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具有最大影响的临床、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。第一项是在曼谷对因急性登革热住院的有症状儿童进行前瞻性研究，以确定严重登革热的病理生理学。这项研究的结果将有助于指导对疑似登革热的发热患者的评估和分类，以及改进对DHF中毛细血管渗漏的评估。我们计划利用非侵入性技术，如超声心动图、超声波和心率变异性测量。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术分析，以识别和表征急性感染期间循环内皮细胞和病毒特异性T细胞。 我们的第二项研究将涉及在泰国Kamphaeng Phet进行的Lib期疫苗效力试验。在这一独特机会期间进行的研究将分析登革热疫苗接种对病毒传播的影响，并确定对更严重疾病的保护或可能的致敏的免疫学相关性。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，并将为项目2中进行的研究提供有价值的标本(血清、外周血单核细胞和病毒分离株)。

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.