Emerging Pyrethroid Resistance among Anopheles arabiensis in Kenya.

Elizabeth Hemming-Schroeder,Daibin Zhong,Guiyun Yan,Amanda Nguyen,Harrysone Atieli,Andrew Githeko,Stephanie Strahl,Eugene Yang,Eugenia Lo

doi:10.4269/ajtmh.17-0445

Elizabeth Hemming-Schroeder, Daibin Zhong + Show 7 more

Open Access

https://doi.org/10.4269/ajtmh.17-0445

Copy DOI

Abstract

.Vector control programs, particularly in the form of insecticide-treated bed nets (ITNs), are essential for achieving malaria elimination goals. Recent reports of increasing knockdown resistance (kdr) mutation frequencies for Anopheles arabiensis in Western Kenya heightens the concern on the future effectiveness of ITNs in Kenya. We examined resistance in An. arabiensis populations across Kenya through kdr mutations and World Health Organization–recommended bioassays. We detected two kdr alleles, L1014F and L1014S. Kdr mutations were found in five of the 11 study sites, with mutation frequencies ranging from 3% to 63%. In two Western Kenya populations, the kdr L1014F allele frequency was as high as 10%. The L1014S frequency was highest at Chulaimbo at 55%. Notably, the kdr L1014F mutation was found to be associated with pyrethroid resistance at Port Victoria, but kdr mutations were not significantly associated with resistance at Chulaimbo, which had the highest kdr mutation frequency among all sites. This study demonstrated the emerging pyrethroid resistance in An. arabiensis and that pyrethroid resistance may be related to kdr mutations. Resistance monitoring and management are urgently needed for this species in Kenya where resistance is emerging and its abundance is becoming predominant. Kdr mutations may serve as a biomarker for pyrethroid resistance in An. arabiensis.

Highlights

Despite intensive malaria control efforts, malaria remains a leading cause of morbidity and mortality in Kenya, especially among younger children and pregnant women.[1]
These findings underscore the importance of the role that An. arabiensis are playing in maintaining residual malaria transmission, and as such, will present a major barrier to malaria control and elimination
Understanding An. arabiensis insecticide resistance mechanisms and monitoring for resistance are essential for achieving malaria elimination goals

Summary

Introduction

Despite intensive malaria control efforts, malaria remains a leading cause of morbidity and mortality in Kenya, especially among younger children and pregnant women.[1]. Pyrethroids are the only approved insecticide for use in ITNs.[6] Its low mammalian toxicity and induction of paralysis using nerve stimulation of dysfunctional sodium channels makes it ideal for ITN usage.[5,7] a single amino acid change at residue position 1014 in the voltage-gated sodium channel (VGSC) gene of insects has made the insecticide increasingly obsolete This mutation has been shown to confer knockdown resistance (kdr) by decreasing sodium channel affinity for the insecticide binding site.[8] The kdr mutations are found as L1014F (kdr-west) and L1014S (kdr-east) in Anopheles gambiae.[9] L1014F refers to a point mutation from leucine to phenylalanine, whereas L1014S represents a mutation from leucine to serine.[9,10] Originally, L1014F was found in Western Africa, leading to its name kdr-west,[11,12,13,14] whereas L1014S (kdr-east) was found in Eastern Africa.[10,15] both mutations are found throughout Africa and have not been solely concentrated geographically, suggesting a shift in kdr mutation frequencies in endemic countries.[16,17,18,19,20] In addition, both kdr mutations have been associated with increased susceptibility to Plasmodium falciparum, further heightening malaria risk in areas with high insecticide resistance.[21]

Objectives

Results

Conclusion