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.
| Park, Sangshin; Srikiatkhachorn, Anon; Kalayanarooj, Siripen et al. (2018) Use of structural equation models to predict dengue illness phenotype. PLoS Negl Trop Dis 12:e0006799 |
| 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 |
| Kalayanarooj, Siripen; Rothman, Alan L; Srikiatkhachorn, Anon (2017) Case Management of Dengue: Lessons Learned. J Infect Dis 215:S79-S88 |
| 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 |
| 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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