Incremental impact on malaria incidence following indoor residual spraying in a highly endemic area with high standard ITN access in Mozambique: results from a cluster-randomized study

Abstract

Background: Attaining the goal of reducing the global malaria burden is threatened by recent setbacks in maintaining the effectiveness of vector control interventions partly due to the emergence of pyrethroid resistant vectors. One potential strategy to address these setbacks could be combining indoor residual spraying (IRS) with non-pyrethroids and standard insecticide-treated nets (ITNs). This study aimed to provide evidence on the incremental epidemiological benefit of using third-generation IRS product in a highly endemic area with high ITN ownership.

Methods: A cluster-randomized, open-label, parallel-arms, superiority trial was conducted in the Mopeia district in Zambezia, Mozambique from 2016 to 2018. The district had received mass distribution of alphacypermethrin ITNs two years before the trial and again mid-way. 86 clusters were defined, stratified and randomized to receive or not receive IRS with pirimiphos-methyl (Actellic®300 CS). Efficacy of adding IRS was assessed through malaria incidence in a cohort of children under five followed prospectively for two years, enhanced passive surveillance at health facilities and by community health workers, and yearly cross-sectional surveys at the peak of the transmission season.

Findings: A total of 1536 children were enrolled in the cohort. Children in the IRS arm experienced 4,801 cases (incidence rate of 3,532 per 10,000 children-month at risk) versus 5,758 cases in the no-IRS arm (incidence rate of 4,297 per 10,000 children-month at risk), resulting in a crude risk reduction of 18% and an incidence risk ratio of 0.82 (95% CI 0.79-0.86, p-value < 0.001). Facility and community passive surveillance showed a malaria incidence of 278 per 10,000 person-month in the IRS group (43,974 cases over 22 months) versus 358 (95% CI 355-360) per 10,000 person-month at risk in the no-IRS group (58,030 cases over 22 months), resulting in an incidence rate ratio of 0.65 (95% CI 0.60-0.71, p < 0.001). In the 2018 survey, prevalence in children under five in the IRS arm was significantly lower than in the no-IRS arm (OR 0.54, 95% CI, 0.31-0.92, p = 0.0241).

Conclusion: In a highly endemic area with high ITN access and emerging pyrethroid resistance, adding IRS with pirimiphos-methyl resulted in significant additional protection for children under five years of age.

Trial registration: ClinicalTrials.gov identifier NCT02910934, registered 22 September 2016, https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1 .

Keywords: Indoor residual spraying; Insecticide resistance; Insecticide‐treated nets; Mozambique; Vector control.

Fig. 1

Study timeline, interventions and assessments. Considering at least nine months of efficacious indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS), there was an overlap of IRS with older nets throughout 2017 and newer nets throughout 2018

Fig. 2

Study flow chart. ACD: active case detection, PCD: passive case detection. *of the enrolled 1,536 children, three were under six months at enrolment and 54 were between 5 and 5.5 years

Fig. 3

Cohort incidence by spray status (a); cohort cumulative incidence by spray status (b); and spray IRR (with 95% confidence interval) at cohort level (c). IRS campaigns highlighted in blue and mass ITN distribution highlighted in grey, ACT treatment correction of time at risk: 10 days

Fig. 4

Monthly population incidence at health facilities by spray status (a); cumulative population incidence at health facilities by spray status (b); and monthly incidence rate ratio (c). IRS campaigns highlighted in blue and mass ITN distribution highlighted in grey