Temperature variation as a driver of Wolbachia release efficacy: implications for dengue control in warming climates

BackgroundWolbachia-based control methods reduce dengue transmission by suppressing Aedes aegypti populations or blocking viral replication, yet their effectiveness across the climatic conditions of endemic regions remains poorly understood. Seasonal and interannual temperature changes shape mosquito dynamics, but how Wolbachia releases perform during anomalous events such as El Nino or heatwaves is largely unknown--a gap that limits our ability to optimize release strategies and predict intervention success across different climates. Methodology/Principal FindingsTo address this gap, we built a mathematical modeling framework that explicitly incorporates temperature-dependent Wolbachia parameters together with the seasonal and interannual climate variability characteristic of dengue-endemic regions, coupling a detailed Wolbachia dynamics model with a susceptible-infectious-recovered (SIR) epidemiological model to evaluate Wolbachia establishment, persistence, and stability under different thermal regimes and trace their downstream impact on disease spread. Higher temperatures eroded both Wolbachia establishment and long-term persistence, sharply narrowing the range of effective release strategies as conditions approached 30 {degrees}C. Seasonality added a further layer of complexity: the timing of thermal stress relative to Wolbachia frequency, not merely its magnitude, determined whether population replacement succeeded. Interannual shifts, progressive warming, widening seasonal swings, and displaced thermal peaks, each eroded Wolbachia prevalence and stability, with effects that compounded over successive years. Dengue transmission tracked these dynamics closely, with warmer conditions producing larger, earlier outbreaks, and intervention success hinging on how release timing, frequency, and targeting were matched to local thermal conditions. Conclusions/SignificanceAs extreme heat events become more frequent under climate change, release programs that ignore local thermal conditions risk falling short where dengue control is most needed. By elucidating the mechanistic interplay among temperature, Wolbachia, and dengue, our findings help refine Wolbachia release programs to suit different climatic conditions, thereby strengthening dengue control as climate variability intensifies. Author summaryDengue sickens hundreds of millions of people each year, and releasing mosquitoes carrying the naturally occurring bacterium Wolbachia, which blunts the viruss spread, has become one of the most promising tools for fighting it. Yet one factor that decides whether these releases succeed or fail is routinely overlooked: temperature. We built a mathematical model linking Wolbachia biology and mosquito population dynamics to temperature, to ask a practical question: which release strategies work under real-world, changing climate conditions? Heat narrowed the margin for success. Higher temperatures shrank the range of effective interventions and slowed the replacement of wild mosquitoes with Wolbachia-carrying ones. Timing mattered just as much as intensity: releases launched before peak heat allowed Wolbachia to establish at higher levels, before thermal stress eroded its fitness benefits. And success was not permanent--growing year-to-year temperature swings could destabilize Wolbachia populations even after they had become established, threatening long-term disease control. The public-health stakes were stark: Wolbachia cut peak dengue cases by 54.6% at 25{degrees}C, but by only 10% at 30{degrees}C. For the communities most burdened by dengue, these results carry an urgent message. As climate change drives temperatures upward across endemic regions, Wolbachia programs designed without accounting for local thermal conditions risk underperforming precisely where they are needed most. Effective deployment requires climate-sensitive planning, adaptive release schedules, and continued investment in field-validated models that reflect the realities of a warming world.