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.

Public Health Relevance

This Project includes two clinical studies in Thailand: (1) in hospitalized children, how the mosquito-borne 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI034533-20
Application #
8377854
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
2013-07-17
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
20
Fiscal Year
2012
Total Cost
$780,712
Indirect Cost
$72,810
Name
University of Rhode Island
Department
Type
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
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