Experimental evolution supports the potential of neonicotinoid-pyrethroid combination for managing insecticide resistance in malaria vectors

Abstract

The introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance of An. gambiae to the separated or combined components of this combination. A field-derived An. gambiae line carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines. This study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation. Clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with those conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was also observed on a P450 gene cluster previously associated with resistance. Within this cluster, the gene CYP6M1 showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure showed that selection retained a protein variant with a modified active site potentially enhancing clothianidin metabolism. In the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.

Mediators of arrested development as attractive malaria vector control tools: The Azadirachta indica and azadirachtin routes

“…Drivers of insecticide resistance depend on geography, population structure, mosquito species, ecological factors, blood feeding choices (Hancock et al, 2020). However, it is reiterated that combination of insecticides are employed to discourage acquisition of resistance (Hancock et al, 2020;Zoh et al 2021).…”

Vector Control Strategies

“…According to the literature, few advances have been made in the development of new insecticides for malaria vector control. In this regard, a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (Fludora Fusion) was recently developed as a new vector control tool, which has been effective in managing resistance [144].…”

Antimalarial and Cytotoxic Activity of Native Plants Used in Cabo Verde Traditional Medicine

“…The emergence of parasites resistant to currently used antimalarials [ 3 ], increasing resistance of vectors to insecticides, and the difficulty in developing efficient vaccines and therapies, underpin the urgent need for new means of malaria control. The current situation is especially alarming due to a convergence of threats, ranging from the COVID-19 and Ebola outbreaks to floods and other humanitarian emergencies, which have led to disruptions in national health service structures and impacted the treatment of several illnesses, including malaria [ 4 ]. Due to the fragility of health systems in several African countries and the limited access to physicians, the search for solutions in traditional medicine has increased considerably for diseases such as malaria [ 5 ].…”