January 2019
  Research highlight

Sticky ligands trigger the inflammasome

Upon infection with Aspergillus, the inflammasome, an innate immune response of receptors and sensors that detect and respond to infection by inducing inflammation, is triggered.
 
A recent publication has described, for the first time, the activation of the inflammasome by Aspergillus at the molecular level. In particular the transcription factor IRF1 and the GTPase IRGB10 were shown to be mediators of inflammasome activation during A. fumigatus infection.
 
The authors found that toll like receptors (TLRs) and Dectin-1 are required for inflammasome activation and that the TLR adaptor proteins TRIF and Myd88 transduce signals for priming and activating the inflammasome, specifically nuclear translocation of IRF1, during A. fumigatus infection. In turn, IRF1 then induces a set of GTPases (specifically IRGB10) that promote inflammasome activation by releasing fungal ligands.
 
Fungal ligands released by innate immune effectors promote inflammasome activation during Aspergillus fumigatus infection. (Briard et al., 2018)
 
  News and notices
 
1st February 2019 was World Aspergillosis Day, The Aspergillosis Trust, a patient charity in the UK launched a range of activities in the UK including campaigns on public transport in London with 15 buses travelling around South West London proudly displaying the Trust's banner. The banner was also published in programmes at major sporting events throughout England and Wales. 
 
The Trust also run their 'Submit Your Selfie' project and we ran the hashtag #WorldAspergillosisDay on Twitter which really took off and we saw lots of off and online activity with support from Dr Emily Grossman, Craig Venter, ISHAM, Manchester CRF, BRC, GAFFI, Polysciences, Alan Titchmarsh and many more. We saw 172 tweets, 377 retweets, 120 links posted from 212 contributors. 549 tweets in all. So a great result and a big improvement on last year.
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There were some interesting talks and research news too on essential diagnostics, new diagnostic tools and a CPA sensitisation seminar for around 80 clinicians and lab scientists in Ghana delivered by Professor David Denning. This talk is available here.
 
Professor Denning also gave a talk in January at the Britsh Society for Antimicrobial Chemotherapy Conference 2019, which is now available to watch online.
 
A Medical Mycology course will run at the Pasteur Institute in 2019, March 18th - April 12th. This four-week course is intended for microbiologists (MDs, PharmDs, PhDs & veterinarians) willing to catch up with the most recent advances in diagnosis and identification procedures and principles of therapy for fungal infections. It will be run in English with French support.
 
Don't forget the 14th Fungal Update Meeting on the 16th March 2019, London or the 30th Fungal Genetics Conference 12th to 17th March 2019, in Pacific Grove, CA, USA. Later in the month, the BSAC Spring Conference 2019 will take place on the 21st and 22nd March, at the International Convention Center, Birmingham, UK.
 
 
  Research articles
 
Removal and biodegradation of different petroleum hydrocarbons using the filamentous fungus Aspergillus sp. RFC‐1 (Al-Hawash et al., 2018)
A study on crude oil from the Rumaila oilfield in southern Iraq has identified an Aspergillus isolate capable of biodegradation and removal of crude oil and two‐, three‐, and four‐ring polycyclic aromatic hydrocarbons (PAHs).
 
The terrible environmental and socioeconomic impact of petroleum hydrocarbon (PH) contamination is well known and PAHs are of particular concern because they are highly toxic carcinogenic, mutagenic, and teratogenic complex compounds and require several years or decades to degrade from their deposit site e.g. surface water or soil.
 
The authors studied strain Aspergillus sp. RFC-1 and found its intra‐ and extracellular enzymes could effectively metabolize PHs, with the latter playing a more important role. This study provides theoretical support for bioremediation of PAHs pollutants.
 
 
Triacetylfusarinine C: A urine biomarker for diagnosis of invasive aspergillosis. (Hoenigl et al., 2018)
Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C (TAFC), a fungal siderophore that has been shown to accumulate in urine in animal models, is a potential new biomarker for diagnosis of IA.
 
The authors developed a method allowing absolute and matrix-independent mass spectrometric quantification of TAFC. Urine TAFC was determined in 44 samples from 24 patients with underlying hematologic malignancies and probable, possible or no IA and compared to other established biomarkers measured in urine and same-day blood samples.
 
The paper claims that, for the first time, we have proof for the occurrence of TAFC in human urine. This is promising for the diagnosis of IA offering clear advantages over more traditional, invasive sampling. Sensitivity and specificity were similar to that reported for galactomannan determination in serum and bronchoalveolar lavage, the gold standard mycological criterion for IA diagnosis.
 
Diagnosing invasive pulmonary aspergillosis in hematology patients: a retrospective multicentre evaluation of a novel lateral flow device. (Mercier et al., 2019)
A large multicentre study has recently been published which assesses the performance of a lateral flow device (LFD) to diagnose aspergillosis in hematology patients who underwent bronchospy with BALf sampling.
 
Invasive pulmonary aspergillosis (IPA) can be a serious complication for hematology patients. So this study is important since new diagnostics tools that are sensitive and fast will impact the speed with which antifungal therapy can be started and so reduce morbidity and mortality of IPA.
 
The LFD showed good diagnostic performance and its sensitivity was identical to that of more traditional methods such as detecting the cell wall protein galactomannan. Its performance for excluding IPA was even better. The LFD could be used as a first line diagnostic tool but the authors conclude that additional testing is still required to definitively confirm or exclude IPA, as for other biomarker tests.
 
Multicenter Evaluation of a Novel Immunochromatographic Test for Anti-aspergillus IgG Detection (Piarroux et al., 2019)
Similar to the Mercier paper, a second study on a lateral flow type device was also published this month but with a focus on the diagnosis of CPA and ABPA. This paper noted the limitations of the anti-Aspergillus IgG detection assay in laboratories with limited resources such as stable electricity supplies and evaluated a novel LFD that needs very little equipment. Results showed good diagnostic performance with a sensitivity of 89% and a specificity of 96%. The authors conclude that the device would be of value in resource poor laboratory settings in complement to CT-scan (when available) or chest X-ray, when CT-Scan is not available, as recently proposed by Denning et al. (2018).
 
Repurposing approach identifies new treatment options for invasive fungal disease. (Capoci et al., 2018)
Drugs already on the market can be put through drug repositioning - a process of discovery and validation to find new uses for the drug. This study describes two such methods and identified an antiviral drug with promising antifungal activity for treatment of paracoccidioidomycosis. Whilst no antifungals active against Aspergillus spp. were found, this method provides a useful means of identifying existing drugs that might be useful treatments for fungal infection.
 
 
 Veterinary articles
 
Aspergillus infections causing mortality and morbidity in birds is well known. In this study, the authors used a variety of molecular techniques to identify which species of Aspergillus was most prevalent in birds with aspergillosis. Isolates were also screened for itraconazole resistance and environmental samples were taken from both natural habitats and sea bird centres.
 
77 isolates (43 clinical and 34 environmental) were identified as Aspergillus fumigatus. Two environmental isolates were identified as Aspergillus nidulans var. dentatus and Aspergillus spinulosporus. None of the Aspergillus isolates tested were resistant to itraconazole. This study emphasizes the dominant association of Aspergillus fumigatus in avian mycoses and shows a lack of itraconazole resistance in the studied isolates.
 
Molecular identification of clinical and environmental avian Aspergillus isolates (Sabino et al., 2019)
 
 
  Reviews
 
Successful treatment with omalizumab of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: case reports and literature review. (Parisi et al., 2019)
Estimates suggest that between 1-15% of cystic fibrosis (CF) patients have Allergic Bronchopulmonary Aspergillosis (ABPA). In this Italian paper, the drug omalizumab, which is usually used to reduce sensitivity to allergens in severe allergic asthma, was used to successfully treat ABPA complicating CF patients.
 
In three cases, following unsuccessful antifungal and steroid treatments, omalizumab was administered and improvements were observed in lung function (forced expiratory volume) and immune response to infection (total IgE increased), and clinical symptoms.
 
Currently, no large scale studies or randomised trials have been done and evidence is limited to case studies such as this. A randomised, double-blind, placebo-controlled study designed to assess a range of omalizumab doses in adult patients with CF complicated by ABPA across several European and North American centers was terminated early without publication after recruitment difficulties.
 
Perhaps the time has come to attempt another study?
 
Usefulness of animal models of aspergillosis in studying immunity against Aspergillus infections. (Mirkov et al., 2019).
What has been the contribution of animal models to the current knowledge of immune mechanisms of resistance or susceptibility to Aspergillus? What has been the significance of data gained from animal models of Aspergillosis? Have animal models helped to form the basis for the design of therapeutic strategies in prevention and/or treatment of Aspergillosis?
 
This review aims to answer all of these questions by describing how invertebrate models have enabled mass screening of virulence attributes of Aspergillus species. It gives a concise summary of cellular and humoral participants in immune response to Aspergillus gained mostly from rodent models and explains how animal models have helped us to understand the role of innate immune cells and receptors in antifungal response, the significance of dendritic cells in activation of specific adaptive T cell-mediated immune responses and the regulatory mechanisms of excessive response.
 
Invasive Aspergillosis in Paediatric Leukemia Patients: Prevention and Treatment (Papachristou et al., 2019)
Invasive Aspergillosis (IA) in children is relatively under studied and treatment and clinical decisions have been made by extrapolating data from adult IA and further research is required in the field of paediatric IA management in order to reach the evidence quantity and quality of the respective field in adults.
 
This article reviews the current strategies for prevention and treatment of IA in paediatric leukaemia patients. Topics covered in the prevention section include:
  • epidemiology and risk factors for IA in paediatric patients with leukaemia
  • anti-fungal prophylaxis
  • other preventive measures
 
  Patients and carers
 
World Aspergillosis Day 2019 (1st Feb) went so well we have already decided to run WAD 2020 next year, but this time we will move it from 1st Feb so that it will coincide with the Advances Against Aspergillosis conference to take place in Switzerland at the end of February 2020. This move will enable us to do even more hopefully with one or more  live broadcasts from AAA, the worlds foremost research meeting on aspergillosis attended by the worlds best aspergillosis doctors and researchers. Watch this space!
 
Aspergillosis patients should note that we have switched from our old website for patients and carers (nacpatients.org.uk) to our new website that can be accessed using our new domain name aspergillosis.org
 
We believe that the new website offers a much clearer way to find everything you need to know about aspergillosis,
Your can also find out about our busy support groups on Facebook and find the best way you might get support, whether you are a patient or a carer or family member.
It would be really great if you could send us your own stories too - it might be a diary of managing your daily life, organising your hospital visits and your daily medication, the good and the bad. People in our support groups often mention that their family and friends do not really understand how difficult aspergillosis can be - this is your chance to tell us all. You will have to register for an account before submitting your story, but it is free and secure.
 
A new blog post is available on Pulmonary Rehabilitation. Have a read and let us know what you think! 
 
Medical Alert cards (see left) for aspergillosis patients are now available in clinic or by emailing us at admin@aspergillus.org.uk
 
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.

(Facebook Broadcast) 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/GMT. If you can't make it in person, you are welcome to listen in, this is limited to UK patients only). 
 
We'd love to know what you think about these meetings.
 
What should we cover in these meeting? What talks would you like? Or would you prefer to be able to chat informally to nurses and clinicians? How can we encourage more people to attend?
Please let us know your thoughts by emailing us admin@aspergillus.org.uk.
 
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/laptop or phone/tablet 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 GMT every Thursday (UHT+1 in the summer). 
 
 
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
 
 
 
30th Fungal Genetics Conference (12-17 March 2019 Asilomar Conference Grounds Pacific Grove, CA)
 
14th Annual Fungal Update (15 - 16 March 2019 QE2 Conference Centre, London.
 
BSAC Spring Conference 2019 (21 - 22 March 2019) International Convention Center, Birmingham, UK.
 
Microbiology Society Annual Conference 2019 (8 - 11th April Belfast Waterfront, UK)
 
29th European Congress of Clinical Microbiology and Infectious Diseases (13-16th April 2019 Amsterdam, The Netherlands)
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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