The long-term persistence of wMel strain in Aedes aegypti is threatened by multiple concomitant factors

Background Wolbachia symbionts introduced into Aedes aegypti provide an effective strategy to mitigate dengue virus transmission and has been increasingly utilized in endemic settings. Deployments in Rio finished in December 2019 with a suboptimal 32% introgression of wMel strain, resulteing in 38% and 10% reduction of dengue and chikungunya, respectively.Methods We conducted a multidisciplinary independent evaluation of wMel during 20 consecutive months starting August 2021 to evaluate whether its distribution would expand or retract. We used 75 BG-Sentinel traps distributed in 12 neighborhoods with estimated 500,000 inhabitants. We collected more than 50,000 mosquitoes and a subset of Ae. aegypti were screened individually for wMel presence. Culex spp., climate, environmental and insecticide application data was used to model the spatiotemporal introgression of wMel.Findings The routine insecticide rotation adopted by the Brazilian Ministry of Health replaced the analogue of juvenile hormone (pyriproxyfen) by the bioinsecticide spinosad. This change in the larvicide crashed both wMel-infected and -uninfected populations shortly after an increase in coverage with spinosad. However, the wMel-uninfected mosquitoes recovered soon to levels even higher than before, whereas the wMel-infected failed to recover after the population crash. The well documented fitness cost of wMel in egg hatching leads to the absence of an egg bank necessary to recover after adult population was disrupted. Finally, we observed a Wolbachia loss of 24.56% in field-caught mosquitoes.Interpretation The reason underlying the poor introgression of Wolbachia wMel strain is multifold. The adoption of an effective larvicide that crashed both wMel-infected and -uninfected populations, the absence of an egg bank due to high fitness cost of egg hatching in the wMel-infected mosquitoes, and a Wolbachia loss contribute to the lower invasion and, by corollary, modest epidemiological outcome in Rio de Janeiro. It becomes essential to implement technical guidance on Integrated Vector Management in Brazil prior the nationwide release of Wolbachia-infected mosquitoes in order to optimize dengue mitigation efforts while ensuring the judicious use of resources.