Infections in Hematopoietic Cell Transplant Recipients

描述(由申请者提供)：面向患者的造血干细胞移植(HCT)感染研究提供了直接影响HCT接受者结局的机会。感染仍然是HCT后发病和死亡的主要原因。这项奖励将为申请者提供受保护的时间来指导受训人员进行与了解HCT后感染生物学直接相关的临床研究。结果将为转化为改进的管理战略提供基础。这项提案将涉及移植传染病的三个领域：呼吸道病毒感染、感染的遗传学以及与传染病结局相关的因素。具体目的是：1.确定新近发现的人类偏肺炎病毒、冠状病毒(包括NL63、HKU1)、鼻病毒和博卡病毒等HCT后呼吸道病毒的病毒学特征和危险因素。对这些病毒的研究将使用500名接受HCT的人的前瞻性观察队列进行，这些人正在接受每周12种病毒的聚合酶链式反应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，确定供受者先天遗传因素对HCT术后感染并发症风险和结局的影响。有1500对患者/捐赠者的HOLE基因组数据。多态与感染的关联将在不同的队列中进行分析和验证。3.开展NCT术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，作为决定当前抗病毒先行治疗时代HCT总体结果的变量。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(使用对世界各地移植中心进行的基于互联网的调查)。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，支持以患者为中心的移植传染病领域研究的创新方法。在这些目标下进行的研究具有很高的潜力，可以促进我们对感染并发症的谱系、疾病的遗传基础以及影响结果的因素的了解。(摘要结束)

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)