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A vaccine for Aspergillosis?
Developing a vaccine for aspergillosis and other fungal infections has been something of a 'holy grail' for some years, but it has always been a formidable challenge as of course fungi are more closely related to ourselves than viruses & bacteria - organisms where huge success has been attained in the past using vaccines. Some patients are going to be more difficult to vaccinate than others - for example those at main risk from rapid invasive fungal infections have a severely disabled immune system and thus pre-preparing what little immune system they have left using a vaccine is going to have limited effect. Other patient groups (e.g. CGD, CF, tuberculosis patients) would potentially benefit hugely. This month we present a review by Stevens et. al., which discusses current progress in the development of vaccines for fungal infections. We find that substantial progress has been made on several fronts. For example heat treated Saccharomyces cerevisiae was found to be an effective vaccine to aspergillosis in mice - this observation made when attempting to express an Aspergillus protein in Saccharomyces in the hope that that would provide protection to mice. The researchers found that the negative control offered just as much protection as that containing the Aspergillus antigen! Suggestions for the most productive routes to a human vaccine are made. Latest News and Articles
A report has been published on the 4th Advances Against Aspergillosis conference that took place earlier this year in Rome. The report summarises the many aspects of this very successful meeting and was written by Donald Sheppard & Liz McNeil Griston (McGill University) behalf of the Future Sciences Group.
Articles: There have been 40 additions to the Articles section, of which 6 are reviews and 18 historical. NOTE we have rearranged the Articles index page to make it easier to look at recent articles as well as those that were added recently but were written some time ago. We have picked out a few of the highlights here: The ciliated cells lining the trachea have a significant role in resistance to infection, including infection by fungal conidia. This epithelial tissue is frequently damaged in patients at risk so this study attempts to set up a reproducible model system that can be used to imitate the lung surface/air interaction in the laboratory. Porcine lung epithelial cells are used to set up a model system for the study of the interaction of conidia and the mycotoxin verruculogen with lung epithelia. The model was demonstrated to function in similar ways to human tracheal mucosa without the variation inherant to the use of the latter. Secretion stress and antifungal resistance: An Achilles' heel of Aspergillus fumigatus? Aspergillus relies on a process referred to as absorption in order to feed itself. It secretes enyymes which break down organic material surrounding the fungus and allows easy re-absorbtion of the resulting food. An intracellular structure known as endoplasmic reticulum is responsible for the production and secretion of the digestive enzymes and it has come to light in this paper that in order to survive optimally in human tissue it must secrete digestive enzymes at an unusually high rate and relies on initiating stress signalling pathways (UPR) to meet demand. The same structure is shown to be responsible for the transport of food to the growing tips of the fungus which are the primary target of several antifungal drugs, leading to drug resistance. UPR pathways are thus an important activity that allows the fungus to invade its host efficiently and resist antifungal drugs. These pathways could form a good candidate to design new drugs to attack the fungus. Aspergillus endocarditis 2003-2009 A retrospective case study of 35 case reports of Aspergillus endocarditis published between 2003 and 2009. Conclusions: "We need to think more about the possibility of
Aspergillus endocarditis, particularly in immunocompromised patients with recent surgery. Aspergillus DNA contamination in blood collection tubes 18% of blood collection tubes in standard use in the clinic were found to be contaminated with fungal DNA in this survey. A fairly extensive range of tubes from different manufacturers and and lots from the same manufacturer were tested. ReviewsNewer combination antifungal therapies for invasive aspergillosis Several experimental approaches have suggested that the treatment of invasive aspergillosis may be improved by the use of combinations of antifungals rather than just one at a time. Unfortunately this has not yet been borne out in the clinic despite several attempts to do so though there is still no definitive accepted strategy. This review suggests other pathways that should be targetted to increase efficacy of this approach i.e. calcineurin and the Hsp90 pathways. Azole antimycotics and drug interactions in the perioperative period Antifungals are increasingly being used in intensive care and during the perioperative period as they have been demonstrated to offer protection from fungal infection for some patients during this period of vulnerability. This frequently coincides with the use of several other powerful drugs and adverse drug interactions are not uncommon. This review focuses on azole antifungals and anaesthetic drugs being used during the perioperative period and discusses the possible clinically significant drug-drug interactions Lab Protocols - Appeal for moreWe have added a large number of protocols to our listing, largely those used at the research labs in the National Aspergillosis Centre but with some more being awaited. We would like this listing to become as comprehensive as possible so as to be able to assist all fungal researchers both new and established to find a protocol they need and which they can rely on. If anyone can add to our listing please let us know - just send us the rough copy and we will work it up to a publishable standard if needed. Historical18 new historical documents have been added this month, including (all in German):
PatientsProfessor Malcolm Richardson gave an excellent talk to the monthly patients meeting at the National Aspergillosis Centre in August. Prof Richardson's subject was on Aspergillus and other moulds in the environment and their effect on our health. Details are given here. The meeting was the best attended so far with 33 attending and a partly successful trial of internet access (video only) to the meeting took place with the hope of eventually allowing full access to the meeting for people who cannot make the journey. We have included access to notes of the meeting, slides used for the talk given at the meeting and the clinic newsletter.
A patient volunteer is making & selling handmade cards for birthdays in aid of the Fungal Research Trust. 6 cards for £6 and 75% of that goes to the FRT. Order here. There is a newly designed Patients website now entitled 'Aspergillosis Patient Support'. Much more comprehensive than before and easier to navigate but with the same successful support group and Q & A board MycotoxinsA remarkable new website describing the international regulations related to permitted mycotoxin levels in food has been launched here. Also features short video courses for farmers and information on how to minimise mycotoxin contamination of your stock & grain. JobsOne job has been advertised since the last newsletter, but its closing date is before this newsletter goes out. 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. Courses and WorkshopsWe 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:
If you know of a course that should be added to this list please add it by contacting us here Conference AbstractsWe have uploaded abstracts of the last 5 meetings entitled 'International Symposium on Infections in the Immunocompromised Host' (ISIIH) stretching back to 2002. 82 new abstracts are presented and there are now over 8800 abstracts in the database in total. VeterinaryDistribution of voriconazole in seven body fluids of adult horses after repeated oral dosing The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. CONCLUSIONS: There was no statistically significant difference between voriconazole concentrations of body fluids when comparing days 7 and 14. Results indicated that voriconazole distributes widely into body fluids. 15 out of 17 cases confirmed free od disease after administration of bifonazole cream. The cream was instilled through perendoscopically placed catheters into the frontal sinuses and was used either as single therapy after debridement (DC) or as adjunctive therapy after 2% enilconazole infusion (DEC). Blog
DonationsLast month we mentioned that we had exceeded £5000 in donations to the Fungal Research Trust in 2010. Thanks to the magnificent efforts of Gems little Gems we have virtually doubled that sum over the last month. See our donations page. Many thanks to everyone who contributed to this fantastic total.. If you donated please check our list of donators for your name. Technical TipsOur discussion group (email and/or website) designed to promote discussion on technical issues for laboratory workers. Searching for Aspergillus Information
RSSDownload our updates and articles automatically every time we add to those pages- no need to wait for the next newsletter. 40 000 pages accesses per month. Use RSS. 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. 68 already follow AspergillusWeb. Facebook CausesThe Fungal Research Trust have a Facebook Causes page. Give your support to the cause here. Join the Aspergillus & Aspergillosis group to get in touch and keep in touch with your professional colleagues working in this field. All free of charge. Thanks for reading!Visit our website again soon. The Aspergillus Team. |
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There are major difficulties when trying to treat a rapidly invasive, difficult to diagnose fungal infection of the immunocompromised such as 
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