Clinical Studies of Acute Dengue Illness

登革病毒(DENV)感染是一个新出现的问题，在热带和亚热带地区引起疾病。 包括美国在内的国家，最近在德克萨斯州、夏威夷和佛罗里达州爆发了疫情。平均水平的提高 与登革热病毒相关的住院年龄已被全球公认为成人疾病更常见 公认的，但在儿童和成人中表征登革热疾病的前瞻性临床研究是 缺乏。登革出血热(DHF)是DENV感染的一种更严重的临床表现，已被 世界卫生组织根据毛细血管渗漏的最小标准将其分为四个严重级别和 血小板减少症。世界卫生组织发布修订后的登革热和严重登革热诊断指南 在2009年。严重的登革热不仅包括血浆渗漏和出血，还包括终末性器官衰竭，这 是一个相对罕见的事件。此外，一些“警告信号”，如腹痛和恶心，也是高度危险的。 不明确。登革热疾病管理中的一个主要难题是难以及早认识到 那些将继续患上严重登革热和/或休克的人。我们之前已经开发了一种 分类和回归树算法，用于识别此类有严重疾病风险的个人。频密 血液测试(白细胞计数、红细胞压积、肝功能检查)是确定严重疾病的必要手段， 这在资源匮乏的环境中是不切实际的。非侵入性监控，可能会捕获具有 并将有助于指导治疗，将极大地加强目前对 登革热病毒病。我们建议以下列具体目标处理这些问题： 一、确定住院儿童和成人严重疾病的临床特征 疑似登革热--确定成人和儿童的早期和晚期疾病的特征，评估新旧疾病 WHO标准，比较免疫学和病毒学与成人和儿童严重疾病的相关性 开发和验证一种算法，使医生能够预测哪些儿童或成年人将 出现明显的血浆泄漏和/或休克，并确定哪些人不会。我们将利用新的非侵入性 监测(近红外光谱和动脉波形)以实现这些目标。

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.