Long-lasting residual efficacy of Actellic®300CS and Icon®10CS on different surfaces against Anopheles stephensi, an invasive malaria vector.

BACKGROUND: Anopheles stephensi, a malaria-transmitting mosquito species, has developed resistance to various insecticides such as DDT, Dieldrin, Malathion, and synthetic pyrethroids. To combat this issue, the World Health Organization (WHO) suggests using Actellic®300CS and Icon®10CS for Indoor Residual Spraying to tackle pyrethroid-resistant mosquitoes. The aim of this research project was to evaluate the susceptibility of An. stephensi to certain insecticides at the diagnostic concentration + intensity 5x diagnostic concentration (5XDC) assays in Iran and to study the lasting effectiveness of Actellic®300CS and Icon®10CS against this particular malaria vector. METHODS: This study assessed the susceptibility of An. stephensi populations in southern Iran to various insecticides, including deltamethrin 0.05%, DDT 4%, malathion 5%, bendiocarb 0.1%, a synergist assay with PBO 4% combined with deltamethrin 0.05%, and an intensity assay using 5x the diagnostic concentration of deltamethrin (0.25%) and bendiocarb 0.5%. Laboratory cone bioassay tests were conducted to determine the residual effectiveness of Actellic®300 and Icon®10CS insecticides on different surfaces commonly found in households, such as cement, mud, plaster, and wood. The tests were carried out following the WHO test kits and standard testing protocols. RESULTS: The An. stephensi populations in Bandar Abbas were found to be susceptible to malathion 5% and deltamethrin 0.25% (5XDC), but exhibited resistance to DDT, standard concentration of deltamethrin, and both standard and intensity concentrations of bendiocarb. In laboratory cone bioassay tests, An. stephensi mortality rates when exposed to Actellic®300CS and Icon®10CS on different surfaces remained consistently more than 80%. Actellic®300CS achieved more than 80% mortality on all substrates for the entire 300-day post-spraying period. Conversely, Icon®10CS maintained mortality rates more than 80% on plaster and wood surfaces for 165 days and on mud and cement surfaces for 270 days post-spraying. Both Actellic®300CS and Icon®10CS demonstrated 100% mortality within 72 h of each test on all surfaces throughout the entire 300-day post-spraying period. CONCLUSION: The study shows the varying levels of resistance of An. stephensi Bandar Abbas population to different insecticides and demonstrates the consistent performance of Actellic®300CS in controlling these mosquitoes on various surfaces. The findings suggest that long-lasting CS formulations may be more effective for malaria vector control compared to the current options. Further research is needed to validate these findings in field settings and assess the impact of these insecticides on malaria transmission.

Residual efficacy of SumiShield™ 50WG for indoor residual spraying in Ethiopia.

BACKGROUND: The rate of decay of the biological efficacy of insecticides used for indoor residual spraying (IRS) is an important factor when making decisions on insecticide choice for national malaria control programmes. A key roadblock to IRS programme is insecticide resistance. If resistance is detected to most of the existing insecticides used for IRS (DDT, pyrethroids, organophosphates and carbamates), the logical next choice could be neonicotinoid insecticides, as pyrethroids are used to treat nets. SumiShield™ 50WG belongs to the neonicotinoid class of insecticides and has shown promising results in several phase I, II and III trials in different settings. The aim of this study was to assess the persistence of SumiShield™ 50WG by spraying on different wall surfaces and determine its decay rates over time in Ethiopia. METHODS: Five huts with different wall surface types (mud, dung, paint and cement) which represented the Ethiopian house wall surfaces were used to evaluate the residual efficacy of SumiShield™ 50WG. Actellic 300CS sprayed on similar wall surfaces of another five huts was used as a comparator insecticide and two huts sprayed with water were used as a control. All huts were sprayed uniformly by an experienced spray operator; non-stop starting from the door and moving clockwise to cover the entire wall surface of the hut. The treatments were assigned to huts randomly. The residual efficacy of the insecticide formulations was evaluated against a susceptible insectary-reared population of Anopheles arabiensis using WHO cone bioassays. RESULTS: SumiShield™ 50WG resulted in mortality rates of over 80% at 120 h post-exposure on all surface types for up to nine months post-spray, while Actellic 300CS yielded mortality rates of over 80% for eight months after spray. CONCLUSIONS: The results of this trial demonstrated that the residual efficacy of SumiShield™ 50WG extends up to nine months on all treated wall surface types. The long-lasting residual efficacy and unique mode of action of the SemiShield™ 50WG shows that it could be an ideal product to be considered as a potential candidate insecticide formulation for IRS in malaria endemic countries such as Ethiopia or other sub-Saharan countries where the transmission season lasts up to four months or longer.

Incremental cost and cost-effectiveness of the addition of indoor residual spraying with pirimiphos-methyl in sub-Saharan Africa versus standard malaria control: results of data collection and analysis in the Next Generation Indoor Residual Sprays (NgenIRS) project, an economic-evaluation.

BACKGROUND: Malaria is a major cause of morbidity and mortality globally, especially in sub-Saharan Africa. Widespread resistance to pyrethroids threatens the gains achieved by vector control. To counter resistance to pyrethroids, third-generation indoor residual spraying (3GIRS) products have been developed. This study details the results of a multi-country cost and cost-effectiveness analysis of indoor residual spraying (IRS) programmes using Actellic®300CS, a 3GIRS product with pirimiphos-methyl, in sub-Saharan Africa in 2017 added to standard malaria control interventions including insecticide-treated bed nets versus standard malaria control interventions alone. METHODS: An economic evaluation of 3GIRS using Actellic®300CS in a broad range of sub-Saharan African settings was conducted using a variety of primary data collection and evidence synthesis methods. Four IRS programmes in Ghana, Mali, Uganda, and Zambia were included in the effectiveness analysis. Cost data come from six IRS programmes: one in each of the four countries where effect was measured plus Mozambique and a separate programme conducted by AngloGold Ashanti Malaria Control in Ghana. Financial and economic costs were quantified and valued. The main indicator for the cost was cost per person targeted. Country-specific case incidence rate ratios (IRRs), estimated by comparing IRS study districts to adjacent non-IRS study districts or facilities, were used to calculate cases averted in each study area. A deterministic analysis and sensitivity analysis were conducted in each of the four countries for which effectiveness evaluations were available. Probabilistic sensitivity analysis was used to generate plausibility bounds around the incremental cost-effectiveness ratio estimates for adding IRS to other standard interventions in each study setting as well as jointly utilizing data on effect and cost across all settings. RESULTS: Overall, IRRs from each country indicated that adding IRS with Actellic®300CS to the local standard intervention package was protective compared to the standard intervention package alone (IRR 0.67, [95% CI 0.50-0.91]). Results indicate that Actellic®300CS is expected to be a cost-effective (> 60% probability of being cost-effective in all settings) or highly cost-effective intervention across a range of transmission settings in sub-Saharan Africa. DISCUSSION: Variations in the incremental costs and cost-effectiveness likely result from several sources including: variation in the sprayed wall surfaces and house size relative to household population, the underlying malaria burden in the communities sprayed, the effectiveness of 3GIRS in different settings, and insecticide price. Programmes should be aware that current recommendations to rotate can mean variation and uncertainty in budgets; programmes should consider this in their insecticide-resistance management strategies. CONCLUSIONS: The optimal combination of 3GIRS delivery with other malaria control interventions will be highly context specific. 3GIRS using Actellic®300CS is expected to deliver acceptable value for money in a broad range of sub-Saharan African malaria transmission settings.

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

BACKGROUND: Broflanilide is a newly discovered insecticide with a novel mode of action targeting insect γ-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. METHODS: VECTRON™ T500 was evaluated at 100 mg/m2 in mud and cement-walled experimental huts against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) in Covè, southern Benin, over 18 months. A direct comparison was made with Actellic® 300CS, a WHO-recommended micro-encapsulated formulation of pirimiphos-methyl, applied at 1000 mg/m2. The vector population at Covè 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. Covè strains. The study complied with OECD principles of good laboratory practice. RESULTS: The vector population at Covè 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® 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® 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® 300CS at 6-7 months post spraying. CONCLUSION: VECTRON™ 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.

Evaluation of the Residual Efficacy of Actellic300 CS in Simple Huts in Central Ethiopia.

Indoor residual spraying (IRS) is one of the key vector control tools with a long history of use in the world. Ethiopia has set a goal to eliminate malaria from selected districts mainly by applying IRS and the distribution of long-lasting insecticidal nets. IRS is applied in low malaria transmission districts which are epidemic prone and in districts with high malaria transmission. Ethiopia uses insecticides that are recommended by World Health Organization; these insecticides must also be registered in Ethiopia. The registration of new and potential products requires confirmatory, local efficacy trials to be performed. Actellic 300CS, now registered, is one of such potential product. Actellic 300CS showed average mortalities of 99.6%, 99.6%, and 99.0% on the sprayed surfaces in the experimental huts, the top, middle, and bottom sections, respectively during the first 6 mo of the study period. Beyond 6 mo, (7, 8, and 9 mo) follow-up, mortalities for the top, middle, and bottom sections were 85.2%, 86.3%, and 85.2%, respectively. The results showed that the residual efficacy of Actellic 300CS was up to 9 mo with the first 6 mo exhibiting mortalities of greater than 99% while the next 3 mo showed mortalities exceeding 85%. Actellic 300CS was effective against fully susceptible laboratory-reared Anopheles arabiensis on all four surface types (rough, smooth, dung, and painted surfaces) tested in this study and could be used as one of the chemical insecticides of choice for the ongoing IRS programs in Ethiopia.

Efficacy of Actellic 300 CS-based indoor residual spraying on key entomological indicators of malaria transmission in Alibori and Donga, two regions of northern Benin.

BACKGROUND: The current study shows the results of three years of IRS entomological monitoring (2016, before intervention; 2017 and 2018, after intervention) performed in Alibori and Donga, northern Benin. METHODS: Mosquito collections were performed on a monthly basis using human landing catches and pyrethrum spray catches in six districts including four treated with Actellic 300 CS (Kandi, Gogounou, Djougou and Copargo) and two untreated (Bembèrèkè and Kouandé) which served as control sites. Key transmission indicators of Anopheles gambiae (s.l.) as well as the residual activity of Actellic 300 CS assessed through WHO cone tests, were determined. RESULTS: The residual efficacy duration of Actellic 300 CS after the two IRS campaigns (2017 and 2018) was 4-5 months (May-September). The parity rate and the sporozoite index of An. gambiae (s.l.) were 36.62% and 0.71%, respectively, after the first spray round in treated areas compared to 57.24% and 3.7%, respectively, in the control areas (P < 0.0001). The same trend was observed after the second spray round. After the first spray round, each person received 1.6 infective bites/month (ib/m) in the treated areas against 12.11 ib/m in the control areas, resulting in a reduction rate of 86.78%. Similarly, the entomological inoculation rate was 1.5 ib/m after the second spray round in the treated areas vs 9.75 ib/m in the control areas, corresponding to a reduction of 84.61%. A decrease in the parity rate (46.26%), sporozoite index (85.75%) and EIR (87.27%) was observed for An. gambiae (s.l.) after the first round of IRS (June-October 2017) compared to the pre-intervention period (June-October 2016). The density of An. gambiae (s.l.) ranged between 0.38-0.48 per house in treated areas vs 1.53-1.76 An. gambiae (s.l.) per house respectively after the first and second IRS rounds. CONCLUSIONS: This study showed the positive impact of IRS in reducing key entomological parameters of malaria transmission in Alibori and Donga. However, the considerable blood-feeding rate of An. gambiae (s.l.) in spray areas, stress the need for the population to sleep under long-lasting insecticidal nets (LLINs) in addition, to prevent from mosquito bites which did not succeed in resting on sprayed walls.

Laboratory Evaluation of Residual Efficacy of Actellic 300 CS (Pirimiphos-Methyl) and K-Othrine WG 250 (Deltamethrin) on Different Indoor Surfaces.

The nature and type of local indoor resting wall surfaces to certain level influences the residual bio-efficacy of insecticides used in indoor residual spraying programs. Knockdown and mortality effects of an organophosphate Actellic 300 CS and pyrethroid K-Othrine WG 250 insecticides on the field-collected Culex quinquefasciatus were assessed bimonthly from July to November 2014, using World Health Organization (WHO) cones bioassay test. Knockdown and mortality rates were subjected to statistical analysis using χ2 and Student t tests. Result of the bioassay test on C quinquefasciatus showed that plywood surfaces had the best residual knockdown activity of Actellic 300 CS with knockdown rate above the WHO-recommended threshold limit of ≥95% for 30 days after treatment. This was followed by mud surface with knockdown rates ≥95% threshold limit 15 days (97%) after treatment. The lowest knockdown rates of less than 95% were observed on cement surface throughout the assessment period. However, the knockdown rates of mosquitoes on deltamethrin WG 250-treated cement and plywood surfaces were 100% and ≥95%, respectively, at 30 days after treatment. But the knockdown activity was below the recommended threshold limit on mud surface during the 17 weeks trial. Knockdown activities varied significantly (p < .05), and it is a function of exposure periods, different surfaces, and insecticide formulations. The 24-hour mortality rates of Actellic 300 CS and K-Othrine WG 250 at 120 days after treatment were 83.6% and 86.7%, and 80% and 83.3%, on plywood and cement surfaces, respectively. A maximum residual period of 75 and 45 days were recorded for Actellic 300 CS and K-Othrine WG 250, respectively, on mud surface. Both Actellic 300 CS and K-Othrine 250 WG were highly effective against Culex mosquito. The extended residual activity of p-methyl CS compared with deltamethrin WG 250 makes it a suitable alternative insecticide against pyrethroid-resistant mosquitoes in Southwest Nigeria.