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Comparison of the knockdown resistance locus (kdr) in Anopheles stephensi, An. arabiensis, and Culex pipiens s.l. suggests differing mechanisms of pyrethroid resistance in east Ethiopia (lay summary)

This is a lay summary of the article published under the DOI: 10.1101/2020.05.13.093898

Published onApr 19, 2023
Comparison of the knockdown resistance locus (kdr) in Anopheles stephensi, An. arabiensis, and Culex pipiens s.l. suggests differing mechanisms of pyrethroid resistance in east Ethiopia (lay summary)
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Ethiopian malaria mosquitoes evolved genes to evade deadly insecticides

Two mosquito species that typically spread malaria parasites in Ethiopia are showing signs of becoming resistant to (or evading) some insecticides used to control them.  

Mosquitoes are the so-called vector or carrier of the Plasmodium parasite that causes malaria. In 2018, more than 228 million people worldwide suffered from this disease.

Authorities prefer using one method or strategy to control many disease-causing species, since it is more cost-effective and practical. Using deadly insecticides to kill mosquitos is one such option.

Many insecticides have unfortunately over the years become less effective. This is because the bodies of some insect species, including mosquitoes, have become able to resist and therefore survive some of the key chemicals insecticides contain.

It is important that authorities consider the issue of insecticide resistance in their control plans. To do so, they must know which species are resistant or not to specific products. 

The malaria-causing mosquito species Anopheles stephensi was first noted in 2018 in Ethiopia.

It worried authorities, because this species typically occurs in South Asia and the Middle East. It needed to be controlled, along with the disease-causing mosquito species typically found in Ethiopia.  

A previous study of Anopheles stephensi mosquitoes collected in eastern Ethiopia showed that it was resistant to the chemical known as pyrethroid. This means that indoor sprays and mosquito-repellent insect nets containing pyrethroids may no longer effectively control this species.

No one knew whether mosquitoes that typically carry malaria in Ethiopia, such as Anopheles arabiensis and Culex pipiens, might similarly be resistant to pyrethroids. Researchers from the USA and Ethiopia therefore decided to find out whether this might be the case. 

They therefore used various genetic methods to study Anopheles stephensi, Anopheles arabiensis and Culex pipiens mosquitoes collected in east Ethiopia.

They extracted DNA from each species. Thereafter they sequenced, or determined the primary or basic genetic structure, of a section of the “vgsc” gene. They chose this gene because they already knew that it plays a role in pyrethroid resistance.

They particularly looked at a section called “kdr”, and the stretch of DNA around it. This was because different variations, or mutations, of this section have been found in other resistant species.

They found that, like Anopheles stephensi, the Culex pipiens and Anopheles arabiensis mosquitoes also showed genetic resistance to pyrethroids.

However, this resistance seems to have evolved or developed differently in the three species.

The findings add to the growing list of mosquito species from across the world that show genetic pyrethroid resistance. It increases knowledge about the particular sections of their genes that play a role in how resistance develops to protect these insects against pyrethroids.  

The researchers note that while they are confident in their findings, they did not study mosquitoes from the same life stages. They studied adult mosquitoes of two species (Anopheles arabiensis and Culex pipiens), but only the larvae and pupae of the other (Anopheles stephensi).  

They hope that their study, along with future ones on insecticide resistance, will help authorities to better control malaria-causing mosquitoes. In Ethiopia alone at least 1,5 million cases were reported in 2017. 

Abstract

The malaria vector, Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Controlling the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid resistant and sensitive variants of An. stephensi in east Ethiopia but similar information on other vector species in the same areas is limited. In this study, kdr and the neighboring intron was analyzed in An. stephensi, An. arabiensis, and Culex pipiens s. l. collected in east Ethiopia between 2016 and 2017. Sequence analysis revealed that all of Cx. pipiens s.l. (n = 42) and 71.6% of the An. arabiensis (n=67) carried kdr L1014F known to confer target-site pyrethroid resistance. Intronic variation was only observed in An. stephensi (segregating sites = 6, haplotypes = 3) previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at the An. stephensi kdr intron which further supports target-site mechanism not being a major resistance mechanism in this An. stephensi population. Overall, these results suggest differences in evolved mechanisms of pyrethroid/DDT resistance in populations of vector species from the same region. Variation in insecticide resistance mechanisms in East Ethiopian mosquito vectors highlight possible species or population specific biological factors and distinct environmental exposures that shape their evolution.

Disclaimer

This summary is a free resource intended to make African research and research that affects Africa, more accessible to non-expert global audiences. It was compiled by ScienceLink's team of professional African science communicators as part of the Masakhane MT: Decolonise Science project. ScienceLink has taken every precaution possible during the writing, editing, and fact-checking process to ensure that this summary is easy to read and understand, while accurately reporting on the facts presented in the original research paper. Note, however, that this summary has not been fact-checked or approved by the authors of the original research paper, so this summary should be used as a secondary resource. Therefore, before using, citing or republishing this summary, please verify the information presented with the original authors of the research paper, or email [email protected] for more information.

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Comparison of the knockdown resistance locus (<i>kdr</i>) in<i>Anopheles stephensi</i>,<i>An. arabiensis</i>, and<i>Culex pipiens s.l.</i>suggests differing mechanisms of pyrethroid resistance in east Ethiopia
Description

AbstractThe malaria vector,Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Controlling the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid resistant and sensitive variants ofAn. stephensiin east Ethiopia but similar information on other vector species in the same areas is limited. In this study,kdrand the neighboring intron was analyzed inAn. stephensi,An. arabiensis, andCulex pipiens s. l. collected in east Ethiopia between 2016 and 2017. Sequence analysis revealed that all ofCx. pipiens s.l.(n = 42) and 71.6% of theAn. arabiensis(n=67) carriedkdrL1014F known to confer target-site pyrethroid resistance. Intronic variation was only observed inAn. stephensi(segregating sites = 6, haplotypes = 3) previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at theAn. stephensi kdrintron which further supports target-site mechanism not being a major resistance mechanism in thisAn. stephensipopulation. Overall, these results suggest differences in evolved mechanisms of pyrethroid/DDT resistance in populations of vector species from the same region. Variation in insecticide resistance mechanisms in East Ethiopian mosquito vectors highlight possible species or population specific biological factors and distinct environmental exposures that shape their evolution.

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