Fungal Infection Trust
January 2017
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Highlights of this month...

Clinical Pharmacogenetics Implementation Group (CPIC) Guidelines Published

The rate at which voriconazole is broken down is very variable between patients making the correct dosage for each patient difficult to achieve. Part of the basis for this variability is genetic and is due to variant alleles of the CYP2C19 gene that metabolises the drug in vivo.

The new CPIC guidelines provide recommendations for the dosing of voriconazole based on knowledge of which allele a patient may have and summarises the evidence in medical literature that support these decisions.
News
The opening ceremony for the European Confederation of Medical Mycology (ECMM) Centre of Excellence at Manchester was recorded and the slides & audio are available for access here.
 
The Mycology Reference Centre Manchester (ECMM Centre of Excellence) is about to launch its pyrosequencing for the detection of azole antifungal resistence mutations in A. fumigatus as a new service. Details are here.
 
The Mycology Reference Centre Manchester has released a free eBook entitled 'Illustrative Cases in Medical Mycology'. Available for iPad only it can be downloaded from iTunes.
 
University of Manchester MSc Medical Mycology applicants might like to check their accounts for updates following a recent upgrade in the account software. If in any doubt that your registration for the course has been processed please contact the organisers at pgtaught.medicine@manchester.ac.uk
 
Experts in Manchester have recently launched the first e-learning course in direct microscopy for identifying fungal infection, also teaching histological staining methods and interpretation of fungal elements. The course is accredited by the University of Manchester & will teach not only how to rapidly and accurately diagnose life-threatening fungal infections, but also how to set up direct microscopy in a diagnostic laboratory. It is available at www.microfungi.net. The first 50 students to complete this course will be offered free ESCMID membership for one year.
Featured Website Section
This month the featured section is the whole website! Over the 19 years of its existence the Aspergillus Website (AW) has seen a steady increase in its use. Website statistics indicate over 90 000 visitors this month and nearly 5 million bits of data requested.
Users may well have seen the impact of those levels of demand on our old server at particular times of the day, slowing our ability to serve pages and documents and making administering and editing the website even slower. Some will remember several website outages when the pressure of demand peaked in 2015 - a change was needed.
 
The Aspergillus Website has now moved to a new vastly upgraded distributed server architecture that has the ability to respond to demand by increasing available resources to suit, all completely automatically. This means that the website is both quicker to load when you browse to it at any time of day and it is more resilient to peaks in demand.
 
We hope this improved service makes it easier to find the content you need. We will still seek further improvements throughout 2017.
Articles
The authors looked at IgE levels in 53 obital fungal granuloma patients before and after surgery to treat the granuloma. They found high levels of serum IgE prior to surgery which gradually declined post-surgery.
 
Results showed that IgE was a good diagnostic guide for infection and a good postoperative tool with a high (p<0.001) statistically significance.

4.9% of 12,339 cases in Japan were found to have fungal infections. Aspergillus was the most frequent causative agent among those who were infected with one pathogen. The authors concluded 'this epidemiological analysis of autopsied cases with fungal infection provides a strong incentive to intensify and improve efforts in diagnosing and treating visceral mycosis.'
 
Bronchial artery embolization (BAE) is an important treatment option for short-term control of hemoptysis in patients with simple aspergilloma (SA). However, there are no data on the outcomes of BAE in patients with chronic pulmonary aspergillosis (CPA).
The authors retrospectively analyzed the clinical data of 55 CPA patients and 9 SA patients. Immediate success was achieved in 64% of patients, complications were observed in 6% with clinical failure in 2%. Reoccurance  of hemoptysis was more frequent in CPA patients (55%) compared with SA (33%).
Authors conclusions: BAE is a safe and effective procedure for the management of life-threatening hemoptysis in patients with CPA. However recurrence of hemoptysis is common, especially in patients with CPA. Therefore, definitive treatment for CPA following successful BAE should be considered to ensure the long-term success of the embolization in these patients.
 
A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen were unknown, as was the most appropriate dosing weight for obese patients.
Authors observations & conclusions: A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese and appears to be a sensible dosing strategy for these patients.
Reviews
The CCAAT binding complex (CBC) is of fundamental importance in eukaryotes, acting as a general transcriptional regulator and influencing regulation of genes in a wide range of tissues. It is also found in fungi and in Aspergillus and this review looks at its known functions in fungi with special focus on those in Aspergillus
Amongst several conclusions this review notes that CBC has a profound influence in fungal pathogen virulence and antifungal drug resistance.
 
In recent years a number of primary immunodeficiencies (PIDs) characterized by elevated Immunoglobulin E (IgE) levels have been uncovered and termed as Hyper-IgE syndrome (HIES). In addition to the elevated levels of IgE, patients with these PIDs display a spectrum of infections by staphylococci and fungi, and in some cases viruses, particularly affecting skin and lungs.
In this review, the authors are presenting the current knowledge on the clinical presentation, infectious phenotype, and the genetic and immunological pathogenesis of hyper-IgE syndromes as well as some other PIDs with elevated levels of IgE.
 
Allergic Fungal Airway Disease.
This review provides an overview of fungal allergens and the patterns of clinical disease associated with exposure. It clarifies the various terminologies associated with fungal allergy in asthma and makes the case for a new term (allergic fungal airway disease) to include all people with asthma at risk of developing lung damage as a result of their fungal allergy. Lastly, the authors discuss the management of fungi related asthma.
Veterinary
In this study, the authors report the first isolation of Aspergillus allahabadii from a Japanese cormorant with pulmonary aspergillosis. We performed molecular identification and antifungal susceptibility testing with the E-test.
 
A short test of diagnostic skills for aspergillosis in an American Bald Eagle, needs subscription to complete.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
 
Course in Diagnostic Medical Mycology 2017University of Leeds, UK April 3-7th 2017
 
Specialization Course in Medical Mycology, KU Leuven Campus Gasthuisberg, Belgium Sept 11-21 2017 (Registration deadline 1st May).
 
Attention!
Contribute to clinical data on rare infections:

Patients & Carers
Our trials with Skype have been successful so we are expanding the principle and will be attempting to hold an hour long weekly meeting on Skype at 11am GMT every Thursday. Instructions will change over the next few weeks so go to http://www.nacpatients.org.uk/content/skype-group for the latest information.
 
We have simplified the blogging facility on the Patients website (www.nacpatients.org.uk) to try to encourage more people to add their own content - writing about event that tell us more about living with aspergillosis or any other relevant material. Write your own blog by registering with the website and then after logging in go to the blogging page at www.nacpatients.org.uk/blog and click on 'Create new blog entry' at the top of the page. Then just start typing, upload pictures, add other media. The only limit is your imagination!
 
In January this year we talked about maintaining a healthy diet with speaker Timothy Entwistle from the UHSM Transplantation Unit in Manchester. Mainly focusing on the principles of the Mediterranean diet with fresh food, plant oils, fruit and vegetables with more fish and less red meat this is a formulae for changing your eating habits for the better rather than losing weight, though weight loss can also happen. A daily glass of red wine is approved!
 
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. On February 3rd we will be listening to talks from several medical mycology students, here to study University of Manchester's MSC in Medical Mycology.

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