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Natural Killer Cells and Fungal Disease
It is increasingly being noted that the natural killer cells (NK) of the host are one of the major lines of defence that protect the host from fungal infection. NK cells are known to attack fungi in a number of ways; binding and then killing fungi by the secretion of perforin and granzyme B, or death receptor mediated apoptosis. Much of this information was discovered some time ago in vitro and in animal models systems, a lot of it
20 - 30 years old.
NK cells also influence the immune response
through chemokines and cytokines, which enhance the activity of
professional phagocytes, dendritic
cells (DC) and T cells, helping the host resist fungal infection.
We also know that the fungus fights back! Recent information suggests that the fungus can actively suppress some of the antifungal activities of NK cells.
Compared with 20-30 years ago we now have far superior analytical techniques and we know much more about our immune systems. This review (Note: membership of the Aspergillus Website is now required to view articles) revisits the subject of NK cells and their antifungal properties and reassesses what we know in the light of recent advances.
Gold Nanoparticles have many potential uses including medical uses but can be difficult, toxic and
expensive to produce. This research team have isolated two strains of Aspergillus, one A. fumigatus and one A. flavus which naturally generate gold nanoparticles around 20nm in size, thus giving us a source of gold nanoparticles that is far less toxic to the environment and will hopefully be cheaper to produce.
ECDC issues risk assessment on azole resistance in Aspergillus from environmental azole fungicide. Today the European Centre for Disease Prevention and Control (ECDC) issued a risk assessment report on azole resistance in Aspergillus spp. and its possible link to environmental usage of azole fungicides. An increase of strains of Aspergillus causing serious human infection showing resistance to azole antifungals has been detected in several European countries although the number of studies is small. However, a high rate of therapy failures has been reported in patients having Aspergillus isolates resistant to triazole antifungals.
The report concludes about the need to improve surveillance to get good and reliable data about resistance in A. fumigatus. It all recommends accelerating progress on direct molecular detection of resistance from clinical specimens, even if culture negative. It also identifies the need for further research into the causes for the development of triazole resistance, in particular to investigate the environmental origin of azole resistance, and how reversible this with alternative fungicide treatments.
Latest Website News and Articles
We have completed adding to our collection of articles
by adding all the articles that are currently listed in the reference lists for our treatment section (around 2000 articles) . We hope this makes our collection of seminal and important papers more complete.
The allergen website Allergome is celebrating 10 years on the web.
A full collection of papers from the 5th Advances Against Aspergillosis meeting is now available here
Selected articles: (713 new articles added,
147 are reviews and 245 precede the year 2000)
Colonization With Small Conidia Aspergillus Species
Is Associated With Bronchiolitis Obliterans Syndrome:
A Two-Center Validation Study Nearly 800 transplant recipients were studied and found that colonisation by those species of Aspergillus that produce the smallest spores (1-3micrometer) were positively correlated with the development of Bronchiolar Obliterans Syndrome (BOS), a major cause of transplant failure and death. Conidial size may not be the only important virulence factor but as the smallest sized spores are able to get into the smallest airways and BOS is a disease of the smallest airways it is tempting to suggest a link.
The authors suggest progress should be made to prevent Aspergillus colonisation of transplant recipients.
EUCAST Technical Note on Voriconazole and Aspergillus spp The European Committee on Antimicrobial Susceptibility Testing
Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST) has determined breakpoints for voriconazole against Aspergillus spp. This Technical Note is based on the EUCAST
rationale document for voriconazole (available on the EUCAST
website). Voriconazole breakpoints are
based on epidemiological cut-off values, pharmacokinetic/pharmacodynamic data and clinical experience. Breakpoints will be
reviewed regularly or when new data emerge.
Impact of liposomal amphotericin B on renal
function in critically ill patients with renal
In critically ill patients with impaired renal
function, the impact of L-AmB on renal function was minimal.
L-AmB can be used for the treatment of fungal infections in
critically ill patients independently of renal function at the initiation of treatment.
Utility of PCR in diagnosis of invasive fungal infections: real-life data from a multicenter study Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the “gold standard.” In this prospective study, 206 specimens with a negative result on routine microscopy were
analyzed with PCR, and patients’ clinical data were reviewed according to the criteria of the European Organization for Research
and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious
Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, speciﬁcity, positive predictive value, and
negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study
deﬁnes a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with
Minireview: host defence in invasive aspergillosis The major pathogen recognition receptors for Aspergillus are Toll-like Receptors(TLR 2, TLR 4 and
TLR 9, dectin-1 and DC-Sign and mediate the development of T-cell responses. In draining lymph nodes,
presentation of fungal antigen by DC leads to activation
of the adaptive immune response. Adequate control of
invading fungi leads to progressive release of proinﬂammatory response (TNF, IFN-c, IL-6) and anti-inﬂammatory cytokines (IL-4 and IL-10). The risk of developing
IA results primarily from a dysfunction in these host
defences in combination with fungal attributes that
permit A. fumigatus survival and growth in this
environment. Resistance and tolerance are host defence
mechanisms to increase response to Aspergillus, and a
master regulator is IDO. Both defence mechanisms are
activated through the equilibrium between TH1 cells,
which provide antifungal resistance and TRegs
limit the associated inﬂammatory pathology.
Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity-mediated disease of worldwide distribution. We reviewed 143 reported global cases of ABPM due to fungi other than
aspergilli. The commonest etiologic agent was Candida albicans, reported in 60% of the cases,
followed by Bipolaris species (13%), Schizophyllum commune (11%), Curvularia species (8%),
Pseudallescheria boydii species complex (3%) and rarely, Alternaria alternata, Fusarium
vasinfectum, Penicillium species, Cladosporium cladosporioides, Stemphylium languinosum,
Rhizopus oryzae, C. glabrata, Saccharomyces cerevisiae and Trichosporon beigelii. India accounted
for about 47% of the globally reported cases of ABPM, attributed predominantly to C. albicans,
followed by Japan (16%) where S. commune predominates, and the remaining one-third from
the USA, Australia and Europe. Notably, bronchial asthma was present in only 32%of ABPM
cases whereas its association with development of allergic bronchopulmonary aspergillosis
(ABPA) is known to be much more frequent. The cases reviewed herein revealed a median IgE
value threefold higher than that of ABPA, suggesting that the etiologic agents of ABPM incite a
stronger immunological response than that by aspergilli in ABPA. ABPM is currently
underdiagnosed, warranting comprehensive basic and clinical studies in order to elucidate
its epidemiology and to devise a more effective therapy.
Susceptibility of adult pigeons and hybrid falcons to experimental aspergillosis Aspergillosis caused by Aspergillus fumigatus seems to be more prevalent in some avian species than in others. We compared the development of aspergillosis in 8-month-old Gyr-Saker hybrid falcons and 8-month-old pigeons after a single intratracheal inoculation of different dosages of A. fumigatus conidia (10(7), 10(5) and 10(3)). Clinical signs, including vomiting, discoloration of the urates, loss of appetite and dyspnoea, were observed in four out of five falcons and in four out of five pigeons inoculated with 10(7) A. fumigatus conidia. Necropsy revealed the presence of granulomas in the air sacs and/or lungs in four out of five falcons and in four out of five pigeons in the high dosage group. A. fumigatus was isolated from these granulomas in three falcons and in three pigeons. The presence of fungal hyphae was detected with Periodic acid Shiff reagent staining in three out of five falcons and in three out of five pigeons in the high dosage group. Avian respiratory macrophages were clearly present in and around the fungal granulomas. In the other dosage groups, no granulomas, positive A. fumigatus cultures or fungal hyphae were present, except for one falcon in the middle dosage group in which a sterile granuloma without fungal hyphae was noticed. In conclusion, the study shows that adult falcons and pigeons are susceptible to aspergillosis after inoculation of a single dose of conidia intratracheally.
You can now search all of our veterinary articles alongside all of the rest of our articles in the website Library
NOTE: Vets in the UK in need of assistance with acquiring antifungals please contact us here
Fungal Ribosomal Internal Transcribed Spacer 1 Database - ITSoneDB is a comprehensive collection of the fungal ribosomal RNA Internal Transcribed Spacer 1 (ITS1) sequences aimed at supporting metagenomic surveys of fungal environmental communities. The sequences were extracted from Genbank (GB) and arranged on the NCBI taxonomy tree. ITS1 start and end boundaries were defined by GB annotations and/or designed by mapping Hidden Markov Model (HMM) profiles of flanking 18S and 5.8S ribosomal RNA coding genes on each sequence.
Request for assistance from clinics in all 5 continents of the world for a study entitled “Pulmonary aspergillosis in kidney transplant recipients” supported by REIPI and GESITRA
This study has two targets. The first target is to define some risk factors that allow the identification of a subgroup of kidney transplant recipients that would be candidates for antifungal prophylaxis active against Aspergillus. The second target is to find factors implicated in the outcome that were amenable to intervention. In this context, we think that it is especially relevant to assess how best to proceed with immunosuppressive drugs when aspergillosis is diagnosed.
The study will retrospectively include cases of probable or probed pulmonary aspergillosis (according to EORTC-MSG definition) diagnosed in kidney transplant recipients from the year 2000 to now.
It will be a case-control study. Each included case must be accompanied by a control. The control will be a subject that received a kidney transplant in the same hospital just before or after the case. The control should have survived at least as long as did the case until the development of pulmonary aspergillosis.
You may like to contribute to the following collaborative groups who are collecting clinical data on these rare infections:
Fungiscope is a global rare fungal infection registry, a working group of ISHAM.
International Pediatric Fungal Network (PFN) collating information on treatment of pediatric patients
AspICU2 is a web-based multicentre observational survey to assess the burden of aspergillosis and other fungi in critically ill patients.
Clinical Training for developing countries
Public Health and Tropical Medicine Fellowships. It has come to our attention that there are a series of Fellowships funded by the Wellcome Trust available to applicants for low and middle income countries. We would like to encourage medical mycology applicants and would be happy to provide facilities and expertise for training at the National Aspergillosis Centre for applicants. We would like to identify applicants for these Fellowships and help facilitate application - please contact us at email@example.com
Aspergillosis Patients & Carers Meeting
After a very eventful Patients Meeting and lots of discussion we have opted to adjust the format of this meeting to allow informal separate meetings for carers and patients as we recognise that each group has different needs. The solution arrived at was to have alternate breaks so that for 20 mins one group leaves the room for tea while we promote discussion with
the other in private.
There was also a request that we expend the amount of time we devote to discussions of topics of interest that have arisen from that months online debates in Yahoo and Facebook or other suitable sources.
This month's speakers Graham Atherton observed that research into Aspergillus and aspergillosis is increasing in volume rapidly, and what is being done about the vast amount of data being generated.
Khaled Al-shair (Medical Research Fellow and medical doctor) returned to speak a little about why patients fail treatment In his talk last month Khaled showed us that
patients attending the National Aspergillosis Centre have a 70% chance of improving after treatment with antifungal medication, even if very poorly when they arrive. The 30% who do not improve are often having problems with other types of infection or other health issues, might be suffering from some of the significant side effects caused by antifungals but there is also a significant proportion who could do more to help themselves by giving up smoking & secondary smoking, exercising each day (build up to a 20min gentle walk each day) and eating plenty of fruit and fresh vegetables. All of these things increase the chance you will be in the 70% who improve.
Caroline Hawkridge (Writer in Residence at NAC) talked about progress in our efforts to engage patients & staff in creative writing, to provide poems for the waiting room and we had a vote on which of ten poems would be selected for the waiting room. We also talked about 'Hope' and each member of the audience was invited to write a line about hope which would be incorporated into a poem by Caroline. This triggered some unexpected conversations revealing some people's expectation for the future and hope, and of course that is one intended effect of involving patients and carers in thinking creatively - it forms a language through which things are said they aren't normally spoken about.
The Patients & Carers Support Meeting on March 15th will now be as follows (provisional speakers):
1.30 Riina Richardson - Flourine
2.00 Physiotherapy talk
2.20 Patients break, Carers discussion
2.40 Carers Break, Patients discussion
3.00 Whole meeting to discussion suggested topics
Follow the meeting online here
The next meeting will be at 1.30 on the 15th March 2013. Everyone is welcome. You can pop in and out as you wish as
each talk will last 20 – 30mins and there will be time for you to ask staff any
questions that you wish. Light lunch, tea & coffee will be provided in the
Altounyan suite Atrium from around 1pm.
NOTE: To stay in touch of any changes at short notice we have a
mobile phone text-based update system that can provide instant updates and
reminders. If you wish to be added to the list we contact send your mobile
number to firstname.lastname@example.org.
NOTE: We are working on broadcasting the meeting via Skype so that all of the proceedings can be heard using an ordinary phone at local cost rates (free if you have Skype phone). If you are interested in helping with a trial contact me at the above email address.
You can see a listing of all
talks here (on the right)
(needs computer) communities
Reaching new people is of fundamental importance to our need to reach people who may be living with aspergillosis and not be supported or occasionally even diagnosed correctly. Facebook is one way to contact those people - Facebook Support group There is also our oldest and largest private group at Yahoo! Aspergillosis Support
Phone Support (no need for computer)
There is a suggestion that we will be able to start a volunteer based peer group phone service to support those who don't have access to the internet or who are more comfortable chatting on the phone rather than typing! Watch this space! If you would like to volunteer to help us provide a a trial of this service please email me at email@example.com
We are also looking at ways to allow people to listen and talk to people in our monthly meetings via low cost phone - more news soon.
Local Support Meetings
Two local meetings have been very successful so far this year. London held a meeting at Google UK headquarters with some attendees on the phone/videoconferencing, and the West Midland group held a fundraisng event attended by over 40 people . 2 people have joined the new Wigan group.
We always need new groups, particularly in the North East of England and Scotland, Southern and Eastern areas of the US so any volunteers would be welcome - all you need to do is arrange a venue (can be a pub/civic centre - we recommend NOT using your home at first) and a date and we will help publicising your group. How often you meet depends on you.
Contact firstname.lastname@example.org for details or phone 0161 291 5866.
| Wigan Group: FacebookEmail Group Leader
| Bristol:Facebook Email Group Leader
|USA: South Louisiana: Facebook Email Group Leader
|West Yorkshire: Facebook Email Group Leader
|Canada: Ontario. Facebook Email
|Liverpool: Next date to be announced, "Wetherspoons", Childwall Fiveways Hotel, Queens Drive, Liverpool, L15 6XS. Map Facebook Email
|London: Video conference available.
Belgrave House, 76 Buckingham Palace Road, London SW1W 9TQ. Map Facebook Email Group Leader
West Midlands: Dudley Golf Club, Rowley Regis,
West Midlands B65 9DP. Map Facebook Email
East Midlands: Next date to be announced at Eat n' Enjoy Cafe, 4 Eaton Walk, Rushden Northants, NN10 9SH Map Facebook Email
|USA: San Francisco. Map Facebook Email Group Leader
|USA: Los Angeles. Meet at Weiler's Deli.
22323 Sherman Way in West Hills. Map Facebook Email
|USA: Vermont. Map Facebook Email
Patient's Own Stories
So far we have collected 51
stories (89 members) which are being updated regularly, written by patients directly into the 'wiki' website at Patients with Aspergillosis.
More stories needed - join up and join in!
Two new leaflets are now available:
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You can donate through Virgin Money Giving. Through this organisation all of your donations goes straight to our charity. If you are a UK taxpayer we can reclaim the tax on your donation.
Research Grant Awards
NPRP-EP Communication Please be informed that our next quarterly Exceptional Proposal-Panel (EP-Panel) review for the Initial Research Proposals (IRPs) of the NPRP-EP will be in March 2013. If you are interested in applying, please submit your IRP ASAP through the process indicated in the NPRP-EP RFP and have the RO of the submitting institution in Qatar vet your IRP in order for it to go to the panel review, this March. For any enquires please use the support link
Gilead UK and Ireland Fellowship Programme details of 2013 programme for fungal disease opens on 10th December 2012.
Merck International Grants (Non-US) requests are now submitted online via Merck Support
See also Jobs for PhD Studenships, Fellowships
Ten positions are currently being advertised:
CLINICAL RESEARCH FELLOW,
at the National Aspergillosis Centre, Manchester, UK
Over the next 2 years at least 2 vacancies will be available for Clinical Research Fellows at the National Aspergillosis Centre. The precise area of research has not been decided and will depend partly on the experience and interest of any successful candidate. Major areas of interest now include the genetics of chronic pulmonary aspergillosis, ABPA and other chronic lung infections (bronchiectasis, cystic fibrosis etc), azole resistance and epidemiology of fungal lung infection worldwide.
PROJECT GRANTS FOR CROSS-DISCIPLINARY PDRA PROJECTS
Applications are invited for projects that will start in October 2014. Applications are invited for projects. A project grant will support a PDRA and research expenses for 3 years. 6 grants are available.
3-YEAR CLINICAL PHD FELLOWSHIP Applications are invited for this exciting new PhD programme to train a new generation of clinicians in medical mycology. The scheme is open to clinicians who wish to develop a long term career in academic medicine specialising in medical mycology.
INTERNATIONAL RESEARCH SCHOLARSHIP (1-YEAR MRES + 3-YEAR PHD) Applications are invited for these prestigious International Research Scholarships. Prospective students will be expected to complete a 12-month MRes in Medical Mycology and Fungal Immunology at the University of Aberdeen, followed by a 3-year PhD at a UK university or research institution in the network.
PROJECT GRANTS FOR PHD PROJECTS Applications are invited for projects that will start in October 2014. PhD candidates will be selected from our cohort of international students completing the MRes stage of the International Research Scholarship. A project grant includes; stipend, home/EU tuition fees and research expenses for 3 years. Host institutions must agree to waive foreign tuition fees.
Dual trained Infectious Diseases Physician/Microbiologist We are seeking a dual trained Infectious Diseases Physician/ Microbiologist to join with 6 others to provide clinical microbiology and infectious diseases services to the ethnically diverse and rapidly growing South Western Sydney Local Health District.
Two PhD positions in the field of Microbiology / Infection Biology / Cellular Microbiology One project will be part of the research project 'Molecular Mechanisms of Candida Sepsis' within the Center for Sepsis Control and Care (CSCC) and the Hans Knoll Institute (HKI). The second project 'The role of filamentation in the pathogenesis of candidiasis' will be funded by the Deutsche Forschungsgemeinschaft (DFG).
Assistant Professor - MicrobiologyTenure track position starting in August of 2013 RESPONSIBILITIES: Teaching responsibilities may include introductory microbiology, virology, immunology, pathogenic bacteriology, and other upper division/graduate courses in the candidates\' area of expertise. The successful candidate is expected to develop an active research program involving graduate and undergraduate students. Service on committees at the Department, College and University level, and with the general public is also expected.
Advertise your vacancy
free of charge on the Aspergillus Website here. *Optional donation to the Fungal Research Trust to cover
costs incurred in providing this newsletter.
Expert Patient Programme
Learn to manage long term illness better by taking part in a 6 week course. Originally designed at Stanford University, USA 20 years ago this programme has proven benefit for the patient, the carer and family. In the UK this is provided free of charge by the NHS.
Contact us for more information
Conferences - coming up
CBS Spring Symposium, One Fungus : Which Gene(s) (1F = ?G) 2013 Amsterdam, The Netherlands. April 10-11
49th Annual Scientific Meeting of the BSMM Newcastle, UK. April 14 - 16
23rd ECCMID, Berlin, Germany. April 27 - 30. Abstract submission deadline November 30th 2012
31st Annual Meeting of the European Society for Paediatric Infectious Diseases Milan, Italy. Abstract Submission Deadline January 14. May 21 - June 1.
2nd Fungal Biofilms Meeting Glasgow, Scotland. May 20-21.
asm2013 113th General Meeting Denver,Colorado May 18-21.
The European Society for Paediatric Infectious Diseases (ESPID). 31st Annual Meeting to be held in Milan, Italy, May 28-June 1, 2013.
Many more here...
Courses and Workshops
We keep a listing of courses and workshops including 'one off' events and courses that repeat regularly. Course subjects are wide ranging and include medical mycology, lab ID, young scientists symposia and much more. Those coming up next are:
Molecular Mycology: Current Approaches to Fungal Pathogenesis (Course) Jul 31 to Aug 16 2013 Marine Biological Laboratories in Woods Hole, Massachusetts, USA. Closing date 10th April 2013
Specialization Course in Medical MycologyKU Leuven Campus Gasthuisberg, Belgium. September 16 - 26th 2013
If you know of a course that should be added to this list please add it by contacting us here
View latest theses online. UK USA
Detection of filamentous fungi in the homes and airways of patients with asthma by Fairs, Abbie, University of Leicester (available for download)
Nitrate transport and assimilation in Aspergillus nidulans by Akhtar, Naureen, University of St. Andrews
Development and evaluation of peptide nucleic acid (PNA) probes for the rapid detection of clinically relevant microorganisms by Cerqueira, L., Universidade do Minho
Establishment of infection models and insights into the pathogenesis of invasive aspergillosis mediated by Aspergillus terreus [Elektronische Ressource] / Silvia Slesiona by Slesiona, Silva., Freie Universitat Berlin
NB Links to theses may require library membership.
We are always looking for more for our collection - please send your suggestions here
We have now moved this to our Aspergillus & Aspergillosis Group in LinkedIn were we have a membership of over 330 professionals from a variety of backgrounds. Once a member you can start discussions and ask questions.
Searching for Aspergillus Information
You can now receive notification of updates to the Aspergillus Website on your mobile phone via SMS texting free of charge. Go to http://twitter.com/AspergillusWeb and open a Twitter account. Follow AspergillusWeb. 294 already follow AspergillusWeb.
If your network does not support Twitter SMS and you have a smartphone you can still monitor our messages over 3G or Wifi via free software and apps installed on your phone
Join the Aspergillus & Aspergillosis group (330 members) to get in touch and keep in touch with your professional colleagues working in this field. Many jobs are advertised here too!
LinkedIn runs discussion forums in each group that all members can start up. Ask questions & debate with colleagues.
Thanks for reading!
Visit our website again soon.
The Aspergillus Team.