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Small, G.

Publications and source records attributed to Small, G..

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How best to co-deploy insecticides to minimise selection for resistance.

Insecticides are widely used to control the insects that spread human infectious diseases, in particular falciparum malaria. This widespread use has driven insecticide resistance (IR) to high levels that may threaten the effectiveness of future control programmes. There is interest in identifying deployment methods that alleviate the pressures driving IR and we investigate three. Mixtures are, as already known, highly effective in slowing IR providing their effectiveness (ability to kill fully sensitive insects) remain close to 100%. Mixtures may be expensive and/or operationally difficult so two alternatives to mixtures were investigated. Panels, where different insecticides are physically closely adjacent, for examples, different panels on the same bednet; mosquitoes may therefore encounter both insecticides in the same foraging cycle. Micro-mosaics where different insecticides are deployed in slightly wider geographic proximity, for example in adjacent dwellings. The mosquitoes are unlikely to encountered both insecticides in the same foraging cycle but may encounter different insecticides in subsequent foraging. It is hoped that panels and/or micro-mosaics may, by allowing individual mosquitoes to potentially encounter both insecticides, be effective, lower-cost alternatives to mixtures. Our results suggest this is unlikely to be the case. When insecticides are fully effective then mixtures remain clearly the best strategy. As effectiveness falls then all three strategies are roughly equal. The operational decision of what deployment methods to use depends on how confident we are that insecticides will have high effectiveness that will be maintained in realistic field conditions post-deployment.

genetics↗

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.

zoology↗

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.

ecology↗