Biotechnological Control of <em>Aedes aegypti </em>for Dengue Suppression: A Global Review of Expectations, Efficacy, and Concerns to Inform the Jeddah Vector Management Strategy, SPIRIT/TIDieR-Framed Protocol, and Simulation-Based Design-of-Experiments

Dengue fever remains one of the most pressing vector-borne diseases worldwide, driven primarily by the mosquito Aedes aegypti. Recent advancements in biotech- nology—ranging from the use of Wolbachia-infected mosquito releases to genetic modification (GM) techniques such as RIDL and CRISPR-based suppression—have redefined vector control paradigms. This paper presents a comprehensive pro- tocol for the synthesis and evaluation of global biotechnological inter- ventions, designed to assess expectations, field efficacy, and ethical and ecological concerns. Drawing from both computational modeling and field trial literature, we integrate findings to inform an optimized vector management strategy for Jed- dah, Saudi Arabia. The strategy is structured according to the SPIRIT/TIDieR framework and supported by a simulation-based Design-of-Experiments (DoE) ap- proach. The protocol describes the interplay between biological interventions and stochastic modeling, emphasizing the need for localized parameter calibration, long-term monitoring, and participatory stakeholder engagement. This integrative review and modeling framework serves as a foundation for the rational design of large-scale, adaptive dengue suppression programs, demonstrating how simu- lated outcomes can guide real-world implementation.