More Information
Introduction
Invasive aspergillosis is rare in healthy people, but increasingly common among patients whose immune system has been weakened either by disease or by drugs that reduce the chance of rejection in transplant operations. Furthermore the fatality rate is high, around 85%, partly because diagnosis is often late and partly because there is no really effective treatment.
So given this combination of high mortality and increased incidence, there is a pressing need for research into both new diagnostic tools and drug treatments. There is a clear need therefore for this Network, which has immediately set about developing new diagnostic laboratory tests. But before successful drug treatments can be developed, progress is needed on two other fronts. First, a greater understanding of the mechanisms that enable aspergillus to resist existing antifungal agents is needed. Secondly, the genome of the fungus is being sequenced, which should help identify the specific genes that cause it to be so virulent. This in turn should help develop drugs that block the action of these genes. The ESF Network is helping with both these objectives, by encouraging the various partners to work in a co-ordinated manner. The ground is already well laid, since Europe has the highest concentration of people working on aspergillus and aspergillosis in the world, with a large number of original publications in the field.
Main section
Invasive aspergillosis is an increasing medical problem, partly because of the growing number of transplant operations leaving patients temporarily at risk while their immune systems are weakened by the drugs administered to reduce the chance of organ rejection. At any rate the frequency of invasive disease in general increased 14 fold in the 12 years up to 1992, and aspergillosis has overtaken candidiasis as the most frequently found fungal pathogen in such patients after death.
The fungal agents responsible for invasive aspergillosis can also cause saprophytic disease where they live on dead tissue, for example within the nasal cavities, and also allergic conditions, particularly in the bronchial tubes.
However, the invasive condition is the greatest threat, and currently there are only two drugs licensed for its treatment, amphotericin B, and itaconazole. The response rate to these drugs is poor, around 35% on average, partly because resistance is growing among several species of fungus that cause the disease. But the main reasons for failure of therapy are that diagnosis is made too late or not at all, and that the patients have weak immune systems.
This ESF Network can do nothing about the state of the patientsÂ’ immune systems, but is tackling the problems of late diagnosis and increased resistance to drug therapies. First, it is developing and evaluating new laboratory diagnostic tools, and studying the best candidates for each of the different conditions, such as solid organ and bone marrow transplantation, lymphoma, leukaemia and AIDS.
Secondly, resistance to old and new antifungal agents is being monitored. Work on resistance is multidisciplinary involving some clinical microbiology, specialised susceptibility testing laboratories, epidemiology, and sophisticated basic science, to unravel the mechanisms for resistance. On this front, the ESF Network will support the new EUCAST (European Committee on Antimicrobial Susceptibility Testing) committee, which now has a sub-committee specialising in fungal microbials.
It so happens that this Network coincides with various other programmes to sequence the genome of the fungus A. fumigatus, which is responsible for 90% of all cases of invasive aspergillosis in humans. The ESF Network is naturally focusing on A. fumigatus.
Activities
- Workshops
- Workshop on Aspergillus and Aspergillosis, 16-17 September 1999, Manchester (UK)
(Report)
- Workshop on Genomics and Post-genomics in Aspergillus fumigatus, 8-11 June 2001, Paris (FR)
(Report) - Website
Go to the Aspergillus website Go to website
