Fungal Infection Trust Aspergillus Newsletter April 2018
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Highlights of this month...

MedLec, a C-type lectin, has crucial role in response to systemic A. fumigatus infection

The C-type lectins, a family of pattern recognition receptors responsible for recognizing microbes, are key players in antifungal immunity. C-type lectins start a chain reaction in the immune system following identification of fungal species.
A letter published in the journal Nature has described a C-type lectin that recognises fungal melanin, aptly named the melanin-sensing C-type lectin (MelLec). This receptor recognises melanin in conidial spores of Aspergillus fumigatus, and in any other type of fungi that have 1,8-dihydrocynaphthalene (DHN)-melanin.
The authors of this letter have found that MedLec is expressed by endothelial cells in mice, and was required for appropriate immune response to disseminated A. fumigatus infection. They also found that MedLec is expressed by both epithelial and myeloid cells in humans, and identified a single nucleotide polymorphism that inhibited myeloid inflammatory responses and increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infection.
The letter speculates that screening for the less effective single nucleotide polymorphism in stem-cell donors could help to reduce the incidence of disseminated aspergillosis in stem-cell transplant recipients.
News
 
A new MRes programme has been developed by researchers at the University of Manchester. The year-long programme is currently accepting applications from potential students.
 
The course provides research training in fundamental aspects of infectious disease, microbial pathogens, host interactions, antimicrobial immunity, and antimicrobial therapy. For the talented student this course provides excellent training prior to registration for a PhD. 
 
 
Medical Mycology Worldwide is a new website that provides mycology societies around the world with an online platform for news items and discussion. 
 
Societies and groups can set up their own 'page' on the site, following simple video instructions. Participation for societies and members is free, and we're hoping that the site leads to better connectivity within and between groups. 
 
If you have any questions about Medical Mycology Worldwide, or would like advice on setting up a page for your society or group, please get in touch via email: admin@medicalmycologyworldwide.org
Articles
The Fogarty International Centre turns 50
 
The Fogarty International Centre (FIC), which supports the missions of the National Institute of Health in the United States, is turning 50 this year. The future of Fogarty appeared to be in peril up until recently, as a result of presidential plans to cut global health research and shut down the FIC. 
 
Fogarty has 5 Strategic Goals that were announced 4 years ago as part of its long-term Strategic Plan:
 
1. Build research capacity through individuals, institutions and networks to meet future and evolving global health challenges
2. Stimulate innovation in the development and implementation of technologies and other locally relevant solutions to address global health problems
3. Support research and research training in implementation science
4. Advance research on prevention and control of the dual burden of communicable and non-communicable diseases and disabilities
5. Build and strengthen partnerships to advance global health research and research capacity
 
All of these goals are relevant for the fungal infection research community. A more detailed discussion of the history and plans of the FIC can be found in the journal Clinical Infectious Diseases.
 
 
In a paper published in the journal ‘Mycoses’, the researchers describe the resistance profiles of 228 isolates from 91 patients treated at the University Clinical Hospital in Brazil. Aspergillus fumigatus and flavus were the most prevalent species isolated, comprising 74% and 12% of the clinical isolates.
 
Aspergillus flavus showed high Minimum Inhibitory Concentrations (MICs) to Amphotericin B to levels associated with treatment failure in patients with Invasive Aspergillosis. 27% of A. fumigatus isolates had Amphotericin B MICs equal to or exceeding 2 mg/L.
 
The authors note that their findings suggest that A. fumigatusA. flavus and A. terreus are developing resistance to one of the most important therapeutic options for invasive aspergillosis. They suggest continued surveillance to monitor resistance of Aspergillus species to azoles and Amphotericin B.
 
 
Chronic pulmonary aspergillosis (CPA) is well known to develop in individuals whose lungs have already been damaged by tuberculosis (TB), but less is known about links with a related condition caused by the same Mycobacterium bacteria. Non-tuberculous mycobacterial lung disease (NTM-LD) is a chronic but generally non-fatal infection that causes small nodules or cavities with symptoms including coughing, breathlessness, fatigue and sometimes haemoptysis. Patients who have CPA associated with NTM-LD are very difficult to treat, not least because antifungals often interact with antibiotics (e.g. itraconazole interacts with rifamycin), and the clinical signs of the conditions overlap. More information about how NTM-LD develop CPA would be of great help. 
 
Jhun and colleagues in Seoul reviewed the medical records of 1,334 consecutive Korean patients with NTM-LD, spanning a period of 5 years. Of 566 who fulfilled the inclusion criteria, 41 (7%) went on to develop CPA at an average time of around 18 months. These patients were more likely to be older male smokers with a low BMI and a history of COPd and/or steroid treatment.
Reviews

A review by Schwartz et al on the advances in diagnosis and treatment of fungal infections in the CNS has recently been published in the journal ‘The Lancet Neurology’.
The review is dedicated to advances in diagnosis and treatment. New antifungal agents that are under development are highlighted, including a series of novel tetrazoles that inhibit cryptococcal CYP51 protein and four new small molecules with activity against azole-resistant mould pathogens.
Despite these advances, the authors conclude that fungal infections of the CNS are still difficult to treat and associated with a poor prognosis. They suggest that more research on defective antifungal host responses could help to identify those at risk, and develop targeted immune modulatory therapies.
Veterinary

A paper published in Diseases of Aquatic Organisms has described the gross and microscopic findings of two cases of fungal infection in cetaceans. Case reports like these are crucial to characterising the presentation of fungal infection in different species.
 
An adult male Atlantic spotted dolphin (Stenella frontalis) had localised pulmonary infection with Aspergillus fumigatus, and pyogranulomatous and necrotising bronchopneoumonia with intralesional hyphae was observed. This is the first published case of pulmonary aspergillosis in this species.
 
An adult male Bryde’s whale (Balaenoptera edeni) presented with orchitis, periorchitis, mesenteric lymphadenitis and pyogranulomatous bronchopneumonia with intralesional hyphae. The fungal species isolated from the whale’s mesenteric lymph node resembled Nanniziopsis obscura and Stagonosporopsis cucurbitacaerum, and the authors speculate that the systemic mycosis could be due to a novel Onygenales.
 
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Patients & Carers
Patient Meetings

The Aspergillus community/patient group meeting 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 Facebook Broadcast

If you want a text reminder when each meeting is approaching (UK only) then send us an email at admin@aspergillus.org.uk with your mobile phone number.
 
For more details see the Patients' Community Newsletter

Skype Meetings

If you would like to listen or chat with fellow patients and a NAC staff member we are running a successful Skype meeting every week! We are a chatty group of 8 - 12 most weeks but we can accommodate up to 24. If you have a computer or smartphone you will be able to join in - just click on https://join.skype.com/nbubWMUM8teC and you will be asked to register, then taken to the group. The Skype meeting is at 11am GMT every Thursday

We have recently started running a USA/Worldwide Skype group at 5pm GMT every Thursday, which can be accessed using this link: https://join.skype.com/ffp8FM6UysGf 
 
Join our Facebook Groups
 
Our Aspergillosis Support Facebook Group has over 1000 members and is a safe place to meet and talk to other people with aspergillosis.
 
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'
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR