Aspergillus Newsletter
May 2015

Allergic Fungal Airway Disease Criteria: Replace ABPA with AFAD?

Woolnough et.al. review the range of allergic fungal disease and its diagnosis  from the broader viewpoint of all the fungi that can be involved and propose the renaming this collection of related diseases allergic fungal airway disease (AFAD).
 
They note that even though large numbers (50%?) of severely asthmatic people are sensitive to fungi the current criteria for the diagnosis of ABPA only allow 10% to be diagnosed with ABPA. Perhaps current criteria are too restrictive? 
 
The authors also note that some fungi are only able to act as allergens while others are capable of growing within the lungs and thus causing damage and consequently propose that diagnostics for AFAD should focus solely on IgE sensitivity to the more damaging species e.g. A. fumigatus together with radiological evidence of lung damage so as to shift the focus of diagnosis to the prevention of lung damage. 
 
"A priority for research is to standardize and improve the methods for detection of noninvasive fungal growth in the lung and to determine the natural history of AFAD to ascertain whether fungal colonization and sensitization are truly causal or a by-product of lung damage."
 
News
Jenny Long's London Marathon run raised nearly £4000 and a subsequent run by another group of fundraisers (Run4Fun(gus)) for the Fungal Infection Trust raised a further £1650 when this went to press. FIT have a target to earn £130 000 to research into why some people get aspergillosis and others do not. We know that genetics is playing a part as we have done some of the preliminary work but much more work is needed to get better answers that will ultimately help us prevent aspergillosis, and may even provide clues to improve diagnosis. Donate via Text send ASPE14 £5 to 70070 or go to www.fit.org.uk
 
 
Snakeoil updated! The people at Information Is Beautiful have updated their useful graphical repsresentation of evidence supporting the use of a hostof herbal remedies and supplements. Well worth a look!
 
New Journal of Fungi Launched this month with a message from Editor in chief David Perlin.
 
New metabolites reported: Terrelumamide A and B
 
Our Societies database is currently being updated -many societies now have far more comprehensive details including a website. Working groups have also been added.
 
The New Antifungal Toolkit: The Pharmacopeia and Beyond is an Internet CME curriculum that will provide current information about new FDA-approved agents/formulations for the management of invasive fungal infections (IFIs) and evaluate the role of these newer options in strategies to optimize antifungal therapy.
 
Articles
Many fungal proteases have been closely linked to asthma. Nearly 10% of people with asthma have severe, treatment-resistant disease, which is frequently associated with immunoglobulin-E sensitization to ubiquitous fungi, typically Aspergillus fumigatus (Af). Nariman Balenga and colleagues show that a major Af allergen, Asp f13, which is a serine protease called alkaline protease 1 (Alp 1), promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle (ASM) cell-extracellular matrix (ECM) interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA-dependent Ca(2+) sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby ASM cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness.
 
Immune reconstitution inflammatory syndrome in neutropenic patients with invasive pulmonary aspergillosis
OBJECTIVES: Clinical and radiologic deterioration is sometimes observed during neutrophil recovery in patients with invasive pulmonary aspergillosis (IPA). This deterioration can be caused by immune reconstitution inflammatory syndrome (IRIS) as well as by progression of the IPA. RESULTS: Of 153 patients, 36 (24%, 95% CI 18%-31%) developed IRIS during neutrophil recovery. More of these patients received voriconazole than did those with non-IRIS (42% vs. 25%, P = 0.05). Thirty- and ninety-day mortalities were lower in the patients with IRIS than in those with non-IRIS (11% vs. 33%, P = 0.01, and 33% vs. 58%, P = 0.01, respectively). CONCLUSION: IRIS is relatively common among neutropenic patients with IPA, occurring in about one quarter of such patients. It is associated with voriconazole use and has a good prognosis.
 
Enhanced diversity and aflatoxigenicity in interspecific hybrids of Aspergillus flavus and Aspergillus parasiticus
Aspergillus flavus and A. parasiticus are the two most important aflatoxin-producing fungi responsible for the contamination of agricultural commodities worldwide. Both species are heterothallic and undergo sexual reproduction in laboratory crosses. Here Olarte et.al. examine the possibility of interspecific matings between A. flavus and A. parasiticus.Higher total aflatoxin concentrations in some F1 progeny strains compared to midpoint parent aflatoxin levels indicate synergism in aflatoxin production; moreover, three progeny strains synthesized G aflatoxins that were not produced by the parents, and there was evidence of allopolyploidization in one strain. These results suggest that hybridization is an important diversifying force resulting in the genesis of novel toxin profiles in these agriculturally important fungi.
 
Allergic Bronchopulmonary Aspergillosis presenting as lobar or total lung collapse
Allergic bronchopulmonary aspergillosis (ABPA) is a T-helper cell 2 (Th2) mediated hypersensitive lung disorder in response to Aspergillus that usually affects asthmatic and cystic fibrosis (CF) patients. ABPA rarely presents as lung collapse and such kind of presentation is very rare in non asthmatic patients. Kumat and colleagues present a series of three cases in which ABPA presented as lobar or total lung collapse. ABPA presenting as opaque hemithorax is a rarity with only a few of them reported in the literature.
The present case series highlights the need for aggressive approach in diagnosing this treatable condition in cases presenting as segmental or total lung collapse. The condition has a good prognosis if detected early.
 
Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection.
Aspergillosis is a major health concern for immunocompromised individuals. Karki et al. show that two cytosolic inflammasome receptors, AIM2 and NLRP3, protect against A. fumigatus infection. AIM2 and NLRP3 activation induces a single cytoplasmic inflammasome platform containing ASC, caspase-1, and caspase-8 that mediates pro-inflammatory cytokine release and A. fumigatus clearance.
Reviews/Overviews
British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases
Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. Silke Schelenz and fellow workers therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically signifi cant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, they provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, they consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients.
 
Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.
Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review by Lamoth, Juvvadi & Steinbach provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.
 
Targeting zinc homeostasis to combat Aspergillus fumigatus infections
Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed individuals and causes invasive pulmonary aspergillosis. The concentration of free zinc in living tissues is much lower than that required for optimal fungal growth in vitro because most of it is tightly bound to proteins. To obtain efficiently zinc from a living host A. fumigatus uses the zinc transporters ZrfA, ZrfB, and ZrfC. Hence, fungal survival in these animals would be undermined upon blocking therapeutically the function of ZrfC. Therefore, both ZafA and ZrfC have emerged as promising targets for the discovery of new antifungals to treat Aspergillus infections.
Deadlines
June 30th Deadline for early bird registration for ProkaGENOMICS 2015
July 31st Deadline for early bird registration ERS 2015
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar (NB we have discontinued use of the Google calendar).
 
Masters in Medical Mycology, University of Manchester, UK 2015-2016 Applications for this one-year taught Masters programme in Medical Mycology are now open. 
 
Specialization Course in Medical Mycology September 7-17, Lueven, Belgium.
 
CBS Course Medical Mycology (China) October 17-25, Shanghai.
 
The Second International Veterinary Mycology Course (ISHAM) October 26-30, Turin, Italy
Veterinary
Cutaneous, Respiratory and Hepatic Aspergillosis in Brazilian White Pekin Mallards (Anas platyrhynchos).
Aspergillosis is one of the most frequent mycosis affecting avian species. Here is reported an outbreak of aspergillosis affecting 60-day-old white Pekin mallards (Anas platyrhynchos). About 10 % of animals in a lot of 200 mallards from a commercial husbandry presented respiratory disorders and skin lesions at slaughter. Three out of 13 animals sent to diagnosis showed, simultaneously, airsacculitis, lung and liver presenting white nodules with variable diameters and elevated, yellowish brown, crusted, multifocal skin lesions located at the base of the feather follicles in the breast. Histopathological examination of lung and liver samples revealed nodules of different sizes with small areas of necrosis surrounded by intense granulomatous inflammation and the presence of fungal hyphae. The skin samples showed dermatitis surrounding a severe necrotizing folliculitis, associated with fungal hyphae. Mycological evaluation of tissues allowed the isolation of Aspergillus fumigatus from the skin samples and Aspergillus flavus from lungs and liver samples. The application of quicklime (CaO) in the litter as part of the disinfection procedures could have contributed to the development of skin lesion in the mallards, predisposing the fungal installation in the damaged site. The occurrence of cutaneous lesions associated with A. fumigatus is a rare manifestation of aspergillosis in birds, and this appears to be the first case reported in white Pekin mallards.
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Jenny Long's Marathon run raised more than £3700
 
Run4Fun(gus) raised over £1600 with their 10k run
 
 
 
 
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