Fine Scale Spatiotemporal Clustering of Dengue Virus Transmission in Children and Aedes aegypti in Rural Thai Villages

Abstract
Based on spatiotemporal clustering of human dengue virus (DENV) infections, transmission is thought to occur at fine spatiotemporal scales by horizontal transfer of virus between humans and mosquito vectors. To define the dimensions of local transmission and quantify the factors that support it, we examined relationships between infected humans and Aedes aegypti in Thai villages. Geographic cluster investigations of 100-meter radius were conducted around DENV-positive and DENV-negative febrile “index” cases (positive and negative clusters, respectively) from a longitudinal cohort study in rural Thailand. Child contacts and Ae. aegypti from cluster houses were assessed for DENV infection. Spatiotemporal, demographic, and entomological parameters were evaluated. In positive clusters, the DENV infection rate among child contacts was 35.3% in index houses, 29.9% in houses within 20 meters, and decreased with distance from the index house to 6.2% in houses 80–100 meters away (pAe. aegypti were DENV-infectious (i.e., DENV-positive in head/thorax) in positive clusters (23/1755; 1.3%) than negative clusters (1/1548; 0.1%). In positive clusters, 8.2% of mosquitoes were DENV-infectious in index houses, 4.2% in other houses with DENV-infected children, and 0.4% in houses without infected children (pAe. aegypti pupae and adult females were more numerous only in houses containing infectious mosquitoes. Human and mosquito infections are positively associated at the level of individual houses and neighboring residences. Certain houses with high transmission risk contribute disproportionately to DENV spread to neighboring houses. Small groups of houses with elevated transmission risk are consistent with over-dispersion of transmission (i.e., at a given point in time, people/mosquitoes from a small portion of houses are responsible for the majority of transmission). Dengue is the leading cause of mosquito-borne viral infections globally. An improved understanding of the spatial and temporal distribution of dengue virus (DENV) transmission between humans and the principal vector, Aedes aegypti, can enhance prevention programs. Human DENV infection is known to occur at very fine spatiotemporal scales. We sought to link and quantify human DENV infections with infectious mosquitoes at these fine scales by conducting geographic cluster investigations around febrile children with and without DENV infection. We found that DENV infection in children was positively associated with houses in which infectious mosquitoes were captured. These houses also had more Ae. aegypti pupae and adult female mosquitoes than neighboring houses. However, the neighboring houses still had elevated rates of human DENV infection. Our results indicate that certain houses with high risk of DENV transmission contribute disproportionately to DENV amplification and spread to surrounding houses. At a given point in time, people and mosquitoes from a small portion of houses are responsible for the majority of DENV transmission.