Patterns of Kdr-L995F Allele Emergence Alongside Detoxifying Enzymes Associated with Deltamethrin Resistance in Anopheles gambiae s.l. from North Cameroon.

Josiane Etang,Jean Claude Toto,Abraham Peter Mnzava,Tessa Bellamy Knox,Philippe Nwane,Wolfgang Eyisap Ekoko,Martin James Donnelly,Stanislas Elysée Mandeng,Etienne Fondjo,Narcisse Mvondo,Raymond Tabue,Immo Kleinschmidt,Rémy Mimpfoundi,Lili Ranaise Mbakop,Achille Jerome Binyang,Herman Parfait Awono-Ambene,Michael Piameu,Jude D Bigoga

doi:10.3390/pathogens11020253

Abstract

Understanding how multiple insecticide resistance mechanisms occur in malaria vectors is essential for efficient vector control. This study aimed at assessing the evolution of metabolic mechanisms and Kdr L995F/S resistance alleles in Anopheles gambiae s.l. from North Cameroon, following long-lasting insecticidal nets (LLINs) distribution in 2011. Female An. gambiae s.l. emerging from larvae collected in Ouro-Housso/Kanadi, Be-Centre, and Bala in 2011 and 2015, were tested for susceptibility to deltamethrin + piperonyl butoxide (PBO) or SSS-tributyl-phosphoro-thrithioate (DEF) synergists, using the World Health Organization’s standard protocol. The Kdr L995F/S alleles were genotyped using Hot Ligation Oligonucleotide Assay. Tested mosquitoes identified using PCR-RFLP were composed of An. arabiensis (68.5%), An. coluzzii (25.5%) and An. gambiae (6%) species. From 2011 to 2015, metabolic resistance increased in Ouro-Housso/Kanadi (up to 89.5% mortality to deltametnrin+synergists in 2015 versus <65% in 2011; p < 0.02), while it decreased in Be-Centre and Bala (>95% mortality in 2011 versus 42–94% in 2015; p < 0.001). Conversely, the Kdr L995F allelic frequencies slightly decreased in Ouro-Housso/Kanadi (from 50% to 46%, p > 0.9), while significantly increasing in Be-Centre and Bala (from 0–13% to 18–36%, p < 0.02). These data revealed two evolutionary trends of deltamethrin resistance mechanisms; non-pyrethroid vector control tools should supplement LLINs in North Cameroon.

Highlights

Since the discovery of chemical insecticides, there has been an increasing dependence on synthetic compounds for vector-borne diseases prevention [1], owing to their effectiveness and ease of use
Mosquitoes that were morphologically identified as belonging to the An. gambiae complex and used as control during deltamethrin susceptibility tests were identified down to species using molecular identification PCR-RFLP techniques
In sub-Saharan Africa, three malaria vector species belonging to the An. gambiae complex, namely An. gambiae, An. coluzzii and An. arabiensis are mostly exhibiting multiple insecticide resistance mechanisms

Summary

Introduction

Since the discovery of chemical insecticides, there has been an increasing dependence on synthetic compounds for vector-borne diseases prevention [1], owing to their effectiveness and ease of use. Its mass prevention heavily relies on the use of pyrethroid insecticides in long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) interventions [1,3]. During the last two decades, the rapid scaling-up of LLINs and IRS interventions has largely contributed to the decline of morbidity and mortality related to malaria [4]. 2019, but increased to 232 per 1000 in 2020, mainly because of disruptions to services during the COVID-19 pandemic. Malaria deaths in this region were reduced by 36%, i.e., from

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