An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance.

Benjamin D Menze,Charles S Wondji,Chouaibou S Mouhamadou,Williams Tchapga,Murielle J Wondji,Micareme Tchoupo,Mersimine F Kouamo,Jacob M Riveron,Michael O Kusimo

doi:10.3390/genes11020143

Abstract

Growing insecticide resistance in malaria vectors is threatening the effectiveness of insecticide-based interventions, including Long Lasting Insecticidal Nets (LLINs). However, the impact of metabolic resistance on the effectiveness of these tools remains poorly characterized. Using experimental hut trials and genotyping of a glutathione S-transferase resistance marker (L119F-GSTe2), we established that GST-mediated resistance is reducing the efficacy of LLINs against Anopheles funestus. Hut trials performed in Cameroon revealed that Piperonyl butoxide (PBO)-based nets induced a significantly higher mortality against pyrethroid resistant An. funestus than pyrethroid-only nets. Blood feeding rate and deterrence were significantly higher in all LLINs than control. Genotyping the L119F-GSTe2 mutation revealed that, for permethrin-based nets, 119F-GSTe2 resistant mosquitoes have a greater ability to blood feed than susceptible while the opposite effect is observed for deltamethrin-based nets. For Olyset Plus, a significant association with exophily was observed in resistant mosquitoes (OR = 11.7; p < 0.01). Furthermore, GSTe2-resistant mosquitoes (cone assays) significantly survived with PermaNet 2.0 (OR = 2.1; p < 0.01) and PermaNet 3.0 (side) (OR = 30.1; p < 0.001) but not for Olyset Plus. This study shows that the efficacy of PBO-based nets (e.g., blood feeding inhibition) against pyrethroid resistant malaria vectors could be impacted by other mechanisms including GST-mediated metabolic resistance not affected by the synergistic action of PBO. Mosaic LLINs incorporating a GST inhibitor (diethyl maleate) could help improve their efficacy in areas of GST-mediated resistance.

Highlights

The scale-up of insecticide-based interventions including Long Lasting Insecticidal Nets (LLINs) and Indoor Residual Spraying (IRS) has significantly contributed to the considerable reduction of malaria burden in the past decade [1]
With the design of the L119F-GST epsilon 2 (GSTe2) diagnostic tool [8], this study has investigated for the first time the impact of GST-mediated metabolic resistance on the efficacy of LLINs
This study has revealed a loss of efficacy of LLINs against pyrethroid resistant populations of

Summary

Introduction

The scale-up of insecticide-based interventions including Long Lasting Insecticidal Nets (LLINs) and Indoor Residual Spraying (IRS) has significantly contributed to the considerable reduction of malaria burden in the past decade [1]. Growing insecticide resistance in malaria vectors beside drugs resistance, lack of vaccine and reduced donor funding are threatening these successes. The actual impact of resistance, notably metabolic resistance, on the effectiveness of vector control tools against pyrethroid resistant mosquito populations remains a topic of debate especially when using entomological outcomes. Some studies have suggested that pyrethroid resistance does not yet impact the effectiveness of LLINs [2] whereas others have revealed a negative impact [3]. To help manage resistance, novel LLINs with the piperonyl butoxide (PBO), an insecticide synergist, have been designed by various manufacturers [4,5,6].

Methods

Discussion

Conclusion