Absence of knockdown mutations in pyrethroid and DDT resistant populations of the main malaria vectors in Colombia

Abstract Background Knockdown resistance (kdr) is a well-characterized target-site insecticide resistance mechanism that is associated with DDT and pyrethroid resistance. Even though insecticide resistance to pyrethroids and DDT have been reported in Anopheles albimanus, Anopheles benarrochi sensu lato (s.l.), Anopheles darlingi, Anopheles nuneztovari s.l., and Anopheles pseudopunctipennis s.l. malaria vectors in Latin America, there is a knowledge gap on the role that kdr resistance mechanisms play in this resistance. The aim of this study was to establish the role that kdr mechanisms play in pyrethroid and DDT resistance in the main malaria vectors in Colombia, in addition to previously reported metabolic resistance mechanisms, such as mixed function oxidases (MFO) and nonspecific esterases (NSE) enzyme families. Methods Surviving (n = 62) and dead (n = 67) An. nuneztovari s.l., An. darlingi and An. albimanus mosquitoes exposed to diagnostic concentrations of DDT and pyrethroid insecticides were used to amplify and sequence a ~ 225 bp fragment of the voltage-gated sodium channels (VGSC) gene. This fragment spanning codons 1010, 1013 and 1014 at the S6 segment of domain II to identify point mutations, which have been associated with insecticide resistance in different species of Anopheles malaria vectors. Results No kdr mutations were detected in the coding sequence of this fragment in 129 samples, 62 surviving mosquitoes and 67 dead mosquitoes, of An. darlingi, An. nuneztovari s.l. and An. albimanus. Conclusion Mutations in the VGSC gene, most frequently reported in other species of the genus Anopheles resistant to pyrethroid and DDT, are not associated with the low-intensity resistance detected to these insecticides in some populations of the main malaria vectors in Colombia. These results suggest that metabolic resistance mechanisms previously reported in these populations might be responsible for the resistance observed.

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Genome-wide gene expression profiling reveals that cuticle alterations and P450 detoxification are associated with pyrethroid resistance in Anopheles arabiensis populations from Ethiopia

10.1101/451336 ◽

2018 ◽

Author(s):

Eba Alemayehu Simma ◽

Wannes Dermauw ◽

Vasileia Balabanidou ◽

Simon Snoeck ◽

Astrid Bryon ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Arabiensis ◽

Pyrethroid Resistance ◽

Resistance Mutation ◽

Resistance Mechanisms ◽

Target Site ◽

Malaria Vectors ◽

Metabolic Resistance ◽

Genome Wide ◽

Target Site Resistance

AbstractBACKGROUNDVector control is the main intervention in malaria control and elimination strategies. However, the development of insecticide resistance is one of the major challenges for controlling malaria vectors. Anopheles arabiensis populations in Ethiopia showed resistance against both DDT and the pyrethroid deltamethrin. Although a L1014F target-site resistance mutation was present in the voltage gated sodium channel of investigated populations, the levels of resistance and biochemical studies indicated the presence of additional resistance mechanisms. In this study, we used genome-wide transcriptome profiling by RNAseq to assess differentially expressed genes between three deltamethrin and DDT resistant An. arabiensis field populations (Tolay, Asendabo, Chewaka) and two susceptible strains (Sekoru and Mozambique).RESULTSBoth RNAseq analysis and RT-qPCR showed that a glutathione-S-transferase, gstd3, and a cytochrome P450 monooxygenase, cyp6p4, were significantly overexpressed in the group of resistant populations compared to the susceptible strains, suggesting that the enzymes they encode play a key role in metabolic resistance against deltamethrin or DDT. Furthermore, a gene ontology enrichment analysis showed that expression changes of cuticle related genes were strongly associated with insecticide resistance, although this did not translate in increased thickness of the procuticle.CONCLUSIONOur transcriptome sequencing of deltamethrin/DDT resistant An. arabiensis populations from Ethiopia suggests non-target site resistance mechanisms and pave the way for further investigation of the role of cuticle composition in resistance.

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Insecticide resistance status of Aedes aegypti in Bangladesh

Parasites & Vectors ◽

10.1186/s13071-020-04503-6 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Hasan Mohammad Al-Amin ◽

Fatema Tuj Johora ◽

Seth R. Irish ◽

Muhammad Riadul Haque Hossainey ◽

Lucrecia Vizcaino ◽

...

Keyword(s):

Aedes Aegypti ◽

Insecticide Resistance ◽

Pyrethroid Resistance ◽

Control Strategies ◽

Resistance Mechanisms ◽

Capital City ◽

Detoxification Enzymes ◽

Knockdown Resistance ◽

Metabolic Resistance ◽

Pyrethroid Insecticides

Abstract Background Arboviral diseases, including dengue and chikungunya, are major public health concerns in Bangladesh where there have been unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is to control the vector Aedes aegypti using pyrethroid insecticides. Although chemical control has long been practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has been conducted to date. The aim of this study was to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms. Methods Eggs of Aedes mosquitoes were collected using ovitraps from five districts across Bangladesh and in eight neighborhoods of the capital city Dhaka, from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3- to 5-day-old F0–F2 non-blood-fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms, and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410. Results High levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 to 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2×) doses of permethrin (5.1–44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr (knockdown resistance) alleles varied across the Dhaka Aedes populations. Leu410 was not detected in any of the tested populations. Conclusions The detection of widespread pyrethroid resistance and multiple resistance mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.

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Insecticide resistance status of Aedes aegypti in Bangladesh

10.1101/2020.07.31.231076 ◽

2020 ◽

Author(s):

Hasan Mohammad Al-Amin ◽

Fatema Tuj Johora ◽

Seth R. Irish ◽

Muhammad Riadul Haque Hossainey ◽

Lucrecia Vizcaino ◽

...

Keyword(s):

Aedes Aegypti ◽

Insecticide Resistance ◽

Pyrethroid Resistance ◽

Control Strategies ◽

Resistance Mechanisms ◽

Capital City ◽

Detoxification Enzymes ◽

Health Concern ◽

Metabolic Resistance ◽

Pyrethroid Insecticides

AbstractBackgroundArboviral diseases including dengue and chikungunya are major public health concern in Bangladesh, with unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is control of Aedes aegypti using pyrethroid insecticides. Although chemical control is long-practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has previously been conducted. This study aimed to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms.MethodsAedes eggs were collected using ovitraps from five districts across the country and in eight neighborhoods of the capital city Dhaka from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3-5-day old F0-F2 non-blood fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410.ResultsHigh levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 – 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2X) doses of permethrin (5.1 – 44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr alleles varied across the Dhaka populations, and Leu410 was not detected in any of the tested populations.ConclusionsThe detection of widespread pyrethroid resistance and multiple mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.

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Insecticide resistance in Anopheles stephensi in Somali Region, eastern Ethiopia

10.21203/rs.2.18020/v3 ◽

2020 ◽

Author(s):

Solomon Yared ◽

Araya Gebressielasie ◽

Lambodhar Damodaran ◽

Victoria Bonnell ◽

Karen Lopez ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Stephensi ◽

Mortality Rates ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Resistance Locus ◽

Eastern Ethiopia ◽

Pyrethroid Insecticides ◽

Pirimiphos Methyl

Abstract Background The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi; and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods Mosquito larvae and pupae were collected from Kebri Dehar. Insecticide susceptibility of An. stephensi was tested withmalathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. In this study, the knockdown resistance locus (kdr) in the voltage gated sodium channel (vgsc) and ace1R locus in the acetylcholinesterase gene (ace-1) were analysed in An. stephensi. Results All An. stephensi samples were resistant to carbamates, with mortality rates of 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the insecticide resistance loci revealed the absence of kdr L1014F and L1014S mutations and the ace1R G119S mutation. Conclusion Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

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Insecticide Resistance in Anopheles stephensi in Somali Region, Eastern Ethiopia

10.21203/rs.2.18020/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Solomon Yared ◽

Araya Gebressielasie ◽

Lambodhar Damodaran ◽

Victoria Bonnell ◽

Karen Lopez ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Stephensi ◽

Mortality Rates ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Eastern Ethiopia ◽

Pyrethroid Insecticides ◽

Pirimiphos Methyl ◽

Health Organization

Abstract Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebridehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. Results: All An. stephensi samples were resistant to carbamates, with mortality rates 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the voltage gate sodium channel gene (vgsc) revealed the absence of kdr L1014 mutations. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

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Resistance of Australian Helicoverpa armigera to fenvalerate is due to the chimeric P450 enzyme CYP337B3

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1202047109 ◽

2012 ◽

Vol 109 (38) ◽

pp. 15206-15211 ◽

Cited By ~ 96

Author(s):

Nicole Joußen ◽

Sara Agnolet ◽

Sybille Lorenz ◽

Sebastian E. Schöne ◽

Renate Ellinger ◽

...

Keyword(s):

Helicoverpa Armigera ◽

Pyrethroid Resistance ◽

Resistance Mechanism ◽

Metabolic Resistance ◽

P450 Monooxygenase ◽

Pyrethroid Insecticides ◽

Wide Range ◽

P450 Enzyme ◽

Helicoverpa Armígera ◽

Genetic Mechanisms

Worldwide, increasing numbers of insects have evolved resistance to a wide range of pesticides, which hampers their control in the field and, therefore, threatens agriculture. Members of the carboxylesterase and cytochrome P450 monooxygenase superfamilies are prominent candidates to confer metabolic resistance to pyrethroid insecticides. Both carboxylesterases and P450 enzymes have been shown to be involved in pyrethroid resistance in Australian Helicoverpa armigera, the noctuid species possessing by far the most reported resistance cases worldwide. However, specific enzymes responsible for pyrethroid resistance in field populations of this species have not yet been identified. Here, we show that the resistance toward fenvalerate in an Australian strain of H. armigera is due to a unique P450 enzyme, CYP337B3, which arose from unequal crossing-over between two parental P450 genes, resulting in a chimeric enzyme. CYP337B3 is capable of metabolizing fenvalerate into 4′-hydroxyfenvalerate, which exhibits no toxic effect on susceptible larvae; enzymes from the parental P450 genes showed no detectable fenvalerate metabolism. Furthermore, a polymorphic H. armigera strain could be bred into a susceptible line possessing the parental genes CYP337B1 and CYP337B2 and a resistant line possessing only CYP337B3. The exclusive presence of CYP337B3 in resistant insects of this strain confers a 42-fold resistance to fenvalerate. Thus, in addition to previously documented genetic mechanisms of resistance, recombination can also generate selectively advantageous variants, such as this chimeric P450 enzyme with an altered substrate specificity leading to a potent resistance mechanism.

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CYP6P9-Driven Signatures of Selective Sweep of Metabolic Resistance to Pyrethroids in the Malaria Vector Anopheles funestus Reveal Contemporary Barriers to Gene Flow

Genes ◽

10.3390/genes11111314 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1314

Author(s):

Delia Doreen Djuicy ◽

Jack Hearn ◽

Magellan Tchouakui ◽

Murielle J. Wondji ◽

Helen Irving ◽

...

Keyword(s):

Gene Flow ◽

Selective Sweep ◽

Pyrethroid Resistance ◽

Resistance Mechanism ◽

Anopheles Funestus ◽

Central Africa ◽

Eastern Africa ◽

Malaria Vectors ◽

Metabolic Resistance ◽

Diversity Pattern

Pyrethroid resistance in major malaria vectors such as Anopheles funestus threatens malaria control efforts in Africa. Cytochrome P450-mediated metabolic resistance is best understood for CYP6P9 genes in southern Africa in An. funestus. However, we do not know if this resistance mechanism is spreading across Africa and how it relates to broader patterns of gene flow across the continent. Nucleotide diversity of the CYP6P9a gene and the diversity pattern of five gene fragments spanning a region of 120 kb around the CYP6P9a gene were surveyed in mosquitoes from southern, eastern and central Africa. These analyses revealed that a Cyp6P9a resistance-associated allele has swept through southern and eastern Africa and is now fixed in these regions. A similar diversity profile was observed when analysing genomic regions located 34 kb upstream to 86 kb downstream of the CYP6P9a locus, concordant with a selective sweep throughout the rp1 locus. We identify reduced gene flow between southern/eastern Africa and central Africa, which we hypothesise is due to the Great Rift Valley. These potential barriers to gene flow are likely to prevent or slow the spread of CYP6P9-based resistance mechanism to other parts of Africa and would to be considered in future vector control interventions such as gene drive.

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Molecular Insight into the Knockdown Resistance (kdr) in the Voltage Gated Sodium Channel (vgsc) Gene of the Main Dengue Vector, Aedes aegypti (Diptera: Culicidae) and the Discovery of Novel Regional Specific Point Mutation A1007G in Malaysia.

10.21203/rs.3.rs-102568/v2 ◽

2021 ◽

Author(s):

Mas Azlin M. Akhir ◽

Mustafa F. F. Wajidi ◽

Sébastien Lavoué ◽

Ghows Azzam ◽

Izhan Shahrin Jaafar ◽

...

Keyword(s):

Insecticide Resistance ◽

Sodium Channel ◽

Vector Control ◽

Resistance Mechanism ◽

Point Mutations ◽

Voltage Gated Sodium Channel ◽

Pyrethroid Insecticides ◽

Voltage Gated ◽

Control Programmes ◽

Pirimiphos Methyl

Abstract Background: Characterization of the insecticide resistance mechanism imparts the society with the information on the evolutionary process involved in the adaptation of Aedes aegypti mosquito to environmental changes. Investigating the phenotypic status of the target mosquitoes, their resistance level as well as elucidating the genotypic profile provides information about the involvement of insecticide resistance mechanism, in terms of portraying the evolution of resistance in the field, to eventually managing vector control programmes. In this current study, we investigated the quantification responses for the phenotypic and genotypic resistance of Ae. aegypti population from different states in Malaysia. Methods: We tested insecticide susceptibility status of adult Ae. aegypti from populations of States of Penang, Selangor and Kelantan (Peninsular Malaysia) against 0.25% permethrin and 0.25% pirimiphos-methyl through WHO bioassay kit. Permethrin-resistant and permethrin susceptible samples were then genotyped for domains II and III in the voltage gated sodium channel (vgsc) gene using allele specific PCR (AS-PCR) for the presence of diagnostic single nucleotide mutations. AS-PCR results were then validated in sequencing these two domains to identify any possible additional point mutations. Results: Adult WHO bioassay revealed that populations of Ae. aegypti from these three states were highly resistant towards 0.25% permethrin and 0.25% pirimiphos-methyl. Genotyping results showed that three knockdown (kdr) mutations (i.e. S989P, V1016G and F1534C) were associated with pyrethroid resistance in these populations. We also report for the first time the presence of the A1007G mutation in Malaysian populations of Ae. aegypti.Conclusions: This study brings an insight on the occurrence and association of point mutations with insecticide resistance in Malaysian populations of Ae. aegypti. The results reveal the widespread of several kdr mutations in the field with the consequence to compromise the use of pyrethroid insecticides in vector control programmes. Knowledge on the distribution of target site resistance throughout Malaysia is vital to ensure the success of the insecticide-based vector control programme.

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Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for anti-malarial intervention deployment

10.1101/2021.02.11.429702 ◽

2021 ◽

Author(s):

Harun Njoroge ◽

Arjen van’t Hof ◽

Ambrose Oruni ◽

Dimitra Pipini ◽

Sanjay C. Nagi ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Gambiae ◽

Pyrethroid Resistance ◽

Border Region ◽

Malaria Vectors ◽

Molecular Diagnostic ◽

Triple Mutant ◽

Pyrethroid Insecticides ◽

High Level ◽

Mutant Haplotype

AbstractInsecticide resistance provides both an increasingly pressing threat to the control of vector-borne diseases and insights into the remarkable capacity of natural populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on deployment of pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs), but resistance in the major malaria vectors has increased over the last 15 years in concert with dramatic expansion of LLIN distributions. Identifying genetic mechanisms underlying high-level resistance in mosquitoes, which may almost entirely overcome pyrethroid efficacy, is crucial for the development and deployment of potentially resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes, including some commonly implicated in resistance. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar-like transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border region around Lake Victoria, with stepwise replacement of the double-mutant (Zanzibar-like TE and Cyp6p4-236M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolise pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin, a commonly-used LLIN insecticide. Importantly, there was increased mortality in mosquitoes carrying the triple-mutation when exposed to nets co-treated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid co-treated LLINs across African countries. Duplications of the Cyp6aa1 gene are common in An. gambiae across Africa and, given the enzymes metabolic activity, are likely to be a useful diagnostic for high levels of pyrethroid resistance.

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

Science Translational Medicine ◽

10.1126/scitranslmed.aat7386 ◽

2019 ◽

Vol 11 (484) ◽

pp. eaat7386 ◽

Cited By ~ 32

Author(s):

Gareth D. Weedall ◽

Leon M. J. Mugenzi ◽

Benjamin D. Menze ◽

Magellan Tchouakui ◽

Sulaiman S. Ibrahim ◽

...

Keyword(s):

Cytochrome P450 ◽

Insecticide Resistance ◽

Malaria Vector ◽

Southern Africa ◽

Malaria Control ◽

Pyrethroid Resistance ◽

Mosquito Vector ◽

Metabolic Resistance ◽

Pyrethroid Insecticides ◽

The Impact

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, Anopheles funestus. We showed that a single cytochrome P450 allele (CYP6P9a_R) in A. funestus reduced the efficacy of insecticide-treated bednets for preventing transmission of malaria in southern Africa. Expression of key insecticide resistance genes was detected in populations of this mosquito vector throughout Africa but varied according to the region. Signatures of selection and adaptive evolutionary traits including structural polymorphisms and cis-regulatory transcription factor binding sites were detected with evidence of selection due to the scale-up of insecticide-treated bednet use. A cis-regulatory polymorphism driving the overexpression of the major resistance gene CYP6P9a allowed us to design a DNA-based assay for cytochrome P450–mediated resistance to pyrethroid insecticides. Using this assay, we tracked the spread of pyrethroid resistance and found that it was almost fixed in mosquitoes from southern Africa but was absent from mosquitoes collected elsewhere in Africa. Furthermore, a field study in experimental huts in Cameroon demonstrated that mosquitoes carrying the resistance CYP6P9a_R allele survived and succeeded in blood feeding more often than did mosquitoes that lacked this allele. Our findings highlight the need to introduce a new generation of insecticide-treated bednets for malaria control that do not rely on pyrethroid insecticides.

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