Malaria and Dengue Mosquito Vectors from Lao PDR Show a Lack of the rdl Mutant Allele Responsible for Cyclodiene Insecticide Resistance

Abstract

The gamma-aminobutyric acid (GABA) receptor, RDL, plays important roles in neuronal signaling and is the target of highly effective insecticides. A mutation in RDL, commonly A296S, underlies resistance to several insecticides such as cyclodienes. Even though the use of cyclodienes has been banned, the occurrence of mutations substituting A296 is notably high in mosquitoes from several countries. Here, we report a survey investigating the prevalence of the Rdl mutant allele in mosquitoes from Laos, a country where mosquito-borne diseases such as malaria and dengue fever are health concerns. Anopheles and Aedes mosquitoes were collected from 12 provinces in Laos. Adult bioassays on Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) showed that all the populations tested were susceptible to dieldrin (4%) following WHO protocols. Exon 7 from a total of 791 mosquitoes was sequenced to identify the amino acid encoded for at 296 of RDL. Only one of these mosquitoes, Anopheles maculatus rampae Harbach and Somboon (Diptera: Culicidae) from Attapeu, carried the mutant allele being heterozygous for A296S. We therefore found a general lack of the Rdl mutant allele indicating that mosquitoes from Laos are not exposed to insecticides that act on the GABA receptor compared to mosquitoes in several other countries. Identifying the prevalence of the Rdl mutation may help inform the potential use of alternative insecticides that act on the GABA receptor should there be a need to replace pyrethroids in order to prevent/manage resistance.

Population genomics reveal distinct and diverging populations of An. minimus in Cambodia

“…Variants occurring at a frequency of more than 2% in at least one of the four populations are reported in the known insecticide-resistance-associated genes Ace1 , Rdl , KDR , and GSTe2 (Supplementary Data 2 ). GSTe2 mutants are present in multiple populations, at a low rate, and there are a few individuals in Thmar Da and Preah Vihear with the Rdl resistance mutation, which is known to confer resistance to cyclodiene insecticides, despite evidence from other studies that species in this region lack this resistance mutation 32 . We did not investigate copy number variation, which is one mechanism by which GSTe2 confers insecticide resistance.…”

Detection of pyrethroid resistance mutations and intron variants in the voltage‐gated sodium channel of Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus mosquitoes from Lao People's Democratic Republic

“…gambiae, which are showing resistance to pyrethroids (Ngufor et al, 2017). A similar strategy could be used for insecticides that act on γ-aminobutyric acid (GABA) receptors, such as fipronil, especially considering that it has been shown that Aedes mosquitoes in Laos lack a mutation at A296 in the GABA receptor, resistance to dieldrin (RDL), which underlies insecticide resistance (Marcombe et al, 2020).…”

“…gambiae , which are showing resistance to pyrethroids (Ngufor et al, 2017 ). A similar strategy could be used for insecticides that act on γ‐aminobutyric acid (GABA) receptors, such as fipronil, especially considering that it has been shown that Aedes mosquitoes in Laos lack a mutation at A296 in the GABA receptor, resistance to dieldrin (RDL), which underlies insecticide resistance (Marcombe et al, 2020 ). A combination of fipronil and permethrin has been shown to provide highly effective inhibition of feeding as well as considerable insecticidal efficacy against Aedes mosquitoes on dogs for at least four weeks, which may aid in the control of mosquitoes in the vicinity of treated domesticated animals (Fankhauser et al, 2015 ).…”

Population genomics reveal distinct and diverging populations of An. minimus in Cambodia – a widespread malaria vector in Southeast Asia

“…Variants occurring at a frequency of more than 2% in at least one of the four populations are reported in the known insecticide-resistance associated genes Ace1, Rdl, KDR, and GSTe2 (Supplementary Table 2). GSTe2 mutants are present in multiple populations, at a low rate, and there are a few individuals in Thmar Da and Preah Vihear with the Rdl resistance mutation, which is known to confer resistance to cyclodiene insecticides, despite evidence from other studies that species in this region lack this resistance mutation (32). We did not investigate copy number variation, which is one mechanism by which GSTe2 confers insecticide resistance.…”