Thursday, December 14, 2006
Presented by the Emerging Infectious Diseases and Microbiology Discussion Group
Organizers: David Perlin, Public Health Research Institute; Eric Pamer, Memorial Sloan-Kettering Cancer Center
Invasive Aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients and is a leading cause of fungal mortality. These infections are particularly difficult to diagnose and treat, and remain a critical health concern for clinicians with high-risk patients. This Symposium brings together five of the leading clinical and research experts in the world to discuss state-of-the-art issues related to IA and prospects for reducing the health burden caused by this disease.
4:00 - 8:00 Presentations:
David W. Denning, University of Manchester, Wythenshawe Hospital, Manchester:
"Clinical Perspective and Research Challenges."
Kieren A. Marr, Fred Hutchinson Cancer Research Center: "Diagnostics: State of Art."
Thomas J. Walsh, National Cancer Institute:
"Therapy: State of Art."
Jean-Paul Latgé, Institut Pasteur, Paris:
"Cell Wall, Antigens and Virulence."
Gordon D. Brown, University of Cape Town, South Africa:
"Innate Recognition of Fungi."
David W. Denning: "Clinical Perspective and Research Challenges"
The genus Aspergillus, and its associated disease, is extraordinary and unparalleled by any other microorganism. The spectrum of aspergillosis extends from allergy in the nose and sinuses to the lungs (manifesting in subtly different ways), to slowly progressive pulmonary or sinus destruction in apparently normal individuals (and other mammals and birds) and to immediately life-threatening invasive infection in immunocompromised patients. The basic genomic structure and many facets of biology in the Aspergillus genus are also remarkable. The apparently close relatives Aspergillus fumigatus and Aspergillus nidulans are as distantly related as fish and man. This represents huge evolutionary changes in the space of about 200 million years in an organism with 10,000-14,000 genes. This probably explains in part the wide environmental comfort zone for the genus in many hostile locales, namely compost, high salinity environments (Dead Sea) and the human lung. Clearly this versatility can only be the result of sophisticated adaptation, while retaining the essential characteristics of the genus. The production of numerous mycotoxins (such as aflatoxin and gliotoxin) and secondary metabolites remains a public health problem in most developing countries. Aflatoxin is found in in food stuffs all over the underdeveloped world with major detrimental effects on growth, immune function and contributes to liver cancer. This remains a significant public health challenge. Many advances have been made in the understanding of the biology of Aspergillus and in controlling disease. We have 8 genomes sequenced and that of A. fumigatus is the most complete of any filamentous fungus; we have new drugs; we have better definitions of disease; we have new allergens; we understand the interaction between Aspergillus and the immune system much more than previously; we have new (often cryptic) species of Aspergillus; and we are starting to understand antifungal resistance. Improvement in disease management will come from better diagnosis of invasive infection as it is still too slow to be meaningful in many patients. We don't know why Aspergillus can disseminate from the lung and why it localizes in the organs it does. We don't know whether to use one or more drugs for treatment. New patient populations with serious infection (especially those with chroni