Abstract Background Metabolic resistance to insecticides is the biggest threat continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful management, remains poorly characterized. Results Here, we demonstrate that single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2 , confers high levels metabolic DDT Anopheles funestus . Genome-wide transcription analysis revealed was most over-expressed detoxification...

Pyrethroid insecticides are critical for malaria control in Africa. However, resistance to this insecticide class the vector Anopheles funestus is spreading rapidly across Africa, threatening success of ongoing and future programs. The underlying mechanisms driving spread wild populations remain largely unknown. Here, we show that increased expression two tandemly duplicated P450 genes, CYP6P9a CYP6P9b , main mechanism pyrethroid Malawi Mozambique, southern African countries where forms...

A cytochrome P450 DNA marker in a major mosquito vector of malaria indicates that pyrethroid resistance reduces bednet efficacy.

Deciphering the dynamics and evolution of insecticide resistance in malaria vectors is crucial for successful vector control. This study reports an increase intensity a rise multiple Anopheles funestus Malawi leading to reduced bed net efficacy. group mosquitoes were collected southern species composition, Plasmodium infection rate, susceptibility insecticides molecular bases analysed. Mosquito collection revealed predominance An. with high hybrid rate (12.2 %) suggesting extensive...

Background Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for management. Here, we report widespread major vector An. funestus across Uganda western Kenya under control metabolic mechanisms. Methodology/Principal Findings Female collected throughout exhibited Plasmodium infection rate between 4.2 to 10.4%. Widespread against both type I (permethrin) II (deltamethrin) pyrethroids DDT was observed Kenya. All...

Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this has a unique origin with same molecular basis or multifactorial. Knowledge of origin, mechanisms and evolution are crucial to designing successful management strategies. Here, we established profile Zambian An. population at northern range front. Similar other African populations, mosquitoes resistant pyrethroids carbamate, but contrast populations...

Despite the recent progress in establishing patterns of insecticide resistance major malaria vector Anopheles funestus, Central African populations this species remain largely uncharacterised. To bridge important gap and facilitate implementation suitable control strategies against vector, we characterised An. funestus population from northern Cameroon.Collection indoor-resting female mosquitoes Gounougou (northern Cameroon) 2012 2015 revealed a predominance during dry season. WHO bioassays...

Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance major vectors such as Anopheles arabiensis is posing a serious challenge success of control. Herein, we elucidated molecular biochemical basis pyrethroid knockdown resistance-free population from Chad, Central Africa. Using heterologous expression P450s Escherichia coli coupled with metabolism assays established that over-expressed P450 CYP6P4,...

Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance pyrethroid insecticides in vectors threatens its continued effectiveness. Deciphering the detailed molecular basis such and designing diagnostic tools is critical implement suitable management strategies. Here, we demonstrated that allelic variation two cytochrome P450 genes most important driver major African vector Anopheles funestus detected key...

Carbamates are increasingly used for vector control notably in areas with pyrethroid resistance. However, a cross-resistance between these insecticides major malaria vectors such as Anopheles funestus could severely limit available resistance management options. Unfortunately, the molecular basis of remains uncharacterized An. funestus, preventing effective management. Here, using genomewide transcription profiling, we revealed that metabolic through upregulation cytochrome P450 genes is...

Cross-resistance to insecticides in multiple resistant malaria vectors is hampering resistance management. Understanding its underlying molecular basis critical implementation of suitable insecticide-based interventions. Here, we established that the tandemly duplicated cytochrome P450s, CYP6P9a/b are driving carbamate and pyrethroid cross-resistance Southern African populations major vector Anopheles funestus . Transcriptome sequencing revealed P450s most over-expressed genes bendiocarb...

Abstract Background Information on common markers of metabolic resistance in malaria vectors from countries sharing similar eco-climatic characteristics can facilitate coordination control. Here, we characterized populations the major vector Anopheles coluzzii Sahel region, spanning four sub-Saharan African countries: Nigeria, Niger, Chad and Cameroon. Results Genome-wide transcriptional analysis identified genes previously implicated pyrethroid and/or cross-resistance to other insecticides,...

Abstract Control of Aedes albopictus , major dengue and chikungunya vector, is threatened by growing cases insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis in Malaysian populations Ae. . Microarray-based transcription profiling revealed that metabolic (cytochrome P450 up-regulation) possibly a reduced penetration mechanism (consistent over-expression cuticular protein genes) were associated with pyrethroid...

Understanding the dynamics of insecticide resistance in African malaria vectors is crucial for successful implementation management strategies continent. This study reports a high and multiple Anopheles funestus from southern Ghana which could compromise Malaria Operational Plan this country, if not tackled. Adult mosquitoes were collected Obuasi Adawukwa, Ghana. Plasmodium infection rates, susceptibility to main insecticides used public health molecular basis established. An. (sensu...

Abstract Metabolic resistance to pyrethroids is a menace the continued effectiveness of malaria vector controls. Its molecular basis complex and varies geographically across Africa. Here, we used multi‐omics approach, followed‐up with functional validation show that directionally selected haplotype cytochrome P450, CYP9K1 major driver in Anopheles funestus . A PoolSeq GWAS using mosquitoes alive dead after permethrin exposure, from Malawi Cameroon, detected candidate genomic regions, but...

Malaria burden is high in Nigeria, yet information on the major mosquito vectors lacking especially Sudan savannah region of country. In order to facilitate design future insecticide-based control interventions region, this study has established resistance profile An. gambiae s.l. populations two northern Nigeria locations and assessed contribution target site mutations.

Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding molecular basis from different regions continent, to establish whether it being driven by a single or independent selective events. Here, using genome-wide transcription profiling pyrethroid resistant populations southern (Malawi),...

Background Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens continued effectiveness of these tools. The molecular basis remains uncharacterised many endemic countries including Malaysia, preventing design evidence-based management. Here, we investigated underlying multiple Ae. aegypti populations across Malaysia detecting major genes driving metabolic resistance. Methodology/Principal...

The scale-up in the distribution of long-lasting insecticidal nets (LLINs) and indoor residual spraying has significantly reduced malaria burden mortality. However, insecticide resistance, among other factors, is responsible for a recent rebound transmission 2015–2016, threatening progress so far made. As contribution towards understanding patterns resistance its mechanism field we characterized population Anopheles gambiae (s.l.) from Gounougou, Guinea savanna north/central Cameroon. Indoor...

Abstract Metabolic resistance to pyrethroids is jeopardizing the effectiveness of insecticide-based interventions against malaria. The complexity Africa-wide spatio-temporal evolution molecular basis this resistance, major genetic drivers should be detected improve management. Here, we demonstrated that a single amino acid change G454A in cytochrome P450 CYP9K1 drives pyrethroid Anopheles funestus vector East and Central Africa. Polymorphism analysis revealed drastic reduction diversity gene...

Abstract Gaining a comprehensive understanding of the genetic mechanisms underlying insecticide resistance in malaria vectors is crucial for optimising effectiveness insecticide-based vector control methods and developing diagnostic tools management. Considering heterogeneity metabolic major vectors, implementation tailored management strategies essential successful control. In this study, we provide evidence demonstrating that two highly selected mutations tandemly duplicated cytochrome...

Pyrethroid resistance in Anopheles funestus is threatening malaria control Africa. Elucidation of underlying mechanisms crucial to improve the success future programs. A positional cloning approach was used identify genes conferring uncharacterised rp2 quantitative trait locus (QTL) previously detected this vector using F6 advanced intercross lines (AIL). 113 kb BAC clone spanning identified and sequenced revealing a cluster 15 P450 one salivary protein gene (SG7-2). Contrary A. gambiae,...

Resistance to pyrethroids (the ingredients in bed net insecticides) the major malaria vector Anopheles funestus is threatening recent gains fight against malaria. Here, we established role of an over-expressed P450, A. CYP6AA1 insecticides resistance. Transcription profiling across Africa using microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that it significantly more southern African populations compared West (Benin) East (Uganda). Heterologous...

Resistance is threatening the effectiveness of insecticide-based interventions in use for malaria control. Pinpointing genes associated with resistance crucial evidence-based management targeting major vectors. Here, a combination RNA-seq based genome-wide transcriptional analysis and RNA-silencing vivo functional validation were used to identify key insecticide DDT DDT/permethrin cross-resistance across Africa. A cluster glutathione-S-transferase from epsilon group found be overexpressed...

To support evidence-based control measures, two Nigerian Aedes populations (BUK and Pantami) were characterised. Larval bioassay using temephos deltamethrin revealed a significant increase in resistance, with LC50 of 0.018mg/L (resistance ratio compared to New Orleans, RR = 2.250) 2018 increasing ~6-fold, by 2019 (LC50 0.100mg/L, 12.5), ~11-fold 2020 0.198mg/L, 24.750). For the median concentration (0.05mg/L), gradual decrease mortality was observed, from 50.6% 2018, 44.9% 2019, 34.2% 2020....