Fungal Infection Trust
November 2015
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March 2016 in
Manchester
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Highlights of this month...

Transfusion can lead to Glucan false positives

1,3-ß-D-glucan (BDG) is increasingly being used to diagnose invasive fungal infections as it has good specificity and sensitivity in immunocompromised patients. However there are caveats and a new warning has emerged in a recent paper that suggests that patients who have received blood products via a transfusion may be prone to false positive results if the blood products that they received give a positive test for glucan prior to transfusion.
 
Patients & carers: please help us contribute to the design of future antifungal drugs by completing our survey for a UK medicines regulatory authority here.
 
Antifungal interaction database has been updated to include terbinafine and isavuconazole. The corresponding APP's will be updated within the next 2 weeks.
Articles
Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. Here, the authors show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. The authors showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery.
 
Azole resistance in Aspergillus fumigatus is becoming an increasing problem. The TR34/L98H and TR46/Y121F/T289A mutations that can occur in patients without previous azole exposure have been reported in Europe, Asia, the Middle East, Africa and Australia. Here we report the detection of both the TR34/L98H and TR46/Y121F/T289A mutations in confirmed A. fumigatus isolates collected in institutions in the United States. These mutations, others known to cause azole resistance, and azole MICs are reported.
 
Invasive aspergillosis (IA) is associated with significant morbidity and mortality, and, among other factors, this is due to a delay in diagnosis performed with conventional techniques. A prospective, multicentre study was conducted by the authors of this paper to evaluate the efficacy of Aspergillus DNA screening in the early diagnosis of IA.
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 last of these key performance indicators (PPV) was moderate in patients receiving primary prophylaxis, at 5.4%. Negative predictive values for both strategies applied were 100% with and 98.3% without antifungal mould prophylaxis. 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.
 
Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. The authors aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis.
The data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia.
Reviews
Indoor Fungal Exposure and Allergic Respiratory Disease.
A gathering body of evidence has repeatedly revealed associations between indoor fungi and initiation, promotion, and exacerbation of allergic respiratory disease. The relationship between the exposure and outcome are complicated by the difficulties in measuring both exposure and outcome, the multifactorial nature of the disease, and the wide range of potential confounders. New technologies are becoming available that may enable better measurement of exposure and tighter case definitions so as to build more confidence in the associations discovered. The growing strength of the evidence base will aid the design of future public health interventions and generate new hypotheses on the cause of the rapid increase in allergic respiratory disease prevalence.
Resistance to the azole antifungals itraconazole, voriconazole, and posaconazole in Aspergillus species is a growing concern. This is especially alarming for A. fumigatus, where acquired resistance has been documented in patients with invasive disease caused by this species that were exposed to these agents, as well as in azole-naive individuals. The primary mechanisms of resistance that have been described in clinical strains include different point mutations in the CYP51A gene, which encodes the enzyme responsible for converting lanosterol to ergosterol via demethylation. Some resistant isolates also contain a tandem repeat in the promoter region of this gene that causes increased expression. These mutations, including TR34/L98H and TR46/Y121F/T289A have also been found in the environment in several areas of the world and have been demonstrated to cause resistance to azole fungicides used in agriculture, thus raising the concern of environmental spread of resistance. Treatment options are limited in patients with infections caused by azole-resistant isolates and include amphotericin B formulations or combination therapy involving an echinocandin. However, there are few clinical data available to help guide therapy, and infections caused by resistant A. fumigatus isolates have been reported to have high mortality rates.
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
Veterinary
Until now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis.
Attention!
Nominate fungal (incl. non-pathogenic) genomes for sequencing at the Joint Genome Institute (JGI) here
 
Contribute to clinical data on rare infections:

Patients & carers
If you are taking oral antifungal medication, you might be interested in the arrival of a new antifungal drug that your doctors may be able to use very soon. We have been asked by a UK drug regulatory body to collect information from as many patients & carers as we can. To help us and assist the generation of future antifungal drugs please complete our new antifungal (isavuconazole) survey. 13 questions will take 20 mins.
 
Aspergillosis Community (National Aspergillosis Centre) meets on the first friday of every 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.

Dedicated newsletter available at the Patients Website 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR