The overall goal of this program core is to establish a surveillance system that will allow us to define, in real time, the contribution to dengue virus (DENV) transmission of a critical, understudied portion of the human population;i.e., individuals with inapparent and mild DENV infections that go undetected by traditional surveillance activities. We know little about their viremia levels over time, their relative infectivity to mosquitoes, and how their behavior in comparison to people with more severe illness might affect their role in DENV transmission. The Surveillance Core (SC) will provide the methodological framework and laboratory infrastructure to (1) capture DENV infected persons across the entire clinical spectrum of disease for mosquito infection studies in Project 1 and disease perception and behavioral studies in Project 2, (2) periderm laboratory testing and entomological monitoring for specific aims in all three projects, and (3) carry out serological and entomological monitoring in a longitudinal human cohort for Project 3. To capture acute dengue infections across a broad range of symptoms we will take an aggressive, innovative, and multi- layered approach that includes the use of cellular phone/SMS technology for surveillance and builds on our experiences and prior successes in Iquitos. Our contact cluster investigation design focuses on where people with a documented DENV infection have been, rather than exclusively on neighboring households, to identify additional inapparent and apparent active DENV infections. We will establish a longitudinal cohort for community-based febrile surveillance with ~ 3,800 residents who will be part of a larger strategy to capture fever cases. The cohort will be monitored in annual blood draws for serotype-specific DENV prevalence and incidence rates by plaque reduction neutralization test (PRNT). PRNT assays have two purposes (1) to provide a population-based estimate of the dengue inapparent to apparent case ratio for Project 3 and (2) to serve as a source of DENV positive participants with a known serologic history for Projects 1 and 2. Laboratory support will provide testing by RT-PCR, IgM-ELISA, qRT-PCR, clinical assays (CBC, AST), ELISA for selected immunological markers, and assay of experimentally infected mosquitoes. Entomological support will include establishing a genetically diverse laboratory strain for experimental mosquito infections.
For the first time, we will capture a large sample of people while they are viremic, but with no apparent dengue illness, and compare their role in the dynamics of dengue virus transmission to people with overt, clinically apparent disease. If the relative role of inapparent dengue infections in disease dynamics is better understood (1) surveillance and triggers for implementing control will be more effectively timed for maximum impact, (2) targets for vaccine delivery and vector control can be better identified, (3) immunological precursors of dengue severity can be studied across a broader range of disease outcomes, and (4) data across all disease manifestations can be included in mathematical and simulation models of dengue transmission and control.