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.

Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated nets.

BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial.

BACKGROUND: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. METHODS: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. RESULTS: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33-59%; p < 0.001) in indoor light traps and by 74% (CI95 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00-1.21) in no-IRS villages and 0.88 (CI95 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. CONCLUSION: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.