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The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programs. The organophosphate (OP), pirimiphos-methyl, is a relatively new chemical in the vector control armory but is now widely used in indoor-residual spray campaigns. While generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in A. gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to OPs in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f, and a complex and diverse pattern of haplotypes under selection in A. gambiae, A. coluzzii and A. arabiensis. As in C. pipiens, copy number variants have arisen at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in A. gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Anopheles mosquito resistance to insecticide remains a serious threat to malaria vector control affecting several sub-Sahara African countries, including Côte d'Ivoire, where high pyrethroid, carbamate and organophosphate resistance have been reported. Since 2017, new insecticides, namely neonicotinoids (e.g.; clothianidin) and pyrroles (e.g.; chlorfenapyr) have been pre-qualified by the World Health Organization (WHO) for use in public health to manage insecticide resistance for disease vector control., Methods: Clothianidin and chlorfenapyr were tested against the field-collected Anopheles gambiae populations from Gagnoa, Daloa and Abengourou using the WHO standard insecticide susceptibility biossays. Anopheles gambiae larvae were collected from several larval habitats, pooled and reared to adulthood in each site in July 2020. Non-blood-fed adult female mosquitoes aged 2 to 5 days were exposed to diagnostic concentration deltamethrin, permethrin, alpha-cypermethrin, bendiocarb, and pirimiphos-methyl. Clothianidin 2% treated papers were locally made and tested using WHO tube bioassay while chlorfenapyr (100 µg/bottle) was evaluated using WHO bottle assays. Furthermore, subsamples of exposed mosquitoes were identified to species and genotyped for insecticide resistance markers including the knock-down resistance (kdr) west and east, and acetylcholinesterase (Ace-1) using molecular techniques., Results: High pyrethroid resistance was recorded with diagnostic dose in Abengourou (1.1 to 3.4% mortality), in Daloa (15.5 to 33.8%) and in Gagnoa (10.3 to 41.6%). With bendiocarb, mortality rates ranged from 49.5 to 62.3%. Complete mortality (100% mortality) was recorded with clothianidin in Gagnoa, 94.9% in Daloa and 96.6% in Abengourou, while susceptibility (mortality > 98%) to chlorfenapyr 100 µg/bottle was recorded at all sites and to pirimiphos-methyl in Gagnoa and Abengourou. Kdr-west mutation was present at high frequency (0.58 to 0.73) in the three sites and Kdr-east mutation frequency was recorded at a very low frequency of 0.02 in both Abengourou and Daloa samples and absent in Gagnoa. The Ace-1 mutation was present at frequencies between 0.19 and 0.29 in these areas. Anopheles coluzzii represented 100% of mosquitoes collected in Daloa and Gagnoa, and 72% in Abengourou., Conclusions: This study showed that clothianidin and chlorfenapyr insecticides induce high mortality in the natural and pyrethroid-resistant An. gambiae populations in Côte d'Ivoire. These results could support a resistance management plan by proposing an insecticide rotation strategy for vector control interventions., (© 2024. The Author(s).)

Background: Vector control using insecticides is a key prevention strategy against malaria. Unfortunately, insecticide resistance in mosquitoes threatens all progress in malaria control. In the perspective of managing this resistance, new insecticide formulations are being tested to improve the effectiveness of vector control tools., Methods: The efficacy and residual activity of Pirikool® 300 CS was evaluated in comparison with Actellic® 300 CS in experimental huts at the Tiassalé experimental station on three substrates including cement, wood and mud. The mortality, blood-feeding inhibition, exiting behaviour and deterrency of free-flying wild mosquitoes was evaluated. Cone bioassay tests with susceptible and resistant mosquito strains were conducted in the huts to determine residual efficacy., Results: A total of 20,505 mosquitoes of which 10,979 (53%) wild female Anopheles gambiae were collected for 112 nights. Residual efficacy obtained from monthly cone bioassay was higher than 80% with the susceptible, laboratory-maintained An. gambiae Kisumu strain, from the first to the tenth study period on all three types of treated substrate for both Actellic® 300CS and Pirikool® 300CS. This residual efficacy on the wild Tiassalé strain was over 80% until the 4th month of study on Pirikool® 300CS S treated substrates. Overall 24-h mortalities of wild free-flying An. gambiae sensu lato which entered in the experimental huts over the 8-months trial on Pirikool® 300CS treatment was 50.5%, 75.9% and 52.7%, respectively, on cement wall, wood wall and mud wall. The positive reference product Actellic® 300CS treatment induced mortalities of 42.0%, 51.8% and 41.8% on cement wall, wood wall and mud wall., Conclusion: Pirikool® 300CS has performed really well against resistant strains of An. gambiae using indoor residual spraying method in experimental huts. It could be an alternative product for indoor residual spraying in response to the vectors' resistance to insecticides., (© 2024. The Author(s).)

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods., (© 2023. Springer Nature Limited.)

From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy., (© 2023. The Author(s).)

Background: Due to the rapid expansion of pyrethroid-resistance in malaria vectors in Africa, Global Plan for Insecticide Resistance Management (GPIRM) has recommended the development of long-lasting insecticidal nets (LLINs), containing insecticide mixtures of active ingredients with different modes of action to mitigate resistance and improve LLIN efficacy. This good laboratory practice (GLP) study evaluated the efficacy of the chlorfenapyr and deltamethrin-coated PermaNet ® Dual, in comparison with the deltamethrin and synergist piperonyl butoxide (PBO)-treated PermaNet ® 3.0 and the deltamethrin-coated PermaNet ® 2.0, against wild free-flying pyrethroid-resistant Anopheles gambiae sensu lato (s.l.), in experimental huts in Tiassalé, Côte d'Ivoire (West Africa)., Methods: PermaNet ® Dual, PermaNet ® 3.0 and PermaNet ® 2.0, unwashed and washed (20 washes), were tested against free-flying pyrethroid-resistant An. gambiae s.l. in the experimental huts in Tiassalé, Côte d'Ivoire from March to August 2020. Complementary laboratory cone bioassays (daytime and 3-min exposure) and tunnel tests (nightly and 15-h exposure) were performed against pyrethroid-susceptible An. gambiae sensu stricto (s.s.) (Kisumu strain) and pyrethroid-resistant An. gambiae s.l. (Tiassalé strain)., Results: PermaNet ® Dual demonstrated significantly improved efficacy, compared to PermaNet ® 3.0 and PermaNet ® 2.0, against the pyrethroid-resistant An. gambiae s.l. Indeed, the experimental hut trial data showed that the mortality and blood-feeding inhibition in the wild pyrethroid-resistant An. gambiae s.l. were overall significantly higher with PermaNet ® Dual compared with PermaNet ® 3.0 and PermaNet ® 2.0, for both unwashed and washed samples. The mortality with unwashed and washed samples were 93.6 ± 0.2% and 83.2 ± 0.9% for PermaNet ® Dual, 37.5 ± 2.9% and 14.4 ± 3.9% for PermaNet ® 3.0, and 7.4 ± 5.1% and 11.7 ± 3.4% for PermaNet ® 2.0, respectively. Moreover, unwashed and washed samples produced the respective percentage blood-feeding inhibition of 41.4 ± 6.9% and 43.7 ± 4.8% with PermaNet ® Dual, 51.0 ± 5.7% and 9.8 ± 3.6% with PermaNet ® 3.0, and 12.8 ± 4.3% and - 13.0 ± 3.6% with PermaNet ® 2.0. Overall, PermaNet ® Dual also induced higher or similar deterrence, exophily and personal protection when compared with the standard PermaNet ® 3.0 and PermaNet ® 2.0 reference nets, with both unwashed and washed net samples. In contrast to cone bioassays, tunnel tests predicted the efficacy of PermaNet ® Dual seen in the current experimental hut trial., Conclusion: The deltamethrin-chlorfenapyr-coated PermaNet ® Dual induced a high efficacy and performed better than the deltamethrin-PBO PermaNet ® 3.0 and the deltamethrin-only PermaNet ® 2.0, testing both unwashed and 20 times washed samples against the pyrethroid-susceptible and resistant strains of An. gambiae s.l. The inclusion of chlorfenapyr with deltamethrin in PermaNet ® Dual net greatly improved protection and control of pyrethroid-resistant An. gambiae populations. PermaNet ® Dual thus represents a promising tool, with a high potential to reduce malaria transmission and provide community protection in areas compromised by mosquito vector resistance to pyrethroids., (© 2023. The Author(s).)

Background: Entomological surveillance provides critical information on vectors for appropriate malaria vector control and strategic decision-making. The widely documented insecticide resistance of malaria vectors in Côte d'Ivoire requires that any vector control intervention deployment be driven by entomological data to optimize its effectiveness and appropriate resource allocations. To achieve this goal, this study documents the results of monthly vector surveillance and insecticide susceptibility tests conducted in 2019 and a review of all previous entomological monitoring data used to guide vector control decision making. Furthermore, susceptibility to pirimiphos-methyl and clothianidin was assessed in addition to chlorfenapyr and pyrethroids (intensity and piperonyl butoxide (PBO) synergism) tests previously reported. Vector bionomic data were conducted monthly in four sites (Sakassou, Béoumi, Dabakala and Nassian) that were selected based on their reported high malaria incidence. Adult mosquitoes were collected using human landing catches (HLCs), pyrethrum spray catches (PSCs), and human-baited CDC light traps to assess vector density, behaviour, species composition and sporozoite infectivity., Results: Pirimiphos-methyl and clothianidin susceptibility was observed in 8 and 10 sites, respectively, while previous data reported chlorfenapyr (200 µg/bottle) susceptibility in 13 of the sites, high pyrethroid resistance intensity and increased mortality with PBO pre-exposure at all 17 tested sites. Anopheles gambiae sensu lato was the predominant malaria vector collected in all four bionomic sites. Vector density was relatively higher in Sakassou throughout the year with mean biting rates of 278.2 bites per person per night (b/p/n) compared to Béoumi, Dabakala and Nassian (mean of 48.5, 81.4 and 26.6 b/p/n, respectively). The mean entomological inoculation rate (EIR) was 4.44 infective bites per person per night (ib/p/n) in Sakassou, 0.34 ib/p/n in Beoumi, 1.17 ib/p/n in Dabakala and 1.02 ib/p/n in Nassian. The highest EIRs were recorded in October in Béoumi (1.71 ib/p/n) and Nassian (3.22 ib/p/n), in July in Dabakala (4.46 ib/p/n) and in May in Sakassou (15.6 ib/p/n)., Conclusion: Based on all results and data review, the National Malaria Control Programme developed and implemented a stratified insecticide-treated net (ITN) mass distribution in 2021 considering new generation ITNs. These results also supported the selection of clothianidin-based products and an optimal spraying time for the first indoor residual spraying (IRS) campaign in Sakassou and Nassian in 2020., (© 2023. The Author(s).)

Background: Insecticides play a key role in rural farming; however, their over- or misuse has been linked with a negative impact on malaria vector control policies. This study was conducted amongst agricultural communities in Southern Côte d'Ivoire to identify which insecticides are used by local farmers and how it relates to the perception of farmers on malaria. Understanding the use of insecticides may help in designing awareness programme on mosquito control and pesticides management., Methods: A questionnaire was administered to 1399 farming households across ten villages. Farmers were interviewed on their education, farming practices (e.g. crops cultivated, insecticides use), perception of malaria, and the different domestic strategies of mosquito control they use. Based on some pre-defined household assets, the socioeconomic status (SES) of each household was estimated. Statistical associations were calculated between different variables, showing significant risk factors., Results: The educational level of farmers was significantly associated with their SES (p < 0.0001). Most of the householders (88.82%) identified mosquitoes as the principal cause of malaria, with good knowledge of malaria resulting as positively related to high educational level (OR = 2.04; 95%CI: 1.35, 3.10). The use of indoor chemical compounds was strongly associated to the SES of the households, their education level, their use of ITNs and insecticide in agricultural (p < 0.0001). Indoor application of pyrethroid insecticides was found to be widespread among farmers as well as the use of such insecticide for crops protection., Conclusion: Our study shows that the education level remains the key factor influencing the use of insecticides by farmers and their awareness of malaria control. We suggest that better communication tailored to education level and including SES, controlled availability and access to chemical products, should be considered when designing campaigns on use of pesticides and vector borne disease control for local communities., (© 2022. The Author(s).)

Surveillance of malaria vector species and the monitoring of insecticide resistance are essential to inform malaria control strategies and support the reduction of infections and disease. Genetic barcoding of mosquitoes is a useful tool to assist the high-throughput surveillance of insecticide resistance, discriminate between sibling species and to detect the presence of Plasmodium infections. In this study, we combined multiplex PCR, custom designed dual indexing, and Illumina next generation sequencing for high throughput single nucleotide polymorphism (SNP)-profiling of four species from the Anopheles (An.) gambiae complex (An. gambiae sensu stricto, An. coluzzii, An. arabiensis and An. melas). By amplifying and sequencing only 14 genetic fragments (500 bp each), we were able to simultaneously detect Plasmodium infection; insecticide resistance-conferring SNPs in ace1, gste2, vgsc and rdl genes; the partial sequences of nuclear ribosomal internal transcribed spacers (ITS1 and ITS2) and intergenic spacers (IGS), Short INterspersed Elements (SINE), as well as mitochondrial genes (cox1 and nd4) for species identification and genetic diversity. Using this amplicon sequencing approach with the four selected An. gambiae complex species, we identified a total of 15 non-synonymous mutations in the insecticide target genes, including previously described mutations associated with resistance and two new mutations (F1525L in vgsc and D148E in gste2). Overall, we present a reliable and cost-effective high-throughput panel for surveillance of An. gambiae complex mosquitoes in malaria endemic regions., (© 2022. The Author(s).)

Background: Resistance to major public health insecticides in Côte d'Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions., Methods: This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from Southeast Côte d'Ivoire in 2019., Results: Phenotypic resistance was intense: >25% of mosquitoes survived exposure to 10 times the doses of pyrethroids required to kill susceptible populations. Similarly, the 24-hour mortality rate with deltamethrin-only LLINs was very low and not significantly different from that with an untreated net. Sublethal pyrethroid exposure did not induce significant delayed vector mortality effects 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide, or new insecticides clothianidin and chlorfenapyr, were highly toxic to A. coluzzii. Pyrethroid-susceptible A. coluzzii were significantly more likely to be infected with malaria, compared with those that survived insecticidal exposure. Pyrethroid resistance was associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1., Conclusions: Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating piperonyl butoxide, chlorfenapyr, or clothianidin in areas of high resistance intensity in Côte d'Ivoire., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Insecticidal mosquito vector control products are vital components of malaria control programmes. Test facilities are key in assessing the effectiveness of vector control products against local mosquito populations, in environments where they will be used. Data from these test facilities must be of a high quality to be accepted by regulatory authorities, including the WHO Prequalification Team for vector control products. In 2013-4, seven insecticide testing facilities across sub-Saharan Africa, with technical and financial support from Innovative Vector Control Consortium (IVCC), began development and implementation of quality management system compliant with the principles of Good Laboratory Practice (GLP) to improve data quality and reliability., Methods and Principle Findings: We conducted semi-structured interviews, emails, and video-call interviews with individuals at five test facilities engaged in the IVCC-supported programme and working towards or having achieved GLP. We used framework analysis to identify and describe factors affeting progress towards GLP. We found that eight factors were instrumental in progress, and that test facilities had varying levels of control over these factors. They had high control over the training programme, project planning, and senior leadership support; medium control over infrastructure development, staff structure, and procurement; and low control over funding the availability and accessibility of relevant expertise. Collaboration with IVCC and other partners was key to overcoming the challenges associated with low and medium control factors., Conclusion: For partnership and consortia models of research capacity strengthening, test facilities can use their own internal resources to address identified high-control factors. Project plans should allow additional time for interaction with external agencies to address medium-control factors, and partners with access to expertise and funding should concentrate their efforts on supporting institutions to address low-control factors. In practice, this includes planning for financial sustainability at the outset, and acting to strengthen national and regional training capacity., Competing Interests: The authors have declared that no competing interests exist.

Insecticide resistance among mosquito species is now a pervasive phenomenon that threatens to jeopardize global malaria vector control efforts. Evidence of links between the mosquito microbiota and insecticide resistance is emerging, with significant enrichment of insecticide degrading bacteria and enzymes in resistant populations. Using 16S rRNA amplicon sequencing, we characterized and compared the microbiota of Anopheles coluzzii in relation to their deltamethrin resistance and exposure profiles. Comparisons between 2- and 3-day-old deltamethrin-resistant and -susceptible mosquitoes demonstrated significant differences in microbiota diversity. Ochrobactrum , Lysinibacillus , and Stenotrophomonas genera, each of which comprised insecticide-degrading species, were significantly enriched in resistant mosquitoes. Susceptible mosquitoes had a significant reduction in alpha diversity compared to resistant individuals, with Asaia and Serratia dominating microbial profiles. There was no significant difference in deltamethrin-exposed and -unexposed 5- to 6-day-old individuals, suggesting that insecticide exposure had minimal impact on microbial composition. Serratia and Asaia were also dominant in 5- to 6-day-old mosquitoes, which had reduced microbial diversity compared to 2- to 3-day-old mosquitoes. Our findings revealed significant alterations of Anopheles coluzzii microbiota associated with deltamethrin resistance, highlighting the potential for identification of novel microbial markers for insecticide resistance surveillance. qPCR detection of Serratia and Asaia was consistent with 16S rRNA sequencing, suggesting that population-level field screening of bacterial microbiota may be feasibly integrated into wider resistance monitoring, if reliable and reproducible markers associated with phenotype can be identified. IMPORTANCE Control of insecticide-resistant vector populations remains a significant challenge to global malaria control and while substantial progress has been made elucidating key target site mutations, overexpressed detoxification enzymes and alternate gene families, the contribution of the mosquito microbiota to phenotypic insecticide resistance has been largely overlooked. We focused on determining the effects of deltamethrin resistance intensity on Anopheles coluzzii microbiota and identifying any microbial taxa associated with phenotype. We demonstrated a significant reduction in microbial diversity between deltamethrin-resistant and -susceptible mosquitoes. Insecticide degrading bacterial species belonging to Ochrobactrum , Lysinibacillus , and Stenotrophomonas genera were significantly enriched in resistant mosquitoes, while Asaia and Serratia dominated microbial profiles of susceptible individuals. Our results revealed significant alterations of Anopheles coluzzii microbiota associated with deltamethrin resistance, highlighting the potential for identification of novel microbial markers for surveillance and opportunities for designing innovative control techniques to prevent the further evolution and spread of insecticide resistance.

Background: Pyrethroid-treated mosquito nets are currently the mainstay of vector control in Côte d'Ivoire. However, resistance to pyrethroids has been reported across the country, limiting options for insecticide resistance management due to the paucity of alternative insecticides. Two types of insecticide-treated nets (ITNs), ITNs with pyrethroids and the synergist piperonyl butoxide (PBO), and Interceptor®G2 nets, a net treated with a combination of chlorfenapyr and alpha-cypermethrin, are believed to help in the control of pyrethroid-resistant mosquitoes., Methods: The susceptibility of Anopheles gambiae sensu lato (s.l.) to pyrethroid insecticides with and without pre-exposure to PBO as well as to chlorfenapyr was investigated in fifteen sites across the country. Susceptibility tests were conducted on 2- to 4-day old adult female An. gambiae s.l. reared from larval collections. The resistance status, intensity, and effects of PBO on mortality after exposure to different concentrations of deltamethrin, permethrin and alpha-cypermethrin were determined using WHO susceptibility test kits. In the absence of a WHO-recommended standard protocol for chlorfenapyr, two interim doses (100 and 200 µg/bottle) were used to test the susceptibility of mosquitoes using the CDC bottle assay method., Results: Pre-exposure to PBO did not result in full restoration of susceptibility to any of the three pyrethroids for the An. gambiae s.l. populations from any of the sites surveyed. However, PBO pre-exposure did increase mortality for all three pyrethroids, particularly deltamethrin (from 4.4 to 48.9%). Anopheles gambiae s.l. from only one site (Bettie) were susceptible to chlorfenapyr at the dose of 100 µg active ingredient (a.i.)/bottle. At the dose of 200 µg (a.i.)/bottle, susceptibility was only recorded in 10 of the 15 sites., Conclusion: Low mosquito mortality was found for pyrethroids alone, and while PBO increased mortality, it did not restore full susceptibility. The vector was not fully susceptible to chlorfenapyr in one third of the sites tested. However, vector susceptibility to chlorfenapyr seems to be considerably higher than for pyrethroids alone or with PBO. These data should be used cautiously when making ITN procurement decisions, noting that bioassays are conducted in controlled conditions and may not fully represent field efficacy where the host-seeking behaviours, which include free-flying activity are known to enhance pro-insecticide chlorfenapyr intoxication to mosquitoes.

Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness.

Background: Malaria control is heavily dependent on the use of insecticides that target adult mosquito vectors via insecticide treated nets (ITNs) or indoor residual spraying (IRS). Four classes of insecticide are approved for IRS but only pyrethroids are available for ITNs. The rapid rise in insecticide resistance in African malaria vectors has raised alarms about the sustainability of existing malaria control activities. This problem might be particularly acute in Côte d'Ivoire where resistance to all four insecticide classes has recently been recorded. Here we investigate temporal trends in insecticide resistance across the ecological zones of Côte d'Ivoire to determine whether apparent pan-African patterns of increasing resistance are detectable and consistent across insecticides and areas., Methods: We combined data on insecticide resistance from a literature review, and bioassays conducted on field-caught Anopheles gambiae mosquitoes for the four WHO-approved insecticide classes for ITN/IRS. The data were then mapped using Geographical Information Systems (GIS) and the IR mapper tool to provide spatial and temporal distribution data on insecticide resistance in An. gambiae sensu lato from Côte d'Ivoire between 1993 and 2014., Results: Bioassay mortality decreased over time for all insecticide classes, though with significant spatiotemporal variation, such that stronger declines were observed in the southern ecological zone for DDT and pyrethroids than in the central zone, but with an apparently opposite effect for the carbamate and organophosphate. Variation in relative abundance of the molecular forms, coupled with dramatic increase in kdr 1014F frequency in M forms (An. coluzzii) seems likely to be a contributory factor to these patterns. Although records of resistance across insecticide classes have become more common, the number of classes tested in studies has also increased, precluding a conclusion that multiple resistance has also increased., Conclusion: Our analyses attempted synthesis of 22 years of bioassay data from Côte d'Ivoire, and despite a number of caveats and potentially confounding variables, suggest significant but spatially-variable temporal trends in insecticide resistance. In the light of such spatio-temporal dynamics, regular, systematic and spatially-expanded monitoring is warranted to provide accurate information on insecticide resistance for control programme management.

Malaria control depends on mosquito susceptibility to insecticides. We tested Anopheles gambiae mosquitoes from Côte d'Ivoire for resistance and screened a subset for target site mutations. Mosquitoes were resistant to insecticides of all approved classes. Such complete resistance, which includes exceptionally strong phenotypes, presents a major threat to malaria control. [ABSTRACT FROM AUTHOR]