Clinical Studies of Acute Dengue Illness

急性登革热疾病的临床研究

• 批准号: 8702984
• 负责人: Sharone Green
• 金额: $ 43.89万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8702984
• 关键词: Abdominal Pain; Acute; Address; Adult; Age; Algorithms; Biological Assay; Blood Tests; Blood capillaries; Child; Childhood; Classification; Classification Scheme; Clinical; Clinical Research; Clinical Treatment; Comparative Study; Country; Data; Dengue; Dengue Hemorrhagic Fever; Dengue Virus; Diagnosis; Diagnostics Research; Disease; Disease Outbreaks; Disease susceptibility; Early Intervention; Early identification; Epidemiology; Evaluation; Event; Extravasation; Fever; Flavivirus Infections; Florida; Funding; Goals; Guidelines; Hawaii; Hematocrit procedure; Hemorrhage; Hospitalization; Hospitalized Child; Immune response; Immunologics; Incidence; Individual; Infection; Instruction; Interleukin-10; Knowledge; Liquid substance; Measurement; Methods; Modality; Monitor; Morbidity - disease rate; Nausea; Near-Infrared Spectroscopy; Organ failure; Outcome; Pathogenesis; Physicians; Plasma; Population; Prevention; Process; Prospective Studies; Research; Resources; Resuscitation; Risk; Serologic tests; Serological; Services; Severities; Shock; Specificity; Specimen; Staging; Texas; Thailand; Thrombocytopenia; Treatment Factor; Trees; Triage; Viremia; Virus Diseases; White Blood Cell Count procedure; capillary; data management; global health; immune activation; improved; liver function; non-invasive monitor; novel; prevent; programs; prospective

Dengue virus (DENV) infections are an emerging problem, causing disease in tropical and subtropical countries, including the U.S, with recent outbreaks in Texas, Hawaii and Florida. An increase in the average age of DENV related hospitalizations has been globally recognized with adult disease more commonly recognized, but prospective clinical studies that characterize dengue illness in both children and adults are lacking. Dengue hemorrhagic fever (DHF), a more severe clinical manifestation of DENV infection, has been classified by the WHO into four grades of severity with minimal criteria of capillary leakage and thrombocytopenia. The WHO released revised guidelines for the diagnosis of "dengue" and "severe dengue" in 2009. Severe dengue comprises not only plasma leakage and bleeding, but also end organ failure, which is a relatively rare event. In addition, several 'warning signs', such as abdominal pain and nausea, are highly non-specific. A major dilemma in the management of dengue illness is the difficulty in early recognition of those individuals who will go on to severe dengue and/or shock. We have previously developed a classification and regression tree algorithm for identifying such individuals at risk for severe illness. Frequent blood tests (white blood cell counts, hematocrit, liver function studies) are needed to identify severe disease, which is not practical in resource poor settings. Non-invasive monitoring which might capture individuals with impending complications and would help to guide therapy would greatly enhance the current management of DENV illness. We propose to address these issues with the following Specific Aims: I.To determine the clinical features which characterize severe disease in hospitalized children and adults with suspected dengue - characterize early and late disease in adults vs. children, evaluate old and new WHO criteria, compare immunologic and virologic correlates to severe disease in adults vs. children II.To develop and validate an algorithm which will enable physicians to predict which children or adults will develop significant plasma leakage and/or shock and to define those who will not. We will utilize novel noninvasive monitoring (near infrared spectroscopy and arterial wave forms) to accomplish these goals.

登革热病毒（DENV）感染是一个新的问题，导致热带和亚热带的疾病 包括美国在内的国家，最近在得克萨斯州，夏威夷和佛罗里达州发生了爆发。平均值增加 与DENV相关的住院年龄在全球范围内已被成人疾病认可 公认的，但在儿童和成人中都表征登革热疾病的前瞻性临床研究是 缺乏。 DENV感染的更严重的临床表现已经 由WHO分类为四年级的严重程度，毛细血管泄漏的标准最小和 血小板减少症。世卫组织发布了修订的指南，以诊断“登革热”和“严重登革热” 2009年。严重的登革热不仅包括血浆泄漏和出血，而且还包括结束器官衰竭，这是 是一个相对罕见的事件。此外，几个“警告信号”，例如腹痛和恶心 非特异性。登革热疾病管理的主要困境是早期认识的困难 那些将继续严重的登革热和/或震惊的人。我们以前已经开发了 分类和回归树算法，用于识别这种患有严重疾病风险的人。频繁 需要进行血液检查（白细胞计数，血细胞比容，肝功能研究）来鉴定严重疾病， 在资源差的环境中，这是不切实际的。非侵入性监测可能会捕获个人 即将发生的并发症，并有助于指导治疗将大大提高目前的管理 DENV疾病。我们建议以以下特定目的解决这些问题： I.确定住院儿童和成人中严重疾病的临床特征 涉嫌登革热 - 成人与儿童的早期和晚期疾病的特征，评估新旧 WHO标准，比较免疫学和病毒学与成人与儿童的严重疾病相关 II.开发和验证一种算法，该算法将使医生能够预测哪些儿童或成人将 开发明显的等离子体泄漏和/或冲击，并定义那些不会的人。我们将利用新颖的无创 监测（近红外光谱和动脉波形）以实现这些目标。