Dynamics of insecticide resistance in malaria vectors in Benin: first evidence of the presence of L1014S kdr mutation in Anopheles gambiae from West Africa

Djègbè, Innocent; Boussari, Olayidé; Sidick, Aboubakar; Martin, Thibaud; Ranson, Hilary; Chandre, Fabrice; Akogbéto, Martin; Corbel, Vincent

doi:10.1186/1475-2875-10-261

Cited by 140 publications

(135 citation statements)

References 55 publications

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“…Such kdr 1014 F frequency in An. gambiae has been recently reported throughout sub-Saharan Africa [18, 27, 28]. In 2011 the kdr 1575Y allele was detected in the- S-form only and occurred solely upon a 1014 F haplotypic background confirming the results of Jones et al [6].…”

Section: Discussionsupporting

confidence: 79%

Molecular characterization of DDT resistance in Anopheles gambiae from Benin

et al. 2014

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BackgroundInsecticide resistance in the mosquito vector is the one of the main obstacles against effective malaria control. In order to implement insecticide resistance management strategies, it is important to understand the genetic factors involved. In this context, we investigated the molecular basis of DDT resistance in the main malaria vector from Benin.MethodsAnopheles gambiae mosquitoes were collected from four sites across Benin and identified to species/molecular form. Mosquitoes from Cotonou (M-form), Tori-Bossito (S-form) and Bohicon (S-form) were exposed to DDT 4% at a range of exposure times (30 min to 300 min). Another batch of mosquitoes from Cotonou and Malanville were exposed to DDT for 1 hour and the survivors 48 hours post exposure were used to quantify metabolic gene expression. Quantitative PCR assays were used to quantify mRNA levels of metabolic enzymes: GSTE2, GSTD3, CYP6P3 and CYP6M2. Expression (fold-change) was calculated using the ∆∆Ct method and compared to susceptible strains. Detection of target-site mutations (L1014F, L1014S and N1575Y) was performed using allelic discrimination TaqMan assays.ResultsDDT resistance was extremely high in all populations, regardless of molecular form, with no observed mortality after 300 min exposure. In both DDT-survivors and non-exposed mosquitoes, GSTE2 and GSTD3 were over-expressed in the M form at 4.4-fold and 3.5-fold in Cotonou and 1.5-fold and 2.5-fold in Malanville respectively, when compared to the susceptible strain. The CYP6M2 and CYP6P3 were over-expressed at 4.6-fold and 3.8-fold in Cotonou and 1.2-fold and 2.5-fold in Malanville respectively. In contrast, no differences in GSTE2 and CYP6M2 were observed between S form mosquitoes from Tori-Bossito and Bohicon compared to susceptible strain. The 1014 F allele was fixed in the S-form and at high frequency in the M-form (0.7-0.914). The frequency of 1575Y allele was 0.29-0.36 in the S-form and nil in the M-form. The 1014S allele was detected in the S form of An. gambiae in a 1014 F/1014S heterozygous specimen.ConclusionOur results show that the kdr 1014 F, 1014S and 1575Y alleles are widespread in Benin and the expression of two candidate metabolic markers (GSTE2 and CYP6M2) are over-expressed specifically in the M-form.

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Section: Discussionsupporting

confidence: 79%

Molecular characterization of DDT resistance in Anopheles gambiae from Benin

et al. 2014

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“…All these reports including the present highlight the level of spread of resistance to all class of insecticides deployed for vector control, either as LLIN already in place or IRS under consideration for implementation in Côte d'Ivoire; an increasing trend commonly shared by several countries in West Africa[34]–[39].…”

Section: Discussionmentioning

confidence: 99%

Re-Visiting Insecticide Resistance Status in Anopheles gambiae from Côte d'Ivoire: A Nation-Wide Informative Survey

et al. 2013

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Insecticide resistance constitutes a major threat that may undermine current gain in malaria control in most endemic countries. National Malaria Control Programmes (NMCPs) need as much information as possible on the resistance status of malaria vectors and underlying mechanisms in order to implement the most relevant and efficient control strategy. Bioassays, biochemical and molecular analysis were performed on An. gambiae collected in six sentinel sites in Côte d'Ivoire. The sites were selected on the basis of their bioclimatic status and agricultural practices. An. gambiae populations across sites showed high levels of resistance to organochloride, pyrethroid and carbamate insecticides. The kdr and ace-1R mutations were detected in almost all sentinel sites with mosquitoes on the coastal and cotton growing areas mostly affected by these mutations. At almost all sites, the levels of detoxifying enzymes (mixed-function oxidases (MFOs), non-specific esterases (NSE) and glutathione-S-transferases (GSTs)) in An. gambiae populations were significantly higher than the levels found in the susceptible strain Kisumu. Pre-exposure of mosquitoes to PBO, an inhibitor of MFOs and NSEs, significantly increased mortality rates to pyrethroids and carbamates in mosquitoes but resistance in most cases was not fully synergised by PBO, inferring a residual role of additional mechanisms, including kdr and ace-1 site insensitivity. The large distribution of resistance in Côte d'Ivoire raises an important question of whether to continue to deploy pyrethroid-based long-lasting insecticidal nets (LLINs) and insecticide residual spraying (IRS) towards which resistance continues to rise with no guarantee that the level of resistance would not compromise their efficacy. Innovative strategies that combine insecticide and synergists in LLINs or spatially LLIN and an effective non-pyrethroid insecticide for IRS could be in the short term the best practice for the NMCP to manage insecticide resistance in malaria vectors in Côte d'Ivoire and other endemic countries facing resistance.

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“…Despite intense intervention efforts, the estimated of morbidity and mortality levels continue to rise. Chemotherapy and vector control programs have been largely ineffective, owing to the emergence and spread of insecticide-resistant mosquito vectors and drug-resistant plasmodium strains [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms

Yamamoto

Iwagami

Seki

et al. 2017

Parasitology International

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Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.

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Dynamics of insecticide resistance in malaria vectors in Benin: first evidence of the presence of L1014S kdr mutation in Anopheles gambiae from West Africa

Cited by 140 publications

References 55 publications

Molecular characterization of DDT resistance in Anopheles gambiae from Benin

Molecular characterization of DDT resistance in Anopheles gambiae from Benin

Re-Visiting Insecticide Resistance Status in Anopheles gambiae from Côte d'Ivoire: A Nation-Wide Informative Survey

Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms

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