Abstract
BACKGROUND: The widespread emergence of insecticide resistance in malaria vectors, particularly Anopheles gambiae, poses a significant challenge to malaria control in sub-Saharan Africa. In Burkina Faso, where pyrethroid resistance is driven by both target-site mutations and enhanced metabolic detoxification, the efficacy of key vector control tools such as insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has declined. In response, alternative non-pyrethroid interventions are being implemented. This study investigated the impact of non-pyrethroid IRS and piperonyl butoxide (PBO)-synergist pyrethroid ITNs on insecticide resistance dynamics in An. gambiae populations in Kampti and Gaoua, southwestern Burkina Faso. METHODS: Anopheles gambiae larvae were collected annually from 2021 to 2023, between the months of August and September. Adult susceptibility to pyrethroids insecticides was assessed using WHO tube assays. Molecular assays were used for species identification within the An. gambiae complex and detection of the kdr mutations. Expression of metabolic resistance genes was quantified using qPCR. KD60 and mortality rates were compared across intervention: during IRS use (2021), after its replacement with PBO-ITNs (2022), and after 2 years of PBO-ITN implementation (2023). RESULTS: Three Anopheles species were identified, 397 An. gambiae sensu stricto (66.17%; 95%CI 62.30-69.80) 149 Anopheles arabiensis (; 24.83%; 95%CI 21.50-28.40) and 54; Anopheles coluzzii (9%; 95CI 6.96-11.60). with An. gambiae being predominant. The L1014F mutation was highly prevalent, while L1014S was undetected. Following the withdrawal of IRS and the introduction of PBO-ITNs in 2022, pyrethroid resistance intensified in Kampti, with reduced mortality to permethrin and alphacypermethrin. PBO pre-exposure partially restored deltamethrin susceptibility in Kampti and fully restored it in Gaoua. By 2023, resistance remained high, particularly to alphacypermethrin, and PBO's synergistic effect diminished. Overexpression of CYP6M2 and CYP6Z1 was consistently observed, suggesting enhanced metabolic resistance. CONCLUSION: The findings indicated that while PBO-ITNs initially improved vector susceptibility to pyrethroids, their efficacy declined over time. This study underscores the dynamic nature of insecticide resistance and highlights the need for sustained resistance monitoring and diversified vector control strategies in high-resistance settings like southwestern Burkina Faso.