Aspergillus Newsletter
July 2015

GAFFI Roadmap

Global Action Fund for Fungal Infections (GAFFI) has published its roadmap for the next 10 years. GAFFI is promoting and supporting the provision of good quality diagnosis and treatment for fungal diseases for every country of the world. Specifically they aim to ensure that 95% of people with serious fungal disease are diagnosed and 95% treated by 2025.
With regard to aspergillosis, as with most estimates of global burden there is variable information available from differing countries. For Chronic Pulmonary Aspergillosis they have collated data from 66% of the world with incidence rates up to 138 per 100 000 in parts of Africa, 68 per 100 000 in People's Republic of Korea and 40 in Myanmar (Burma). 
For Allergic Bronchopulmonary Aspergillosis in patients with Cystic Fibrosis there is good data available for relatively few countries but several thousand predicted cases. Global burden of ABPA with asthma is estimated to be in excess of 4.8 million people.
There is clearly much more work for GAFFI to do in the next 10 years.
Users of the Aspergillus Website may well be aware that access was difficult for some time during late June. This was due to a major problem with our content management system which has now been resolved. We apologise for the break in service.
Advances Against Aspergillosis conference (March 2016) is the only conference specialising in Aspergillus: registrations opening soon (Early registration deadline 30th September 2015).
Here, the incidence of voriconazole, posaconazole and itraconazole resistance in clinical isolates from high-risk patients from either the haematology ward or the ICU of the University Medical Center Utrecht in the period 2011–13 is analysed. Putative clonality of resistant strains was tested through cyp51A and microsatellite typing.
This study reveals a high incidence of voriconazole resistance (16.2%) in A. fumigatus in high-risk patients. The data stresses the need for laboratory detection of azole resistance prior to treatment.
Fungal aerosols consist of spores and fragments with diverse array of morphologies; however, the size, shape, and origin of the constituents require further characterization. In this study, we characterize the profile of aerosols generated from Aspergillus fumigatus, A. versicolor, and Penicillium chrysogenum grown for 8 weeks on gypsum boards. We observed spore particle fraction consisting of single spores and spore aggregates in four size categories, and a fragment fraction that contained submicronic fragments and three size categories of larger fragments. Single spores dominated the aerosols from A. fumigatus(median: 53%), while the submicronic fragment fraction was the highest in the aerosols. This study shows that fungal particles of various size, shape, and origin are aerosolized, and supports the need to include a broader range of particle types in fungal exposure assessment.
OBJECTIVE: To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up.
RESULTS:  There was a statistically significant reduction in the mean serum IgE levels at 3 (p < 0.00) and 6 months (p < 0.001) of follow-up in BAL as compared to conventional group. CONCLUSION: Therapeutic bronchoalveolar lavage may be a useful adjunct to treatment in patients with allergic bronchopulmonary aspergillosis, serum in terms of IgE level reduction.
The aim of this study was to investigate the effect of prior azole exposure on AmB sensitivity in Aspergillus fumigatus biofilms. It was hypothesised that sequential antifungal therapy has the potential to impact adaptive resistance mechanisms. The in vitro data revealed that A. fumigatus sensitivity to AmB was decreased when it was tested in combination with AmB±voriconazole (VRZ). In addition, a two- to four-fold decreased sensitivity to AmB was recorded against VRZ-exposed germlings compared with controls. It was also shown that depletion of extracellular DNA (eDNA) by DNase treatment enhanced AmB activity against VRZ-exposed cells by eight-fold, which visually could be explained by destabilisation of the biofilm when examined microscopically. Pharmacological inhibition of Hsp90 by geldanamycin (GDA) significantly improved biofilm susceptibility to AmB by four- to eight-fold. In conclusion, A. fumigatus pre-exposure to VRZ concomitantly induces eDNA release and activates the stress response, which collectively confers AmB resistance in vitro.
Aspergillus PCR: a systematic review of evidence for clinical use in comparison with antigen testing Aspergillus PCR was excluded from the EORTC/MSG definitions of invasive fungal disease because of limited standardisation and validation. The definitions are being revised. A systematic literature review was performed to identify analytical and clinical information available on inclusion of galactomannan-EIA (2002) and β-D-Glucan (2008), providing a minimal threshold when considering PCR. The authors propose there is sufficient evidence, that is at least equivalent to that used to include galactomannan-EIA and β-D-Glucan testing, and PCR is now mature enough for inclusion in the EORTC/MSG definitions.
Since pulmonary aspergillosis is a very serious complication in CF children, it seems reasonable to include screening for early detection of Aspergillus colonization in the annual assessment of CF patients who are over 6 years old. Due to the small sample size and retrospective design of our analysis, the identification of risk factors of pulmonary aspergillosis in CF children require further prospective studies. 
The authors address recent advances in our understanding of the host-fungus interaction and discuss the application of this knowledge in potential strategies with the aim of moving toward personalized diagnostics and treatment (theranostics) in immunocompromised patients. Ultimately, the integration of individual traits into a clinically applicable process to predict the risk and progression of disease, and the efficacy of antifungal prophylaxis and therapy, holds the promise of a pioneering innovation benefiting patients at risk of IA.
The authors discuss the comparative merits of the available tests in the various clinical settings and their suitability for use in the resource-poor settings where the majority of cases of aspergillosis are thought to occur. We summarize the gaps in existing knowledge and opportunities for further study that could allow optimal use of antibody testing in this field
July 31st for early bird registration ERS 2015
August 4th abstract submission 57th ASH
6th August discounted registration deadline ICAAC
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
Feline upper respiratory tract infection due to Aspergillus spp. is considered an emerging disease, with the number of reported cases continuing to rise. In this study, we report the first case of feline sinonasal aspergillosis caused by Aspergillus fischeri in Japan. The patient presented after 2 months of progressive facial deformity around the nose and nasal discharge. The isolate from this case was susceptible to itraconazole (ITZ), voriconazole, and micafungin, but was resistant to amphotericine B. However, the infected cat died approximately 1 month after referral, despite treatment for 12 days ITZ administered orally at 10 mg/kg.
Attention Clinicians & Scientists
Nominate fungal (incl. non-pathogenic) genomes for sequencing at the Joint Genome Institute (JGI) here
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The Aspergillosis Community meeting takes place on 5th June at our regular venue in the Altounyan Suite, North West Lung Centre at 1pm. 
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