Clinical Studies on the Mechanisms of DF/DHF

项目1（临床研究）的总体目标是确定对确定泰国儿童登革热病毒感染的最终临床表现影响最大的临床、免疫学、病毒学和流行病学因素。该项目将涉及两项临床研究。第一项研究将在曼谷对急性登革热住院的有症状儿童进行前瞻性研究，以确定重症登革热的病理生理学。本研究结果将有助于指导疑似登革热发热患者的评估和分诊，并改进对DHF毛细血管渗漏的评估。我们计划利用无创技术，如超声心动图、超声检查和心率变异性测量。新型近红外光谱将用于无创测定红细胞压积，

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.