scholarly journals Experimental evolution supports the potential of neonicotinoid-pyrethroid combination for managing insecticide resistance in malaria vectors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marius Gonse Zoh ◽  
Jean-Marc Bonneville ◽  
Jordan Tutagata ◽  
Frederic Laporte ◽  
Behi K. Fodjo ◽  
...  
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Vector Control ◽  
Target Site ◽  
Site Mutation ◽  
Protein Variant ◽  
Selection Signature ◽  
The Impact ◽  
Selection Of ◽  
Selection Of Resistance

AbstractThe introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance of An. gambiae to the separated or combined components of this combination. A field-derived An. gambiae line carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines. This study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation. Clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with those conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was also observed on a P450 gene cluster previously associated with resistance. Within this cluster, the gene CYP6M1 showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure showed that selection retained a protein variant with a modified active site potentially enhancing clothianidin metabolism. In the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.

scholarly journals Neonicotinoid and pyrethroid combination: A tool to manage insecticide resistance in malaria vectors? Insights from experimental evolution

2021 ◽  
Author(s):  
Marius Gonse Zoh ◽  
Jean-Marc Bonneville ◽  
Jordan Tutagana ◽  
Frederic Laporte ◽  
Behi Kouadio Fodjo ◽  
...  
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Vector Control ◽  
Target Site ◽  
Cross Resistance ◽  
Site Mutation ◽  
Selection Signature ◽  
The Impact ◽  
Selection Of ◽  
Selection Of Resistance

Background: The introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance of An. gambiae to the separated or combined components of this combination. A field-derived An. gambiae line carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines. Results: This study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation while clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with the ones conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was observed on a cytochrome P450 gene cluster previously associated with resistance. Within this cluster, the gene CYP6M1 showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure suggested that the selection of variants affecting its active site can enhance clothianidin metabolism. Conclusions: In the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.

scholarly journals Insecticide resistance status of Anopheles arabiensis in irrigated and non-irrigated areas in western Kenya

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Pauline Winnie Orondo ◽  
Steven G. Nyanjom ◽  
Harrysone Atieli ◽  
John Githure ◽  
Benyl M. Ondeto ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Anopheles Arabiensis ◽  
Crop Protection ◽  
Indoor Residual Spraying ◽  
Malaria Vectors ◽  
Western Kenya ◽  
Animal Protection ◽  
Selection Of ◽  
Selection Of Resistance

Abstract Background Malaria control in Kenya is based on case management and vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). However, the development of insecticide resistance compromises the effectiveness of insecticide-based vector control programs. The use of pesticides for agricultural purposes has been implicated as one of the sources driving the selection of resistance. The current study was undertaken to assess the status and mechanism of insecticide resistance in malaria vectors in irrigated and non-irrigated areas with varying agrochemical use in western Kenya. Methods The study was carried out in 2018–2019 in Homa Bay County, western Kenya. The bioassay was performed on adults reared from larvae collected from irrigated and non-irrigated fields in order to assess the susceptibility of malaria vectors to different classes of insecticides following the standard WHO guidelines. Characterization of knockdown resistance (kdr) and acetylcholinesterase-inhibiting enzyme/angiotensin-converting enzyme (Ace-1) mutations within Anopheles gambiae s.l. species was performed using the polymerase chain reaction (PCR) method. To determine the agricultural and public health insecticide usage pattern, a questionnaire was administered to farmers, households, and veterinary officers in the study area. Results Anopheles arabiensis was the predominant species in the irrigated (100%, n = 154) area and the dominant species in the non-irrigated areas (97.5%, n = 162), the rest being An. gambiae sensu stricto. In 2018, Anopheles arabiensis in the irrigated region were susceptible to all insecticides tested, while in the non-irrigated region reduced mortality was observed (84%) against deltamethrin. In 2019, phenotypic mortality was decreased (97.8–84% to 83.3–78.2%). In contrast, high mortality from malathion (100%), DDT (98.98%), and piperonyl butoxide (PBO)-deltamethrin (100%) was observed. Molecular analysis of the vectors from the irrigated and non-irrigated areas revealed low levels of leucine-serine/phenylalanine substitution at position 1014 (L1014S/L1014F), with mutation frequencies of 1–16%, and low-frequency mutation in the Ace-1R gene (0.7%). In addition to very high coverage of LLINs impregnated with pyrethroids and IRS with organophosphate insecticides, pyrethroids were the predominant chemical class of pesticides used for crop and animal protection. Conclusion Anopheles arabiensis from irrigated areas showed increased phenotypic resistance, and the intensive use of pesticides for crop protection in this region may have contributed to the selection of resistance genes observed. The susceptibility of these malaria vectors to organophosphates and PBO synergists in pyrethroids offers a promising future for IRS and insecticide-treated net-based vector control interventions. These findings emphasize the need for integrated vector control strategies, with particular attention to agricultural practices to mitigate mosquito resistance to insecticides. Graphic abstract

scholarly journals Insecticide exposure impacts vector–parasite interactions in insecticide-resistant malaria vectors

2014 ◽  
Vol 281 (1786) ◽  
pp. 20140389 ◽  
Author(s):  
Haoues Alout ◽  
Innocent Djègbè ◽  
Fabrice Chandre ◽  
Luc Salako Djogbénou ◽  
Roch Kounbobr Dabiré ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Competence ◽  
Resistance Mechanisms ◽  
Malaria Vectors ◽  
Anopheles Gambiae S.S ◽  
Strong Trend ◽  
Insecticide Exposure ◽  
The Impact ◽  
Selection Of ◽  
Selection Of Resistance

Currently, there is a strong trend towards increasing insecticide-based vector control coverage in malaria endemic countries. The ecological consequence of insecticide applications has been mainly studied regarding the selection of resistance mechanisms; however, little is known about their impact on vector competence in mosquitoes responsible for malaria transmission. As they have limited toxicity to mosquitoes owing to the selection of resistance mechanisms, insecticides may also interact with pathogens developing in mosquitoes. In this study, we explored the impact of insecticide exposure on Plasmodium falciparum development in insecticide-resistant colonies of Anopheles gambiae s.s. , homozygous for the ace-1 G119S mutation (Acerkis) or the kdr L1014F mutation (Kdrkis). Exposure to bendiocarb insecticide reduced the prevalence and intensity of P. falciparum oocysts developing in the infected midgut of the Acerkis strain, whereas exposure to dichlorodiphenyltrichloroethane reduced only the prevalence of P. falciparum infection in the Kdrkis strain. Thus, insecticide resistance leads to a selective pressure of insecticides on Plasmodium parasites, providing, to our knowledge, the first evidence of genotype by environment interactions on vector competence in a natural Anopheles–Plasmodium combination . Insecticide applications would affect the transmission of malaria in spite of resistance and would reduce to some degree the impact of insecticide resistance on malaria control interventions.

scholarly journals Assessing the anti-resistance potential of public health vaporizer formulations and insecticide mixtures with pyrethroids using transgenic Drosophila lines

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hang Ngoc Bao Luong ◽  
Arunas Damijonaitis ◽  
Ralf Nauen ◽  
John Vontas ◽  
Sebastian Horstmann
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Vector Control ◽  
Pyrethroid Resistance ◽  
Indoor Residual Spraying ◽  
Target Site ◽  
Detoxification Enzymes ◽  
Modes Of Action ◽  
Commercial Mixture ◽  
Insecticide Mixtures

Abstract Background Insecticide resistance—and especially pyrethroid resistance—is a major challenge for vector control in public health. The use of insecticide mixtures utilizing alternative modes of action, as well as new formulations facilitating their uptake, is likely to break resistance and slow the development of resistance. Methods We used genetically defined highly resistant lines of Drosophila melanogaster with distinct target-site mutations and detoxification enzymes to test the efficacy and anti-resistance potential of novel mixture formulations (i.e. Fludora® Fusion consisting of deltamethrin and clothianidin), as well as emulsifiable concentrate transfluthrin, compared to alternative, currently used pyrethroid insecticide formulations for vector control. Results The commercial mixture Fludora® Fusion, consisting of both a pyrethroid (deltamethrin) and a neonicotinoid (clothianidin), performed better than either of the single active ingredients against resistant transgenic flies. Transfluthrin, a highly volatile active ingredient with a different molecular structure and primary exposure route (respiration), was also efficient and less affected by the combination of metabolic and target-site resistance. Both formulations substantially reduced insecticide resistance across different pyrethroid-resistant Drosophila transgenic strains. Conclusions The use of mixtures containing two unrelated modes of action as well as a formulation based on transfluthrin showed increased efficacy and resistance-breaking potential against genetically defined highly resistant Drosophila flies. The experimental model remains to be validated with mosquito populations in the field. The possible introduction of new transfluthrin-based products and mixtures for indoor residual spraying, in line with other combination and mixture vector control products recently evaluated for use in public health, will provide solutions for better insecticide resistance management. Graphical abstract

scholarly journals Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vectorCulex quinquefasciatus

2019 ◽  
Author(s):  
Walter Fabricio Silva Martins ◽  
Craig Stephen Wilding ◽  
Alison Taylor Isaacs ◽  
Emily Joy Rippon ◽  
Karine Megy ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Lymphatic Filariasis ◽  
Fold Increase ◽  
Target Site ◽  
Detoxification Enzymes ◽  
Site Mutation ◽  
Public Health Importance ◽  
Metabolic Resistance ◽  
Vector Borne Diseases ◽  
Bendiocarb Resistance

ABSTRACTCulex quinquefasciatusplays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackleC. quinquefasciatusvectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, includingC. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistantC. quinquefasciatuswas explored to identify candidate genes associated with insecticide resistance. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1h exposure and 58.02% after 4h. Genotyping of the G119SAce-1target site mutation detected a highly significant association (p<0.0001; OR=25) between resistance andAce1-119S. However, synergist assays using the P450 inhibitor PBO or the esterase inhibitor TPP resulted in markedly increased mortality (to ≈80%), suggesting a role of metabolic resistance in the resistance phenotype. Using a novel, custom 60K whole-transcriptome microarray 16 genes significantly overexpressed in resistant mosquitoes were detected, with the P450Cyp6z18showing the highest differential gene expression (>8-fold increase vs unexposed controls). These results provide evidence that bendiocarb-resistance in UgandanC. quinquefasciatusis mediated by both target-site mechanisms and over-expression of detoxification enzymes.

Evolution of Drosophila insecticide resistance

Genome ◽  
1993 ◽  
Vol 36 (1) ◽  
pp. 1-7 ◽  
Author(s):  
R. A. Morton
Keyword(s):  
Insecticide Resistance ◽  
Quantitative Traits ◽  
Molecular Genetic ◽  
Resistance Evolution ◽  
Target Molecules ◽  
Genetic Techniques ◽  
The Cost ◽  
The Impact ◽  
The Relationship ◽  
Selection Of

The impact of insecticide resistance is well documented. It includes the toxic effects of pesticides on the environment and the cost of the increased amounts of insecticides required to effectively control resistant insects. Resistance evolves by the selection of genes that confer tolerance to insecticides. Several resistance genes have been identified and cloned in Drosophila, including genes for mutant target molecules and genes that increase insecticide degradation. Drosophila is a useful system to understand the evolution of quantitative traits in general as well as the population genetics of insecticide resistance. Through it, we may hope to understand the relationship between discrete genetic change and continuously varying characters. In addition, molecular genetic techniques developed using Drosophila can eventually be transferred to other insects in order to help control pest populations.Key words: insecticide resistance, evolution of tolerance, selection of resistant genes, molecular genetics, Drosophila.

scholarly journals Monitoring of Insecticide Resistance in Anopheles culicifacies in Twelve Districts of Madhya Pradesh, Central India (2017–2019)

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Ashok K. Mishra ◽  
Praveen K Bharti ◽  
Gyan Chand ◽  
Aparup Das ◽  
Himanshu Jayswar ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Indoor Residual Spraying ◽  
Central India ◽  
Control Programme ◽  
Madhya Pradesh ◽  
Control Measures ◽  
Malaria Vectors ◽  
Malaria Vector Control ◽  
The Impact

Background. Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are malaria vector control measures used in India, but the development of insecticide resistance poses major impediments for effective vector control strategies. As per the guidelines of the National Vector Borne Disease Control Programme (NVBDCP), the study was conducted in 12 districts of Madhya Pradesh to generate data on insecticide resistance in malaria vectors. Methods. The susceptibility tests were conducted on adult An. culicifacies as per the WHO standard technique with wild-caught mosquitoes. The blood-fed female mosquitoes were exposed in 3 to 4 replicates on each occasion to the impregnated papers with specified discriminating dosages of the insecticides (DDT: 4%, malathion: 5%, deltamethrin: 0.05%, and alphacypermethrin: 0.05%), for one hour, and mortality was recorded after 24-hour holding. Results. An. culicifacies was found resistant to DDT 4% in all the 12 districts and malathion in 11 districts. The resistance to alphacypermethrin was also observed in two districts, and possible resistance was found to alphacypermethrin in seven districts and to deltamethrin in eight districts, while the vector was found susceptible to both deltamethrin and alphacypermethrin in only 3 districts. Conclusion. An. culicifacies is resistant to DDT and malathion and has emerging resistance to pyrethroids, alphacypermethrin, and deltamethrin. Therefore, regular monitoring of insecticide susceptibility in malaria vectors is needed for implementing effective vector management strategies. However, studies to verify the impact of IRS with good coverage on the transmission of disease are required before deciding on the change of insecticide in conjunction with epidemiological data.

scholarly journals Monitoring Insecticide Resistance and Target Site Mutations of L1014 Kdr And G119 Ace Alleles in Five Mosquito Populations in Korea

2020 ◽  
Vol 58 (5) ◽  
pp. 543-550
Author(s):  
Seo Hye Park ◽  
Hojong Jun ◽  
Seong Kyu Ahn ◽  
Jinyoung Lee ◽  
Sung-Lim Yu ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Mosquito Control ◽  
Resistance Management ◽  
Species Group ◽  
Target Site ◽  
Site Mutation ◽  
Control Programs ◽  
The Cost ◽  
Homozygous Resistant ◽  
Resistant Genotypes

Mosquitoes are globally distributed and important vectors for the transmission of many human diseases. Mosquito control is a difficult task and the cost of preventing mosquito-borne diseases is much lower than that for curing the associated diseases. Thus, chemical control remains the most effective tool for mosquito. Due to the long-term intensive use of insecticides to control mosquito vectors, resistance to most chemical insecticides has been reported. This study aimed to investigate the relationship between insecticide resistance and target site mutation of L1014 kdr and G119 ace alleles in 5 species/species group of mosquitoes (Aedes vexans, Ae. albopictus, Anopheles spp., Culex pipiens complex, and Cx. tritaeniorhynchus) obtained from 6 collection sites. For Anopheles spp., the proportion of mosquitoes with mutated alleles in L1014 was 88.4%, homozygous resistant genotypes were observed in 46.7%, and heterozygous resistant genotypes were observed in 41.8%. For the Cx. pipiens complex and Cx. tritaeniorhynchus species, homozygous resistant genotypes were found in 25.9% and 9.8%, respectively. However, target site mutation of L1014 in the Ae. vexans nipponii and Ae. albopictus species was not observed. Anopheles spp., Cx. pipiens complex, and Cx. tritaeniorhynchus mosquitoes were resistant to deltamethrin and chlorpyriphos, whereas Ae. vexans nipponii and Ae. albopictus were clearly susceptible. We also found a correlation between the resistance phenotype and the presence of the L1014 kdr and G119 ace mutations only in the Anopheles spp. population. In this study, we suggest that insecticide resistance poses a growing threat and resistance management must be integrated into all mosquito control programs.

scholarly journals The economic impact and cost-effectiveness of combined vector-control and dengue vaccination strategies in Thailand: results from a dynamic transmission model

2020 ◽  
Vol 14 (10) ◽  
pp. e0008805
Author(s):  
Gerhart Knerer ◽  
Christine S. M. Currie ◽  
Sally C. Brailsford
Keyword(s):  
Public Health ◽  
Cost Effectiveness ◽  
Vector Control ◽  
Dengue Fever ◽  
Control Strategies ◽  
Cost Effective ◽  
Scenario Analyses ◽  
Life Years ◽  
The Cost ◽  
The Impact

Background and aims Dengue fever is a major public health problem in tropical/subtropical regions. Prior economic analyses have predominantly evaluated either vaccination or vector-control programmes in isolation and do not really consider the incremental benefits and cost-effectiveness of mixed strategies and combination control. We estimated the cost-effectiveness of single and combined approaches in Thailand. Methods The impacts of different control interventions were analysed using a previously published mathematical model of dengue epidemiology and control incorporating seasonality, age structure, consecutive infection, cross protection, immune enhancement and combined vector-host transmission. An economic model was applied to simulation results to estimate the cost-effectiveness of 4 interventions and their various combinations (6 strategies): i) routine vaccination of 1-year olds; ii) chemical vector control strategies targeting adult and larval stages separately; iii) environmental management/ public health education and awareness [EM/ PHEA]). Payer and societal perspectives were considered. The health burden of dengue fever was assessed using disability-adjusted life-years (DALYs) lost. Costs and effects were assessed for 10 years. Costs were discounted at 3% annually and updated to 2013 United States Dollars. Incremental cost-effectiveness analysis was carried out after strategies were rank-ordered by cost, with results presented in a table of incremental analysis. Sensitivity and scenario analyses were undertaken; and the impact and cost-effectiveness of Wolbachia was evaluated in exploratory scenario analyses. Results From the payer and societal perspectives, 2 combination strategies were considered optimal, as all other control strategies were dominated. Vaccination plus adulticide plus EM/ PHEA was deemed cost-effective according to multiple cost-effectiveness criteria. From the societal perspective, incremental differences vs. adulticide and EM/ PHEA resulted in costs of $157.6 million and DALYs lost of 12,599, giving an expected ICER of $12,508 per DALY averted. Exploratory scenario analyses showed Wolbachia to be highly cost-effective ($343 per DALY averted) vs. other single control measures. Conclusions Our model shows that individual interventions can be cost-effective, but that important epidemiological reductions and economic impacts are demonstrated when interventions are combined as part of an integrated approach to combating dengue fever. Exploratory scenario analyses demonstrated the potential epidemiological and cost-effective impact of Wolbachia when deployed at scale on a nationwide basis. Our findings were robust in the face of sensitivity analyses.

scholarly journals A day in the life of a Senior Research Scientist

2019 ◽  
Vol 41 (1) ◽  
pp. 46-47
Keyword(s):  
Public Health ◽  
Insecticide Resistance ◽  
Vector Control ◽  
University Of Florida ◽  
Senior Research Scientist ◽  
Postdoctoral Position ◽  
Senior Research ◽  
The Uk ◽  
The University ◽  
First Job

Jennina Taylor-Wells received a BSc in Biotechnology at Oxford Brookes University in 2008, followed by a PhD in Physiology. Her first job in 2013 was a postdoctoral position also at Oxford Brookes University, where she identified mutations in insect receptors, that were linked to insecticide resistance. Her interest in mosquitoes led her to the University of Florida in 2016. In Florida she investigated how insecticides elicit their action on mosquitoes, which provided her with a wider interest in vector control and public health. Jennina has since returned to the UK and now works in industry, continuing to research novel methods to control mosquitoes.

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