RNA Biosignatures: A Paradigm Change for the Management of Young Febrile Infants

RNA 生物特征：低龄发热婴儿管理的范式变革

• 批准号: 9130851
• 负责人: NATHAN KUPPERMANN
• 金额: $ 112.89万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-21 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9130851
• 关键词: Accident and Emergency department; Address; Age; Aliquot; Antibiotics; Applied Research; Bacteremia; Bacterial Infections; Bacterial Meningitis; Blood; Blood specimen; Body Fluids; Cerebrospinal Fluid; Child; Childhood; Clinical; Complex; Confidence Intervals; Cross-Sectional Studies; Decision Making; Development; Diagnosis; Diagnostic; Discrimination; Disease; Emergency Care; Enrollment; Evaluation; Gene Expression Profile; Genes; Genetic Transcription; Genomics; Goals; Guidelines; Hospitalization; Hour; Infection; Inflammatory; Informed Consent; Interferons; Investigation; Laboratories; Lead; Meningitis; Methods; Mission; Molecular Profiling; National Institute of Child Health and Human Development; Patients; Pattern; Procedures; RNA; RNA Stability; Reference Standards; Research; Research Infrastructure; Research Personnel; Sampling; Spinal Puncture; Swab; Technology; Testing; Time; Urinary tract infection; Urine; Viral; Virus Diseases; Vulnerable Populations; Whole Blood; Work; antipyretic; base; biosignature; co-infection; cost; diagnostic accuracy; disability; experience; febrile infant; improved; innovation; multidisciplinary; novel; overexpression; prospective; public health relevance; respiratory; sample collection; whole genome

 DESCRIPTION (provided by applicant): Every year ~ 500,000 febrile infants = 60 days of age present to US emergency departments (ED). 6-10% of these febrile infants will have invasive bacterial infections (bacteremia, urinary tract infections or meningitis). Current approaches for the evaluation of young febrile infants are suboptimal because they include frequent invasive procedures, overuse of empirical antibiotics and unnecessary hospitalizations, which can lead to iatrogenic complications and have substantial cost implications. The primary cause of these problems is lack of highly accurate and short turn-around testing to reliably distinguish young febrile infants with and without bacterial infections. The long-term objective of our research is t investigate whole genome RNA expression profiles to define RNA biosignatures that allow precise diagnosis of isolated bacterial infections, isolated viral infections and bacterial-viral c-infections in febrile infants = 60 days of age. Our specific aims are to (1) define the RNA biosignatures in febrile infants = 60 days of age with isolated bacterial infections, isolated vira infections and viral-bacterial co-infections; (2) demonstrate the stability of the above defined RNA biosignatures over a 24-72 hour time period; and (3) validate the RNA biosignatures on a novel, PCR-based platform that has a rapid (2 - 4 hour) turnaround time. We will conduct a prospective, multi-center, cross-sectional study of febrile infants = 60 days of age who are being evaluated for bacterial infections. After obtaining informed consent from the guardian we will collect 2 ml of whole blood (1 ml for RNA expression analysis; 1 ml for comprehensive viral studies) and 1 nasopharyngeal (NP) swab for a comprehensive respiratory viral diagnosis. Additionally, in a selected group of febrile infants who are either hospitalized from the ED or those who return to the ED, we will obtain a second 1 ml blood sample for sequential RNA biosignature analysis at 24 - 72 hours after the initial sample collection. Using an aliquot of blood from the same sample we will validate RNA biosignatures on the PCR-based platform. Addressing the optimal evaluation and management of the febrile infant will assure that this vulnerable population of children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability and is consistent with the mission of NICHD.

 描述（由申请方提供）：每年约有500，000例发热婴儿（≤ 60天）到美国急诊科（艾德）就诊。这些发热婴儿中有6-10%会有侵袭性细菌感染（菌血症、尿路感染或脑膜炎）。目前用于评估发热婴儿的方法是次优的，因为它们包括频繁的侵入性操作、经验性抗生素的过度使用和不必要的住院治疗，这可能导致医源性并发症并具有显著的成本影响。这些问题的主要原因是缺乏高度准确和短期的周转测试，以可靠地区分有和没有细菌感染的年轻发热婴儿。我们研究的长期目标是研究全基因组RNA表达谱，以确定RNA生物特征，从而精确诊断年龄≤ 60天的发热婴儿中的孤立细菌感染、孤立病毒感染和细菌-病毒感染。我们的具体目标是（1）确定年龄= 60天的患有孤立细菌感染、孤立病毒感染和病毒-细菌合并感染的发热婴儿中的RNA生物特征;（2）证明上述定义的RNA生物特征在24-72小时时间段内的稳定性;以及（3）在具有快速（2 - 4小时）周转时间的新型基于PCR的平台上验证RNA生物特征。我们将对年龄≥ 60天的发热婴儿进行一项前瞻性、多中心、横断面研究，这些婴儿正在接受细菌感染评估。在获得监护人的知情同意后，我们将采集2 ml全血（1 ml用于RNA表达分析; 1 ml用于全面病毒研究）和1个鼻咽（NP）拭子用于全面呼吸道病毒诊断。此外，在从艾德住院或返回艾德的发热婴儿的选定组中，我们将在初始样本采集后24 - 72小时获得第二份1 ml血液样本用于连续RNA生物特征分析。使用来自同一样本的等份血液，我们将在基于PCR的平台上验证RNA生物特征。对发热婴儿进行最佳评估和管理，将确保这一弱势儿童群体有机会充分发挥其健康和有所作为的潜力，远离疾病或残疾，并符合NICHD的使命。