Transfusion Infection Pediatric Prospective Study (TRIPPS)

描述（由申请方提供）：本继续申请的具体目的是前瞻性研究接受同种异体输血的儿科受者，以（1）确定传播目前有供体筛选试验的已知感染因子的剩余风险和（2）评估没有或有限检测的已知和紧急因子的潜在风险。当这些病原体感染受血者时，其临床和病理影响可能无法识别，并且干预方法要么不完善，要么成本效益可疑。另一个具体目的是前瞻性研究在大量输血的儿科人群中输血相关微嵌合体（TA-MC）的患病率和持续性。此外，我们将建立一个“预警”储存库，储存捐献者和接受者的相关样本，以便将来出现传染性病原体时，系统性检测可以迅速确定该病原体是否对血液供应构成威胁。目前的儿科应用将与NIH临床中心在成人中进行的相同设计的研究合作进行。在这两项研究中，受者在输血前入组，并在输血后随访至少6个月;在输血前和输血后2-4、8、12 -16和24周收集样品。已确认的捐赠者提供了允许与接受者联系的储存标本。将对多种病原体进行血清学和分子检测。这些包括几种独特的分子检测：微阵列技术，使用病原体芯片监测巴氏疟原虫，疟疾物种，锥虫，疏螺旋体和其他代理人，以及病毒爆炸发现，使用序列独立的单引物扩增。此外，将使用HLA-DR和插入/缺失多态性面板分析TA-MC。NIH和CNMC的联合研究扩展了数据的分析能力和能力，允许确定感染性和选定的非感染性风险，允许比较成人和儿科患者之间的这些风险，并根据年龄比较病毒持续性和临床结局。该应用程序为其他NHLBI研究者提供了一个独特的血浆和细胞库，可用于未来确定新兴药物的输血传播性、对输血受者的风险以及TA-MC的影响。与公共卫生的相关性：本申请与IOM、FDA和NHLBI的任务相关，以确保采集用于输血的血液是安全的。这一应用的重点是婴儿和儿童，一个脆弱的，迄今为止研究不足的受体群体。

DESCRIPTION (provided by applicant): The specific aims of this continuation application are to prospectively study pediatric recipients of allogeneic blood transfusion to (1) determine the residual risk of transmitting known infections agents for which there are current donor screening assays and (2) assess the potential risk of known and emergent agents for which there is no or limited testing. When such agents infect blood recipients, the clinical and pathological implications may be unrecognized and approaches to intervention are either poorly established or have questionable cost-benefit. An additional specific aim is to prospectively study the prevalence and persistence of transfusion-associated microchimerism (TA-MC) in a highly transfused pediatric population. Further, we will establish an "early warning" repository of linked donor and recipient samples so that when an infectious agent emerges in the future, systematic testing can rapidly establish whether or not that agent(s) presents a threat to the blood supply. The current pediatric application will be undertaken collaboratively with an identically designed study in adults being conducted at the NIH Clinical Center. In both studies, recipients are enrolled prior to transfusion and followed for at least 6 months post-transfusion; samples are collected pre- and 2-4, 8,12-16 and 24 weeks post-transfusion. Consented donors provide repository specimens that permit linkage with recipients. Both serologic and molecular assays for a wide spectrum of agents will be performed. These include several unique molecular assays: microarray technology using a pathogen chip to monitor babesia, malaria species, trypanosoma, borrelia and other agents, as well as viral blast discovery, using sequence independent single primer amplification. Further, TA-MC will be analyzed using both HLA- DR and insertion/deletion polymorphism panels. The combined NIH and CNMC study expands the analytic capabilities and power of the data to permit determination of infectious and selected non-infectious risks, allow for a comparison of these risks between adult and pediatric patients and comparison of viral persistence and clinical outcome according to age. This application provides a unique plasma and cell repository available to other NHLBI investigators that will allow for future determination of the transfusion transmissibility of emerging agents, the risk to transfusion recipients and the implications of TA-MC. Relevance to public health: This application is relevant to the missions of the IOM, FDA and NHLBI to ensure that blood collected for transfusion is safe. This application focuses on infants and children, a vulnerable and heretofore poorly studied recipient group.