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

Keywords: 3GIRS; An. funestus; Cluster-randomized trial; Indoor residual spraying; Pyrethroid resistance.

Fig. 1

Locations of the entomological surveillance sites used during the cluster-randomized controlled trial of IRS with PM in Mopeia District, Mozambique: 2016 to 2018. In each village, indoor mosquito densities were sampled at eight sentinel houses for three consecutive nights every month (240 total trap-nights per month) using a human-baited CDC LT. In eight of the ten villages, paired indoor-outdoor HLCs were also conducted at one additional house for three consecutive nights every month (24 collection-nights per month). CDC LT US Centers for Disease Control light trap, HLC human landing collection, IRS indoor residual spraying, PM pirimiphos-methyl

Fig. 2

Overall densities and species group distributions for Anopheles mosquitoes collected a in CDC LTs and b with HLCs, during the cluster-randomized trial in Mozambique: 2016–2018. Monthly totals, grouped by village IRS status, for An. funestus s.l. and An. gambiae s.l. are presented in Tables 2, 3. All species group designations were based on morphological identifications in the field. CDC LT US Centers for Disease Control light trap, HLC human landing collection, IRS indoor residual spraying

Fig. 3

Monthly trends in total mosquitoes collected during the cluster-randomized trial using indoor, human-baited CDC LTs: a An. funestus s.l. and b An. gambiae s.l.; and paired indoor-outdoor HLCs: c An. funestus s.l. and d An. gambiae s.l. Each study arm had an equal number of collection nights per month. CDC LT US Centers for Disease Control light trap, HLC human landing collection

Fig. 4

Monthly trends in the average number of mosquitoes collected per trap-night in indoor human-baited CDC LTs during the cluster-randomized trial for a An. funestus s.l. and b An. gambiae s.l. Geometric means are presented. In a, * indicates mosquito collection IRRs that are significantly different from 1 (zero-inflated negative binomial regression model, p < 0.05). The number of An. gambiae s.l. collected was too low to enable a similarly meaningful statistical analysis, but the trends are similar. Note the different scales on the y-axes that reflect much higher densities (almost ×20) of An. funestus s.l. than An. gambiae s.l. CDC LT US Centers for Disease Control light trap, IRR incidence rate ratio, IRS indoor residual spraying

Fig. 5

The total number of mosquitoes collected during paired HLCs during the cluster-randomized trial, by collector position, and by IRS status. a Anopheles funestus collected in no-IRS clusters; b An. funestus collected in IRS clusters. c Anopheles gambiae collected in no-IRS clusters; d An. gambiae collected in IRS clusters. HLC human landing collection, IRS indoor residual spraying

Fig. 6

Indoor-outdoor biting ratios observed during HLCs throughout the cluster-randomized trial. Shown is the ratio of mosquitoes collected indoors to outdoors. HLC human landing collection, IRS indoor residual spraying

Fig. 7

Monthly trends in the average nightly number of mosquitoes collected during HLCs for An. funestus s.l. Geometric means of total mosquitoes collected (indoors + outdoors) by collection-night are presented. HLC human landing collection, IRS indoor residual spraying