Fungal Infection Trust
January 2015
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Highlights of this month...

Gliotoxin aids diagnosis of Invasive Aspergillosis

It has been suggested recently that gliotoxin, a secondary metabolite produced by several Aspergillus species including A. fumigatus, is a virulence determinant. It does seem that gliotoxin is readily produced during infection with >96% of  Aspergillus strains capable of producing detectable levels in vitro. In contrast gliotoxin is rarely produced by environmental isolates of Aspergillus.
 
Given that inhaled environmental spores have the potential to confuse current diagnostic techniques which rely on detection of our immune reaction to the fungus or detection of fungal elements (DNA, cell wall fragments) both of which might arise from inhaled material, detection of gliotoxin might be a valuable diagnostic marker.
 
This paper compared the sensitivity, specificity and performance of gliotoxin detection with that of galactomannan (GM) detection, the latter being commonly used to help diagnose invasive aspergillosis (IA). Data from 79 patients at risk of IA suggested that gliotoxin detection is more sensitive with better positive predictor value (PPV) than GM. Combination of the two tests increased PPV to 100% and negative predictor value to 97.5%.
 
The potential of this development for more specific diagnosis and better management of IA patients is clear.
News
New treatment summary for Aspergillus bronchitis published
 
The Aspergillus Website articles collection passed 10 000 papers this month!
 
The Aspergillus Website has refreshed its 'New antifungals' section. It now contains many more new antifungals that are easier to find and we will update this periodically. It isn't quite finished yet though and there will be one or two additions to come.
 
The National Aspergillosis Centre, Manchester UK is advertising for an Infectious Diseases Consultant
 
Articles
Two thousand one hundred and twenty-eight sera from 213 patients were investigated and stratified according to the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria for invasive fungal disease. The incidence rates of probable and possible IA were 18% and 38%, respectively. The sensitivity, specificity and positive predictive value (PPV) of PCR were superior in antifungal drug-naive patients, being 71.4%, 92.3%, and 62.5%, respectively.
The authors conclude that PCR has the potential to play a decisive role in the diagnosis and management of Aspergillus infections in centres not applying primary antifungal mould prophylaxis.
 
A new species Aspergillus hongkongensis isolated from nail infection posessing unique morphology different to other Aspergillus species and was not identified as known by multilocus sequencing.
MIC testing suggests itraconazole or voriconazole are better drug options for Aspergillus onychomycosis, fluconazole is ineffective.
 
Technique developed for the introduction of mutations into the widely used industrial strains of Aspergillus oryzae. These strains are more difficult to work with using existing mutational techniques as their multinucleate conidia make the process of separating out homokaryotic transformants very laborious & inefficient
This development of the CRISPR/Cas9 gene editing system will hopefully enable increased research in these important strains, improving our knowledge and perhaps increasing their usefullness & efficiency when generating food, engineeered enzymes and other protein products.
 
Aspergillus-specific IgG is a key component in CPA diagnosis. The authors aimed to establish the optimal diagnostic cut offs for CPA and the comparative performance of six assays in this context.
CONCLUSIONS: ImmunoCAP and Immulite were statistically significantly superior to the other assays (though note that three more assays are available and have not yet been tested). Precipitins testing performed poorly. The currently accepted ImmunoCAP cut-off of 40 mg/L appears sub-optimal for CPA diagnosis and may require revision.
 
Single nucleotide polymorphisms (SNP) associated with increased risk of invasive aspergillosis (in immunocompromised patients) have been identified in this study. These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70 and VEGFα variants might be used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.
Reviews
Fundamental to A. fumigatus pathogenesis is hyphal growth. However, the precise mechanisms underlying hyphal growth and virulence are poorly understood. Over the past 10 years, the authors' research towards the identification of molecular targets responsible for hyphal growth, drug resistance and virulence has led to the elucidation of calcineurin as a key signaling molecule governing these processes. In this review, they summarize their salient findings on the significance of calcineurin for hyphal growth and septation in A. fumigatus and propose future perspectives on exploiting this pathway for designing new fungal-specific therapeutics.
 
Acute invasive fungal sinusitis is the most aggressive form of fungal sinusitis and can be fatal, especially in patients who are immunosuppressed. Early diagnosis and intervention are crucial and potentially lifesaving, so primary care providers must maintain a high index of suspicion for this disease. Patients may need to be admitted to hospital for IV antifungal therapy and surgical debridement, possibly multiple procedures. Platelet  recovery in neutropenic patients should be seen before radical surgery to minimise the risk of catastrophic haemorrhage.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
State-of-the-art infection models to study molecular mechanisms of human fungal infections: FEBS advanced practical course February 14, 2016, Jena, Germany
 
Course of Medical Mycology of the Institut Pasteur will be held in Paris, 21 March-15 April, 2016. The course will be taught in English and is aimed to microbiologists (MDs, PhDs and veterinarians) with previous practice in a medical mycology laboratory
 
38th Mycotoxin Workshop takes place in Berlin, Germany May 2-4, 2016
Veterinary
 
Findings supported the use of CT as a diagnostic test for avian species with respiratory disease and tracheal coiling or elongated tracheae where endoscopic evaluation is impractical.
 
This study involved a death which occurred in four Himalayan griffons housed in Beijing zoo, China. Based on pathogen identification and the pathological changes observed, the authors characterized the fungi and Hepatitis E virus (HEV) in four dead Himalayan griffons. 
 
A retrospective cohort study was conducted using the institution's records of penguins received from January 2004 to December 2009. Animals were categorized according to the outcome "aspergillosis," and analyzed by age group, sex, oil fouling, origin, prophylactic administration of itraconazole, period in captivity, body mass, hematocrit, and total plasma proteins. A total of 327 Magellanic penguins (Spheniscus magellanicus) was studied, 66 of which died of aspergillosis.
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Patients & carers
NOTE: there was no meeting in January 2016, the next meeting is on February 5th.
 
Aspergillosis Community (National Aspergillosis Centre) 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