The overall objective of this Program Project is to identify and refine strategies for the prevention, diagnosis, and treatment of dengue. Dengue remains a significant global public health burden, particularly in resource-poor countries of tropical and subtropical regions of the world, as well as an NIAID biodefense research priority agent. We hypothesize that dengue-related morbidity and mortality result from a sequence of events involving the individual and the community and influenced by both viral and host factors, each of which may be amenable to intervention. This research program involves a coordinated series of epidemiologic, clinical, virologic, and immunologic investigations, to be conducted by an experienced team, extending an established track record of productive research collaboration and building on a superb research infrastructure. Project 1 will involve clinical, virologic, and immunologic studies of subjects with suspected acute dengue illness to define optimal strategies for triage and management of adult and pediatric patients and test novel non-invasive monitoring approaches. Project 2 will involve prospective field epidemiologic studies to define relationships between individual and herd immunity and dengue virus (DENV) circulation and their implications for vaccine introduction. Project 3 will define immunologic correlates of protective and pathogenic immunity in natural DENV infections and in subjects in a phase III dengue vaccine trial. Three Cores will provide common infrastructure to support all three projects: Administration, Data Management and Statistics, and Clinical Research Laboratory. Interactions between the projects and cores, with exchange of research material, data, and concepts, will create synergy as a scientific program. The findings from these proposed research studies should have broad basic science as well as clinical and public health implications.

Public Health Relevance

Dengue has a major economic and public health impact, especially in resource-poor areas of the world. There remain important gaps in knowledge regarding dengue virus transmission, host immunity, and the application of such information to patients with dengue illness. This program project involves clinical studies in Thailand and the Philippines to guide efforts for the prevention, diagnosis, and treatment of dengue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI034533-21
Application #
8476046
Study Section
Special Emphasis Panel (ZAI1-KP-M (J3))
Program Officer
Cassetti, Cristina
Project Start
1997-01-01
Project End
2018-06-30
Budget Start
2013-07-18
Budget End
2014-06-30
Support Year
21
Fiscal Year
2013
Total Cost
$2,411,226
Indirect Cost
$353,695
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
Rothman, Alan L; Medin, Carey L; Friberg, Heather et al. (2014) Immunopathogenesis Versus Protection in Dengue Virus Infections. Curr Trop Med Rep 1:13-20
Srikiatkhachorn, Anon; Spiropoulou, Christina F (2014) Vascular events in viral hemorrhagic fevers: a comparative study of dengue and hantaviruses. Cell Tissue Res 355:621-33
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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