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Title: Mutations in the voltage-gated sodium channel gene of anophelines and their association with resistance to pyrethroids - A review
Authors: Silva, Ana Paula B.
Santos, Joselita Maria M.
J, Martins, Ademir
Keywords: Pyrethroid
Voltage Gated Sodium Channel
Sodium Channel
Anopheles Aconitus
Anopheles Albimanus
Anopheles Arabiensis
Anopheles Culicifacies
Anopheles Gambiae
Anopheles Paraliae
Anopheles Peditaeniatus
Anopheles Sacharovi
Anopheles Sinensis
Anopheles Stephensi
Anopheles Subpictus
Anopheles Sundaicus
Anopheles Vagus
Gene Expression
Genetic Association
Genetic Variability
Indoor Residual Spraying
Insecticide Resistance
Insecticide Treated Net
Kdr Gene
Life Cycle Stages
Nav Gene
Plasmodium Berghei
Plasmodium Falciparum
Point Mutation
Population Dynamics
Amino Acid Substitution
Disease Carrier
Drug Effects
Gene Frequency
Insecticide Resistance
Point Mutation
Amino Acid Substitution
Gene Frequency
Insect Vectors
Insecticide Resistance
Point Mutation
Sodium Channels
Issue Date: 2014
metadata.dc.publisher.journal: Parasites and Vectors
metadata.dc.relation.ispartof: Volume 7, Número 1
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. © 2014 Silva et al.; licensee BioMed Central Ltd.
metadata.dc.identifier.doi: 10.1186/1756-3305-7-450
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