A Systematic Review of Wolbachia-Based Aedes aegypti Interventions: Identifying Drivers of Variation Across Empirical and Theoretical Approaches

Abstract

Arboviral diseases such as dengue, Zika, and chikungunya remain significant global public health burdens, and traditional control methods are increasingly ineffective. The introduction of Wolbachia-infected Aedes aegypti mosquitoes has emerged as a promising alternative for reducing arboviral disease transmission. However, reported outcomes across studies vary substantially, highlighting the need to understand the factors driving variability. This systematic review examines variation in reported outcomes of Wolbachia-based interventions by synthesizing findings from empirical trials and mathematical modeling studies. A PRISMA-guided literature search was conducted across three major databases, and 42 studies were included in the final review. Selected studies were analyzed to compare patterns of Wolbachia establishment, spatial spread, and incidence reduction to identify key drivers of variation across studies. Across both empirical and theoretical approaches, substantial reductions in arboviral incidence were observed when Wolbachia achieved stable establishment. However, outcomes varied widely across implementations due to differences in environmental conditions, biological parameters, operational constraints, and surveillance methodologies. While modeling approaches capture key mechanisms, they often rely on fixed parameter assumptions that do not fully reflect the variability observed in field settings. These findings underscore the importance of integrating modeling and empirical approaches. Incorporating field-derived data into models, alongside the use of context-specific, model-informed intervention strategies in the field, can improve both predictive accuracy and implementation efficiency. A more integrated and context-dependent approach is essential for optimizing Wolbachia interventions and its applicability across diverse ecological and operational settings.