scholarly journals The G119S Acetylcholinesterase (Ace-1) Target Site Mutation Confers Carbamate Resistance in the Major Malaria Vector Anopheles gambiae from Cameroon: A Challenge for the Coming IRS Implementation

Author(s):  
Emmanuel Elanga-Ndille ◽  
Lynda Nouage ◽  
Cyrille Ndo ◽  
Achille Binyang ◽  
Tatiane Assatse ◽  
...  

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the Ace-1R mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8 ± 3.5 % mortality) and propoxur (55.71 ± 2.9 %) but a full susceptibility to the organophosphate fenithrothion. The TaqMan genotyping of the Ace-1R mutation with field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1R and carbamate resistance at allelic [(bendiocarb; OR = 75.9; P<0.0001) and (propoxur; OR= 1514; P<0.0001)] and genotypic [RR vs SS (bendiocarb; OR = 120.8; P<0.0001) and (propoxur; OR= 3277; P<0.0001) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1R represents a serious challenge to future implementation of IRS-based interventions using carbamates or organophosphates in Cameroon.

Author(s):  
Emmanuel Elanga-Ndille ◽  
Lynda Nouage ◽  
Cyrille Ndo ◽  
Achille Binyang ◽  
Tatiane Assatse ◽  
...  

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the G119S mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8 ± 3.5 % mortality) and propoxur (55.71 ± 2.9 %) but a full susceptibility to the organophosphate fenithrothion. The TaqMan genotyping of the G119S mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1R and carbamate resistance at allelic [(bendiocarb; OR = 75.9; P<0.0001) and (propoxur; OR= 1514; P<0.0001)] and genotypic [RR vs SS (bendiocarb; OR = 120.8; P<0.0001) and (propoxur; OR= 3277; P<0.0001) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1R represents a serious challenge to future implementation of IRS-based interventions using carbamates or organophosphates in Cameroon


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 790 ◽  
Author(s):  
Elanga-Ndille ◽  
Nouage ◽  
Ndo ◽  
Binyang ◽  
Assatse ◽  
...  

Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the G119S mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field-collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8% ± 3.5% mortality) and propoxur (55.71% ± 2.9%) but a full susceptibility to the organophosphate fenitrothion. The TaqMan genotyping of the G119S mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1R and carbamate resistance at allelic ((bendiocarb; odds ratio (OR) = 75.9; p < 0.0001) and (propoxur; OR = 1514; p < 0.0001)) and genotypic (homozygote resistant vs. homozygote susceptible (bendiocarb; OR = 120.8; p < 0.0001) and (propoxur; OR = 3277; p < 0.0001)) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1R represents a serious challenge to future implementation of indoor residual spraying (IRS)-based interventions using carbamates or organophosphates in Cameroon.


2011 ◽  
Vol 7 (6) ◽  
pp. 947-949 ◽  
Author(s):  
Laith Yakob

A cryptic subgroup of Anopheles gambiae sensu stricto mosquitoes was recently discovered in West Africa. This ‘GOUNDRY’ subgroup has increased susceptibility to Plasmodium falciparum , the most deadly form of malaria. Unusual for this major malaria vector, GOUNDRY mosquitoes also seem to bite exclusively outdoors. A mathematical model is developed to assess the epidemiological implications of current vector control tools, bednets and indoor residual spray, preferentially suppressing the more typical indoor biting mosquitoes. It is demonstrated that even if the GOUNDRY mosquitoes have a decreased preference for human blood, vector controls which select for increased GOUNDRY abundance relative to their indoor biting counterparts risks intensifying malaria transmission. Given the widely observed phenomenon of outdoor biting by major malaria vectors, this behaviour should not be ignored in future modelling efforts and warrants serious consideration in control programme strategy.


2016 ◽  
Vol 57 (3) ◽  
pp. 345-365
Author(s):  
MANUEL SÁNCHEZ-ELIPE LORENTE ◽  
ALFREDO GONZÁLEZ-RUIBAL ◽  
JESÚS F. JORDÁ PARDO ◽  
CARLOS MARÍN SUÁREZ

AbstractOver the last few decades the number of radiocarbon dates available for West Central Africa has increased substantially, even though it is still meagre compared with other areas of the continent. In order to contribute to a better understanding of the Iron Age of this area we present and analyze a total of 22 radiocarbon dates obtained from sites from the island of Corisco (Equatorial Guinea). By comparing them with those from Equatorial Guinea, southern Cameroon, and coastal Gabon and Congo we intend to clarify the picture of the West Central African Iron Age and propose a more accurate archaeological sequence.


2018 ◽  
Author(s):  
Chris S. Clarkson ◽  
Alistair Miles ◽  
Nicholas J. Harding ◽  
David Weetman ◽  
Dominic Kwiatkowski ◽  
...  

AbstractResistance to pyrethroid insecticides is a major concern for malaria vector control, because these are the compounds used in almost all insecticide-treated bed-nets (ITNs), and are also widely used for indoor residual spraying (IRS). Pyrethroids target the voltage-gated sodium channel (VGSC), an essential component of the mosquito nervous system, but substitutions in the amino acid sequence can disrupt the activity of these insecticides, inducing a resistance phenotype. Here we use Illumina whole-genome sequence data from phase 1 of the Anopheles gambiae 1000 Genomes Project (Ag1000G) to provide a comprehensive account of genetic variation in the Vgsc gene in mosquito populations from eight African countries. In addition to the three known resistance alleles, we describe 20 non-synonymous nucleotide substitutions at appreciable frequency in one or more populations that are previously unknown in Anopheles mosquitoes. Thirteen of these novel alleles were found to occur almost exclusively on haplotypes carrying the known L995F resistance allele (L1014F in Musca domesticus codon numbering), and may enhance or compensate for the L995F resistance pheno-type. A novel mutation I1527T, which is adjacent to a predicted pyrethroid binding site, was found in tight linkage with either of two alleles causing a V402L substitution, similar to a combination of substitutions found to cause pyrethroid resistance in several other insect species. We analyse the genetic backgrounds on which non-synonymous alleles are found, to determine which alleles have experienced recent positive selection, and to refine our understanding of the spread of resistance between species and geographical locations. We describe twelve distinct haplotype groups with evidence of recent positive selection, five of which carry the known L995F resistance allele, five of which carry the known L995S resistance allele, one of which carries the novel I1527T allele, and one of which carries a novel M490I allele. Seven of these groups are localised to a single geographical location, and five comprise haplotypes from different countries, in one case separated by over 3000 km, providing new information about the geographical distribution and spread of resistance. We also find evidence for multiple introgression events transmitting resistance alleles between An. gambiae and An. coluzzii. We identify markers that could be used to design high-throughput, low-cost genetic assays for improved surveillance of pyrethroid resistance in the field. Our results demonstrate that the molecular basis of target-site pyrethroid resistance in malaria vectors is more complex than previously appreciated, and provide a foundation for the development of new genetic tools to track the spread insecticide resistance and improve the design of strategies for insecticide resistance management.


2020 ◽  
Vol 14 (8) ◽  
pp. 2724-2736
Author(s):  
Rock Aikpon ◽  
Antoine Missihoun ◽  
Antoine Lokossou ◽  
Gorgias Aikpon ◽  
Sahidou Salifou ◽  
...  

La résistance des vecteurs du paludisme aux insecticides utilisés dans la lutte anti vectorielle est un obstacle majeur pour les programmes nationaux de lutte contre le paludisme. La présente étude avait pour but d’évaluer la diversité génétique des populations de Anopheles gambiae et la résistance aux insecticides (mutation Kdr et Ace-1) en zone cotonnière au Bénin. Deux méthodes de capture ont été utilisées pour la collecte d’échantillon. La capture sur appât humain et la récolte de la faune résiduelle matinale par spray. La PCR SINE a permis de distinguer deux espèces jumelles et d’obtenir les différents génotypes pour les deux gènes. Deux espèces du complexe An. gambiae s.l ont été trouvées en sympatrie (Anopheles coluzzii et Anopheles gambiae). La résistance kdr et Ace-1 connaissent un flux saisonnier. L’allèle résistant du gène kdr est fixé dans la population de vecteurs (Fis>0). Par contre, un déficit de l’allèle résistant est noté au niveau du gène Ace-1 (Fis<0).Mots clés : Hétérogénéité, génétique, résistance, vecteur, paludisme. English Title: Genetic heterogeneity and resistance to insecticides in malaria vector Anopheles gambiae s.l in the cotton growing area in Benin Resistance of malaria vectors to insecticides used in vector control is a major threat for national malaria control programs. The purpose of this study was to assess the genetic diversity of Anopheles gambiae populations and resistance to insecticides (Kdr Ace-1 mutation) in the cotton growing area in Benin. Two samples methods were used for mosquito collection: Human Landing catch (HLC) and the residual fauna collection by spray. The SINE PCR allow to identify species the different genotypes resistance genes. Two species of the An. gambiae s.l complex have been found in sympatry (Anopheles coluzzii and Anopheles gambiae). kdr and Ace-1 resistance had seasonal variation trend. The kdr resistance allele is fixed in the vector population (Fis> 0). Moreover, a deficit of the Ace-1 resistance allele was observed (Fis <0). Keywords: Heterogeneity, genetic, resistance, vector, malaria.


2020 ◽  
Vol 5 ◽  
pp. 146
Author(s):  
Francis N. Nkemngo ◽  
Leon M. J. Mugenzi ◽  
Ebai Terence ◽  
Abdoulaye Niang ◽  
Murielle J. Wondji ◽  
...  

Background: Reducing the burden of malaria requires better understanding of vector populations, particularly in forested regions where the incidence remains elevated. Here, we characterized malaria vectors in a locality near the Yaoundé international airport, Cameroon, including species composition, abundance, Plasmodium infection rate, insecticide resistance profiles and underlying resistance mechanisms. Methods: Blood-fed adult mosquitoes resting indoors were aspirated from houses in April 2019 at Elende, a village located 2 km from the Yaoundé-Nsimalen airport. Female mosquitoes were forced to lay eggs to generate F1 adult progeny. Bioassays were performed to assess resistance profile to insecticides. The threshold of insecticide susceptibility was defined above 98% mortality rate and mortality rates below 90% were indicative of confirmed insecticide resistance. Furthermore, the molecular basis of resistance and Plasmodium infection rates were investigated. Results: Anopheles funestus s.s. was most abundant species in Elende (85%) followed by Anopheles gambiae s.s. (15%) with both having a similar sporozoite rate. Both species exhibited high levels of resistance to pyrethroids (<40% mortality). An. gambiae s.s. was also resistant to DDT (9.9% mortality) and bendiocarb (54% mortality) while susceptible to organophosphate. An. funestus s.s. was resistant to dieldrin (1% mortality), DDT (86% mortality) but susceptible to carbamates and organophosphates. The L119F-GSTe2 resistance allele (8%) and G119S ace-1 resistance allele (15%) were detected in An. funestus s.s. and An. gambiae s.s., respectively. Furthermore, the high pyrethroid/DDT resistances in An. gambiae s.s. corresponded with an increase frequency of 1014F kdr allele (95%). Transcriptional profiling of candidate cytochrome P450 genes reveals the over-expression of CYP6P5, CYP6P9a and CYP6P9b. Conclusion: The resistance to multiple insecticide classes observed in these vector populations alongside the high Plasmodium sporozoite rate highlights the challenges that vector control programs encounter in sustaining the regular benefits of contemporary insecticide-based control interventions in forested areas.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Adandé A. Medjigbodo ◽  
Luc S. Djogbénou ◽  
Oswald Y. Djihinto ◽  
Romaric B. Akoton ◽  
Emmanuella Abbey ◽  
...  

Abstract Background Existing mechanisms of insecticide resistance are known to help the survival of mosquitoes following contact with chemical compounds, even though they could negatively affect the life-history traits of resistant malaria vectors. In West Africa, the knockdown resistance mechanism kdrR (L1014F) is the most common. However, little knowledge is available on its effects on mosquito life-history traits. The fitness effects associated with this knockdown resistance allele in Anopheles gambiae sensu stricto (s.s.) were investigated in an insecticide-free laboratory environment. Methods The life-history traits of Kisumu (susceptible) and KisKdr (kdr resistant) strains of An. gambiae s.s. were compared. Larval survivorship and pupation rate were assessed as well as fecundity and fertility of adult females. Female mosquitoes of both strains were directly blood fed through artificial membrane assays and then the blood-feeding success, blood volume and adult survivorship post-blood meal were assessed. Results The An. gambiae mosquitoes carrying the kdrR allele (KisKdr) laid a reduced number of eggs. The mean number of larvae in the susceptible strain Kisumu was three-fold overall higher than that seen in the KisKdr strain with a significant difference in hatching rates (81.89% in Kisumu vs 72.89% in KisKdr). The KisKdr larvae had a significant higher survivorship than that of Kisumu. The blood-feeding success was significantly higher in the resistant mosquitoes (84%) compared to the susceptible ones (34.75%). However, the mean blood volume was 1.36 µL/mg, 1.45 µL/mg and 1.68 µL/mg in Kisumu, homozygote and heterozygote KisKdr mosquitoes, respectively. After blood-feeding, the heterozygote KisKdr mosquitoes displayed highest survivorship when compared to that of Kisumu. Conclusions The presence of the knockdown resistance allele appears to impact the life-history traits, such as fecundity, fertility, larval survivorship, and blood-feeding behaviour in An. gambiae. These data could help to guide the implementation of more reliable strategies for the control of malaria vectors.


2018 ◽  
Author(s):  
Diego Ayala ◽  
Ousman Akone-Ella ◽  
Nil Rahola ◽  
Pierre Kengne ◽  
Marc F. Ngangue ◽  
...  

AbstractDuring the last decade, the endosymbiont bacterium Wolbachia has emerged as a biological tool for vector disease control. However, for long time, it was believed that Wolbachia was absent in natural populations of Anopheles. The recent discovery that species within the Anopheles gambiae complex hosts Wolbachia in natural conditions has opened new opportunities for malaria control research in Africa. Here, we investigated the prevalence and diversity of Wolbachia infection in 25 African Anopheles species in Gabon (Central Africa). Our results revealed the presence of Wolbachia in 16 of these species, including the major malaria vectors in this area. The infection prevalence varied greatly among species, confirming that sample size is a key factor to detect the infection. Moreover, our sequencing and phylogenetic analyses showed the important diversity of Wolbachia strains that infect Anopheles. Co-evolutionary analysis unveiled patterns of Wolbachia transmission within Anopheles species, suggesting that past independent acquisition events were followed by co-cladogenesis. The large diversity of Wolbachia strains that infect natural populations of Anopheles offers a promising opportunity to select suitable phenotypes for suppressing Plasmodium transmission and/or manipulating Anopheles reproduction, which in turn could be used to reduce the malaria burden in Africa.


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