Mutations in the voltage-gated sodium channel gene of anophelines and their association with resistance to pyrethroids – a review

Abstract

Constant and extensive use of chemical insecticides has created a selection pressure and favored resistance development in many insect species worldwide. One of the most important pyrethroid resistance mechanisms is classified as target site insensitivity, due to conformational changes in the target site that impair a proper binding of the insecticide molecule. The voltage-gated sodium channel (NaV) is the target of pyrethroids and DDT insecticides, used to control insects of medical, agricultural and veterinary importance, such as anophelines. It has been reported that the presence of a few non-silent point mutations in the NaV gene are associated with pyrethroid resistance, termed as ‘kdr’ (knockdown resistance) for preventing the knockdown effect of these insecticides. The presence of these mutations, as well as their effects, has been thoroughly studied in Anopheles mosquitoes. So far, kdr mutations have already been detected in at least 13 species (Anopheles gambiae, Anopheles arabiensis, Anopheles sinensis, Anopheles stephensi, Anopheles subpictus, Anopheles sacharovi, Anopheles culicifacies, Anopheles sundaicus, Anopheles aconitus, Anopheles vagus, Anopheles paraliae, Anopheles peditaeniatus and Anopheles albimanus) from populations of African, Asian and, more recently, American continents. Seven mutational variants (L1014F, L1014S, L1014C, L1014W, N1013S, N1575Y and V1010L) were described, with the highest prevalence of L1014F, which occurs at the 1014 site in NaV IIS6 domain. The increase of frequency and distribution of kdr mutations clearly shows the importance of this mechanism in the process of pyrethroid resistance. In this sense, several species-specific and highly sensitive methods have been designed in order to genotype individual mosquitoes for kdr in large scale, which may serve as important tolls for monitoring the dynamics of pyrethroid resistance in natural populations. We also briefly discuss investigations concerning the course of Plasmodium infection in kdr individuals. Considering the limitation of insecticides available for employment in public health campaigns and the absence of a vaccine able to brake the life cycle of the malaria parasites, the use of pyrethroids is likely to remain as the main strategy against mosquitoes by either indoor residual spraying (IR) and insecticide treated nets (ITN). Therefore, monitoring insecticide resistance programs is a crucial need in malaria endemic countries.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-3305-7-450) contains supplementary material, which is available to authorized users.

Pyrethroid and DDT Resistance and Organophosphate Susceptibility amongAnophelesspp. Mosquitoes, Western Kenya

“…However, although most studied sites showed sustained low-level transmission, other sites had stable or resurging malaria cases and vector populations ( 2 – 5 ). It is generally believed that the recent resurgence in malaria was caused in part by increased vector resistance to pyrethroid insecticides related to the intensive use of ITNs and IRS ( 6 – 8 ). Insecticide resistance is among the most critical challenges in malaria control.…”

Chromosomal inversions and ecotypic differentiation in Anopheles gambiae: the perspective from whole‐genome sequencing

“…; Silva et al . ; Toe et al . ); thus, it is plausible that they may have been recent targets of positive selection in Bamako.…”

Multiple-Insecticide Resistance and Classic Gene Mutations to Japanese Encephalitis VectorCulex tritaeniorhynchusfrom China

“…Comparisons of partial and complete sequences from 15 susceptible and kdr and kdr-like resistant house fly strains revealed that 2 point mutations (L1014F and/or M918T) were associated with knockdown resistance (Ingles et al 1996, Miyazaki 1996, Williamson 1996. The L1014F substitution has also been reported in many other pyrethroidresistant mosquitoes, including some Anopheles and Culex species (Hemingway et al 2004, Silva et al 2014, Liu 2015.…”