Potential Roles of Environmental and Socio-Economic Factors in the Distribution of Insecticide Resistance in Anopheles gambiae sensu lato (Culicidae: Diptera) Across Togo, West Africa

Abstract Vector control strategies recommended by the World Health Organization are threatened by resistance of Anopheles mosquitoes to insecticides. Information on the distribution of resistant genotypes of malaria vectors is increasingly needed to address the problem. Ten years of published and unpublished data on malaria vector susceptibility/resistance and resistance genes have been collected across Togo. Relationships between the spatial distribution of resistance status and environmental, socio-economic, and landscape features were tested using randomization tests, and calculating Spearman rank and Pearson correlation coefficients between mosquito mortality and different gridded values. Anopheles gambiae sensu lato was resistant to DDT, pyrethroids, and the majority of carbamates and organophosphates. Three sibling species were found (i.e., An. gambiae, Anopheles coluzzii, and Anopheles arabiensis) with four resistance genes, including kdr (L1014F, L1014S, and N1575Y) and ace1 (G119S). The most frequent resistance gene was L1014F. Overall, no association was found between the susceptibility/resistance status and environmental features, suggesting that evolution of resistance may be most closely related to extreme selection from local insecticide use. Nevertheless, further research is necessary for firm conclusions about this lack of association, and the potential role of landscape characteristics such as presence of crops and percentage of tree cover.

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High Levels of Knockdown Resistance in Anopheles coluzzii and Anopheles gambiae (Diptera: Culicidae), Major Malaria Vectors in Togo, West Africa: A 2011 Monitoring Report

Journal of Medical Entomology ◽

10.1093/jme/tjz030 ◽

2019 ◽

Vol 56 (4) ◽

pp. 1159-1164

Author(s):

Koffi Mensah Ahadji-Dabla ◽

Adjovi Djifa Amoudji ◽

Seth Wolali Nyamador ◽

Georges Yawo Apétogbo ◽

Joseph Chabi ◽

...

Keyword(s):

West Africa ◽

Anopheles Gambiae ◽

National Malaria Control Programme ◽

Control Programme ◽

World Health ◽

Malaria Vectors ◽

Malaria Control Programme ◽

Anopheles Coluzzii ◽

Knockdown Resistance ◽

Anopheles Gambiae S.S

Abstract A survey of susceptibility to DDT, deltamethrin, bendiocarb, and chlorpyrifos-methyl was conducted in five localities in 2011 in Togo, West Africa, to assess the insecticide resistance status of Anopheles gambiae s.l. (Diptera: Culicidae). Female populations of An. gambaie s.l. emerged from collected larvae (F0) were exposed to insecticide-impregnated papers using World Health Organization test kits for adult mosquitoes; the susceptible reference strain Kisumu was used as a control. Resistance to DDT and deltamethrin was observed within the mosquito populations tested. Anopheles gambiae s.s. and Anopheles coluzzii represented the only species recorded in the study sites. The frequency of knockdown resistance (kdr L1014F) mutation determined using polymerase chain reaction diagnostic tests was lower in An. gambiae than in An. coluzzii in all of the localities except Kolokopé. Further investigations of An. gambiae s.l. resistance are needed in Togo to help the National Malaria Control Programme in vector control decision making and implementation of resistance management strategy.

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

Frontiers in Tropical Diseases ◽

10.3389/fitd.2021.739771 ◽

2021 ◽

Vol 2 ◽

Author(s):

Yaw Akuamoah-Boateng ◽

Ruth C. Brenyah ◽

Sandra A. Kwarteng ◽

Patrick Obuam ◽

Isaac Owusu-Frimpong ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Gambiae ◽

Malaria Transmission ◽

Urban Setting ◽

World Health ◽

Malaria Vectors ◽

Urban Site ◽

Human Landing Catch ◽

Anopheles Coluzzii ◽

Anopheles Gambiae S.S

IntroductionRecent surge of Anopheles resistance 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 from Anopheles larvae 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 and Plasmodium falciparum circumsporozoite ELISA.ResultsThe malaria vectors from the study area were resistant to all classes of insecticides tested. Out of the 284 Anopheles complex specimen assayed for the resistance study, 265 (93.30%) were identified as Anopheles gambiae s.s. The kdr gene was detected in 90% of the Anopheles gambiae s.s. assayed. In an area where Anopheles coluzzii resistance to insecticides had never been reported, the kdr gene was detected in 78% of the Anopheles coluzzii sampled. 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.

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Potential Metabolic Resistance Mechanisms to Ivermectin in Anopheles Gambiae: A Synergist Bioassay Study

10.21203/rs.3.rs-121991/v1 ◽

2020 ◽

Author(s):

Patricia Nicolas ◽

Caroline Kiuru ◽

Martin Wagah ◽

Martha Muturi ◽

Urs Duthaler ◽

...

Keyword(s):

Cytochrome P450 ◽

Anopheles Gambiae ◽

Control Strategies ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Malaria Vector Control ◽

Cytochrome P450 Enzymes ◽

Metabolic Resistance ◽

Active Efflux

Abstract Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal-concentration 50 for ivermectin in colonized Anopheles gambiae, then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin.Conclusion there is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

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Spatial modelling for population replacement of mosquito vectors at continental scale

10.1101/2021.10.06.463299 ◽

2021 ◽

Author(s):

Nicholas J. Beeton ◽

Andrew Wilkins ◽

Adrien Ickowicz ◽

Keith R. Hayes ◽

Geoffrey R. Hosack

Keyword(s):

Anopheles Gambiae ◽

Control Strategies ◽

Drive System ◽

Sub Saharan Africa ◽

Malaria Vectors ◽

Anopheles Coluzzii ◽

Gene Drive ◽

Continental Scale ◽

Wide Range ◽

Sub Saharan

AbstractMalaria is one of the deadliest vector-borne diseases in the world. Researchers are developing new genetic and conventional vector control strategies to attempt to limit its burden. To be deployed responsibly and successfully, proposed novel control strategies require detailed safety assessment. Anopheles gambiae sensu stricto (s.s.) and Anopheles coluzzii, two closely related subspecies within the species complex Anopheles gambiae sensu lato (s.l.), are among the dominant malaria vectors in sub-Saharan Africa. These two subspecies readily hybridise and compete in the wild and are also known to have distinct niches, each with spatially and temporally varying carrying capacities driven by precipitation and land use factors.We model the spread and persistence of a population-modifying gene drive system in these subspecies across sub-Saharan Africa, by simulating introductions of genetically modified mosquitoes across the African mainland as well as on some offshore islands. We explore transmission of the gene drive between the subspecies, different hybridisation mechanisms, the effects of both local dispersal and potential wind-aided migration to the spread, and the development of resistance to the gene drive. We find that given best current available knowledge on the subspecies’ life histories, an introduced gene drive system with typical characteristics can plausibly spread from even distant offshore islands to the African mainland with the aid of wind-driven migration, with resistance taking over within a decade. Our model demonstrates a range of realistic dynamics including the effect of prevailing wind on spread and spatio-temporally varying carrying capacities for subspecies. We thus show both the plausibility and importance of accounting for a wide range of mechanisms from regional to continental scales.

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Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study

Parasites & Vectors ◽

10.1186/s13071-021-04675-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Patricia Nicolas ◽

Caroline Kiuru ◽

Martin G. Wagah ◽

Martha Muturi ◽

Urs Duthaler ◽

...

Keyword(s):

Cytochrome P450 ◽

Anopheles Gambiae ◽

Control Strategies ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Malaria Vector Control ◽

Cytochrome P450 Enzymes ◽

Metabolic Resistance ◽

Active Efflux

Abstract Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin. Conclusion There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

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Anopheles gambiae Genome Conservation as a Resource for Rational Gene Drive Target Site Selection

Insects ◽

10.3390/insects12020097 ◽

2021 ◽

Vol 12 (2) ◽

pp. 97

Author(s):

Nace Kranjc ◽

Andrea Crisanti ◽

Tony Nolan ◽

Federica Bernardini

Keyword(s):

Anopheles Gambiae ◽

Data Storage ◽

Genomic Variation ◽

Malaria Vectors ◽

Anopheles Coluzzii ◽

Structural Constraints ◽

Gene Drive ◽

Genetic Traits ◽

A Genome ◽

Insight Into

The increase in molecular tools for the genetic engineering of insect pests and disease vectors, such as Anopheles mosquitoes that transmit malaria, has led to an unprecedented investigation of the genomic landscape of these organisms. The understanding of genome variability in wild mosquito populations is of primary importance for vector control strategies. This is particularly the case for gene drive systems, which look to introduce genetic traits into a population by targeting specific genomic regions. Gene drive targets with functional or structural constraints are highly desirable as they are less likely to tolerate mutations that prevent targeting by the gene drive and consequent failure of the technology. In this study we describe a bioinformatic pipeline that allows the analysis of whole genome data for the identification of highly conserved regions that can point at potential functional or structural constraints. The analysis was conducted across the genomes of 22 insect species separated by more than hundred million years of evolution and includes the observed genomic variation within field caught samples of Anopheles gambiae and Anopheles coluzzii, the two most dominant malaria vectors. This study offers insight into the level of conservation at a genome-wide scale as well as at per base-pair resolution. The results of this analysis are gathered in a data storage system that allows for flexible extraction and bioinformatic manipulation. Furthermore, it represents a valuable resource that could provide insight into population structure and dynamics of the species in the complex and benefit the development and implementation of genetic strategies to tackle malaria.

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A Spatial and Temporal Assessment of Vegetation Greening and Precipitation Changes for Monitoring Vegetation Dynamics in Climate Zones over Africa

ISPRS International Journal of Geo-Information ◽

10.3390/ijgi10030129 ◽

2021 ◽

Vol 10 (3) ◽

pp. 129

Author(s):

Vincent Nzabarinda ◽

Anming Bao ◽

Wenqiang Xu ◽

Solange Uwamahoro ◽

Madeleine Udahogora ◽

...

Keyword(s):

Vegetation Index ◽

Normalized Difference Vegetation Index ◽

Forest Type ◽

Pearson Correlation ◽

Correlation Coefficients ◽

Plant Health ◽

Tree Cover ◽

Climatic Zones ◽

Dramatic Decline ◽

Precipitation Changes

Vegetation is vital, and its greening depends on access to water. Thus, precipitation has a considerable influence on the health and condition of vegetation and its amount and timing depend on the climatic zone. Therefore, it is extremely important to monitor the state of vegetation according to the movements of precipitation in climatic zones. Although a lot of research has been conducted, most of it has not paid much attention to climatic zones in the study of plant health and precipitation. Thus, this paper aims to study the plant health in five African climatic zones. The linear regression model, the persistence index (PI), and the Pearson correlation coefficients were applied for the third generation Normalized Difference Vegetation Index (NDVI3g), with Climate Hazard Group infrared precipitation and Climate Change Initiative Land Cover for 34 years (1982 to 2015). This involves identifying plants in danger of extinction or in dramatic decline and the relationship between vegetation and rainfall by climate zone. The forest type classified as tree cover, broadleaved, deciduous, closed to open (>15%) has been degraded to 74% of its initial total area. The results also revealed that, during the study period, the vegetation of the tropical, polar, and warm temperate zones showed a higher rate of strong improvement. Although arid and boreal zones show a low rate of strong improvement, they are those that experience a low percentage of strong degradation. The continental vegetation is drastically decreasing, especially forests, and in areas with low vegetation, compared to more vegetated areas, there is more emphasis on the conservation of existing plants. The variability in precipitation is excessively hard to tolerate for more types of vegetation.

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Pyrethroid and Etofenprox Resistance in Anopheles gambiae and Anopheles coluzzii from Vegetable Farms in Yaoundé, Cameroon: Dynamics, Intensity and Molecular Basis

Molecules ◽

10.3390/molecules26185543 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5543

Author(s):

Michael Piameu ◽

Philippe Nwane ◽

Wilson Toussile ◽

Konstantinos Mavridis ◽

Nadja Christina Wipf ◽

...

Keyword(s):

Anopheles Gambiae ◽

Mortality Rates ◽

World Health ◽

Anopheles Coluzzii ◽

Cross Sectional ◽

Metabolic Genes ◽

Anopheles Gambiae S.L ◽

Underlying Mechanisms ◽

Health Organization ◽

The City

Previous studies have indicated widespread insecticide resistance in malaria vector populations from Cameroon. However, the intensity of this resistance and underlying mechanisms are poorly known. Therefore, we conducted three cross-sectional resistance surveys between April 2018 and October 2019, using the revised World Health Organization protocol, which includes resistance incidences and intensity assessments. Field-collected Anopheles gambiae s.l. populations from Nkolondom, Nkolbisson and Ekié vegetable farms in the city of Yaoundé were tested with deltamethrin, permethrin, alpha-cypermethrin and etofenprox, using 1× insecticide diagnostic concentrations for resistance incidence, then 5× and 10× concentrations for resistance intensity. Subsamples were analyzed for species identification and the detection of resistance-associated molecular markers using TaqMan® qPCR assays. In Nkolbisson, both An. coluzzii (96%) and An. gambiae s.s. (4%) were found together, whereas only An. gambiae s.s. was present in Nkolondom, and only An. coluzzii was present in Ekié. All three populations were resistant to the four insecticides (<75% mortality rates―MR1×), with intensity generally fluctuating over the time between mod-erate (<98%―MR5×; ≥98%―MR10×) and high (76–97%―MR10×). The kdr L995F, L995S, and N1570Y, and the Ace-1 G280S-resistant alleles were found in An. gambiae from Nkolondom, at 73%, 1%, 16% and 13% frequencies, respectively, whereas only the kdr L995F was found in An. gambiae s.s. from Nkolbisson at a 50% frequency. In An. coluzzii from Nkolbisson and Ekié, we detected only the kdr L995F allele at 65% and 60% frequencies, respectively. Furthermore, expression levels of Cyp6m2, Cyp9k1, and Gste2 metabolic genes were highly upregulated (over fivefold) in Nkolondom and Nkolbisson. Pyrethroid and etofenprox-based vector control interventions may be jeopardized in the prospected areas, due to high resistance intensity, with multiple mechanisms in An. gambiae s.s. and An. coluzzii.

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Phenotypic Insecticide Resistance in Anopheles gambiae (Diptera: Culicidae): Specific Characterization of Underlying Resistance Mechanisms Still Matters

Journal of Medical Entomology ◽

10.1093/jme/tjaa195 ◽

2020 ◽

Author(s):

Adandé A Medjigbodo ◽

Luc S Djogbenou ◽

Aubin A Koumba ◽

Laurette Djossou ◽

Athanase Badolo ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Gambiae ◽

Resistance Mechanisms ◽

Malaria Vectors ◽

Effective Control ◽

Anopheles Coluzzii ◽

Anopheles Gambiae S.S ◽

Diagnostic Dose ◽

Pirimiphos Methyl ◽

Old Adult

Abstract An effective control of malaria vectors requires an extensive knowledge of mechanisms underlying the resistance-phenotypes developed by these vectors against insecticides. We investigated Anopheles gambiae mosquitoes from Benin and Togo for their intensity of insecticide resistance and we discussed the involvement of genotyped mechanisms in the resistance-phenotypes observed. Three- to five-day-old adult mosquitoes emerged from field and laboratory An. gambiae larvae were assayed using WHO tube intensity tests against various doses of deltamethrin: 1× (0.05%); 2× (0.1%); 5× (0.25%); 7.5× (0.375%) and those of pirimiphos-methyl: 0.5× (0.125%); 1× (0.25%). Members of An. gambiae complex were screened in field populations using polymerase chain reaction (PCR) assays. The presence of kdrR(1014F/1014S) and ace-1R(119S) mutations was also investigated using TaqMan and PCR-RFLP techniques, respectively. Anopheles gambiae from field were very resistant to deltamethrin, whereas KisKdr and AcerKdrKis strains displayed 100% mortality rates at 2× the diagnostic dose. In contrast, the field mosquitoes displayed a low resistance-intensity against 1× the diagnostic dose of pirimiphos-methyl, whereas AcerKis and AcerKdrKis strains showed susceptibility at 0.5× the diagnostic dose. Anopheles gambiae s.s., Anopheles coluzzii, and Anopheles arabiensis were identified. Allelic frequencies of kdrR (1014F) and ace-1R (119S) mutations in the field populations varied from 0.65 to 1 and 0 to 0.84, respectively. The field An. gambiae displayed high-resistance levels against deltamethrin and pirimiphos-methyl when compared with those of the laboratory An. gambiae-resistant strains. These results exhibit the complexity of underlying insecticide resistance mechanisms in these field malaria vectors.

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