Entomological assumptions of dengue control (NIH Program Project): The goal of dengue prevention and control programs is cost-effective utilization of limited resources to reduce vector populations to levels at which they are no longer of significant public health importance. There is no clinical cure for dengue and a licensed vaccine is not currently available. An implicit assumption of the vector control approach is that as entomological risk increases so does the potential for dengue virus transmission and the incidence of severe forms of disease. The vector control approach emphasizes vector surveillance, with the objectives of maintaining Ae. aegypti populations below or close to transmission threshold values, slowing dengue virus transmission, and reducing sequential infections with heterologous serotypes that can increase the incidence of serious disease. However, no well-controlled field studies have been carried out to define the relationships between vector density and human infection. Using a prospective epidemiologic approach, we are defining the temporal and spatial relationships among entomological risk factors, incidence of human infection, and clinical disease manifestations in Kamphaeng Phet, north central Thailand. We will test the hypothesis that entomological risk (vector density) is positively correlated with the intensity of dengue virus transmission, incidence of clinical illness, and severity of dengue disease, which is a fundamental premise of current public health policy for dengue prevention. All entomological, serological, and clinical data are being managed in a Geographic Information System so that we can analyze spatial and temporal patterns of dengue cases and entomological risk factors. We will determine whether measures of risk associated with Ae. aegypti are positively correlated with the force of dengue virus transmission and the spectrum of clinical disease manifestations. Our study design focuses on identifying active human dengue cases, following contacts of those cases, and characterizing entomological parameters at the time of transmission in and around index and contact homes. We are also partitioning risk of dengue virus infection in homes versus schools by comparing entomological risk factors to the force of transmission and severity of disease at those two locations. Ultimately we will link, in time and space, dynamics in dengue transmission to entomological risk, incidence of human infection, and the severity of disease.

Measuring entomological risk for dengue (NIH): The impact of human movement patterns on exposure of people to bites from mosquito vectors is a major knowledge gap in the understanding of dengue virus transmission dynamics. Because Aedes aegypti is a daytime biting mosquito we anticipate that the daytime activity patterns of human hosts will profoundly affect their risk of exposure to infective mosquito bites. Testing these ideas will require identification of operationally feasible measures of entomological risk estimated at an appropriate geographic scale that accounts for movements of susceptible humans in and out of high risk areas. Relative risk of dengue virus infection has never been rigorously measured at the multiple locations that susceptibles individual visit during their daily activities; like the homes of neighbors or relatives, schools, markets, workplaces or other communities. In the Amazonian city of Iquitos, Peru—where we have over 6 years of Ae. aegypti and dengue research experience—we propose to test the hypothesis that spatial dimensions of dengue virus transmission are defined by daily patterns of human movement. We predict that dengue virus incidence rates are positively correlated with the number of bites received from Ae. aegypti at high risk locations, serotype specific herd immunity, and ambient temperature. We intend to test our hypothesis in the context of 2 specific aims. First, a combination of retrospective and prospective cohort studies will be used to determine whether measurement of entomological risk across a person’s activity space provides a better prediction of dengue virus infection risk than limiting assessment to their household. Second, we will use DNA profiling of blood in engorged mosquitoes to determine the risk of a person being bitten by Ae. aegypti at different sites across their activity space. Data collected in these field studies will be analyzed using a series of spatial statistical techniques and social network modeling to define the spatial dimensions of dengue virus transmission and the predictive value of entomological surveillance. Our goal is to clarify the value of entomological indices in dengue surveillance programs by defining the spatial dimensions of dengue virus transmission. Our research will be the most definitive test to-date of the empirical relationship between entomological risk and dengue virus transmission. Our results will be relevant for dengue prevention programs based on vector control and/or vaccine strategies and will have immediate, practical applications for dengue surveillance and control worldwide.

Genetic strategies for control of dengue virus transmission (Grand Challenge in Global Health, Foundation for the NIH): This project is designed to advance development of genetics-based, effective, and safe field practices for preventing Aedes aegypti from transmitting dengue viruses by reducing mosquito population densities or eliminating their ability to transmit virus. We expect that these practices will result in decreased morbidity and mortality caused by dengue viruses. Major challenges in the project include optimizing effector genes for population replacement and reduction, developing safe and efficient drive systems for introgressing effector genes into mosquito populations, and establishing a field site for genetic control trials. Project objectives are being achieved through an integrated network of collaborating researchers. Within the five-year period of this award, the project began during late 2005, we expect to have reached three goals. First, developed control methods that target larval and adult mosquitoes. We will have functional effector genes for both reducing mosquito populations and altering their abilities to transmit dengue viruses. Second, tested and compared the efficacy and specificity of gene drive mechanisms and determined their potential role in overall integrated strategies of dengue virus control. Third, established a field site that has the approval of the local community and relevant government, regulatory bodies and where we will have tested genetics-based methods in large outdoor cages. The emphasis of the Scott lab will be on establishing field sites and carrying out experiments in outdoor cages. There will be no release into the natural environment of modified mosquitoes in this project.

Innovative Vector Control Consortium (Bill & Melinda Gates Foundation): The goal of this project is to reduce peridomestic transmission of mosquito-borne pathogens through improved control of adult mosquito vectors in households with innovative tools. We have two objectives (1) to produce improved insecticides and formulations and (2) to develop a vector control decision support system for use at the community level to reduce disease transmission. The strategies we will use to achieve these objectives include the following. We will develop alternatives to existing pyrethroids and longer lasting insecticide formulations for insecticide treated materials and indoor residual spray treatments. We will develop insecticide combinations, e.g. bi-treated nets and insecticide treated materials that are useful in areas where insecticide resistance might otherwise pose a problem. We will refine and further develop an informatic tool for use at the community level that includes data, decision support software, and access to one or more central databases of entomological, epidemiological and related data in a geographic information system-based format. We will develop and extend simulation models that can be used to establish the various entomological end points that will need to be achieved for optimal vector control and disease prevention. We will develop a field-appropriate kit for quantifying the amount of pyrethroid insecticide remaining on insecticide treated materials. We will develop one or more field-appropriate tools for monitoring essential characteristics of local vector populations. Research carried out by the Scott lab will focus on control of Ae. aegypti and dengue prevention in the Amazonian city of Iquitos, Peru.

Polyandry among Aedes aegypti: In this project we intend to resolve the controversy surrounding monandry vs. polyandry for the dengue vector Ae. aegypti by carrying out field studies that test the principle components of each side of the argument. Understanding mosquito mating behavior is important for designing effective genetic control strategies. We are using polymorphic genetic markers to detect sperm from different males in the spermatheca of individual female Ae. aegypti in Thailand. By examining a sufficiently large number of field-collected females, we will be able to detect polyandry even if it is rare or if the frequency of multiple inseminations varies through time and space. Determining whether there is a positive correlation between female age and frequency of polyandry will test the hypothesis that frequency of multiple inseminations increases with advancing female age and gonotrophic activity. To do this we are using SSCP of PCR amplified variable scnDNAs (single copy nuclear genes) to determine if Ae. aegypti females were inseminated by more than one male. Mosquito age will be determined by detection of age-dependent changes in cuticular hydrocarbons.

Rapid assessment of transmission potential of West Nile Virus by Culex mosquitoes (University-wide California Mosquito Research Program): In this project we are investigating antiviral genes responsible for refractoriness in mosquitoes in the Culex pipiens complex in California and determining if immune peptides in local mosquito populations can be used as markers to predict local risk of WNV transmission. Our ultimate goal is to develop a genetic probe for field-caught mosquitoes that can be applied to assess a mosquito population's potential for virus transmission. Such an assay would be rapid, without the virus biohazard, time, and expense associated with traditional vector competence assays.

California based mosquito and arbovirus research: We participate in a variety of projects on mosquitoes in northern California that focus on mosquito biology and ecology with the ultimate goal of improving surveillance and control for arboviruses. Collaborations include colleagues at UC Davis, other campuses in the University of California system, Mosquito Abatement Districts across the state, and the California Department of Health Services.