scholarly journals Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly Plasmodium-Infected Malaria Vector Anopheles funestus Sensu Stricto from Sahel of Northern Nigeria

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 454
Author(s):  
Sulaiman S. Ibrahim ◽  
Muhammad M. Mukhtar ◽  
Helen Irving ◽  
Jacob M. Riveron ◽  
Amen N. Fadel ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Sensu Stricto ◽  
Bed Nets ◽  
Metabolic Resistance ◽  
Biting Rate ◽  
Insecticide Treated Bed Nets ◽  
Sahel Region

The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector Anopheles funestus sensu stricto from Sahel of Nigeria was characterised. An. funestus s.s. was the only vector found, with a high human blood index (100%) and a biting rate of 5.3/person/night. High Plasmodium falciparum infection was discovered (sporozoite rate = 54.55%). The population is resistant to permethrin (mortality = 48.30%, LT50 = 65.76 min), deltamethrin, DDT (dichlorodiphenyltrichloroethane) and bendiocarb, with mortalities of 29.44%, 56.34% and 54.05%, respectively. Cone-bioassays established loss of efficacy of the pyrethroid-only long-lasting insecticidal nets (LLINs); but 100% recovery of susceptibility was obtained for piperonylbutoxide (PBO)-containing PermaNet®3.0. Synergist bioassays with PBO and diethyl maleate recovered susceptibility, implicating CYP450s (permethrin mortality = 78.73%, χ2 = 22.33, P < 0.0001) and GSTs (DDT mortality = 81.44%, χ2 = 19.12, P < 0.0001). A high frequency of 119F GSTe2 mutation (0.84) was observed (OR = 16, χ2 = 3.40, P = 0.05), suggesting the preeminent role of metabolic resistance. These findings highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in Nigeria.

scholarly journals Evidence of Insecticide Resistance to Pyrethroids and Bendiocarb in Anopheles funestus from Tsararano, Marovoay District, Madagascar

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Tsiriniaina Rakotondranaivo ◽  
Solohery Fanomezana Randriamanarivo ◽  
Mihajarilala Rakotoniaina Tanjona ◽  
Inès Vigan-Womas ◽  
Milijaona Randrianarivelojosia ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Insecticide Resistance ◽  
Resistance Mechanism ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Enzymatic Activities ◽  
Eastern Coast ◽  
Bed Nets ◽  
Metabolic Resistance ◽  
Central Highland

Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insecticide treated bed nets (LLINs) and on indoor residual spraying (IRS) in the central highland area as well as a small area on the eastern coast. We tested insecticide resistance mechanisms of Anopheles funestus from Tsararano, a malaria endemic village in the coastal health district of Marovoay. Methods. Insecticide susceptibility bioassays were done in July 2017 on first-generation Anopheles funestus (F1) to assess (i) the susceptibility to permethrin (0.05%), deltamethrin (0.05%), DDT (4%), malathion (5%), fenitrothion (1%), and bendiocarb (0.1%); (ii) the effect of preexposure to the piperonyl butoxide (PBO) synergist; and (iii) the enzymatic activities of cytochrome P450, esterases, and glutathione S-transferases (GST). Results. Our results demonstrated that An. funestus was phenotypically resistant to pyrethroids and bendiocarb, with a mortality rate (MR) of 33.6% (95%CI: 24.5-43.7%) and 86% (95%CI: 77.6-92.1%), respectively. In contrast, An. funestus were 100% susceptible to DDT and organophosphates (malathion and fenitrothion). Preexposure of An. funestus to PBO synergist significantly restored the susceptibility to bendiocarb (MR=100%) and increased the MR in the pyrethroid group, from 96% (95%CI: 90.0-98.9%) to 100% for deltamethrin and permethrin, respectively (χ2 = 43, df = 3, P< 0.0001). Enzymatic activities of cytochrome P450 and α-esterases were significantly elevated among An. funestus compared with the IPM reference strain (Mann-Whitney U= 30, P<0.0001; U = 145.5, P <0.0001, respectively). No significant differences of β-esterases activities compared to the IPM reference strain were observed (Mann-Whitney U = 392.5, P = 0.08). Conclusion. In Tsararano, despite the absence of an IRS programme, there is evidence of high levels of insecticide resistance to pyrethroids and bendiocarb in An. funestus. Biochemical data indicated that a metabolic resistance mechanism through the cytochrome P450 genes is operating in the An. funestus population.

scholarly journals Influence of GST- and P450-based metabolic resistance to pyrethroids on blood feeding in the major African malaria vector Anopheles funestus

2020 ◽  
Author(s):  
Lynda Nouage ◽  
Emmanuel Elanga-Ndille ◽  
Achille Binyang ◽  
Magellan Tchouakui ◽  
Tatiane Atsatse ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Resistance Genes ◽  
Blood Meal ◽  
Anopheles Funestus ◽  
Blood Feeding ◽  
Meal Size ◽  
Metabolic Resistance ◽  
Feeding Success ◽  
Blood Meal Size

AbstractInsecticide resistance genes are often associated with pleiotropic effects on various mosquito life-history traits. However, very little information is available on the impact of insecticide resistance, especially metabolic resistance, on blood feeding process in mosquitoes. Here, using two recently detected DNA-based metabolic markers in the major malaria vector, An. funestus, we investigated how metabolic resistance genes could affect blood meal intake.After allowing both field F1 and lab F8 Anopheles funestus strains to feed on human arm for 30 minutes, we assessed the association between key parameters of blood meal process including, probing time, feeding duration, blood feeding success and blood meal size, and markers of glutathione S-transferase (L119F-GSTe2) and cytochrome P450 (CYP6P9a_R) - mediated metabolic resistance. None of the parameters of blood meal process was associated with L119F-GSTe2 genotypes. In contrast, for CYP6P9a_R, homozygote resistant mosquitoes were significantly more able to blood-feed than homozygote susceptible (OR = 3.3; CI 95%: 1.4-7.7; P =0.01) mosquitoes. Moreover, the volume of blood meal ingested by CYP6P9a-SS mosquitoes was lower than that of CYP6P9a-RS (P<0.004) and of CYP6P9a-RR (P<0.006). This suggests that CYP6P9a gene affects the feeding success and blood meal size of An. funestus. However, no correlation was found in the expression of CYP6P9a and that of genes encoding for salivary proteins involved in blood meal process.This study suggests that P450-based metabolic resistance may increase the blood feeding ability of malaria vectors and potential impacting their vectorial capacity.

scholarly journals High insecticide resistance in the major malaria vector Anopheles coluzzii in Chad Republic

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Sulaiman S. Ibrahim ◽  
Amen N. Fadel ◽  
Magellan Tchouakui ◽  
Ebai Terence ◽  
Murielle J. Wondji ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Molecular Mechanisms ◽  
Pyrethroid Resistance ◽  
Indoor Residual Spraying ◽  
Taqman Assay ◽  
Anopheles Coluzzii ◽  
Metabolic Resistance ◽  
Low Genetic Diversity ◽  
Bendiocarb Resistance ◽  
Sahel Region

Abstract Background The Sahel region of Chad Republic is a prime candidate for malaria pre-elimination. To facilitate pre-elimination efforts in this region, two populations of Anopheles coluzzii from Central Chad Republic were characterized, their insecticide resistance profile and the possible molecular mechanisms driving the resistance in the field investigated. Methods Bloodfed female Anopheles gambiae s.l. resting indoor, were collected at N’djamena and Massakory, Chad in 2018 and characterized for species composition, and infection rate was determined using the TaqMan assay. Susceptibility to various insecticides was assessed using WHO tube bioassays. Cone bioassays were conducted using various long-lasting insecticidal nets (LLINs). Results were analysed using Chi Square test. Knockdown resistance (kdr) and ace-1 markers were investigated by TaqMan genotyping. Results Anopheles coluzzii was the major vector found in N’djamena (100%) and Massakory (~ 94%). No Plasmodium was found in 147 bloodfed F0An. coluzzii (82 from N’djamena and 65 from Massakory). High intensity pyrethroid resistance was observed with mortalities of < 2% for permethrin, deltamethrin and etofenprox, and with < 50% and < 60% dead following exposure to 10× diagnostic doses of deltamethrin and permethrin, respectively. For both sites, < 10% mortalities were observed with DDT. Synergist bioassays with piperonylbutoxide significantly recovered pyrethroid susceptibility in Massakory populations, implicating CYP450s (mortality = 13.6% for permethrin, χ2 = 22.8, df = 1, P = 0.0006; mortality = 13.0% for deltamethrin, χ2 = 8.8, df = 1, P < 0.00031). Cone-bioassays established complete loss of efficacy of the pyrethroid-based LLINs; and a 100% recovery of susceptibility following exposure to the roof of PermaNet®3.0, containing piperonylbutoxide. Both populations were susceptible to malathion, but high bendiocarb resistance was observed in Massakory population. The absence of ace-1 mutation points to the role of metabolic resistance in the bendiocarb resistance. Both 1014F and 1014S mutations were found in both populations at around 60% and < 20% respectively. Sequencing of intron-1 of the voltage-gated sodium channel revealed a low genetic diversity suggesting reduced polymorphism. Conclusions Multiple resistance in An. coluzzii populations from Chad highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in the Sahel of this country. The pyrethroid-synergists LLINs (e.g. PermaNet®3.0) and organophosphate-based IRS maybe the alternatives for malaria control in this region.

scholarly journals Anopheles arabiensis and Anopheles funestus biting patterns in Dielmo, an area of low level exposure to malaria vectors

2020 ◽  
Author(s):  
Souleymane Doucoure ◽  
Omar Thiaw ◽  
Amélé N. Wotodjo ◽  
Charles Bouganali ◽  
Nafissatou Diagne ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Anopheles Arabiensis ◽  
Anopheles Funestus ◽  
Sensu Stricto ◽  
Molecular Techniques ◽  
Malaria Vectors ◽  
Bed Nets ◽  
Low Level ◽  
Biting Rate ◽  
Outdoor Biting

Abstract Background In Dielmo, Senegal, the widespread use of long-lasting insecticidal nets has decreased both the incidence of malaria and the density of the Anopheles population. However, persistent low-level malaria transmission may hamper efforts to eliminate the disease. Therefore, continuous monitoring of the vector population is needed in order to improve knowledge of Anopheles biting behaviour and to readjust control interventions.Methods In 2015, Anopheles were collected every month for a whole year and each specimen was identified using morphological and molecular techniques. The biting pattern of each species was analysed according to night (7pm–7am) and morning (7am–11am) periods, the place of biting and the season. The ELISA CSP technique was used to assess the Plasmodium falciparum sporozoite rate to evaluate the entomological inoculation rate (EIR).Results Anopheles arabiensis and Anopheles funestus sensu stricto were found to be the main vectors biting humans. Overall, the biting rate was low, at 3.84bites per night (bpn) and 1.27 bites per morning (bpm), respectively (IRR =3.04, CI = [1.84-5.00], p<0.001). The EIR was 2.51 and 5.03 infectious bites per year during the night and morning, respectively. During the night, the An. arabiensis and An. funestus biting rate was 1.81 bpn and 1.71 bpn, respectively (IRR=0.95, CI= [0.46-1.92], p=0.88). During the morning, their density decreased to 0.51 bpm and 0.73 bpm for An. arabiensis and An. funestus, respectively (IRR=1.47, CI= [0.58-3.71], p=0.41). During the night and the morning, no specific trend of indoor or outdoor biting was observed in the dry and rainy season for both vectors. Conclusion This study highlighted low level Anopheles nocturnal and diurnal biting and the associated risk of malaria transmission. It showed also the influence of the season on the indoor and outdoor biting pattern, indicating that the human population could be exposed all year round to a low level of Anopheles bites. Control programmes should increase awareness of the use of bed nets throughout the year and promote the development and implementation of complimentary tools to target Anopheles biting shortly after dawn when people are still indoors.

scholarly journals Multiple Insecticide Resistance in the Malaria Vector Anopheles funestus from Northern Cameroon Is Mediated by Metabolic Resistance Alongside Potential Target Site Insensitivity Mutations

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0163261 ◽  
Author(s):  
Benjamin D. Menze ◽  
Jacob M. Riveron ◽  
Sulaiman S. Ibrahim ◽  
Helen Irving ◽  
Christophe Antonio-Nkondjio ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Target Site ◽  
Metabolic Resistance ◽  
Potential Target ◽  
Northern Cameroon

scholarly journals Bio-efficacy of new long-lasting insecticide-treated bed nets against Anopheles funestus and Anopheles gambiae from central and northern Mozambique

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Ana Paula Abílio ◽  
Pelágio Marrune ◽  
Nilsa de Deus ◽  
Francisco Mbofana ◽  
Pedro Muianga ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Anopheles Funestus ◽  
Bed Nets ◽  
Insecticide Treated Bed Nets

scholarly journals Evidence of a multiple insecticide resistance in the malaria vector Anopheles funestus in South West Nigeria

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Rousseau J. Djouaka ◽  
Seun M. Atoyebi ◽  
Genevieve M. Tchigossou ◽  
Jacob M. Riveron ◽  
Helen Irving ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
South West

scholarly journals A differential expression of pyrethroid resistance genes in the malaria vector Anopheles funestus across Uganda is associated with patterns of gene flow

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240743
Author(s):  
Maurice Marcel Sandeu ◽  
Charles Mulamba ◽  
Gareth D. Weedall ◽  
Charles S. Wondji
Keyword(s):  
Population Structure ◽  
Gene Flow ◽  
Genetic Structure ◽  
Genetic Differentiation ◽  
Insecticide Resistance ◽  
Pyrethroid Resistance ◽  
Anopheles Funestus ◽  
Metabolic Resistance ◽  
Transcription Analysis ◽  
Genome Wide

Background Insecticide resistance is challenging the effectiveness of insecticide-based control interventions to reduce malaria burden in Africa. Understanding the molecular basis of insecticides resistance and patterns of gene flow in major malaria vectors such as Anopheles funestus are important steps for designing effective resistance management strategies. Here, we investigated the association between patterns of genetic structure and expression profiles of genes involved in the pyrethroid resistance in An. funestus across Uganda and neighboring Kenya. Methods Blood-fed mosquitoes An. funestus were collected across the four localities in Uganda and neighboring Kenya. A Microarray-based genome-wide transcription analysis was performed to identify the set of genes associated with permethrin resistance. 17 microsatellites markers were genotyped and used to establish patterns of genetic differentiation. Results Microarray-based genome-wide transcription profiling of pyrethroid resistance in four locations across Uganda (Arua, Bulambuli, Lira, and Tororo) and Kenya (Kisumu) revealed that resistance was mainly driven by metabolic resistance. The most commonly up-regulated genes in pyrethroid resistance mosquitoes include cytochrome P450s (CYP9K1, CYP6M7, CYP4H18, CYP4H17, CYP4C36). However, expression levels of key genes vary geographically such as the P450 CYP6M7 [Fold-change (FC) = 115.8 (Arua) vs 24.05 (Tororo) and 16.9 (Kisumu)]. In addition, several genes from other families were also over-expressed including Glutathione S-transferases (GSTs), carboxylesterases, trypsin, glycogenin, and nucleotide binding protein which probably contribute to insecticide resistance across Uganda and Kenya. Genotyping of 17 microsatellite loci in the five locations provided evidence that a geographical shift in the resistance mechanisms could be associated with patterns of population structure throughout East Africa. Genetic and population structure analyses indicated significant genetic differentiation between Arua and other localities (FST>0.03) and revealed a barrier to gene flow between Arua and other areas, possibly associated with Rift Valley. Conclusion The correlation between patterns of genetic structure and variation in gene expression could be used to inform future interventions especially as new insecticides are gradually introduced.

scholarly journals An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 143 ◽  
Author(s):  
Benjamin D. Menze ◽  
Mersimine F. Kouamo ◽  
Murielle J. Wondji ◽  
Williams Tchapga ◽  
Micareme Tchoupo ◽  
...  
Keyword(s):  
Anopheles Funestus ◽  
Blood Feeding ◽  
Malaria Vectors ◽  
Bed Nets ◽  
Glutathione S Transferase ◽  
Metabolic Resistance ◽  
Experimental Hut ◽  
The Impact ◽  
Long Lasting Insecticidal Nets ◽  
Permanet 3.0

Growing insecticide resistance in malaria vectors is threatening the effectiveness of insecticide-based interventions, including Long Lasting Insecticidal Nets (LLINs). However, the impact of metabolic resistance on the effectiveness of these tools remains poorly characterized. Using experimental hut trials and genotyping of a glutathione S-transferase resistance marker (L119F-GSTe2), we established that GST-mediated resistance is reducing the efficacy of LLINs against Anopheles funestus. Hut trials performed in Cameroon revealed that Piperonyl butoxide (PBO)-based nets induced a significantly higher mortality against pyrethroid resistant An. funestus than pyrethroid-only nets. Blood feeding rate and deterrence were significantly higher in all LLINs than control. Genotyping the L119F-GSTe2 mutation revealed that, for permethrin-based nets, 119F-GSTe2 resistant mosquitoes have a greater ability to blood feed than susceptible while the opposite effect is observed for deltamethrin-based nets. For Olyset Plus, a significant association with exophily was observed in resistant mosquitoes (OR = 11.7; p < 0.01). Furthermore, GSTe2-resistant mosquitoes (cone assays) significantly survived with PermaNet 2.0 (OR = 2.1; p < 0.01) and PermaNet 3.0 (side) (OR = 30.1; p < 0.001) but not for Olyset Plus. This study shows that the efficacy of PBO-based nets (e.g., blood feeding inhibition) against pyrethroid resistant malaria vectors could be impacted by other mechanisms including GST-mediated metabolic resistance not affected by the synergistic action of PBO. Mosaic LLINs incorporating a GST inhibitor (diethyl maleate) could help improve their efficacy in areas of GST-mediated resistance.

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