Patient-oriented research of infections in hematopoietic stem cell transplantation (HCT) provides the opportunity to directly affect outcome of HCT recipients. Infections continue to be a major cause of morbidity and death after HCT. This award will provide protected time for the applicant to mentor trainees in clinical research that is directly related to understanding the biology of infections after HCT. Results will provide the basis for translation into improved management strategies. This proposal will address three areas of transplant infectious diseases: respiratory virus infections, genetics of infections, and factors associated with outcome of infectious diseases.
The Specific Aims are: 1. To determine the spectrum virologic chracteristics, and risk factors of recently discovered respiratory viruses after HCT, including human metapneumonovirus, coronaviruses (including (NL63, HKU1), rhinoviruses and bocavirus. Studies of these viruses will be done using a prospective observational cohort of 500 HCT recipients who are undergoing weekly PCR surveillance for 12 viruses and assessment of respiratory symptoms. 2. To determine the impact of donor and recipient innate genetic factors on the risk and outcome of infectious complications following HCT by genome-wide analysis and subsequent validation in separate cohorts. Hole genome data are available for 1500 patient/donor pairs. Associations of polymorphisms with infections will be analyzed and validated in separate cohorts. 3. To conduct outcome studies of invasive infections after NCT. We will evaluate pathogen burden, with CMV viral load as an example, as a variable that determines overall outcome of HCT in the current era of antiviral preemptive therapy. We will also determine factors associated wit the outcome of invasive diseases. Using large databases, we will assess factors associated with response to treatment of CMV gastrointestinal disease and RSV pneumonia (using an internet-based survey administered to transplant centers worldwide).
These aims support an innovative approach toward patient-oriented research in the field of transplant infectious disease by utilizing state-of-the-art methodologies including quantitative molecular diagnostics, whole genome analysis, and internet-based data collection for rare disease. The studies conducted under these aims have a high potential of advancing our knowledge of the spectrum of infectious complications, the genetic basis of diseases, and factors that affect outcome.
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