| Dengue is the most important arthropod-borne viral disease of humans with millions of people infected every year. Because a portion of infections are asymptomatic, prospective serological studies yield best estimates of transmission parameters necessary for optimizing disease prevention programs. I conducted three studies to address serological analysis of dengue virus infections and the effect of heterogeneous mosquito biting rates on transmission dynamics.;First, the single dilution plaque reduction neutralization test (PRNT) was evaluated. Results from a receiver operator curve indicated that specificity of dengue-1 positive sera against a dengue-2 test virus can be improved 20% by increasing the serum dilution cut point from 1/60 to 1/80. Using maximum likelihood and Bayesian methods, sensitivity and specificity were estimated at 90% and 70%, respectively.;Second, serological data from a cohort in Iquitos, Peru were analyzed by survival analysis to estimate the hazard ratio for adults versus children. Ratios for adults:children changed over the course of an interepidemic period from 1.69 (95% CI: 1.20, 2.40) to 0.7 (95% CI: 0.43, 1.12). During a dengue-3 epidemic, the hazard ratio was estimated at 1.21 (95% CI: 1.03, 1.41). Adults seroconverted at a higher rate than children, consistent with the hypothesis that mosquito vectors preferentially bite adults.;Third, a simulation model for Iquitos was developed to evaluate the effects of age-dependent biting by mosquitoes on dengue transmission dynamics. Results depended on mosquito density, age-specific seroprevalence in the human population, and age-specific distribution of mosquito bites. In endemic areas with less than 100% adult immunity to all four dengue serotypes, disregarding age-specific infection rates can lead to underestimating critical thresholds for disease prevention, such as entomological thresholds or the proportion of the human population to vaccinate. The magnitude of difference between age-dependent and age-independent estimates increased as mosquito density increased. Consequently, continuing vector control programs in concert with dengue vaccination will tend to reduce effects of age-dependent biting. |
