Aedes aegypti Density and Risk of Dengue Virus Seroconversion

Routine entomological monitoring data are used as a surrogate for overall risk of dengue virus (DENV) infection and to trigger implementation of control interventions. Indicators that characterize Aedes aegypti abundance have not consistently been associated with an increased risk of dengue virus (DENV) seroconversion. Using longitudinal entomological and serological data from Iquitos, Peru, this dissertation estimated the risk of DENV infection for several entomological indicators to determine if any measure of Ae. aegypti abundance was associated with transmission. Entomological survey data from two longitudinal cohort studies linked with 8,153 paired serological observations were analyzed. Indicators of Ae. aegypti density were calculated from entomological. The risk ratios (RR) estimating the association between Ae. aegypti abundance at the household and block levels and the six-month risk of DENV seroconversion were obtained. Cross-sectional Ae. aegypti densities were not associated with an increased risk of DENV seroconversion. Longitudinal measures of adult stage density resulted in adjusted RRs ranging from 1.01 (95% CI: 1.01, 1.02) to 1.30 (95% CI: 1.17, 1.46) and categorical immature indices (RRs ranging from 1.21 (95% CI: 1.07, 1.37) to 1.75 (95% CI: 1.23, 2.5)). A total of 90,046 entomological monitoring observations were used to model the space/time covariance of ln(adult Ae. aegypti per m2). Mosquito density modeled using the Bayesian Maximum Entropy (BME) geostatistical framework was associated with an increased risk of DENV infection among densities ranging from 0.005 to 0.01 mosquitoes per m2 (adjusted risk ratio: 1.14; 95% CI: 1.01, 1.28). A multi-level logistic model was used to test for heterogeneity of the association between DENV risk and longitudinal measures of Ae. aegypti density. The multi-level model results suggest that the population-level risk ratios are more appropriate estimates of the Ae. aegypti-DENV seroconversion association. Ae. aegypti densities calculated from repeat entomological monitoring were associated with DENV seroconversion, whereas estimates of Ae. aegypti abundance measured cross-sectionally were not. It is possible that Ae. aegypti populations exhibit too much variability across space and time for periodic, cross-sectional measurement to adequately characterize entomological risk, in addition to having no correlation with true infection events due to human movement in space and time.Doctor of Philosoph