Insecticides For Vector Control Research Articles

Successful yeast microencapsulation of fluralaner and its potential as a larvicide for vector control

Fly control for any species is most effectively implemented in the immature stages when insects can be eliminated before emerging as adults capable of transmitting pathogens or becoming nuisance pests. Yet a limited number of insecticide classes are available for treating larval development sites for dipteran pest species. The most recently introduced class of insecticides in the United States (US) is the isoxazolines, including fluralaner. In the US, fluralaner is currently exclusively labeled for use against ectoparasites in companion animals. However, research has shown that it has a wider effective target range beyond ectoparasites and could be developed as an insecticide for vector control. Here we tested a novel, proprietary, yeast microencapsulated (YME) formulation of fluralaner against the larvae of three pest species: Musca domestica L. (Diptera: Muscidae), Aedes albopictus Skuse (Diptera: Culicidae), and Culicoides sonorensis Wirth and Jones (Diptera: Ceratopogonidae). These species all naturally consume microorganisms as larvae, including yeasts. Fluralaner was successfully microencapsulated in Saccharomyces cerevisiae yeast. YME fluralaner was reconstituted in water at concentrations of 0.00001–0.1 mg/mL (Aedes and Culicoides) or 1–50 mg/mL (Musca) for use in dose-response assays. For each species, the LC50 at 24 h was estimated using probit analyses. YME fluralaner was highly effective against all species tested (Ae. albopictus LC50 = 0.000077 mg/mL; C. sonorensis LC50 = 0.00067 mg/mL; M. domestica LC50 = 2.58 mg/mL). Additionally, laboratory assays were conducted to determine product reapplication rates using LC50 rates. Reapplication rates to maintain <50 % emergence were five weeks (Ae. albopictus) and greater than eight weeks (C. sonorensis). The results presented here indicate YME fluralaner is a promising candidate for controlling larval insects that naturally feed on detritus, thereby bypassing cuticular penetration barriers and safely delivering the active ingredient to the target species.

The impact of agrochemical pollutant mixtures on the selection of insecticide resistance in the malaria vector Anopheles gambiae: insights from experimental evolution and transcriptomics

BackgroundThere are several indications that pesticides used in agriculture contribute to the emergence and spread of resistance of mosquitoes to vector control insecticides. However, the impact of such an indirect selection pressure has rarely been quantified and the molecular mechanisms involved are still poorly characterized. In this context, experimental selection with different agrochemical mixtures was conducted in Anopheles gambiae. The multi-generational impact of agrochemicals on insecticide resistance was evaluated by phenotypic and molecular approaches.MethodsMosquito larvae were selected for 30 generations with three different agrochemical mixtures containing (i) insecticides, (ii) non-insecticides compounds, and (iii) both insecticide and non-insecticide compounds. Every five generations, the resistance of adults to deltamethrin and bendiocarb was monitored using bioassays. The frequencies of the kdr (L995F) and ace1 (G119S) target-site mutations were monitored every 10 generations. RNAseq was performed on all lines at generation 30 in order to identify gene transcription level variations and polymorphisms associated with each selection regime.ResultsLarval selection with agrochemical mixtures did not affect bendiocarb resistance and did not select for ace1 mutation. Contrastingly, an increased deltamethrin resistance was observed in the three selected lines. Such increased resistance was not majorly associated with the presence of kdr L995F mutation in selected lines. RNA-seq identified 63 candidate resistance genes over-transcribed in at least one selected line. These include genes coding for detoxification enzymes or cuticular proteins previously associated with insecticide resistance, and other genes potentially associated with chemical stress response. Combining an allele frequency filtering with a Bayesian FST-based genome scan allowed to identify genes under selection across multiple genomic loci, supporting a multigenic adaptive response to agrochemical mixtures.ConclusionThis study supports the role of agrochemical contaminants as a significant larval selection pressure favouring insecticide resistance in malaria vectors. Such selection pressures likely impact kdr mutations and detoxification enzymes, but also more generalist mechanisms such as cuticle resistance, which could potentially lead to cross-tolerance to unrelated insecticide compounds. Such indirect effect of global landscape pollution on mosquito resistance to public health insecticides deserves further attention since it can affect the nature and dynamics of resistance alleles circulating in malaria vectors and impact the efficacy of control vector strategies.

Design, Synthesis, and Biological Evaluation of Pyrido [1,2-α] Pyrimidinone Mesoionic Derivatives Bearing Propenylbenzene as the Vector Control Insecticide.

A series of novel pyrido [1,2-α] pyrimidinone mesoionic derivatives bearing a propenylbenzene group at the 1-position were synthesized on the basis of the structure of mesoionic insecticides triflumezopyrim and dicloromezotiaz via a rationally conceived pharmacophore model and evaluated for their insecticidal activities against three insect vectors. The bioassay results showed that some compounds exerted remarkable insecticidal activities against M. domestica, Ae. albopictus, and B. germanica. Particularly, compound 26l displayed outstanding insecticidal activity against Ae. Albopictus, with an LC50 value of 0.45 μg/mL, far superior to that of imidacloprid (LC50 = 1.82 μg/mL) and equivalent to that of triflumezopyrim (0.35 μg/mL). Meanwhile, compound 34l presented a broad insecticidal spectrum, with LC50 values of 1.51 μg/g sugar, 0.52 μg/mL and 0.14 μg/adult, which were about 2.88, 3.50, and 1.50 times better than that of imidacloprid (LC50 = 4.35 μg/g sugar, 1.82 μg/mL and 0.21 μg/adult against M. domestica, Ae. albopictus, and B. germanica, respectively) and equivalent to that of triflumezopyrim against M. domestica (1.13 μg/g sugar) and Ae. albopictus (0.35 μg/mL) but lower than the potency against B. germanica (0.06 μg/g sugar). The molecular docking study by energy minimizations revealed that introducing propenylbenzene at the 1-position of compounds 26l and 34l could embed into the binding pocket of nicotinic acetylcholine receptors and form pi-alkyl interaction with LEU306. These results demonstrated that compounds 26l and 34l could be promising candidates for vector control insecticides, which deserved further investigation.

Isolation, characterization and docking analysis of insecticidal compound from Ocimum canum methanolic leaf extracts and its potential against three mosquito vectors

Vector management is an important challenge and burden to developing countries. Frequent and indiscriminate application of chemical insecticides for vector control has resulted in the development of resistance and undesirable effects on beneficial organisms. Hence an alternative approach is needed for the mosquito control programme. The present study investigated the insecticidal activity and spectral analysis of Ocimum canum methanol leaf extract against three mosquito species. One out of four fractions (F1-F4), the 4th fraction, revealed showed good insecticidal activity in larva and adult Cx. quinquefasciatus, Ae. aegypti and An. stephensi (0.114, 0.325 and 0.173 ppm) and (1.798, 1.061 and 0.871 ppm). The mortality was found to be dosage dependant. Spectral analysis of 1H NMR and 13C NMR indicates the presence of 6 protons at δH value of 7.45 (s) and 3 protons at δH value of 7.85 (s) ppm. FT-IR identified the possible band near the capping region at 3417.16 cm-1. LC-MS confirmed the eugenol compound with 99.79% purity at the molecular weight of 164. Further, eugenol docking analysis revealed high homology similarity with insect odorant binding protein 3OGN and AchE protein 2BG9. Overall, the result suggests that isolated eugenol compounds were found to be effective for the eco-friendly management of mosquito vectors. These findings could be useful for designing an efficient mosquitocidal compound in the future.

Process and Methodological Considerations for Observational Analyses of Vector Control Interventions in Sub-Saharan Africa Using Routine Malaria Data.

Progress in malaria control has stalled in recent years. With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment. As NMCPs are increasingly conducting subnational stratification of malaria control interventions, including malaria vector control, country-specific frameworks and platforms are increasingly needed to guide data use for vector control deployment. Integration of routine health systems data, entomological data, and vector control program data in observational longitudinal analyses offers an opportunity for NMCPs and research institutions to conduct evaluations of existing and novel vector control interventions. Drawing on the experience of implementing 22 vector control evaluations across 14 countries in sub-Saharan Africa, as well as published and gray literature on vector control impact evaluations using routine health information system data, this article provides practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments. These recommendations may increase the frequency, rigor, and utilization of routine data sources to inform national program decision-making for vector control.

Larvicidal Effect of Hyptis suaveolens (L.) Poit. Essential Oil Nanoemulsion on Culex quinquefasciatus (Diptera: Culicidae).

Mosquitoes can be vectors of pathogens and transmit diseases to both animals and humans. Species of the genus Culex are part of the cycle of neglected diseases, especially Culex quinquefasciatus, which is an anthropophilic vector of lymphatic filariasis. Natural products can be an alternative to synthetic insecticides for vector control; however, the main issue is the poor water availability of some compounds from plant origin. In this context, nanoemulsions are kinetic stable delivery systems of great interest for lipophilic substances. The objective of this study was to investigate the larvicidal activity of the Hyptis suaveolens essential oil nanoemulsion on Cx. quinquefasciatus. The essential oil showed a predominance of monoterpenes with retention time (RT) lower than 15 min. The average size diameter of the emulsions (sorbitan monooleate/polysorbate 20) was ≤ 200 nm. The nanoemulsion showed high larvicidal activity in concentrations of 250 and 125 ppm. CL50 values were 102.41 (77.5253−149.14) ppm and 70.8105 (44.5282−109.811) ppm after 24 and 48 h, respectively. The mortality rate in the surfactant control was lower than 9%. Scanning micrograph images showed changes in the larvae’s integument. This study achieved an active nanoemulsion on Cx. quinquefasciatus through a low-energy-input technique and without using potentially toxic organic solvents. Therefore, it expands the scope of possible applications of H. suaveolens essential oil in the production of high-added-value nanosystems for tropical disease vector control.

First Report of Mutations Associated With Pyrethroid (L1014F) and Organophosphate (G119S) Resistance in Belgian Culex (Diptera: Culicidae) Mosquitoes.

The emergence of West Nile virus and Usutu virus in Europe poses a significant risk to public health. In the absence of efficient antiviral therapy or vaccine candidates, the only strategy to control these arboviruses is to target the Culex (Diptera: Culicidae) mosquito vector. However, the selection pressure caused by exposure to insecticides for vector control or agricultural pest control can lead to insecticide resistance, thereby reducing the efficacy of insecticide-based vector control interventions. In Culex mosquitoes, two of the most common amino acid substitutions associated with insecticide resistance are the kdr L1014F in voltage gated sodium channels and G119S in acetylcholinesterase. In this study, Culex pipiens biotype pipiens, Culex torrentium, and Culex modestus were sampled from 2019 to 2021 in three distinct environmental habitats (urban, peri-urban, and agricultural) in and around the city of Leuven, Belgium. Individual mosquitoes were screened for two mutations resulting in L1014F and G119S amino acid substitutions. Both mutations were observed in Cx. pipiens and Cx. modestus but not in Cx. torrentium mosquitoes across the four collection sites. Furthermore, multi-resistance or cross-resistance in Cx. pipiens could be a threat in these areas, as both mutations were observed at low frequencies. These results provide the first report of kdr L1014F and ace-1 G119S resistance mutations in Cx. pipiens and Cx. modestus mosquitoes from Belgium, highlighting the importance of mosquito surveillance to design effective arbovirus outbreak control strategies.

A lentic microcosm approach to determine the toxicity of DDT and deltamethrin on diatom communities

Worldwide the use of pesticides has increased, especially in the industry and agriculture sector even though they contain highly toxic substances. The use of pesticides has various negative effects on the aquatic ecosystem and organisms within these ecosystems. The paper aimed to assess the effects of increased concentrations of malaria vector control insecticides (Dichlorodiphenyltrichloroethane (DDT) and Deltamethrin (DTM)) on the freshwater diatom community structure using a microcosm approach as well as determine whether a mixture (DDT 1:1 Deltamethrin) exposure will have a greater influence on the diatom community when compared to single exposures of these insecticides. Diatoms were exposed to a high and low concentration (based on LC50 data for freshwater Xenopus laevis from the USEPA Ecotox database) of DDT, DTM and a mixture in lentic microcosms over a total period of 28 days. Results indicated that irrespective of exposure concentrations, DDT, DTM and a mixture had negative effects on the diatom community including functionality and vitality as these insecticides induced changes to their chloroplasts. There was an increased percentage dead cells for all exposures compared to the control, with the insecticides having a phototoxic effect on the diatom community. Exposure to the selected insecticides caused a significant decrease in some diatom metrics indicating the negative effects these insecticides have on the diatom metrics. Therefore, diatoms may prove to be useful as bio-indicators in ecotoxicology studies when assessing the effects of any insecticide exposures.

Laboratory and experimental hut trial evaluation of VECTRON ™ T500 for indoor residual spraying (IRS) against insecticide resistant malaria vectors in Burkina Faso.

Background: Malaria cases in some areas could be attributed to vector resistant to the insecticide. World Health Organization recommended insecticides for vector control are limited in number. It is essential to find rotational partners for existing Indoor Residual Spraying (IRS) products. VECTRON ™ T500 is a novel insecticide with broflanilide as active ingredient. It has a mode of action on mosquitoes completely different to usually used. The aim of this study was to determine the optimum effective dose and efficacy of VECTRON TMT500 against susceptible and resistant strains of Anopheles in Burkina Faso. Methods: VECTRON™T500 was sprayed at 50, 100 and 200 mg/m² doses onto mud and concrete blocks using Potter Spray Tower. The residual activity of broflanilide was assessed through cone bioassays 1 week and then monthly up to 14 months post spraying. Its efficacy was evaluated at 100 and 150 mg/m² against wild free-flying mosquitoes in experimental huts on both substrates. Actellic 300CS was applied at 1000 mg/m² as reference product. Cone assays were conducted monthly, using susceptible and resistant mosquito strains. Results: In the laboratory, VECTRON ™T500 showed residual efficacy (≥80% mortality) on An. gambiae Kisumu up to 12 and 14 months, respectively, on concrete and mud blocks. Similar results were found with 100 and 200 mg/m² using An. coluzzii pyrethroid resistant strain. In experimental huts, a total of 19,552 An. gambiae s.l. were collected. Deterrence, blood-feeding inhibition and exophily with VECTRON™ treated huts were very low. At 100 and 150 mg/m², mortality of wild An. gambiae s.l. ranged between 55% and 73%. Monthly cone bioassay mortality remained >80% up to 9 months. Conclusions: VECTRON™ T500 shows great potential as IRS formulation for malaria vector control. It can be added to the arsenal of IRS products for use in rotations to control malaria and manage mosquito insecticide resistance.

Maternal exposure to DDT, DDE, and pyrethroid insecticides for malaria vector control and hypospadias in the VHEMBE birth cohort study, Limpopo, South Africa

Hypospadias is the ectopic opening of the urethra on the penis or scrotum. Exposure to estrogenic and/or anti-androgenic chemicals in utero may play an etiologic role. DDT and the pyrethroids cypermethrin and deltamethrin, are used to control malaria. DDT is estrogenic and its breakdown product DDE is anti-androgenic; cypermethrin and deltamethrin can also disrupt androgen pathways. We examined the relationship between maternal exposure to these insecticides during pregnancy and hypospadias among boys participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) in Limpopo Province, South Africa. We measured peripartum levels of p,p'-DDT and p,p'-DDE in maternal serum and urinary pyrethroid metabolites. We conducted urogenital examination on 359 one-year-old boys. A total of 291 (81.0 %) had phimosis, which prevented full urogenital examination, leaving a final sample of 68 boys for determination of the presence of hypospadias. Diagnosis was based on concordance of two independent physicians. We identified hypospadias in 23 of the 68 boys (34 %). Maternal urinary concentrations of cis-DCCA and trans-DCCA metabolites of cypermethrin and other pyrethroids, were associated with an increased risk for hypospadias, but the other metabolite 3-PBA was not (adjusted relative risk per 10-fold increase = 1.58, 95 % CI 1.07–2.34; 1.61, 95 % CI 1.09–2.36; and 1.48, 95 % CI 0.78–2.78, respectively). No associations were found between p,p'-DDT, p,p'-DDE, 3-PBA or cis-DBCA and hypospadias. We observed a high prevalence of hypospadias among boys without phymosis. Boys with higher prenatal exposure to pyrethroid insecticides were at higher risk of hypospadias. Our findings may have global implications given that pyrethroid insecticides are widely used for malaria control, in agriculture and for home use.

Exposure of Anopheles gambiae larvae to a sub-lethal dose of an agrochemical mixture induces tolerance to adulticides used in vector control management.

The heavy use of pesticides in agricultural areas often leads to the contamination of nearby mosquito larvae breeding sites. Exposure to complex mixtures of agrochemicals can affect the insecticide sensitivity of mosquito larvae. Our study objective was to determine whether agrochemical residues in Anopheline larval breeding sites can affect the tolerance of adults to commonly used adulticides. We focussed on Fludora® Fusion, a vector control insecticide formulation combining two insecticides (deltamethrin and clothianidin) with different modes of action. An. gambiae larvae were exposed to a sub-lethal dose of a mixture of agrochemical pesticides used in a highly active agricultural area on the Ivory Coast. Comparative bioassays with Fludora Fusion mixture and its two insecticide components (deltamethrin and clothianidin) were carried out between adult mosquitoes exposed or not to the agrochemicals at the larval stage. A transcriptomic analysis using RNA sequencing was then performed on larvae and adults to study the molecular mechanisms underlying the phenotypic changes observed. Bioassays revealed a significantly increased tolerance of adult females to clothianidin (2.5-fold) and Fludora Fusion mixture (2.2-fold) following larval exposure to agrochemicals. Significantly increased tolerance to deltamethrin was not observed suggesting that insecticide exposure affects the adult efficacy of the Fludora Fusion mixture mainly through mechanisms acting on clothianidin. Transcriptomic analysis revealed the potential of agrochemicals to induce various resistance mechanisms including cuticle proteins, detoxification action and altered insecticide sequestration. These results suggest that although the Fludora Fusion mixture is effective for adult vector control, its efficacy may be locally affected by the ecological context. The present study also suggests that, although the complex interactions between the use of agrochemicals and vector control insecticides are difficult to decipher in the field, they still must be considered in the context of insecticide resistance management programmes.

Laboratory and experimental hut trial evaluation of VECTRON ™ T500 for indoor residual spraying (IRS) against insecticide resistant malaria vectors in Burkina Faso

Background: Malaria cases in some areas could be attributed to vector resistant to the insecticide. World Health Organization recommended insecticides for vector control are limited in number. It is essential to find rotational partners for existing Indoor Residual Spraying (IRS) products. VECTRON ™ T500 is a novel insecticide with broflanilide as active ingredient. It has a mode of action on mosquitoes completely different to usually used. The aim of this study was to determine the optimum effective dose and efficacy of VECTRON TM T500 against susceptible and resistant strains of Anopheles in Burkina Faso. Methods: VECTRON™T500 was sprayed at 50, 100 and 200 mg/m² doses onto mud and concrete blocks using Potter Spray Tower. The residual activity of broflanilide was assessed through cone bioassays 1 week and then monthly up to 14 months post spraying. Its efficacy was evaluated at 100 and 150 mg/m² against wild free-flying mosquitoes in experimental huts on both substrates. Actellic 300CS was applied at 1000 mg/m² as reference product. Cone assays were conducted monthly, using susceptible and resistant mosquito strains. Results: In the laboratory, VECTRON ™ T500 showed residual efficacy (≥80% mortality) on An. gambiae Kisumu up to 12 and 14 months, respectively, on concrete and mud blocks. Similar results were found with 100 and 200 mg/m² using An. coluzzii pyrethroid resistant strain. In experimental huts, a total of 19,552 An. gambiae s.l. were collected. Deterrence, blood-feeding inhibition and exophily with VECTRON™ treated huts were very low. At 100 and 150 mg/m², mortality of wild An. gambiae s.l. ranged between 55% and 73%. Monthly cone bioassay mortality remained >80% up to 9 months. Conclusions: VECTRON™ T500 shows great potential as IRS formulation for malaria vector control. It can be added to the arsenal of IRS products for use in rotations to control malaria and manage mosquito insecticide resistance.

Ecotoxicological Evaluation of Products Obtained from Technical Cashew Nutshell Liquid (tCNSL) Proposed as Larvicide to Control Aedes aegypti (Diptera: Culicidae)

The development of new insecticides for vector control that are toxicologically safe and eco-friendly (such as those obtained from industrial by-products) is an important public health concern. Previous research has shown that the obtained tCNSL (technical cashew nutshell liquid) + NatCNSLS (sodium tCNSL sulfonate mixture) emulsion displayed both surfactant properties and larvicidal activity (LC50-24 h 110.6 mg/L). Thus, the emulsion is considered a promising alternative product for the control of Aedes aegypti. The goal of this study was an ecotoxicological evaluation of the tCNSL + NatCNSLS mixture emulsion and its components. In addition, we compared the toxicity of the tCNSL + NatCNSLS mixture emulsion with toxicity data from larvicide currently recommended by the World Health Organization (WHO). Ecotoxicological tests were performed to assess acute toxicity, phytotoxicity, cytotoxicity, genotoxicity, and mutagenicity using Daphnia similis, Pseudokirchneriella subcapitata, Oreochromis niloticus, Allium cepa, and Salmonella enterica serovar Typhimurium. Regarding acute toxicity, D. similis was the most sensitive test organism for the three evaluated products, followed by P. subcapitata and O. niloticus. The highest acute toxicity product was tCNSL. The tCNSL + NatCNSLS mixture emulsion did not show cytotoxic, genotoxic, or mutagenic effects, and showed low acute toxicity to D. similis. In addition, the tCNSL + NatCNSLS mixture emulsion presented a lower or similar toxicological classification to the larvicides recommended by the WHO. Therefore, ecotoxicological tests suggest that the tCNSL + NatCNSLS mixture emulsion can be considered a larvicide environmentally safe way to control Ae. aegypti.

Laboratory and experimental hut trial evaluation of VECTRON™ T500 for indoor residual spraying (IRS) against insecticide resistant malaria vectors in Burkina Faso

Background: Malaria cases in some areas could be attributed to vector resistant to the insecticide. World Health Organization recommended insecticides for vector control are limited in number. It is essential to find rotational partners for existing Indoor Residual Spraying (IRS) products. VECTRON™ T500 is a novel insecticide with broflanilide as active ingredient. It has a mode of action on mosquitoes completely different to usually used. The aim of this study was to determine the optimum effective dose and efficacy of VECTRONTM against susceptible and resistant strains of Anopheles in Burkina Faso. Methods: VECTRON™ was sprayed at 50, 100 and 200 mg/m² doses onto mud and concrete blocks using Potter Spray Tower. The residual activity of broflanilide was assessed through cone bioassays 1 week and then monthly up to 14 months post spraying. Its efficacy was evaluated at 100 and 150 mg/m² against wild free-flying mosquitoes in experimental huts on both substrates. Actellic 300CS was applied at 1000 mg/m² as reference product. Cone assays were conducted monthly, using susceptible and resistant mosquito strains. Results: In the laboratory, VECTRON™ showed residual efficacy (≥80% mortality) on An. gambiae Kisumu up to 12 and 14 months, respectively, on concrete and mud blocks. Similar results were found with 100 and 200 mg/m² using An. coluzzii pyrethroid resistant strain. In experimental huts, a total of 19,552 An. gambiae s.l. were collected. Deterrence, blood-feeding inhibition and exophily with VECTRON™ treated huts were very low. At 100 and 150 mg/m², mortality of wild An. gambiae s.l. ranged between 55% and 73%. Monthly cone bioassay mortality remained &gt;80% up to 9 months. Conclusions: VECTRON™ shows great potential as IRS formulation for malaria vector control. It can be added to the arsenal of IRS products for use in rotations to control malaria and manage mosquito insecticide resistance.

Essential oils and their binary combinations have synergistic and antagonistic insecticidal properties against Anopheles gambiae s. l. (Diptera: Culicidae)

Botanical biopesticides have potential for use in mosquito control because they exhibit low mammalian toxicity, are readily biodegraded, show target specificity and insecticidal activity. As populations of mosquito species grow more resistant to currently used organic insecticides, a need for new and effective insecticides for vector control becomes more urgent. This study reports the effects of synergistic and antagonistic essential oils (EOs) from Cymbopogon schoenanthus, Lantana camara, Lippia chevalieri and Lippia multiflora and their binary combinations against Anopheles gambiae s. l. larvae and adults. EOs insecticidal properties were tested with third to fourth-instar larvae and, non-blood-fed 3–5-day old field-collected An. gambiae using WHO and CDC bottle bioassays, respectively. Many compounds were found in the EOs mixtures. All EOs showed larvicidal and adulticidal activities with mortality from 0 to 100% against An. gambiae which were concentration dependent and EOs specific. EO mixture from C. schoenanthus and L. multiflora showed synergistic effect with LC50 of 38 ppm and EOs from L. chevalieri and C. schoenanthus showed antagonistic effect against larvae with LC50 of 100.84 ppm. On the other hand, EOs combinations showed additive effect on all adults. This study describes the potential of using EOs and their synergistic mixtures as potential insecticide(s) as a safer alternative to synthetic insecticides.

Modelling spatiotemporal trends in the frequency of genetic mutations conferring insecticide target-site resistance in African mosquito malaria vector species

BackgroundResistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. Target-site resistance is an important genetic resistance mechanism caused by mutations in the voltage-gated sodium channel (Vgsc) gene that encodes the pyrethroid target-site. Understanding the geographic distribution of target-site resistance, and temporal trends across different vector species, can inform strategic deployment of vector control tools.ResultsWe develop a Bayesian statistical spatiotemporal model to interpret species-specific trends in the frequency of the most common resistance mutations, Vgsc-995S and Vgsc-995F, in three major malaria vector species Anopheles gambiae, An. coluzzii, and An. arabiensis over the period 2005–2017. The models are informed by 2418 observations of the frequency of each mutation in field sampled mosquitoes collected from 27 countries spanning western and eastern regions of Africa. For nine selected countries, we develop annual predictive maps which reveal geographically structured patterns of spread of each mutation at regional and continental scales. The results show associations, as well as stark differences, in spread dynamics of the two mutations across the three vector species. The coverage of ITNs was an influential predictor of Vgsc allele frequencies, with modelled relationships between ITN coverage and allele frequencies varying across species and geographic regions. We found that our mapped Vgsc allele frequencies are a significant partial predictor of phenotypic resistance to the pyrethroid deltamethrin in An. gambiae complex populations.ConclusionsOur predictive maps show how spatiotemporal trends in insecticide target-site resistance mechanisms in African An. gambiae vary across individual vector species and geographic regions. Molecular surveillance of resistance mechanisms will help to predict resistance phenotypes and track their spread.

Current status of insecticide resistance in malaria vectors in the Asian countries: a systematic review

Background: The application of insecticides for malaria vector control has led to a global problem, which is the current trend of increased resistance against these chemicals. This study aimed to review the insecticide resistance status was previously determined in Asia and how to implement the necessary interventions. Moreover, the implications of resistance in malaria vector control in this region were studied. Methods: This systematic review was conducted using a predefined protocol based on PRISMA-retrieved articles from four science databases, namely ProQuest, Science Direct, EBSCO, and PubMed in the last ten years (2009 to 2019). The searching process utilized four main combinations of the following keywords: malaria, vector control, insecticide, and Asia. In ProQuest, malaria control, as well as an insecticide, were used as keywords. The following criteria were included in the filter, namely full text, the source of each article, scholarly journal, Asia, and publication date as in the last ten years. Results: There were 1408 articles retrieved during the initial search (ProQuest=722, Science Direct=267, EBSCO=50, PubMed=285, and Scopus=84). During the screening, 27 articles were excluded because of duplication, 1361 based on title and abstract incompatibility with the inclusion criteria, and 20 due to content differences. In the final screening process, 15 articles were chosen to be analyzed. From the 15 articles, it is known that there wasorganochlorine (DDT), organophosphate (malathion), and pyrethroids resistance in several Anopheles species with a less than 80% mortality rate. Conclusion:This review found multiple resistance in several Anopheles includes resistance to pyrethroid.The reports of pyrethroid resistance were quite challenging because it is considered effective in the malaria vector control. Several countries in Asia are implementing an insecticide resistance management (IRM) strategy against malaria vectors following the Global Plan for IRM.

Optimization of covalent docking for organophosphates interaction with Anopheles acetylcholinesterase

Organophosphates (OPs) used as potent insecticides for malaria vector control, covalently phosphorylate the catalytic serine residue of Anopheles gambiae AChE (AgAChE) in a reaction that liberates their leaving groups. In the recent 10-year insecticide use assessment, OPs were the most frequently used World Health Organization prequalified insecticides. Molecular modelling programs are best suited to display molecular interactions between ligands and the target proteins. The docking modes that generate ligand poses closer to the binding site show high accuracy in predicting the ligand binding mode. The implicit solvation approach such as molecular mechanics-generalized born surface area (MM-GBSA) is a more reliable method to predict ligand onformations and binding affinities. Apart from covalent docking studies being scarce, current molecular docking programs do not adequately possess the covalent docking reaction algorithm to display the molecular mechanism of OPs at the AgAChE catalytic site. This results into OP docking studies commonly being conducted through noncovalent pannels. The aim of this study was to establish the optimim covalent docking system for OPs through manual customization of Schrödinger's Glide covalent docking reaction algorithm. To achieve this, a newly customized covalent reaction algorithm was assessed on a set of ligands covering aromatic, non-aromatic and hydrophobic OPs and compared to the noncovalent docking results in terms of reliability based on the reported X-ray diffraction molecular interactions and crystal poses. The study established that by virtue of omitting the well-known OP hydrolysis, noncovalent mode suggested molecular interactions that were further from the catalytic triad and could not otherwise occur when the molecule is hydrolyzed as in the customized covalent docking mode. Moreover, the MM-GBSA concurred with the optimized covalent docking in eliminating such inaccurate molecular interactions. Additionally, the covalent docking mode confined the interactions and ligand poses to the catalytic site indicating relatively high accuracy and reliability. This study reports the optimized covalent docking panel that effectively confirmed the molecular mechanisms of OPs, as well as indentifying the corresponding amino acid residues required to stabilize the aromatic, non-aromatic and hydrophobic OPs at the AgAChE catalytic site in line with the reported X-ray diffraction studies. As such, the proposed manual customization of the Schrödinger's Glide covalent docking platform can be used to reliably predict molecular interactions between OPs and AgAChE target.

Malaria Transmission, Vector Diversity, and Insecticide Resistance at a Peri-Urban Site in the Forest Zone of Ghana

IntroductionRecent surge ofAnophelesresistance to major classes of World Health Organization (WHO)-approved insecticides globally necessitates the need for information about local malaria vector populations. It is believed that insecticide efficacy loss may lead to operational failure of control interventions and an increase in malaria infection transmission. We investigated the susceptibility levels of malaria vectors to all classes of WHO-approved vector control insecticides and described the dynamics of malaria transmission in a peri-urban setting.MethodsFit 3–5-day-old adults that emerged fromAnopheleslarvae collected from several different sites in the study area were subjected to the WHO bioassay for detecting insecticide resistance. The knockdown resistance gene (kdr) mutations within the vector populations were detected using PCR. Entomological inoculation rates were determined using the human landing catch technique andPlasmodium falciparumcircumsporozoite ELISA.ResultsThe malaria vectors from the study area were resistant to all classes of insecticides tested. Out of the 284Anophelescomplex specimen assayed for the resistance study, 265 (93.30%) were identified asAnopheles gambiae s.s.The kdr gene was detected in 90% of theAnopheles gambiae s.s.assayed. In an area whereAnopheles coluzziiresistance to insecticides had never been reported, the kdr gene was detected in 78% of theAnopheles coluzziisampled. The entomological inoculation rate (EIR) for the dry season was 1.44 ib/m/n, whereas the EIR for the rainy season was 2.69 ib/m/n.ConclusionsThis study provides information on the high parasite inoculation rate and insecticide resistance of malaria vectors in a peri-urban community, which is critical in the development of an insecticide resistance management program for the community.

Management of insecticides for use in disease vector control: a global survey

BackgroundVector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the management practices of vector control insecticides at country level to identify gaps to inform future strategies on pesticide management, seeking to improve efficacy of interventions and reduce the side-effects of chemicals used on health and the environment.MethodsA survey by questionnaire on the management practices of vector control insecticides was disseminated among all WHO Member States. Data were analysed using descriptive statistics in MS Excel.ResultsResponses were received from 94 countries, or a 48% response rate. Capacity for insecticide resistance monitoring was established in 68–80% of the countries in most regions, often with external support; however, this capacity was largely lacking from the European & Others Region (i.e. Western & Eastern Europe, North America, Australia and New Zealand). Procurement of vector control insecticides was in 50–75% of countries taking place by agencies other than the central-level procuring agency, over which the central authorities lacked control, for example, to select the product or assure its quality, highlighting the importance of post-market monitoring. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Large fractions (29–78%) of countries across regions showed shortcomings in worker safety, pesticide storage practices and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Region, which has long been relatively free from mosquito-borne diseases but has recently faced challenges of re-emerging vector-borne diseases.ConclusionsCritical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country levels to address these challenges.