Clinical Studies on the Mechanisms of DF/DHF

项目1(临床研究)的总体目标是确定临床、免疫学、病毒学和 对决定肺炎最终临床表现影响最大的流行病学因素 泰国儿童感染登革热病毒。该项目将涉及两项临床研究。第一个将是一个 曼谷对因急性登革热住院的有症状儿童进行的前瞻性研究 严重登革热的病理生理学。这项研究的结果应有助于指导评价和 对疑似登革热的发烧患者进行分流，并改进对 DHF。我们计划利用非侵入性技术，如超声心动图、超声波和测量 心率变异性。新型近红外光谱技术将用于非侵入性测定红细胞压积， 肌肉的pH值和肌肉的氧分压。我们还将进行流式细胞仪分析，以确定和表征 在急性感染期间循环内皮细胞以及病毒特异性T细胞。 我们的第二项研究将涉及在Kamphaeng Phet进行的Lib期疫苗效力试验， 泰国。在这个独特的机会中进行的研究将分析登革热的影响 关于病毒传播的疫苗接种，并确定预防或可能致敏的免疫学相关因素 更严重的疾病。这些研究研究不会由疫苗制造商进行，而将 这对今后登革热疫苗临床现场试验的设计和实施至关重要。这些临床 研究将得到核心A和B的支持，并将提供有价值的样本(血清、外周血 单个核细胞和病毒分离株)，以便在项目2中进行研究。 该项目包括在泰国的两项临床研究：(1)在住院儿童中，蚊子是如何 登革热病毒导致临床疾病和(2)在候选登革热疫苗的现场试验中，研究 疫苗如何预防登革热病毒感染。

The overall goal of Project 1 (Clinical Studies) is to identity the clinical, immunologic, virologic and epidemiologic factors that have the strongest influence on determining the ultimate clinical manifestations of dengue virus infections in Thai children. This project will involve two clinical studies. The first will be a prospective study in Bangkok of symptomatic children hospitalized with acute dengue illness to define the pathophysiology of severe dengue. The findings of this study should be useful to guide the evaluation and triage of febrile patients with suspected dengue as well as to improve the assessment of capillary leakage in DHF. We plan to utilize noninvasive technologies such as echocardiogram, ultrasonography, and measures of heart rate variability. Novel near infrared spectroscopy will be used to noninvasively determine hematocrit, muscle pH and muscle pO2. We also will perform flow cytometric assays to identify and characterize circulating endothelial cells as well as virus-specific T cells during acute infection. Our second study will involve a Phase lib vaccine efficacy trial that will take place in Kamphaeng Phet, Thailand. Research studies conducted during this unique opportunity will analyze the effects of dengue vaccination on viral transmission and define immunologic correlates of protection or possible sensitization to more severe illness. These research studies would not be performed by the vaccine manufacturer and will be crucial for the design and implementation of future clinical field trials of dengue vaccines. These clinical studies will be supported by Cores A and B and will provide valuable specimens (serum, peripheral blood mononuclear cells and virus isolates) for studies to be performed in Project 2. This Project includes two clinical studies in Thailand: (1) in hospitalized children, how the mosquitoborne dengue virus causes clinical disease and (2) in a field trial of a candidate dengue vaccine, to study how vaccines may protect against dengue virus infection.