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
Moulton, Steven L; Mulligan, Jane; Srikiatkhachorn, Anon et al. (2016) State-of-the-art monitoring in treatment of dengue shock syndrome: a case series. J Med Case Rep 10:233
Srikiatkhachorn, Anon; Yoon, In-Kyu (2016) Immune correlates for dengue vaccine development. Expert Rev Vaccines 15:455-65
Townsley, E; O'Connor, G; Cosgrove, C et al. (2016) Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol 183:419-30
Nisalak, Ananda; Clapham, Hannah E; Kalayanarooj, Siripen et al. (2016) Forty Years of Dengue Surveillance at a Tertiary Pediatric Hospital in Bangkok, Thailand, 1973-2012. Am J Trop Med Hyg 94:1342-7
Clapham, Hannah E; Rodriguez-Barraquer, Isabel; Azman, Andrew S et al. (2016) Dengue Virus (DENV) Neutralizing Antibody Kinetics in Children After Symptomatic Primary and Postprimary DENV Infection. J Infect Dis 213:1428-35
Woda, Marcia; Friberg, Heather; Currier, Jeffrey R et al. (2016) Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions. J Infect Dis 214:1001-9
Rothman, Alan L; Ennis, Francis A (2016) Dengue Vaccine: The Need, the Challenges, and Progress. J Infect Dis 214:825-7
Clapham, Hannah; Cummings, Derek A T; Nisalak, Ananda et al. (2015) Epidemiology of Infant Dengue Cases Illuminates Serotype-Specificity in the Interaction between Immunity and Disease, and Changes in Transmission Dynamics. PLoS Negl Trop Dis 9:e0004262
Yoon, In-Kyu (2015) FOCAL DENGUE VIRUS TRANSMISSION IN KAMPHAENG PHET, THAILAND AND IMPLICATIONS FOR MANAGEMENT. Southeast Asian J Trop Med Public Health 46 Suppl 1:17-25
Medin, Carey L; Valois, Sierra; Patkar, Chinmay G et al. (2015) A plasmid-based reporter system for live cell imaging of dengue virus infected cells. J Virol Methods 211:55-62

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