September 2018
Lung colonisation by Aspergillus fumigatus is controlled by ZNF77 gene variants Gago et al (2018)
Humans breathe in thousands of fungal spores every day, which are normally cleared by the immune system before they can germinate and cause disease. Immunocompromised patients (neutropenia, HIV/AIDS, transplant recipients) are notoriously susceptible to fungal infections, as are those who lungs have been damaged (tuberculosis, bronchiectasis, cystic fibrosis), but why do seemingly healthy people develop aspergillosis?
Until recently only a handful of human gene variants were known to be associated with ABPA, which were all part of the adaptive immune response. Dr Sara Gago and colleagues at the University of Manchester and Wythenshawe Hospital recently published an article in Nature Communications about a protein called ZNF77, which appears to be a transcription factor that controls the expression of epithelial genes such as defensins, elastase and calmodulin. They used CRISPR/Cas9 genome editing to create a line of bronchial epithelial (lining) cells carrying a non-functional variant. Aspergillus spores were more likely to stick to the mutant cells, and quicker to germinate and grow hyphae. The mutant cells also failed to mount a normal immune response when challenged with spores. ABPA patients carrying this variant had a higher fungal burden and may be more likely to benefit from antifungal therapy.
The NAC team recently showcased their activities at ERS 2018, which was attended by more than 23,000 respiratory specialists including clinicians and physiotherapists. We had an exhibition booth with seven posters covering the NAC clinic, MRCM reference laboratory, reference websites (Aspergillus&Aspergillosis, LIFE Worldwide), educational tools (Drug Interactions Pro, Microfungi.net) and research into Aspergillus carried out by the MFIG network.
This week is CDC Fungal Disease Awareness Week (1-5 Oct). They encourage doctors and patients to 'think fungus' whenever someone with an infection is not responding to antibiotics. Early diagnosis can mean the difference between life and death, especially for immunocompromised patients or those with other underlying conditions. Visit their website for factsheets, posters, social media buttons and videos.
The Aspergillus Trust are now raising funds and raising awareness with their promotional items including post-it notes, wristbands, ribbons and keyrings.
Voriconazole-induced cell wall carbohydrate patches kill Aspergillus fumigatus Geißel et al (2018)
Triazole antifungals are initially fungistatic against Aspergillus, with their effects only becoming fungicidal later when the cell wall salvage system is induced. The reason for this was not known, although a number of mechanisms had been suggested. Dr Geßiel and colleagues in Germany used fluorescence microscopy to reveal that hyphae treated with voriconazole over-produce cell wall carbohydrates (e.g. BDG) in patches, which penetrate and rupture the plasma membrane, leading to the death of the fungus.
Aspergillus infective endocarditis may present without fever Meshaal et al (2018)
Aspergillus endocarditis is a severe complication of invasive procedures or immune suppression, which is sadly often detected only at postmortem as diagnosis is so difficult: blood cultures are generally negative and fever may be absent. Dr Meshaal and colleagues in Cairo (Egypt) recently described a cohort of 374 patients with infective endocarditis: 43 were fungal infections, including 31 caused by Aspergillus and 9 by Candida. Compared to non-fungal cases, Aspergillus cases were less likely to present with fever but more likely to present with acute limb ischaemia, and patients were more likely to have received a prosthetic heart valve.
Many hospital outbreaks are associated with construction works near high-risk immunocompromised patients (e.g. in haematology wards). However, an increasing number of cases are being reported among immunocompetent patients. Dr Morgan Lane and colleagues in the US reviewed hospital records spanning seven years. Of 3,929 sputum cultures tested for fungal, 123 were positive for Aspergillus, of whom 33 were treated with antifungals. Many of these patients had chronic lung disease. However, six immunocompetent patients who had initially been admitted for trauma or surgery only developed pneumonia after admission to the ICU (7-75 days later). It has previously been suggested that ICU patients may undergo immunodepression during sepsis, which may lead to infections.
Following a lung transplant, patients are most at risk of fungal infections between 2 weeks and 6 months. As part of an overview of the five most common post-transplant complications, Dr Habre and colleagues in Switzerland review the radiological signs and differential diagnosis of lung infections.
It is critical for dermatologists to recognise the cutaneous manifestations of serious fungal infections as they may be the first clinician the patient encounters. Superficial dermatophyte or deep fungal (blastomycosis, histoplasmosis) infections are already well described in the literature, but a new two-part review published in the Journal of the American Academy of Dermatology provides a useful guide to angioinvasive infections such as aspergillus, fusariosis or mucormycosis. They summarise the epidemiology, clinical presentation, diagnosis, management and potential complications of these infections, and provide many useful reference images.
Efforts to control morbidity and mortality from Aspergillus infections in birds are hampered by the lack of a diagnostic 'gold standard'. Dr Savelieff and colleagues provide an overview of the current methods available including imaging, serology/biomarkers, culture, microscopy/histopathology, proteomics/metabolomics and molecular tests. They discuss the advantages and disadvantages of each test in detail and describe future directions.
The Aspergillosis Community meeting for patients and carers in September was used this month to describe why some patients at the National Aspergillosis Centre have been prescribed gamma-Interferon as part of their treatment regimen. Interferons are widely used for their antiviral properties and it has been found that they can also have an impact on fungal infections too, in some cases. If we find that a patient is low in their own natural gamma-Interferon levels we think it is helpful to boost their levels back up a little.
Graham Atherton talked a little about how interferons were discovered, how they work and also some of their limitations. gamma-Interferon works by stimulating the immune system of the person receiving it and it can make them feel like they are experiencing a bout of 'flu for a day or two, without the inflamed lungs of course!
The ERS (European Respiratory Society) 2018 conference was also mentioned as we were all about to attend the meeting and Beth Bradshaw covered some of what we hoped to see. We hosted a stand at the conference and met hundreds of clinicians who were asking for details on how best to look after aspergillosis patients, so it did turn out to be a very rewarding experience over 4 days. We will report back at the next patients meeting on the 5th October.
Our meetings occur on the first Friday of each month at the Altounyan Suite, North West Lung Centre, Manchester at 12.30pm BST/GMT (not 1pm). If you can't make it in person, you are welcome to listen in to our Facebook Broadcast. To receive a text reminder when each meeting is approaching (UK only) please send us an email at admin@aspergillus.org.uk with your mobile phone number.
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 1900 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'
Visit our sites
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(MFIG)
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(MRCM)
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(free online microscopy course)
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(fungal education for clinicians)
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Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR
