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Todjinou, D.

Publications and source records attributed to Todjinou, D..

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Laboratory evaluation of the regeneration time, efficacy and wash-resistance of PermaNet(R) Dual (a deltamethrin-chlorfenapyr net) against susceptible and pyrethroid-resistant strains of Anopheles gambiae

Pyrethroid-chlorfenapyr nets have been recommended for malaria control by the World Health Organisation (WHO) after an alpha-cypermethrin-chlorfenapyr net showed improved impact in epidemiological trials. PermaNet(R) Dual is a new deltamethrin-chlorfenapyr net developed by Vestergaard Sarl to expand options to control programmes. We performed a series of laboratory studies according to WHO guidelines to assess the regeneration time, efficacy and wash-resistance of PermaNet(R) Dual. Regeneration time was determined by subjecting net pieces to cone bioassays and tunnel tests before and 0, 1, 2, 3, 5 and 7 days after washing. The wash-resistance of PermaNet(R) Dual was evaluated compared to WHO-prequalified pyrethroid-only (PermaNet(R) 2.0) and pyrethroid-chlorfenapyr (Interceptor(R) G2) nets by testing net pieces washed 0, 1, 3, 5, 10, 15 and 20 times in cone bioassays and tunnel tests. Tests were performed with susceptible and pyrethroid-resistant strains of Anopheles gambiae to separately assess the pyrethroid and chlorfenapyr components. Net pieces were also analysed to determine insecticide content. In regeneration time studies, the biological activity of the deltamethrin and chlorfenapyr components of PermaNet(R) Dual regenerated within 1 day after washing and a 1-day washing interval was adopted for wash-resistance studies. PermaNet(R) Dual induced high mortality (98%) and blood-feeding inhibition (98%) of the susceptible strain after 20 washes fulfilling WHO efficacy criteria in tunnel tests ([≥]80% mortality, [≥]90% blood-feeding inhibition). Similar results were obtained with PermaNet(R) 2.0 (99% mortality, 99% blood-feeding inhibition) and Interceptor(R) G2 (99% mortality, 98% blood-feeding inhibition) washed 20 times. In wash-resistance tunnel tests against the pyrethroid-resistant strain, PermaNet(R) Dual washed 20 times induced high mortality (91%) and blood-feeding inhibition (73%) which was similar to Interceptor(R) G2 (87% mortality, 79% blood-feeding inhibition) and superior to PermaNet(R) 2.0 (47% mortality, 68% blood-feeding inhibition). PermaNet(R) Dual fulfilled WHO efficacy criteria in laboratory bioassays and showed potential to improve control of pyrethroid-resistant malaria vectors.

zoology↗

PermaNet(R) Dual, a new deltamethrin-chlorfenapyr mixture net, shows improved efficacy against pyrethroid-resistant Anopheles gambiae sensu lato in southern Benin

Pyrethroid-chlorfenapyr nets have demonstrated improved entomological and epidemiological impact in trials across Africa. This is driving increased demand for this novel net class in malaria endemic countries. PermaNet(R) Dual is a new deltamethrin-chlorfenapyr net developed by Vestergaard Sarl to provide more options to malaria control programmes. We performed an experimental hut trial to evaluate the efficacy of PermaNet(R) Dual against wild, free-flying pyrethroid-resistant Anopheles gambiae sensu lato in Cove, Benin. PermaNet(R) Dual induced superior levels of mosquito mortality compared to a pyrethroid-only net and a pyrethroid-piperonyl butoxide net both when unwashed (77% with PermaNet(R) Dual vs. 23% with PermaNet(R) 2.0 and 56% with PermaNet(R) 3.0, p<0.001) and after 20 standardised washes (75% with PermaNet(R) Dual vs. 14% with PermaNet(R) 2.0 and 30% with PermaNet(R) 3.0, p<0.001). Using a provisional non-inferiority margin defined by the World Health Organisation, PermaNet(R) Dual was also non-inferior to a pyrethroid-chlorfenapyr net that has demonstrated improved public health value (Interceptor(R) G2), for vector mortality (79% vs. 76%, OR=0.854, 95% CIs: 0.703-1.038) but not for blood-feeding protection (35% vs. 26%, OR=1.445, 95% CIs: 1.203-1.735). PermaNet(R) Dual presents an additional option of this highly effective net class for improved control of malaria transmitted by pyrethroid-resistant mosquitoes.

zoology↗

VECTRON™ T500, a new broflanilide insecticide for indoor residual spraying, provides prolonged control of pyrethroid-resistant malaria vectors

BackgroundBroflanilide is a newly discovered insecticide with a novel mode of action targeting insect {gamma}-aminobutyric acid receptors. The efficacy of VECTRON T500, a wettable powder formulation of broflanilide, was assessed for IRS against wild pyrethroid-resistant malaria vectors in experimental huts in Benin. MethodsVECTRON T500 was evaluated at 100 mg/m{superscript 2} in mud and cement-walled experimental huts against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) in Cove, southern Benin, over 18 months. A direct comparison was made with Actellic(R) 300CS, a WHO-recommended micro-encapsulated formulation of pirimiphos-methyl, applied at 1000 mg/m{superscript 2}. The vector population at Cove was investigated for susceptibility to broflanilide and other classes of insecticides used for vector control. Monthly wall cone bioassays were performed to assess the residual efficacy of VECTRON T500 using insecticide susceptible An. gambiae Kisumu and pyrethroid-resistant An. gambiae s.l. Cove strains. The study complied with OECD principles of good laboratory practice. ResultsThe vector population at Cove was resistant to pyrethroids and organochlorines but susceptible to broflanilide and pirimiphos-methyl. A total of 23,171 free-flying wild pyrethroid-resistant female An. gambiae s.l. were collected in the experimental huts over 12 months. VECTRON T500 induced 56%-60% mortality in wild vector mosquitoes in both cement and mud-walled huts. Mortality with VECTRON T500 was 62%-73% in the first three months and remained >50% for 9 months on both substrate-types. By comparison, mortality with Actellic(R) 300CS was very high in the first three months (72%-95%) but declined sharply to <40% after 4 months. Using a non-inferiority margin defined by the World Health Organization, overall mortality achieved with VECTRON T500 was non-inferior to that observed in huts treated with Actellic(R) 300CS with both cement and mud wall substrates. Monthly in situ wall cone bioassay mortality with VECTRON T500 also remained over 80 % for 18 months but dropped below 80% with Actellic(R) 300CS at 6-7 months post spraying. ConclusionVECTRON T500 shows potential to provide substantial and prolonged control of malaria transmitted by pyrethroid-resistant mosquito vectors when applied for IRS. Its addition to the current list of WHO-approved IRS insecticides will provide a suitable option to facilitate rotation of IRS products with different modes of action.

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Investigating discriminating concentrations for monitoring susceptibility to broflanilide and cross resistance to other insecticide classes in Anopheles gambiae sensu lato, using the new WHO bottle bioassay method

BackgroundBroflanilide is a new insecticide being developed for malaria vector control. As new insecticide chemistries become available, strategies to preserve the susceptibility of local malaria vectors and extend their useful life need to be considered before large scale deployment. This requires the development of appropriate testing procedures and identification of suitable discriminating concentrations for monitoring susceptibility in wild vector populations to facilitate decision making by control programmes. MethodsDose-response WHO bottle bioassays were conducted using the insecticide-susceptible Anopheles gambiae s.s. Kisumu strain to determine a discriminating concentration of broflanilide. Bioassays were performed without the adjuvant Mero(R) and with two concentrations of Mero(R) (500 ppm and 800 ppm) to investigate its impact on the discriminating concentration of the insecticide. Probit analysis was used to determine the lethal doses at 50% (LC50) and 99% (LC99) at 24-, 48- and 72-hours post-exposure. Cross-resistance to broflanilide and pyrethroids, DDT, dieldrin and carbamates, was investigated using An. gambiae s.l. Cove and An. coluzzii Akron strains. The susceptibility of wild pyrethroid-resistant mosquitoes from communities in Southern Benin to broflanilide was assessed using the estimated discriminating concentrations. ResultsBroflanilide induced a dose-dependent and delayed mortality effect. Mortality rates in bottles treated without Mero(R) were <80% using the range of broflanilide doses tested (0-100 {micro}g/bottle) leading to high and unreliable estimates of LC99 values. The discriminating concentrations defined as 2XLC99 at 72 hours post exposure were estimated to be 2.2 {micro}g/bottle with 800 ppm of Mero(R) and 6.0 {micro}g/bottle with 500 ppm of Mero(R). Very low resistance ratios (0.6-1.2) were determined with the insecticide resistant An. gambiae s.l. Cove and An. coluzzii Akron strains suggesting the absence of cross-resistance via the mechanisms of resistance to pyrethroids, DDT, dieldrin and carbamates they possess. Bottle bioassays performed with broflanilide at both discriminating concentrations of 6 {micro}g/bottle with 500 ppm of Mero(R) and 2.2 {micro}g/bottle with 800 ppm of Mero(R), showed susceptibility of wild highly pyrethroid-resistant An. gambiae s.l. from villages in Southern Benin. ConclusionHere we determined discriminating concentrations for monitoring susceptibility to broflanilide in bottle bioassays, using susceptible An. gambiae vectors. Using the estimated discriminating concentrations, we showed that wild pyrethroid-resistant populations of An. gambiae s.l. from southern Benin were fully susceptible to the insecticide. Broflanilide also shows potential to be highly effective against An. gambiae s.l. vector populations that have developed resistance to other public health insecticides.

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Can pyrethroid-piperonyl butoxide (PBO) nets reduce the efficacy of indoor residual spraying with pirimiphos-methyl against pyrethroid-resistant malaria vectors?

As the uptake of pyrethroid-PBO ITNs increases, their combination with IRS insecticides could become an operational reality in many malaria-endemic communities. Pirimiphos-methyl is a pro-insecticide requiring activation by mosquito cytochrome P450 enzymes to induce toxicity while PBO blocks activation of these enzymes in pyrethroid-resistant vector mosquitoes. PBO may thus antagonise the toxicity of pirimiphos-methyl IRS when combined with pyrethroid-PBO ITNs. The impact of combining two major brands of pyrethroid-PBO ITNs (Olyset(R) Plus, PermaNet(R) 3.0) with pirimiphos-methyl IRS (Actellic(R) 300CS) was evaluated against pyrethroid-resistant Anopheles gambiae sl in two parallel experimental hut trials in southern Benin in comparison to bendiocarb IRS and each intervention alone. The wild vector population was resistant to pyrethroids but susceptible to pirimiphos-methyl and bendiocarb. PBO pre-exposure partially restored deltamethrin toxicity but not permethrin. Mosquito mortality in experimental huts was significantly improved in the combinations of bendiocarb IRS with Olyset(R) Plus (33%) and PermaNet(R) 3.0 (38%) compared to bendiocarb IRS alone (14-16%, p<0.001), demonstrating an additive effect. Conversely, mortality was significantly reduced in the combinations of pirimiphos-methyl IRS with Olyset(R) Plus (59%) and PermaNet(R) 3.0 (55%) compared to pirimiphos-methyl IRS alone (77-78%, p<0.001), demonstrating an antagonistic effect. Combining pirimiphos-methyl IRS with the pyrethroid-PBO ITNs provided significantly improved mosquito mortality (55-59%) compared to the pyrethroid-PBO ITNs alone (22-26%) and improved blood-feeding inhibition relative to the IRS alone. This study provided evidence of an antagonistic effect when pyrethroid-PBO ITNs were combined with pirimiphos-methyl IRS in the same household resulting in lower levels of vector mosquito mortality compared to the IRS alone. Pirimiphos-methyl IRS also showed potential to significantly enhance malaria control when deployed to complement pyrethroid-PBO ITNs in an area where PBO fails to fully restore susceptibility to pyrethroids.

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