Date of Award

January 2025

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Albert Ko

Abstract

Dengue is an arboviral disease of increasing global public health importance for which more than half the world’s population is at risk. The burden of dengue has increased greatly in the last decade; in 2024, over 14 million cases and 10,000 dengue-related deaths were reported, marking a historical milestone. The endosymbiotic bacterium Wolbachia (wMel strain) offers a promising alternative to traditional control methods through its reduction of Aedes aegypti vector competence and introgression into wild Ae. aegypti populations. This thesis evaluated the dynamics of Wolbachia introgression and its effect on reducing dengue incidence up to 31 months after the completion of large-scale releases of adult wMel-infected Ae. aegypti mosquitoes in Rio de Janeiro, Brazil. To characterize the dynamics of wMel introgression, wMel prevalence estimates across the release area were interpolated, by analyzing geocoded oviposition trap monitoring data from May 2020 to April 2024 using a spatiotemporally structured random effects model. This was implemented by employing the Integrated Nested Laplace Approximation (INLA) approach. To evaluate the effectiveness of wMel introgression on dengue incidence in the release area, geocoded dengue case data were analyzed using a similar spatiotemporally explicit model. Predictors included a spatially structured random effect that varied by epidemic year, a temporally structured random effect, and the interpolated wMel introgression. During the four study years, overall monthly wMel introgression was 37% to 47%, yet there was significant spatial heterogeneity in introgression across the release area. Between May 2022 to April 2023, wMel prevalence was associated with a significant protective effect against dengue incidence and a 52% reduction in dengue incidence was observed [RR: 0.48 (95% CI 0.34 - 0.68)]. However, from May 2023 to April 2024, during which a large epidemic occurred in the city, no protective effect of wMel introgression was observed. Notably, during this period, higher levels of introgression were associated with a non-significant trend in increased dengue risk; ≥50%, ≥60%, and ≥70% wMel introgression was associated with 13%, 15%, and 13% increases in dengue incidence respectively [RR: 1.13 (95% CI 0.99 - 1.30), RR: 1.15 (95% 1.00 - 1.32), RR: 1.13 (95% CI 0.98 - 1.30)]. The findings of my thesis raise several hypotheses. First, there may exist a threshold level of dengue transmission beyond which the protective effect of wMel is reduced. Second, ongoing dengue transmission may be influenced by factors such as changes in population immune dynamics and residual wildtype Ae. aegypti abundance, which may confound the observed association between wMel introgression and dengue incidence. Understanding these dynamics is critical for the optimization of Wolbachia release strategies and the scale-up of Wolbachia-based interventions in dengue endemic regions.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/16/2026

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