RNA Biosignatures in the Emergency Evaluation of Febrile Infants

RNA 生物特征在发热婴儿紧急评估中的应用

• 批准号: 8466347
• 负责人: NATHAN KUPPERMANN
• 金额: $ 54.59万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-05 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466347
• 关键词: Accident and Emergency department; Acids; Address; Age; Antibiotics; Applied Research; Bacterial Infections; Blood; Blood Tests; Blood Volume; Body Fluids; Caring; Cerebrospinal Fluid; Characteristics; Child; Childhood; Clinical; Complete Blood Count; Consent; Data; Diagnosis; Diagnostic; Discrimination; Emergency Care; Emergency Situation; Emergency medical service; Emotional; Enrollment; Evaluation; Family; Fever; Genome; Genomics; Grant; Guidelines; Healthcare Systems; Hospitalization; Hour; Immune response; Infant; Infection; Informed Consent; Leukocytes; Measures; Methods; Microarray Analysis; Microbe; Patients; Prospective Studies; RNA; Reference Standards; Research Infrastructure; Research Personnel; Research Priority; Sampling; Specimen; Spinal Puncture; Techniques; Testing; Time; Translational Research; Urine; Validation; Virus Diseases; Visit; biosignature; clinical practice; clinically relevant; cost; digital; evaluation/testing; experience; febrile infant; high risk; improved; meetings; multidisciplinary; nano-string; novel; novel diagnostics; novel strategies; pathogen; procalcitonin; public health relevance; research clinical testing; response; screening

DESCRIPTION (provided by applicant): The diagnostic evaluation and management of febrile infants, especially those 60 days of age and younger, remains a challenge for clinicians, especially in the emergency department (ED); Although most young febrile infants will have a non-bacterial infection, nearly 10% will have a serious bacterial infection (SBI), yet febrile infants with and without SBIs are often clinically indistinguishable. The currently recommended approach for the evaluation of febrile infants is inadequate and controversial as many of the routine screening tests for SBI are inaccurate. In the current era, however, there are novel methods, including advances in genomic sequencing and techniques for conducting high through-put deoxynucleic acid (DNA) and ribonucleic acid (RNA) analysis that have led to a better understanding of the host-pathogen response to infections. Thus, a novel approach to distinguish febrile infants infected with bacterial pathogens from those infected with non- bacterial pathogens is to examine the host response to infection. Recent data indicate that different pathogens induce distinct transcriptional "biosignatures" in the RNA of blood leukocytes that can be reliably measured by microarray analysis. We hypothesize that application of diagnostic biosignatures will allow accurate discrimination between young febrile infants evaluated in the ED with bacterial infections and those infected with non-bacterial pathogens. The eventual paradigm shift of how we evaluate young febrile infants will result in improved and less invasive diagnostic evaluations of febrile infants, and will have a significant and beneficial impact by reducing the number of (1) unnecessary invasive tests (including lumbar punctures), (2) use of empirical antibiotics, (3) hospitalizations and associated iatrogenic complications, and (4) emotional and financial burdens on families. In this prospective study, eligible febrile infants 60 days of age or younger who present to 22 participating EDs of the Pediatric Emergency Care Applied Research Network (PECARN) will be enrolled after informed consent is obtained. We will define and validate bacterial and non-bacterial diagnostic biosignatures from small volumes of blood obtained during routine clinical evaluation for SBI. Additionally, we will evaluate the newer screening test (procalcitonin) and compare its tests characteristics with the traditional screening tests, (complete blood counts) with the reference standard (microbiologic cultures of relevant specimens such as blood, CSF and urine) and the diagnostic biosignatures in the evaluation of febrile infants for SBI.

描述（由申请人提供）：发热婴儿的诊断评估和管理，特别是60天及以下的发热婴儿，对于临床医生，特别是急诊科（艾德）的临床医生来说仍然是一个挑战;尽管大多数发热婴儿会有非细菌感染，但近10%会有严重的细菌感染（SBI），但有和没有SBI的发热婴儿通常在临床上难以区分。目前推荐的方法来评估发热婴儿是不充分的和有争议的，因为许多常规筛查测试SBI是不准确的。然而，在当今时代，有一些新的方法，包括基因组测序和进行高通量脱氧核酸（DNA）和核糖核酸（RNA）分析的技术的进步，这些方法使人们更好地了解宿主-病原体对感染的反应。因此，一种区分感染细菌病原体的发热婴儿与感染非细菌病原体的发热婴儿的新方法是检查宿主对感染的反应。最近的数据表明，不同的病原体在血液白细胞的RNA中诱导不同的转录“生物签名”，可以通过微阵列分析可靠地测量。我们假设，应用诊断生物特征将允许准确区分在艾德评价的细菌感染和非细菌病原体感染的发热婴儿。我们如何评估年幼发热婴儿的最终范式转变将导致发热婴儿的诊断评估得到改善和侵入性更小，并将通过减少（1）不必要的侵入性检查的数量产生重大和有益的影响（包括腰椎穿刺），（2）经验性抗生素的使用，（3）住院和相关医源性并发症，（4）家庭的精神和经济负担。在这项前瞻性研究中，在获得知情同意后，将入组符合条件的60天或更小的发热婴儿，这些婴儿将参加儿科急诊应用研究网络（PECARN）的22个参与ED。我们将从SBI常规临床评价期间获得的少量血液中定义和验证细菌和非细菌诊断生物特征。此外，我们将评估新的筛查试验（降钙素原），并将其试验特征与传统筛查试验（全血细胞计数）和参考标准（相关标本的微生物培养物，如血液，CSF和尿液）进行比较，并在发热婴儿的SBI评估中进行诊断生物特征。