Dynamics of pyrethroid resistance in malaria vectors in southern Benin following a large scale implementation of vector control interventions.

Gildas A Yahouédo,Vincent Corbel,Sylvie Cornelie,Sidick Aboubakar,Justine Ahlonsou,Martin Akogbéto,Christophe Soares,Innocent Djègbè

doi:10.1186/s13071-016-1661-8

Abstract

BackgroundLarge-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014. The purpose of this study was to monitor the frequency and mechanisms of pyrethroid resistance in malaria vectors following the implementation of vector control tools for malaria prevention.MethodsAnopheles larvae were collected in 13 villages twice a year from 2012 to 2014. WHO tube tests were used to assess the phenotypic resistance of each population to 0.05 % deltamethrin. Sibling species within Anopheles gambiae complex were identified by PCR techniques. Taqman and biochemical assays were performed to identify the presence of kdr mutations in individual mosquitoes and to detect any increase in the activity of enzymes putatively involved in insecticide metabolism (oxidases, esterase and glutathione-S-transferases). Quantitative real time PCR was used to measure the expression of three metabolic genes involved in pyrethroid resistance (CYP6P3, CYP6M2 and GSTD3).ResultsAnopheles populations showed < 90 % mortality to deltamethrin in all villages and at all time points. The 1014 F kdr allele frequency was close to fixation (> 0.9) over the sampling periods in both An. gambiae and An. coluzzii. Biochemical assays showed higher activities of alpha esterase and GST in field malaria vector populations compared to susceptible mosquitoes. qPCR assays showed a significant increase of CYP6P3, CYP6M2 GSTD3 expression in An. gambiae after a three-year implementation of LLINs.ConclusionThe study confirmed that deltamethrin resistance is widespread in malaria vectors in Southern Benin. We suspect that the increase in deltamethrin resistance between 2012 and 2014 resulted from an increased expression of metabolic detoxification genes (CYP6M2 and CYP6P3) rather than from kdr mutations. It is urgent to evaluate further the impact of metabolic resistance on the efficacy of vector control interventions using pyrethroid insecticides.

Highlights

Large-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014
Global malaria vector control efforts rely on the use of Long Lasting Insecticide Nets (LLINs) and Indoor Residual Spraying (IRS)
Twelve insecticides belonging to four chemical classes are approved by the World Health Organization (WHO) for malaria vector control

Summary

Introduction

Large-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014. The second resistance mechanism is called “metabolic” through higher catalytic properties and/or overexpression of carboxylesterases (COEs), cytochrome P450 mono-oxygenases (P450s) and Glutathione S-Transferases (GSTs) [5] Some members of these families such as CYP6M2, CYP6Z2, CYP6P3 are known to contribute to pyrethroid detoxification in Anopheles mosquitoes [6]. Both metabolic and target site (kdr) resistance are present west Africa [7] and Benin [8] and are suspected to reduce the efficacy of vector control intervention [9, 10]

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