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MUTATIONS IN THE VOLTAGE-GATED SODIUM CHANNEL GENE OF ANOPHELINES AND THEIR ASSOCIATION WITH RESISTANCE TO PYRETHROIDS – A REVIEW
Afiliación
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Malária e Dengue. Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Malária e Dengue. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil / 3Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil..
Instituto Nacional de Pesquisas da Amazônia. Laboratório de Malária e Dengue. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil / 3Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil..
Resumen en ingles
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.
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