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

World's 1st CPA guidelines presented at European Respiratory Meeting

Professor Denning of the National Aspergillosis Centre presented the first guidelines for chronic pulmonary aspergillosis (CPA) at the European Respiratory Society (ERS) Conference in Amsterdam late in September. The guidelines have been drawn up in conjunction the ERS and ESCMID and will be published in the European Respiratory Journal in October.
The guidelines describe the 5 clinical phenotypes of CPA and how to diagnose and manage these patients.
The guidelines support the strong message that CPA needs action and antifungals are the cornerstone of treatment for this condition which therefore should include therapeutic drug monitoring.
The objective of antifungal therapy in CPA patients would be 4 fold: to control infection, arrest pulmonary fibrosis, prevent haemoptysis and improve the quality of life.
 
The publication of these guidelines in a few weeks time, will assist and guide the training of medical professionals working with CPA patients and improve patient outcome.
 
Life Worldwide tell us that 15 papers were simultaneously published in October on the estimated burden of all serious fungal diseases in Belgium, Czech Republic, Denmark, Hungary, Nepal, Qatar, Tanzania, Trinidad and Tobago, Uganda, Germany, Mexico, Senegal, Tanzania, Ukraine, Vietnam and that posters on burden from Mozambique, Madagascar, Pakistan, Algeria, Venezuela, Serbia, Greece, Portugal and France were presented at 7th TIMM, Lisbon, Portugal. This is a milestone - the fungal disease for 5 billion people are now presented and/or published.
 
As we go to press a paper (Pisa etal 2015) has emerged that claims to demonstrate quite convincingly that fungi and fungal elements (not Aspergillus) are present in the brain tissue of Alzheimers patients. Whilst this is not an entirely new observation this is the first time hyphal-like structures have been demonstrated and the authors mention two cases where patients believed to have Alzheimers were treated successfully with antifungal medication.
Articles
Fungal lung colonisation has been demonstrated to correlate with faster lung function loss in these patients, but it also looks like those who have a poorer lung function also have increased likelyhood of a fungal lung colonisation (Noni et al 2015).
It isn't difficult to imagine that the two could go hand in hand with very undesirable consequences.
 
Low rates of homologous recombination have broadly encumbered genetic studies in the fungal pathogen Aspergillus fumigatus. The CRISPR/Cas9 system of bacteria has recently been developed for targeted mutagenesis of eukaryotic genomes with high efficiency and, importantly, through a mechanism independent of homologous repair machinery. As this new technology has not been developed for use in A. fumigatus, Fuller et al.(2015) sought to test its feasibility for targeted gene disruption in this organism. As a proof-of-principle, they first demonstrate that CRISPR/Cas9 can indeed be used for high-efficiency (25-53%) targeting of the A. fumigatus polyketide synthase gene (pksP), as evidenced by the generation of colorless (albino) mutants harboring the expected genomic alteration. They further demonstrate that the constitutive expression of the Cas9 nuclease by itself is not deleterious with respect to A. fumigatus growth or virulence, thus making the CRISPR system compatible with studies involved in pathogenesis.
 
The aim of this study by Peghin et al.(2015)was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. 
 
Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long-term administration of prophylaxis with n-LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.
 
Aspergillus fumigatus is the most virulent species within the Aspergillus genus, and causes invasive infections with high mortality rates. The exopolysaccharide galactosaminogalactan (GAG) contributes to the virulence of A. fumigatus. A co-regulated five-gene cluster has been identified and proposed to encode the proteins required for GAG biosynthesis. One of these genes, sph3, is predicted to encode a protein belonging to the spherulin 4 family, a protein family with no known function. Construction of an sph3-deficient mutant demonstrated that the gene is necessary for GAG production. To determine the role of Sph3 in GAG biosynthesis Bamford et al.(2015) determined the structure of Aspergillus clavatus Sph3 to 1.25 Å. The structure revealed a (β/α)8 fold, with similarities to glycoside hydrolase families 18, 27, and 84. Recombinant Sph3 displayed hydrolytic activity against both purified and cell wall-associated GAG. Structural and sequence alignments identified three conserved acidic residues, D166, E167, and E222, which are located within the putative active site groove. In vitro and in vivo mutagenesis analysis demonstrated that all three residues are important for activity. Variants of D166 yielded the greatest decrease in activity suggesting a role in catalysis. This work shows that Sph3 is a glycoside hydrolase essential for GAG production and defines a new glycoside hydrolase family, GHXXX.
Reviews
Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are increasingly being investigated.
OBJECTIVES: Cruciani et al.(2015) provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people.
 
Although in textbooks asthma and chronic obstructive pulmonary disease (COPD) are viewed as distinct disorders, there is increasing awareness that many patients have features of both. This article by Postma & Rabe (2015) reviews the asthma-COPD overlap syndrome.
 
Several tiny organisms of various size ranges present in air are called airborne particles or bioaerosol which mainly includes live or dead fungi and bacteria, their secondary metabolites, viruses, pollens, etc. which have been related to health issues of human beings and other life stocks.
Characterization i.e. identification and quantification of different airborne microorganisms in various indoor environments is necessary to identify the associated risks and to establish exposure threshold.
 
Along with the bioaerosol sampling and their analytical techniques, various literatures revealing the concentration levels of bioaerosol have been mentioned in this review by Ghosh, Lil & Srivastava (2015) thereby contributing to the knowledge of identification and quantification of bioaerosols and their different constituents in various indoor environments (both occupational and non-occupational sections).
 
Apart from recognition of bioaerosol, developments of their control mechanisms also play an important role. Hence several control methods have also been briefly reviewed. However, several individual levels of efforts such as periodic cleaning operations, maintenance activities and proper ventilation system also serve in their best way to improve indoor air quality.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
The Second International Veterinary Mycology Course (ISHAM) October 26-30, Turin, Italy
 
 
Veterinary
The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article by Seyedmousavi et.al. (2015) represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals.
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
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