June 2020
A Multi-Institutional Review of Outcomes in Biopsy-Proven Chronic Invasive Fungal Sinusitis
Chronic invasive fungal sinusitis (CIFS) is a rare but deadly fungal infection about which we need to know much more, this review attempts to identify factors that impact survival in a large cohort consisting mostly of patients with haematological malignancy or diabetes. Absolute neutrophil count (ANC) of less than 1000 at time of diagnosis and recent chemotherapy (within 1 month of diagnosis) are associated with poorer survival, whereas a rising ANC >1000 is associated with improved survival at 12 month
News and notices
Advances Against Aspergillosis & Mucormycosis (2020, Lugano)
A playlist of talks from AAAM 2020, is now available on YouTube.
LIFE Worldwide Fungal Diagnostics Webinars
LIFE Worldwide are offering FREE webinars in fungal diagnostics. Webinars are accredited by the Royal College of Pathology and attendees will earn 1 CPD credit per webinar. Webinars will take place on the first Wednesday of every month from 13:00 -14:00 BST, continuing this week on 1st July 2020.
Research articles
Sandra Hicks summarises her experience with hyperIgE syndrome (HIES), a primary immunodeficiency syndrome, and how living with this rare genetic condition and associated lung infections impacts her life (video S1). As a direct consequence of HIES and its effect on the immune cascade, Sandra concurrently manages chronic Aspergillus infection (aspergillosis), nontuberculous mycobacterial infection (Mycobacterium avium-intracellulare), bronchiectasis colonised with Pseudomonas and asthma. She discusses the effect this rare disease and infection burden have on her daily life, including the influence of other factors such as temperature, humidity and antimicrobial resistance.
Pulmonary infections in patients with myelodysplastic syndromes receiving frontline azacytidine treatment. Latagliata R., et. al. 2020
Pulmonary infections (PIs) are a major complication of patients with myelodysplastic syndromes (MDS). We retrospectively evaluated 234 MDS patients treated with azacytidine (AZA). There were 111 episodes of PI (3.8% of AZA cycles) in 81 patients (34.6%). PIs were considered of fungal origin in 27 cases (24.3%). The authors concluded that PIs are common in MDS patients receiving AZA, in particular during the first cycles of treatment and are associated with an unfavorable outcome. The results of their study raise the issue of the need of a tailored infection prevention strategy.
PD-1 Blockade Improves Survival and Fungal Clearance, Induces Pro-Inflammatory Lung Cytokines and Synergizes With Caspofungin in a Pulmonary Aspergillosis Model Wurster S., et. al. 2020
Pharmacological immune checkpoint blockade has revolutionized oncological therapies and its remarkable success has sparked interest in expanding checkpoint inhibitor therapy in infectious diseases. Herein, we evaluated the efficacy of PD-1 blockade in a murine invasive pulmonary aspergillosis model. We found that, compared to isotype-treated infected control mice, anti-PD-1-treated mice had improved survival, reduced fungal burden, increased lung concentrations of pro-inflammatory cytokines and neutrophil-attracting chemokines, and enhanced pulmonary leukocyte accumulation. Furthermore, combined treatment with anti-PD-1 and caspofungin resulted in a significant survival benefit compared with caspofungin or anti-PD-1 therapy alone, indicating a synergistic effect between PD-1-inhibitors and immunomodulatory antifungal agents.
During Aspergillus Infection, Monocyte-Derived DCs, Neutrophils, and Plasmacytoid DCs Enhance Innate Immune Defense through CXCR3-Dependent Crosstalk. Yahui G., et. al. 2020
Host defense against IA relies on lung-infiltrating neutrophils and monocyte-derived dendritic cells (Mo-DCs). Here, we demonstrate that plasmacytoid dendritic cells (pDCs), which are prototypically antiviral cells, participate in innate immune crosstalk underlying mucosal antifungal immunity. During aspergillosis, circulating pDCs entered the lung in response to CXCR3-dependent signals. Via targeted pDC ablation, we found that pDCs were essential for host defense in the presence of normal neutrophil and Mo-DC numbers. Although interactions between pDC and fungal cells were not detected, pDCs regulated neutrophil NADPH oxidase activity and conidial killing. Thus, pDCs act as positive feedback amplifiers of neutrophil effector activity against inhaled mold conidia.
Role of recombinant Aspergillus fumigatus antigens in diagnosing Aspergillus sensitization among asthmatics.Muthu V., et. al. 2020
The diagnosis of Aspergillus-sensitized asthma (ASA) and allergic bronchopulmonary aspergillosis (ABPA) is made using IgE against crude antigens of A.fumigatus (cAsp). However, the IgE against cAsp has limitations due to cross-reactivity with other fungi. The authors set out to evaluate the utility of recombinant A.fumigatus (rAsp) antigens in detecting ASA, and their role in differentiating true from cross-sensitization. Conclusions: Crude Aspergillus antigens may misclassify Aspergillus sensitization among asthmatics. IgE against rAsp antigens (f 1 and f 2) potentially detect true Aspergillus sensitization and could be used for this purpose.
A Multicentre Study to Optimize Echinocandin Susceptibility Testing of Aspergillus Species With the EUCAST Methodology and a Broth Microdilution Colorimetric Method Meletiadis J., et. al. 2020
Background: The determination of the minimal effective concentration (MEC) of echinocandins against Aspergillus species is subjective, time-consuming and has been associated with very major errors. Methods: The MECs/MICs of 40 WT [10 each of Aspergillus fumigatus species complex (SC), Aspergillus flavus SC, Aspergillus terreus SC and Aspergillus niger SC] and 4 non-WT A. fumigatus isolates were determined with EUCAST E.Def 9.3.1 read microscopically, macroscopically, spectrophotometrically and colorimetrically in three centres. The optimal conditions for spectrophotometric (single- versus multi-point readings) and colorimetric (XTT/menadione concentration and stability, incubation time) methods were evaluated in preliminary studies using different cut-offs for the determination of macroscopic, spectrophotometric and colorimetric MIC endpoints compared with the microscopically determined MEC. Inter-centre and inter-method essential (within one 2-fold dilution) agreement (EA) and categorical agreement (CA) were determined. Results: Both macroscopic and spectrophotometric endpoint readings showed poor inter-centre EA (53%–66%) and low CA (41%–88%) in distinguishing WT from non-WT A. fumigatus SC isolates, while significant differences compared with the microscopic MECs were observed for all echinocandins (EA 6%–54%). For the colorimetric method, the optimal conditions were 400 mg/L XTT/6.25 lM menadione, incubation for 1–2 h until the drug-free control reached an absorbance at 450/630 nm of >0.8 and use of 50% inhibition of XTT conversion as a cut-off for all species and echinocandins. All non-WT isolates had high XTT MICs >1 mg/L, whereas the overall intercentre EA and CA were 72%–89% and 100%, respectively. Conclusions: The XTT colorimetric assay improved the antifungal susceptibility testing of echinocandins against Aspergillus spp., reliably detecting non-WT isolates.
Veterinary article
Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-α-1,3-galactose (α-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing α-Gal regulate the immune response to this glycan in animals lacking endogenous α-Gal. Here, the authors asked whether the production of anti-α-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses α-Gal in its surface.
The authors demonstrate that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high α-Gal content, reduces the occurrence of granulomas in lungs and protects turkeys from developing acute aspergillosis.
Reviews
The approach to diagnose invasive pulmonary aspergillosis in the absence of lung biopsy in ICU patients is reviewed. This approach should be based on four pillars: mycology, medical imaging, underlying conditions, and acute disease expression.
This review summarizes recent literature for applying pharmacogenomics to antifungal selection and dosing, providing an approach to implementing antifungal pharmacogenomics in clinical practice.
The cell walls of plants and microbes are a central source for bio-renewable energy and the major targets of antibiotics and antifungal agents. It is highly challenging to determine the molecular structure of complex carbohydrates, protein and lignin, and their supramolecular assembly in intact cell walls. This article selectively highlights the recent breakthroughs that employ 13C/15N solid-state NMR techniques to elucidate the architecture of fungal cell walls in Aspergillus fumigatus
Pulmonary Aspergillosis: What the Generalist Needs to Know. El-Baba F, Gao Y, Soubani AO. 2020
This review introduces the spectrum of pulmonary aspergillosis geared toward generalists, including disease manifestations, most recent diagnostic criteria, and first-line treatment options. Involving a multidisciplinary team is vital to the early diagnosis and management of these diseases.
Melittin, the main constituent in the venom of European honeybee Apis mellifera, has attracted considerable attention among researchers owing to its potential therapeutic applications extending to antifungal properties. In this respect, melittin inhibits a broad spectrum of fungal genera including Aspergillus, Botrytis, Candida, Colletotrichum, Fusarium, Malassezia, Neurospora, Penicillium, Saccharomyces, Trichoderma, Trichophyton, and Trichosporon. Melittin hinders fungal growth by several mechanisms such as membrane permeabilization, apoptosis induction by reactive oxygen species-mediated mitochondria/caspase-dependent pathway, inhibition of (1,3)-β-D-glucan synthase, and alterations in fungal gene expression.
Patients and carers
Maybe you or a loved one has just received a diagnosis of aspergillosis and you’re not sure where to start. Or maybe you need to share information about your condition with your doctor, carer, housing association or benefits assessor. Our patients and carers website can provide you with everything you need to know about aspergillosis.
This month we have focussed on the implications of partially lifting the coronavirus lockdown for people who are vulnerable and highly vulnerable.
Further information on this, and other COVID-19 information is available on aspergillosis.org.
Other meetings and support
We host a weekly video phone call (Software: Zoom) with around 4-8 patients and a member of National Aspergillosis Centre (NAC) staff twice each week. You can use a computer or mobile device to join the video but you need to register in advance. This meeting runs from 10:00-11:00 BST every Tuesday & Thursday and is also presented in our private Facebook group (see below).
There is an additional meeting on the first Friday of every month which normally takes place at NAC but for the period of time when we are unable to hold face-to-face meetings we are meeting on Zoom, using the same registration details.To receive a text reminder when each monthly meeting is approaching send us your mobile phone number (NB this doesn't operate in the US) to admin@aspergillus.org.uk.
Join our Private Facebook Groups for the Aspergillosis community
- Our Aspergillosis Support Facebook Group has over 2000 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 for 'aspergillosis' in Facebook.
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More and more conferences are switching to exclusively online presentation as COVID-19 continues to restrict travel and social contact throughout the world.
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(free online microscopy course)
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Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR
