Infections in Hematopoietic Cell Transplant Recipients

描述（由申请人提供）：造血干细胞移植（HCT）中感染的患者导向研究提供了直接影响HCT受者结局的机会。感染仍然是HCT后发病和死亡的主要原因。该奖项将为申请人提供受保护的时间，指导临床研究中的学员，这些研究与理解HCT后感染的生物学直接相关。评估结果将为转化为更好的管理战略奠定基础。该提案将涉及移植传染病的三个领域：呼吸道病毒感染、感染遗传学和与传染病结局相关的因素。具体目标是：1。目的探讨HCT后新发现的呼吸道病毒，包括人偏甲病毒、冠状病毒（包括（NL 63、HKU 1））、鼻病毒和博卡病毒的病毒谱特征及危险因素。这些病毒的研究将使用500名HCT接受者的前瞻性观察队列进行，这些接受者每周接受12种病毒的PCR监测和呼吸道症状评估。2.通过全基因组分析和随后在不同队列中的验证，确定供体和受体先天遗传因素对HCT后感染并发症风险和结局的影响。Hole基因组数据可用于1500个患者/供体对。多态性与感染的关联将在单独的队列中进行分析和验证。3.进行NCT后侵袭性感染的结局研究。我们将评估病原体负荷，以CMV病毒载量为例，作为在当前抗病毒先发制人治疗时代决定HCT总体结局的变量。我们还将确定与侵袭性疾病结局相关的因素。使用大型数据库，我们将评估与CMV胃肠道疾病和RSV肺炎治疗反应相关的因素（使用基于互联网的全球移植中心调查）。相关性（参见说明）：这些目标通过利用最先进的方法，包括定量分子诊断，全基因组分析和基于互联网的罕见疾病数据收集，支持移植感染性疾病领域以患者为导向的创新研究方法。在这些目标下进行的研究具有很大的潜力，可以提高我们对感染性并发症谱、疾病遗传基础和影响结果的因素的认识。 (End摘要）

DESCRIPTION (provided by applicant): 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). RELEVANCE (See instructions): 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. (End of Abstract)