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， 包括美国在内的许多国家最近在德克萨斯州、夏威夷和佛罗里达爆发疫情。平均值的增加 全球公认DENV相关住院年龄与成人疾病更常见 承认，但在儿童和成人中表征登革热疾病的前瞻性临床研究， 缺乏登革出血热（DHF）是登革病毒感染的一种更严重的临床表现， WHO将其分为四个严重等级，最低标准为毛细血管渗漏， 血小板减少症世卫组织发布了诊断“登革热”和“重症登革热”的修订指南 2009年严重的登革热不仅包括血浆渗漏和出血，而且还包括终末器官衰竭， 是一个相对罕见的事件。此外，几个“警告信号”，如腹痛和恶心， 不确定登革热疾病管理的一个主要困境是难以早期识别 这些人将继续严重登革热和/或休克。我们以前开发了一个 分类和回归树算法，以确定这些人在严重疾病的风险。频繁 需要血液检查（白色血细胞计数、血细胞比容、肝功能研究）来识别严重疾病， 这在资源贫乏的环境中是不实际的。非侵入性监测，可能会捕捉个人与 即将发生的并发症，并将有助于指导治疗将大大提高目前的管理， DENV病我们建议以下列具体目标处理这些问题： 确定住院儿童和成人重症患者的临床特征 疑似登革热-表征成人与儿童的早期和晚期疾病， 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 II.开发和验证一种算法，使医生能够预测哪些儿童或成人将 发生严重的等离子体泄漏和/或休克，并确定不会发生这种情况的人。我们将利用新型非侵入性 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.