Infections in Hematopoietic Cell Transplant Recipients

描述（由申请人提供）：以患者为导向的造血干细胞移植（HCT）感染研究提供了直接影响HCT接受者预后的机会。感染仍然是艾滋病毒传播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，指导受训者进行与了解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。本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果相关的因素。具体目标是：1。确定HCT后新发现的呼吸道病毒（包括人元肺炎病毒、冠状病毒（包括NL63、HKU1）、鼻病毒和bocavavirus）的病毒学谱特征及危险因素。对这些病毒的研究将采用500名HCT接受者的前瞻性观察队列进行，这些人每周接受12种病毒的PCR监测并评估呼吸道症状。2. 通过全基因组分析和随后的单独队列验证，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。1500对患者/供体的Hole基因组数据可用。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. 开展NCT后侵袭性感染的结局研究。我们将评估病原体负担，以巨细胞病毒载量为例，作为一个变量，决定当前抗病毒先发制人治疗时代HCT的总体结果。我们还将确定与侵袭性疾病的结果相关的因素。使用大型数据库，我们将评估与巨细胞病毒胃肠道疾病和呼吸道合胞病毒肺炎治疗反应相关的因素（使用对全球移植中心进行的基于互联网的调查）。相关性（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，支持移植传染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，可以提高我们对传染性并发症谱、疾病的遗传基础和影响结果的因素的认识。（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)