Fungal Infection Trust
March 2016
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7th AAA

7th Advances Against Aspergillosis promoting medical & scientific collaboration
 
 
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Highlights of this month...

7th Advances Against Aspergillosis

7th AAA took place on 3rd - 5th March in Manchester, UK and was a great success with over 350 attendee's at the main conference and a further 30 at the parallel meeting for patients and carers that took place at the same venue.
 
Manchester is home to several global resources that work extensively on aspergillosis (clinical and research) such as 
There are also companies developing new antifungal drugs and diagnostics and of course Manchester is the home of the Aspergillus Website so in a sense this meeting was a visit to an area of the world that has become a 'home' for  Aspergillus & aspergillosis.
News
Prof David Denning recently gave a talk on chronic pulmonary aspergillosis to the Infectious Diseases Society of Pakistan via video which was recorded and is now available for wider consumption. See it here
 
NOTE new EUCAST-AFST breakpoints for isavuconazole for Aspergillus and itraconazole for Candida in new articles section below.
 
Articles
Novel antifungal drugs are needed as existing drugs have limited efficacy and rates of resistance gradually increase. To achieve this new targets and new classes of drug are important and this paper identifies histidine biosynthesis as a candidate target.
Absent in mammals deletion of the gene encoding imidazoleglycerol-phosphate dehydratase (HisB) in A. fumigatus causes (i) histidine auxotrophy, (ii) decreased resistance to both starvation and excess of various heavy metals, including iron, copper and zinc, which play a pivotal role in antimicrobial host defense, (iii) attenuation of pathogenicity in four virulence models.
 
The authors demonstrate that haemofungin causes swelling and lysis of growing fungal cells. It inhibits the growth of pathogenic Aspergillus, Candida, Fusarium and Rhizopus isolates at micromolar concentrations, while only weakly affecting the growth of mammalian cell lines. Genetic and biochemical analyses in A. nidulans and Aspergillus fumigatus indicate that haemofungin primarily inhibits ferrochelatase (HemH), the last enzyme in the haem biosynthetic pathway. Haemofungin was non-toxic and significantly reduced mortality rates of G. mellonella and D. melanogaster infected with A. fumigatus and Rhizopus oryzae, respectively.
 
The EUCAST-AFST (European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing) has determined breakpoints for isavuconazole and Aspergillus and for itraconazole and Candida spp., released a new document summarising existing and new MIC ranges for quality control strains, and has revised the method documents for yeast and mould susceptibility testing.
 
The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique. Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational-based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction.
Reviews
Cerebral aspergillosis, is an infrequent, opportunistic infection of the central nervous system that accounts for 5-10% of all intracranial fungal pathology. It is uncommon in immunocompetent patients and has a significant disease burden, with high morbidity and mortality, even with appropriate treatment. Basic principles of abscess management should be employed, including aspiration and targeted anti-fungal therapy for 12-18 months. However, reported outcomes with a purely minimally invasive approach are poor and there should be a low threshold for surgical excision, especially in resource poor settings and in patients with deteriorating neurology harbouring sizeable masses. Evidence favouring gross total excision over subtotal resection is lacking, however. It is notable that these recommendations are largely based on retrospective case series and isolated case reports. There is a need therefore for international collaboration to evaluate management strategies for immunocompetent patients with cerebral aspergillosis.
 
In patients with respiratory allergy, cross-reactivity between aeroallergens and foods may induce food allergy, symptoms ranging from oral allergy syndrome to severe anaphylaxis. Clinical entities due to IgE sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin, fungal origin (Alternaria-spinach syndrome), and invertebrate, mammalian or avian origin. Clinical cases of allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens are mentioned. Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved, and by the understanding of these clinical entities which may vary significantly or may be overlapping. The association between primary IgE sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice.
 
Of 35 antimicrobials tested (5 antifungals), 25 contained enough β-d-Glucan (BDG) to trigger a positive diagnostic test for invasive fungal infection. Prior exposure to these drugs potentially limits the utility of BDG testing . The authors point out that the cumulative effects of repeated BDG exposure are unknown, and efforts should be made to reduce contamination of these drugs by BDG.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
38th Mycotoxin Workshop takes place in Berlin, Germany May 2-4, 2016
 
 
 
Medical Mycology taught MSc, University of Manchester. One year course beginning in September every year
Veterinary
Fungal placentitis is an infectious disease inducing abortion in pregnant mares. In the present report, the authors describe a field case of abortion caused by fungal placentitis with consecutive examinations. The progesterone level and combined thickness of the uterus and placenta (CTUP) were abnormal before the onset of clinical signs. Additionally, the estradiol level started to change before the appearance of clinical signs. Abnormal serum amyloid A values and an abnormal fetal heart rate were observed after the onset of clinical signs. The present report demonstrates that the progesterone level and CTUP may be adequate as early diagnostic markers of fungal placentitis and bacterial infection. Endocrinological evaluation based on cutoff values or serial measurements were also useful for early diagnosis.
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Patients & carers
Last month we held the patient & carers meeting at the 7th Advances Against Aspergillosis Conference in Manchester with 30 people attending a very informative afternoon chatting with some the the worlds foremost experts in aspergillosis diagnosis and treatment. You can listen to the talks here and see video's from the whole meeting here.
 
Aspergillosis Community (National Aspergillosis Centre) 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 live broadcast.

If you want a text reminder when each meeting is approaching (UK only) then send us an email at admin@aspergillus.org.uk.
 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR