Arbovirus Transmission Dynamics Across a Metapopulation Undergoing Environmental and Social Change

Abstract Aedes-borne viral diseases are associated with explosive urban epidemics, but rural transmission is undergoing expansion and its role in virus maintenance is poorly understood. Transmission dynamics at a regional level requires us to go beyond conceptualizing dengue as urban or rural, terms that are administrative and political rather than etiologic. Borrowing from metapopulation theory, the transmission dynamics of dengue are better analyzed using spatial terms like patches that describe environmental, social, and biological dynamic processes at multiple scales. Our overall hypothesis is that dengue and Zika virus (DENV, ZIKV) transmission dynamics occur at multiple geographic scales, driven by connections among human movement patterns, social networks, and mosquito densities at fine scales (within locations) and by regional, national, and international transportation networks at larger scales. Given its relevance we will study DENV as the predominant pathogen; given the immune imprint that ZIKV leaves, we will include it and monitor any other Aedes-borne viruses that may circulate or emerge in any given year. The relative contribution of intra- and inter-location movements depends on key geolocatable characteristics that we categorize as landscapes (e.g., weather, structural and surface features), bioscapes (e.g., mosquito behavior and human immunity), and socioscapes (e.g., movement, social networks). We propose to study DENV transmission dynamics in northwestern coastal Ecuador where communities reside in a heterogeneous array of changing environments and where we have documented very recent introduction and establishment of DENV as well as high Zika seroprevalence. We will address our overarching hypotheses through parallel longitudinal cohorts of human (Aim 1) and vector (Aim 2) populations in regionally representative communities to characterize the transmission dynamics at multiple geographic scales (Aim 3). Aim 1 focuses on the question: What is the force of DENV infection and the rate of virus introduction across the diverse landscape within 6 communities (across a remoteness gradient)? Aim 2 focuses on the question: How do key entomological parameters (vector bioscape) drive local DENV transmission within distinct landscapes of unique interconnected communities in Northwestern Ecuador? And Aim 3 focuses on the question: Can a collection of smaller communities, connected through a transportation and social network, function (socioscape) like a larger population center to sustain and seed transmission? This R01 will provide fundamental insights into how a changing environment influences heterogeneous transmission patterns as well as epidemiological and immunological interactions between DENV and ZIKV. These insights can provide information crucial to developing optimal control strategies for Aedes-borne diseases.