmegen, Netherlands.  The deadline for abstract submission is 15th September, and for registration is 15th October.
 
11th World Congress of the World Society for Pediatric Infectious Diseases, Manila, Philippines. Late breaking abstract submission deadline: 17th September.
 
31st ICC – 4th GCCMID 2019, Dubai. Last date for online early bird registration is 12th September. Last date for online registration at standard rates is 30th October.
 
17th INFOCUS - 1st ISHAM Latin America Congress, Brazil. Abstract submission deadline is the 16th September.
 
  Research articles
 
Voriconazole-associated periostitis presenting as hypertrophic osteoarthropathy following lung transplantation report of two cases and review of the literature. (Elmore et al., 2019)
Hypertrophic osteoarthropathy (HOA) is a condition that combines periostitis of the small hand joints and digital clubbing. It is usually associated with intrathoracic malignancies, congenital heart disease and chemotherapy but recently, HOA and periostitis has been reported as a side effect of using antifungal therapy (voriconazole) in lung transplant recipients. This paper reports two such cases and notes the rapid improvement of the painful symptoms of HOA following removal of voriconazole treatment. The paper also gives a review of the medical literature around this subject.
 
Clinical pattern of fungal balls in the paranasal sinuses: our experience with 70 patients. (Seo et al., 2019)
This interesting study charts the growth characteristics of paranasal sinus (PNS) fungal balls via sinus imaging techniques. The authors looked at 70 patients and investigated changes in symptoms and lesion size, as well as any new occurrences. Where a fungal ball was found at the initial examination, the authors found an increase in size in about two-thirds of the lesions and confirmed that the size increment was present within five months. No case of local invasion was observed during the follow-up period of more than 17 years in this study, suggesting that surgery to remove fungal balls should not be performed routinely without thorough consideration of other clinical features of symptoms, any changes in the lesion and the immune-competence of the patient.
 
Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents (Zhao et al., 2019)
This paper describes the antifungal activities of a novel class of L-amino alcohol derivatives which have been designed and synthesised to try and discover broad spectrum antifungal agents. It follows previous work on a series of azole derivatives with an ester group which were found to be inactive against Aspergillus fumigatus due to a steric clash. This paper sought to overcome that clash by replacing the bulky ester group with smaller alkyl side chains. These changes resulted in increased activity against A. fumigatus but reduced the activity against other fungi such as Candida albicans, Cryptococcus neoformans and Candida tropicalis.
 
Burden of hospitalisations over time with invasive aspergillosis in the United States, 2004-2013. (Zilberberg et al., 2019)
Invasive aspergillosis (IA) is associated with high crude and attributable mortality, and by some estimates, the economic costs of IA approaches $600 million annually in the US. This paper seeks to describe in detail the epidemiology and outcomes associated with IA. It explores time trends in the prevalence, mortality and hospital resource utilisation associated with IA among a diverse cohort of hospitalised 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. canius infection in Japan. It follows the transfer of the fungus from the genus Phialosimplex to Aspergillus. The dog responded poorly to itraconazole and voriconazole treatment despite the isolate being susceptible to both drugs (only resistance to fluconazole was observed). The authors therefore conclude that more aggressive management using combination therapies of itraconazole with other antifungals may be necessary for treating canine A. caninus infection in dogs.
 
  Reviews
 
Adverse effects associated with long-term administration of azole antifungal agents (Benitez and Carver, 2019)
This comprehensive review gives a thorough description of a variety of side effects associated with the ongoing use of antifungals including liver damage and hormone-related effects, including enlarged male breast tissue, hair loss, decreased libido, reduced sperm count, impotence, low blood potassium and sodium, and (rarely) adrenal insufficiency. The authors note that there are no known or hypothesized genetic profiles that increase the risk of development. More research is needed in order to determine whether specific patient populations are at increased risk. The review also highlights the cost of newer triazole drugs and the financial implications of managing adverse effects.   
 
Galactomannan detection in broncho-alveolar lavage fluid for invasive aspergillosis in immunocompromised patients. (de Heer et al., 2019)
This review aims to determine the error rate of galactomannan testing on BAL. To this end, the authors searched for papers on this subject in three bibliographic databases including MEDLINE and found 17 relevant studies. The galactomannan test results in an ’optical density index’ (ODI), not a yes or no answer. The studies differed with respect to the cut-off value above which a result was considered positive and the review discusses optimal cuts off values in terms of false negative and false positive results as well as local incidence and clinical pathway data.
 
Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi (Hokken et al., 2019)
The existing and newly emerging molecular resistance mechanisms of fungi to antifungals is explored in this interesting review. It also summarises and explains how genetic variability that helps fungi to adapt to stressful environments, takes place. The authors note that understanding these processes and potential niches that can lead to the emergence of resistance can provide leads for new management strategies to battle the emerging resistant populations in the clinic and the environment.
 
  Patients and carers
 
We need your help! It looks like we have an upcoming opportunity for all patients with ABPA to have a say in the development of a new drug type intended to treat ABPA. This is a new inhalable drug which has been through its initial trialling successfully and they are now at the stage where they are refining how they provide the medication as a package. To do this they need some feedback from patients and as this is the biggest community of ABPA patients anywhere they came to us.
This will involve completing a 10 min questionnaire at some point in the next few months, to give your opinion on what would work best for you. We need about 100 patients to give their opinions in order to make this a really good contribution.
Join our ABPA research volunteers Facebook group to hear more when we get the questionnaires.
 
August’s patient meeting at Wythenshawe Hospital in Manchester was a movie marathon! Dr Darren Thomson, Experimental Officer with the Manchester Fungal Infection Group, delivered a fantastic talk about the work of the group with particular reference to live cell imaging complete with lots of amazing videos including fungal cells evading host immune cells, and components being trafficked around the cell. You can watch his fantastic talk on our Facebook page.
 
We reported last month that Aspergillosis Trust (AT) supporters Andy, John and David completed a cycle ride from Land’s End to John O’Groats in July to raise funds for AT. This month their success has been featured as the lead story in the European Lung Foundation Patient Organisation Round-up newsletter! Read all about it.
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
 
 
 
(5-7 September, Mannheim, Germany)
 
(9-10 September, Singapore)
 
(10-11 September, Warwick, UK)
 
(19-20 September, Schloss Montabaur, Germany)
 
(20-21 September, London, UK)
 
(23-24 September, London, UK)
 
 
 
 
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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