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

Abstract

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 registrationclinicaltrials.gov, NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

Evaluating recurrent episodes of malaria incidence in Timika, Indonesia, through a Markovian multiple-state model

“…The use of this IRS can also reduce the length of Plasmodium infection ( Kané et al., 2020 ). This is because IRS can prevent contact with malaria vectors at home, even for those who do not use ITNs while sleeping ( Wagman et al., 2021 ; West et al., 2015 ). IRS is also suitable for use in areas either high or low malaria endemicity ( West et al., 2015 ).…”

To spray or target mosquitoes another way: focused entomological intelligence guides the implementation of indoor residual spraying in southern Mozambique

“…tenebrosus individuals is warranted, as in Mopeia District (Zambezia Province, central Mozambique) individuals that were identified morphologically as An. tenebrosus were subsequently identified as Anopheles namibiensis based ITS2 gene sequencing results [ 31 ]. Although no ELISA positive mosquitoes from the An.…”

“…Data collected demonstrated expected and substantial heterogeneity across indicators-including species composition, and biting and resting behaviours-in the six districts, with values differing between sampling periods (approximately 8 week difference representing the wet and dry seasons). Data heterogeneity may be attributed to the limited number of sampling days associated with the 'snapshot' approach, typical or normal entomological surveillance and normal variation in drivers of mosquito populations including interventions, topography, land use, climate, human population densities, and connectivity, amongst other factors [27,31,[42][43][44][45]. As such, obtaining estimates of the IRS efficacy indicators during the months when IRS typically implemented would be valuable.…”

Malaria risk and receptivity: Continuing development of insecticide resistance in the major malaria vector Anopheles arabiensis in northern KwaZulu-Natal, South Africa

“…funestus in southern Africa. [27][28][29][30] Volume 118| An assessment of resistance mechanisms can yield important information on where cross-resistances between insecticide classes are likely, and on how quickly resistance might develop to high levels in an affected vector population under selection pressure. The synergist data given here suggests that cytochrome P450s (oxygenases) and general esterases are at least partially responsible for the pyrethroidand carbamate-resistant phenotypes, although these data need to be interpreted with caution.…”