Optimal Control and Global Sensitivity Analysis of a Multiroute Zika Transmission Model With Wolbachia

The Zika virus exhibits complex transmission dynamics involving vector-borne, sexual, and vertical pathways, which complicates the design of effective control strategies. In this work, we develop an integrated SICR–SI mathematical model coupling human and mosquito populations, incorporating Wolbachia-based biocontrol, sexual prevention, and vector control as intervention strategies. The model parameters are calibrated using epidemiological time-series data from seven Pacific island archipelagos, and the basic reproduction number R0 is analytically derived. Our results show that Wolbachia substantially reduces the vector component of transmission but cannot eliminate Zika in the presence of sexual transmission, which maintains a residual epidemic risk. We demonstrate that combining Wolbachia releases with sexual prevention yields a synergistic reduction in incidence greater than the sum of their individual effects. Using optimal control theory, we identify time-dependent intervention strategies that minimize both infection burden and implementation costs. A global sensitivity analysis (Sobol indices) highlights the dominant influence of mosquito-related parameters and Wolbachia coverage on epidemic outcomes. Overall, this study underscores the necessity of multitarget and coordinated intervention strategies to effectively reduce Zika transmission and its severe neurological complications.