The overall objective of this Program Project is to identify and refine strategies for the prevention and management of dengue. Dengue continues to be an expanding public health problem, disproportionally affecting resource-poor countries in tropical and subtropical regions. Although morbidity from clinically mild infections is still considerable, the principal challenge presented by dengue virus is its ability to cause dengue hemorrhagic fever (DHF), a potentially fatal plasma leakage syndrome. There is no specific therapy or vaccine available against dengue, and development of treatments or vaccines has been problematic because of the evidence that DHF is immunologically mediated. In this application, an experienced interdisciplinary team of university, military, and industry investigators in the US and Thailand proposes to conduct coordinated studies to a) advance understanding of DHF epidemiology, pathophysiology, and immunopathogenesis and b) use this knowledge to identify and validate approaches to management and prevention of dengue disease. Project 1 (Clinical Studies) will involve a prospective study in Bangkok of symptomatic children hospitalized with acute dengue illness, to define the pathophysiology of severe dengue and improve the evaluation and triage of cases, and a prospective population-based study of dengue transmission and disease in Kamphaeng Phet province, to take place concurrently with a phase lib vaccine efficacy trial, to define optimal methods for evaluation of vaccine efficacy and identify correlates of protective immunity. Project 2 (Molecular Immunopathogenesis) will involve detailed laboratory studies of innate and adaptive immune responses to dengue in vitro and in vivo to define the immunologic mechanisms underlying protection and disease pathogenesis. A Clinical Laboratory Core and an Administrative Core will support both Projects. Close interactions and sharing of data between these Projects and Cores will ensure the maximum yield from these research studies, with broad basic science as well as clinical and public health implications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI034533-20
Application #
8245026
Study Section
Special Emphasis Panel (ZAI1-MMT-M (J2))
Program Officer
Cassetti, Cristina
Project Start
1997-01-01
Project End
2013-07-17
Budget Start
2012-04-01
Budget End
2013-07-17
Support Year
20
Fiscal Year
2012
Total Cost
$1,985,380
Indirect Cost
$185,157
Name
University of Rhode Island
Department
Anatomy/Cell Biology
Type
Schools of Earth Sciences/Natur
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
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Srikiatkhachorn, Anon; Kelley, James F (2014) Endothelial cells in dengue hemorrhagic fever. Antiviral Res 109:160-70
Mathew, Anuja; Townsley, Elizabeth; Ennis, Francis A (2014) Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections. Future Microbiol 9:411-25
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Soller, Babs; Srikiatkachorn, Anon; Zou, Fengmei et al. (2014) Preliminary evaluation of near infrared spectroscopy as a method to detect plasma leakage in children with dengue hemorrhagic fever. BMC Infect Dis 14:396
Co, Mary Dawn T; Terajima, Masanori; Thomas, Stephen J et al. (2014) Relationship of preexisting influenza hemagglutination inhibition, complement-dependent lytic, and antibody-dependent cellular cytotoxicity antibodies to the development of clinical illness in a prospective study of A(H1N1)pdm09 Influenza in children. Viral Immunol 27:375-82
Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J et al. (2014) Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection. Immunology 141:27-38
Rothman, Alan L (2014) DHIM supporting immunologic investigations and the identification of immune correlates of protection. J Infect Dis 209 Suppl 2:S61-5
Anderson, Kathryn B; Gibbons, Robert V; Cummings, Derek A T et al. (2014) A shorter time interval between first and second dengue infections is associated with protection from clinical illness in a school-based cohort in Thailand. J Infect Dis 209:360-8

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