Optimal control approach to developing sex-structured release strategies for dengue prevention.

Dengue remains a public health challenge due to the persistence of Aedes aegypti populations and the limited effectiveness of medical and vector control interventions. The release of Wolbachia-infected mosquitoes has been used in multiple regions; yet, release protocols are often heuristically structured, with limited optimization. In particular, the impacts of mosquito sex structure and strain-specific effects remain unclear. This study develops a sex-structured dynamical model that links within-vector Wolbachia dynamics, such as cytoplasmic incompatibility and vertical transmission, with between-host dengue transmission. An optimal control framework is used to determine cost-effective releases of male and female mosquitoes over a finite intervention horizon, with mosquito dispersal on a finite time interval. The cost effectiveness of a release program relies on minimizing releases and dengue cases. The approach is applied to three Wolbachia strains, wAlbB, wMel, and wMelPop, to assess how strain-specific fitness and viral blocking influence optimal release plans. The analysis identified sex-structured strategies that diverge from in-field protocols, supporting the notion that commonly used plans may benefit from optimization by sex. Additionally, differences were noted among strains, which suggests that optimal sex-structured releases may vary with Wolbachia strain used.