The Interactive Roles of Aedes aegypti Super-Production and Human Density in Dengue Transmission Harish Padmanabha 1,2 *, David Durham 1 , Fabio Correa 2 , Maria Diuk-Wasser 1 , Alison Galvani 1 1 Yale School of Public Health, New Haven, Connecticut, United States of America, 2 Instituto Nacional de Salud, Bogota, Colombia Abstract Background: A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling. Methodology/Principal Findings: Using data from seven censuses of A. aegypti pupae (2007–2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue- endemic urban ‘patches’ (1–3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R 0 ) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R 0 , and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities. Significance/Conclusions: These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super- productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person’s home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy. Citation: Padmanabha H, Durham D, Correa F, Diuk-Wasser M, Galvani A (2012) The Interactive Roles of Aedes aegypti Super-Production and Human Density in Dengue Transmission. PLoS Negl Trop Dis 6(8): e1799. doi:10.1371/journal.pntd.0001799 Editor: Scott C. Weaver, University of Texas Medical Branch, United States of America Received March 29, 2012; Accepted July 16, 2012; Published August 28, 2012 Copyright: ß 2012 Padmanabha et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by the World Bank Integrated National Adaptation Pilot to Climate Change, awarded to the Colombian National Institute of Health, and the Yale Climate and Energy Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: harish.padmanabha@yale.edu Introduction In the latter half of the 20th century dengue emerged as the most prevalent urban vector borne disease of humans, readily propagating among urban populations of humans and Aedes aegypti mosquitoes. Intervention against A. aegypti domestic container habitats, known as source reduction, is central to the dengue prevention activities of most health departments of endemic cities [1–4]. However, few programs have the resources necessary to intervene effectively in all areas infested by A. aegypti [5]. Therefore, dengue prevention could benefit from an understand- ing of the areas in which the impact of source reduction would be maximized. Most evidence indicates that urban A. aegypti populations are regulated by mortality that occurs in the egg/larval stages [6–9]. This results in the common finding that most infested containers produce few pupae, whereas the majority of the adult vector population derives from only a few containers and houses, called super-producers [4,8,10,11]. The elimination of super-productive containers forms the conceptual basis for targeting source reduction programs [2,3,12]. This approach is grounded in modeling studies that show that the targeted elimination of containers above a threshold pupal abundance can significantly reduce the risk of dengue [13,14]. However, this consistent regulatory pattern of A. aegypti also causes the majority of vectors to emerge in the same location, generating significant spatial heterogeneity in adult vector distributions [15–18]. However, because most models of the impact of source reduction on dengue assume homogenous mixing between humans and mosquitoes, little is known about how the phenomenon super-production per se affects transmission dynamics. This knowledge is critical to understanding how the natural regulation of A. aegypti influences the dynamics of dengue. Traditionally, field estimates of the entomological risk of mosquito-borne disease have focused on the ratio of vectors to humans, in order to estimate the rate at which humans receive infectious bites [19]. This rationale has been used to assess the entomological risk of dengue through surveys of human and pupal PLOS Neglected Tropical Diseases | www.plosntds.org 1 August 2012 | Volume 6 | Issue 8 | e1799