Functional Validation of Endogenous Redox Partner Reveals the Key P450s /- as Broad Substrate Metabolizers Conferring Cross-Resistance to Different Insecticide Classes in .

The versatility of cytochrome P450 reductase () in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using (), as a homologous surrogate, to validate the role of P450s in insecticide resistance.

Gene Conversion Explains Elevated Diversity in the Immunity Modulating Gene of the Malaria Vector .

Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to and other microbial pathogens in mosquitoes. The gene of the malaria vector has exceptional levels of non-synonymous polymorphism across the range of with an average π of 0.027 versus a genome-wide average of 0.

Multi-omics analysis identifies a CYP9K1 haplotype conferring pyrethroid resistance in the malaria vector Anopheles funestus in East Africa.

Metabolic resistance to pyrethroids is a menace to the continued effectiveness of malaria vector controls. Its molecular basis is complex and varies geographically across Africa. Here, we used a multi-omics approach, followed-up with functional validation to show that a directionally selected haplotype of a cytochrome P450, CYP9K1 is a major driver of resistance in Anopheles funestus.

Genome-Wide Transcriptional Analysis and Functional Validation Linked a Cluster of Epsilon Glutathione S-Transferases with Insecticide Resistance in the Major Malaria Vector across Africa.

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

Investigation of DDT resistance mechanisms in Anopheles funestus populations from northern and southern Benin reveals a key role of the GSTe2 gene.

Background: Understanding the molecular basis of insecticide resistance in mosquito, such as Anopheles funestus, is an important step in developing strategies to mitigate the resistance problem. This study aims to assess the role of the GSTe2 gene in DDT resistance and determine the genetic diversity of this gene in An. funestus.

Influence of a Major Mountainous Landscape Barrier (Mount Cameroon) on the Spread of Metabolic () and Target-Site () Resistance Alleles in the African Malaria Vector .

Increased levels of insecticide resistance in major malaria vectors such as threaten the effectiveness of insecticide-based control programmes. Understanding the landscape features impacting the spread of resistance makers is necessary to design suitable resistance management strategies. Here, we examined the influence of the highest mountain in West Africa (Mount Cameroon; 4095 m elevation) on the spread of metabolic and target-site resistance alleles in .

A 6.5-kb intergenic structural variation enhances P450-mediated resistance to pyrethroids in malaria vectors lowering bed net efficacy.

Elucidating the complex evolutionary armory that mosquitoes deploy against insecticides is crucial to maintain the effectiveness of insecticide-based interventions. Here, we deciphered the role of a 6.5-kb structural variation (SV) in driving cytochrome P450-mediated pyrethroid resistance in the malaria vector, Anopheles funestus.

Investigating the molecular basis of multiple insecticide resistance in a major malaria vector Anopheles funestus (sensu stricto) from Akaka-Remo, Ogun State, Nigeria.

Background: Understanding the mechanisms used by Anopheles mosquitoes to survive insecticide exposure is key to manage existing insecticide resistance and develop more suitable insecticide-based malaria vector control interventions as well as other alternative integrated tools. To this regard, the molecular basis of permethrin, DDT and dieldrin resistance in Anopheles funestus (sensu stricto) at Akaka-Remo was investigated.

Methods: Bioassays were conducted on 3-5-day-old adult An.

An Africa-wide genomic evolution of insecticide resistance in the malaria vector Anopheles funestus involves selective sweeps, copy number variations, gene conversion and transposons.

Insecticide resistance in malaria vectors threatens to reverse recent gains in malaria control. Deciphering patterns of gene flow and resistance evolution in malaria vectors is crucial to improving control strategies and preventing malaria resurgence. A genome-wide survey of Anopheles funestus genetic diversity Africa-wide revealed evidences of a major division between southern Africa and elsewhere, associated with different population histories.

Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly -Infected Malaria Vector Sensu Stricto from Sahel of Northern Nigeria.

The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector sensu stricto from Sahel of Nigeria was characterised. s.

An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Reveals a Loss of Bed Nets Efficacy Associated with Metabolic Resistance.

Growing insecticide resistance in malaria vectors is threatening the effectiveness of insecticide-based interventions, including Long Lasting Insecticidal Nets (LLINs). However, the impact of metabolic resistance on the effectiveness of these tools remains poorly characterized. Using experimental hut trials and genotyping of a glutathione S-transferase resistance marker (L119F-), we established that GST-mediated resistance is reducing the efficacy of LLINs against .

Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus.

Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa.

A marker of glutathione S-transferase-mediated resistance to insecticides is associated with higher Plasmodium infection in the African malaria vector Anopheles funestus.

Metabolic resistance to insecticides is threatening malaria control in Africa. However, the extent to which it impacts malaria transmission remains unclear. Here, we investigated the association between a marker of glutathione S-transferase mediated metabolic resistance and Plasmodium infection in field population of Anopheles funestus s.

Escalation of Pyrethroid Resistance in the Malaria Vector Anopheles funestus Induces a Loss of Efficacy of Piperonyl Butoxide-Based Insecticide-Treated Nets in Mozambique.

Background: Insecticide resistance poses a serious threat to insecticide-based interventions in Africa. There is a fear that resistance escalation could jeopardize malaria control efforts. Monitoring of cases of aggravation of resistance intensity and its impact on the efficacy of control tools is crucial to predict consequences of resistance.

A cytochrome P450 allele confers pyrethroid resistance on a major African malaria vector, reducing insecticide-treated bednet efficacy.

Metabolic resistance to insecticides such as pyrethroids in mosquito vectors threatens control of malaria in Africa. Unless it is managed, recent gains in reducing malaria transmission could be lost. To improve monitoring and assess the impact of insecticide resistance on malaria control interventions, we elucidated the molecular basis of pyrethroid resistance in the major African malaria vector, We showed that a single cytochrome P450 allele (_R) in reduced the efficacy of insecticide-treated bednets for preventing transmission of malaria in southern Africa.

Exposure to the insecticide-treated bednet PermaNet 2.0 reduces the longevity of the wild African malaria vector Anopheles funestus but GSTe2-resistant mosquitoes live longer.

Background: Despite the increased report of insecticide resistance in malaria vectors, its impact on mosquito's life-traits after exposure to insecticide-treated nets remains under investigated. Here, we assessed the effects of exposure to PermaNet 2.0 on several life traits of An.

Contrasting patterns of gene expression indicate differing pyrethroid resistance mechanisms across the range of the New World malaria vector Anopheles albimanus.

Decades of unmanaged insecticide use and routine exposure to agrochemicals have left many populations of malaria vectors in the Americas resistant to multiple classes of insecticides, including pyrethroids. The molecular basis of pyrethroid resistance is relatively uncharacterised in American malaria vectors, preventing the design of suitable resistance management strategies. Using whole transcriptome sequencing, we characterized the mechanisms of pyrethroid resistance in Anopheles albimanus from Peru and Guatemala.

Fitness Costs of the Glutathione -Transferase Epsilon 2 (L119F-GSTe2) Mediated Metabolic Resistance to Insecticides in the Major African Malaria Vector .

Metabolic resistance to insecticides threatens malaria control. However, little is known about its fitness cost in field populations of malaria vectors, thus limiting the design of suitable resistance management strategies. Here, we assessed the association between the glutathione -transferase GSTe2-mediated metabolic resistance and life-traits of natural populations of .

Exploring insecticide resistance mechanisms in three major malaria vectors from Bangui in Central African Republic.

Malaria remains the main cause of mortality and morbidity in the Central African Republic. However, the main malaria vectors remain poorly characterised, preventing the design of suitable control strategies. Here, we characterised the patterns and mechanisms of insecticide resistance in three important vectors from Bangui.

Experimental huts trial of the efficacy of pyrethroids/piperonyl butoxide (PBO) net treatments for controlling multi-resistant populations of in Kpomè, Southern Benin.

Insecticides resistance in mosquitoes limits Long-Lasting Insecticidal Nets (LLIN) used for malaria control in Africa, especially Benin. This study aimed to evaluate the bio-efficacy of current LLINs in an area where and have developed multi-resistance to insecticides, and to assess in experimental huts the performance of a mixed combination of pyrethroids and piperonyl butoxide (PBO) treated nets on these resistant mosquitoes. The study was conducted at Kpomè, Southern Benin.

Bionomics and insecticides resistance profiling of malaria vectors at a selected site for experimental hut trials in central Cameroon.

Background: Malaria vectors are increasingly developing resistance to insecticides across Africa. The impact of such resistance on the continued effectiveness of insecticide-based interventions remains unclear due to poor characterization of vector populations. This study reports the characterization of malaria vectors at Mibellon, a selected site in Cameroon for experimental hut study, including species composition, Plasmodium infection rate, resistance profiles and mechanisms.

Bionomics and vectorial role of anophelines in wetlands along the volcanic chain of Cameroon.

Background: The epidemiological profiles of vector-borne diseases, such as malaria, are strongly associated with landscape components. The reduction of malaria burden in endemic and epidemic regions mainly depends on knowledge of the malaria-transmitting mosquito species, populations and behavioural characteristics, as well as malaria exposure risks. This work aimed at carrying out a holistic study in order to characterise Anopheles species in relation to human malaria in seven wetlands along the lower section of the volcanic chain of Cameroon.

Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa.

Resistance to pyrethroids (the ingredients in bed net insecticides) in the major malaria vector Anopheles funestus is threatening recent gains in the fight against malaria. Here, we established the role of an over-expressed P450, A. funestus CYP6AA1 in insecticides resistance.

High Plasmodium Infection Rate and Reduced Bed Net Efficacy in Multiple Insecticide-Resistant Malaria Vectors in Kinshasa, Democratic Republic of Congo.

Accounting for approximately 11% of all malaria cases, the Democratic Republic of the Congo (DRC) is central to malaria elimination efforts. To support vector control interventions in DRC, we characterized the dynamics and impact of insecticide resistance in major malaria vectors in 2015. High Plasmodium infection rates were recorded in Anopheles gambiae and Anopheles funestus, with Plasmodium falciparum predominant over Plasmodium malariae.