Optimizing wolbachia-based interventions to ensure effective and equitable prevention of arboviral infections

The National Institute of Allergy and Infectious Diseases awarded Yale University $182,728 on February 6, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to optimize Wolbachia-based interventions for arboviral prevention.

The project develops statistical and mathematical models to identify factors influencing the speed of Wolbachia introgression into wild Aedes aegypti populations and to determine optimal release timing and dosing strategies. Wolbachia is an endo-symbiotic bacterium that renders mosquitoes resistant to dengue, Zika, and chikungunya viruses. The research leverages existing datasets and field data from large-scale Wolbachia release programs in Rio de Janeiro and Belo Horizonte, Brazil, to address implementation barriers in complex urban settings with high arboviral burden and socioeconomic disparities. Preliminary research indicates that the ratio of release doses to existing Aedes aegypti abundance predicts introgression success, and calibrated high-dose releases have demonstrated promising results. The findings will inform equitable, efficient, and effective deployment of Wolbachia interventions in the United States, where over 10,500 locally acquired dengue cases were reported in 2024–25 and no approved treatments or licensed vaccines currently exist.

Performance occurs at Yale University in New Haven, Connecticut. The period of performance runs through September 28, 2027.

Abstract

Arboviruses, viruses spread to humans through the bite of infected arthropods such as dengue, zika, and chikungunya, represent an immense and growing burden to global health. The endo-symbiotic intra-cellular bacterium wolbachia is a novel form of disease control that has been shown to successfully decrease the transmission of several arboviruses. Wildtype aedes aegypti population replacement can occur after releases of transinfected female AE. Aegypti mosquitoes, driven by cytoplasmic incompatibility and maternal inheritance. Once wolbachia introgression reaches a predetermined threshold (~50-60% prevalence), population replacement can be sustained without additional releases and reductions in arboviral transmission can be observed. However, successful delivery of wolbachia release interventions require an understanding of the factors that drive introgression speed and stability and strategies that enable efficient implementation in a diverse range of urban environments. Achieving rapid, sustained wolbachia introgression remains challenging in complex urban settings, particularly in areas with high arboviral burdens and socioeconomic disparities, such as RIO DE janeiro. My preliminary research has identified that the ratio of release doses to existing AE. Aegypti abundance predicts introgression success, and calibrated high-dose releases have demonstrated promising results. This study leverages these findings and unique data from wolbachia release programs in RIO DE janeiro and belo horizonte, brazil to address critical barriers to equitable, efficient, and effective implementation of wolbachia interventions. Specifically, the proposed study aims to: (1) develop a statistical and mathematical models to identify factors influencing introgression speed and optimal wolbachia release timing and dosing strategies based on comprehensive data from RIO DE janeiro and (2) empirically test the effects of release doses on the speed of wolbachia introgression utilizing data from experimental releases in belo horizonte. By combining advanced modeling and real-world experimental data, this research will identify scalable, efficient, and equitable strategies for wolbachia interventions. These findings will enhance global efforts to combat dengue and other arboviral diseases in diverse urban contexts.