Dataset Information

Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Cote d'Ivoire.

ABSTRACT: Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d'Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose-response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22-43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r² = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures.

SUBMITTER: Oumbouke WA

PROVIDER: S-EPMC7493912 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d'Ivoire.

Oumbouke Welbeck A WA Pignatelli Patricia P Barreaux Antoine M G AMG Tia Innocent Z IZ Koffi Alphonsine A AA Ahoua Alou Ludovic P LP Sternberg Eleanore D ED Thomas Matthew B MB Weetman David D N'Guessan Raphael R

Scientific reports 20200915 1

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d'Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. c ...[more]

PMID: 32934291

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Project description:Although malaria is endemic in coastal Côte d'Ivoire, updated data on the resistance profile of the main vector, Anopheles gambiae sensu lato (s.l.), are still lacking, thus compromising decision-making for an effective vector control intervention. This study investigated the complex members and the insecticide resistance in the Anopheles gambiae s.l. populations in coastal Côte d'Ivoire. Between 2018 and 2020, cross sectional survey bioassays were conducted on female An. gambiae s.l. mosquitoes in three coastal health districts (Aboisso, Jacqueville and San Pedro) of Côte d'Ivoire. Pyrethroids deltamethrin, permethrin and alphacypermethrin (1X, 5X and 10X), clothianidin and synergist piperonyl butoxide (PBO) combined with pyrethroid 1X were tested using WHO tube bioassays. Chlorfenapyr was evaluated using CDC bottle bioassays. An. gambiae complex members and kdr 995F, kdr 995S and Ace-1 280S mutations were identified using polymerase chain reaction (PCR) technique. Overall, An. gambiae s.l. populations were primarily composed of Anopheles coluzzii (88.24%, n = 312), followed by Anopheles gambiae sensu stricto (7.56%) and hybrids (4.17%). These populations displayed strong resistance to pyrethroids at standard diagnostic doses, with mortality remaining below 98% even at 10X doses, except for alphacypermethrin in Aboisso. Pre-exposure to PBO significantly increased mortality but did not induce susceptibility, except for alphacypermethrin in Jacqueville. Clothianidin induced full susceptibility in Jacqueville and San Pedro, while chlorfenapyr induced susceptibility in Aboisso at 100 μg ai/bottle and all three districts at 200 μg ai/bottle. kdr 995F mutation dominated, with frequencies varying from 71.2% to 79.3%. kdr 995S had low, rates with frequencies ranging from 2.3% to 5.7%. Ace-1 280S prevalence varied between 4.2% and 42.9%. Coastal Côte d'Ivoire's An. gambiae s.l. populations were mainly composed of An. coluzzii and showed high resistance to pyrethroids. Clothianidin, chlorfenapyr, and PBO with pyrethroids increased mortality, indicating their potential use as an alternative for malaria vector control.

Project description:BackgroundPyrethroid resistance in vectors could limit the efficacy of long-lasting insecticidal nets (LLINs) because all LLINs are currently treated with pyrethroids. The goal of this study was to evaluate the efficacy and wash resistance of PermaNet® 3.0 compared to PermaNet® 2.0 in an area of high pyrethroid in Côte d'Ivoire. PermaNet® 3.0 is impregnated with deltamethrin at 85 mg/m2 on the sides of the net and with deltamethrin and piperonyl butoxide on the roof. PermaNet® 2.0 is impregnated with deltamethrin at 55 mg/m2 across the entire net.MethodsThe study was conducted in the station of Yaokoffikro, in central Côte d'Ivoire. The efficacy of intact unwashed and washed LLINs was compared over a 12-week period with a conventionally-treated net (CTN) washed to just before exhaustion. WHO cone bioassays were performed on sub-sections of the nets, using wild-resistant An. gambiae and Kisumu strains. Mosquitoes were collected five days per week and were identified to genus and species level and classified as dead or alive, then unfed or blood-fed.ResultsMortality rates of over 80% from cone bioassays with wild-caught pyrethroid-resistant An. gambiae s.s were recorded only with unwashed PermaNet® 3.0. Over 12 weeks, a total of 7,291 mosquitoes were collected. There were significantly more An. gambiae s.s. and Culex spp. caught in control huts than with other treatments (P < 0.001). The proportion of mosquitoes exiting the huts was significantly lower with the control than for the treatment arms (P < 0.001). Mortality rates with resistant An. gambiae s.s and Culex spp, were lower for the control than for other treatments (P < 0.001), which did not differ (P > 0.05) except for unwashed PermaNet® 3.0 (P < 0.001), which gave significantly higher mortality (P < 0.001).ConclusionsThis study showed that unwashed PermaNet® 3.0 caused significantly higher mortality against pyrethroid resistant An. gambiae s.s and Culex spp than PermaNet® 2.0 and the CTN. The increased efficacy with unwashed PermaNet® 3.0 over PermaNet® 2.0 and the CTN was also demonstrated by higher KD and mortality rates (KD > 95% and mortality rate > 80%) in cone bioassays performed with wild pyrethroid-resistant An. gambiae s.s from Yaokoffikro.

Project description:BackgroundKnowing the species composition and insecticide resistance status of the target vector population is important to guide malaria vector control. The aim of this study was to characterize the malaria vector population in terms of species composition, insecticide susceptibility status and potential underlying resistance mechanisms in Ellibou, southern Côte d'Ivoire.MethodsA 1-year longitudinal entomological survey was conducted using light traps and pyrethroid spray catches to sample adult mosquitoes in combination with larval sampling. The susceptibility status of Anopheles gambiae sensu lato (s.l.) to bendiocarb, deltamethrin, DDT and malathion was assessed using the World Health Organization insecticide susceptibility test. Additionally, An. gambiae specimens were screened for knockdown (kdr) and acetylcholineesterase (ace1) target site resistance alleles, and the expression levels of eight metabolic resistance genes, including seven cytochrome P450 monooxygenases (P450s) and one glutathione S-transferase (GST), measured with reverse transcription quantitative real-time polymerase chain reaction (qPCR).ResultsOverall, 2383 adult mosquitoes from 12 different taxa were collected with Culex quinquefasciatus and An. gambiae being the predominant taxa. Molecular identification of An. gambiae s.l. revealed the presence of Anopheles arabiensis, Anopheles coluzzii, An. gambiae sensu stricto (s.s.) and Anopheles coluzzii/An. gambiae s.s. hybrids. Anopheles gambiae mosquitoes were resistant to all insecticides except malathion. PCR diagnostics revealed the presence of ace1-G280S and the kdr L995F, L995S and N1570Y target-site mutations. Additionally, several genes were upregulated, including five P450s (i.e., CYP6P3, CYP6M2, CYP9K1, CYP6Z1, CYP6P1) and GSTE2.ConclusionThis is the first documented presence of An. arabiensis in Côte d'Ivoire. Its detection - together with a recent finding further north of the country - confirms its existence in the country, which is an early warning sign, as An. arabiensis shows a different biology than the currently documented malaria vectors. Because the local An. gambiae population was still susceptible to malathion, upregulation of P450s, conferring insecticide resistance to pyrethroids, together with the presence of ace1, suggest negative cross-resistance. Therefore, organophosphates could be an alternative insecticide class for indoor residual spraying in the Ellibou area, while additional tools against the outdoor biting An. arabiensis will have to be considered.

Project description:BackgroundPyrethroid-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.MethodsThe 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.ResultsPre-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.ConclusionLow 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.

Project description:Background. The intensification of insecticide use for both public health and agriculture in Africa has contributed to growing insecticide resistance. Today, resistance to World Health Organization (WHO)-approved insecticide classes is widespread. In an agricultural area of Southern Côte d'Ivoire, the main malaria vector Anopheles coluzzii shows multiple resistance across insecticides mediated by both target site mutation and metabolic mechanisms. To plan new vector control strategies and avert future resistance liabilities caused by cross-resistance mechanisms extant within populations, it is crucial to monitor the development and spread of both resistance and mechanisms. Methods. Larvae of Anopheles gambiae were collected from natural breeding sites in Tiassalé and Elibou, between April and November 2016 and raised to adults . Adult female non-blood fed mosquitoes, three to five days old, were exposed to deltamethrin in WHO bioassays. Extracted DNA samples from exposed mosquitoes were used for species characterisation and genotyping. Results. Most adult An. gambiae tested were resistant to deltamethrin, with mortality rates of only 25% in Tiassalé and 4.4% in Elibou. Molecular analysis of DNA from samples tested showed the presence of both An. coluzzii and An. gambiae s.s in Elibou and only An. coluzzii for Tiassalé. As previously, the L1014F kdr mutation was present at high frequency (79%) in Tiassalé and the L1014S mutation was absent. The N1575Y mutation, which amplifies resistance conferred by L1014F was detected in a single unique individual from a Tiassalé An. coluzzii female whereas in Elibou 1575Y was present in 10 An. gambiae s.s, but not in An. coluzzii. Conclusion. This is the first report of the N1575Y mutation in Côte d'Ivoire, and as in other populations, it is found in both dominant West African malaria vector species. Continued monitoring of N1575Y is underway, as are studies to elucidate its contribution to the resistance of local vector populations.

Dataset Information

Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Cote d'Ivoire.

Publications

Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d'Ivoire.

Similar Datasets

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