The overall objective of this project is to define DENV transmission vi/ithin a family in the presence of an ill, dengue viremic family member. This prospective family cohort study m identify immunologic correlates of protection, disease and the full spectrum ofthe host response from primary to secondary DENV infection. This study will also define infection among adults and herd immunity that influences the force of infection. DENV is an important arboviral infection causing a severe febrile illness and its more serious manifestation, dengue hemorrhagic fever (DHF). Our previous prospective cohort studies on dengue pathogenesis and epidemiology has contributed to the understanding of dengue virus transmission and the virus-host interactions leading to mild or severe dengue infection. What is unknown about dengue transmission and pathogenesis include correlates of immunity that define protection or illness, herd immunity defining the force of infection, and illness in adults and the consequences of fading immunity. Our previous studies point to the household of a DENV viremic patient as a potential source of DENV transmission and ultimately dengue transmission may be defined by the family unit members and their degree of risk or protection from infection. In this proposal's novel study design, we will prospectively follow family cohorts and be able to detect the ill viremic family member who becomes the sentinel case for additional transmission within the family and neighborhood. This study will be able to define familial herd immunity and force of infection within a family and risk to the neighborhood, characterize and define the correlates of protective immunity (T-cell, neutralizing antibody titer) among family members who are protected from infection or develop subclinical disease, and define the spectrum ofthe virus-host response through sequential infections and virus serotypes. This proposal will be the first study of its kind with its findings having implications on our understanding of the virus-host pathogenesis that defines the gradient of disease severity from subclinical to severe DENV infection and the development of effective DENV vaccines.

Public Health Relevance

Dengue virus is a global health problem with a dengue vaccine considered a high priority in dengue endemic countries or those at risk for epidemics. This proposal seeks to define correlates of protective and herd immunity, force of infection and immunity in children to adults. These results have a direct impact on the development of a dengue vaccine and public health interventions to control transmission.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-KP-M (J3))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rhode Island
United States
Zip Code
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

Showing the most recent 10 out of 119 publications