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.
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.
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| Salje, Henrik; Cummings, Derek A T; Rodriguez-Barraquer, Isabel et al. (2018) Reconstruction of antibody dynamics and infection histories to evaluate dengue risk. Nature 557:719-723 |
| Kang, Jeon-Young; Aldstadt, Jared (2017) The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model. Int J Environ Res Public Health 14: |
| Srikiatkhachorn, Anon; Mathew, Anuja; Rothman, Alan L (2017) Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol 39:563-574 |
| Rattanamahaphoom, Jittraporn; Leaungwutiwong, Pornsawan; Limkittikul, Kriengsak et al. (2017) Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression. Asian Pac J Allergy Immunol 35:171-178 |
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| Srikiatkhachorn, Anon; Yoon, In-Kyu (2016) Immune correlates for dengue vaccine development. Expert Rev Vaccines 15:455-65 |
| Rothman, Alan L; Ennis, Francis A (2016) Dengue Vaccine: The Need, the Challenges, and Progress. J Infect Dis 214:825-7 |
| 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 |
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