• Leslie Choi, Joseph Pryce, and Paul Garner.
• Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK, L3 5QA.
• Cochrane Db Syst Rev. 2019 May 23; 5 (5): CD012688CD012688.

BackgroundInsecticide-treated nets (ITNs) and indoor residual spraying (IRS) are used to control malaria vectors. Both strategies use insecticides to kill mosquitoes that bite and rest indoors. For ITNs, the World Health Organization (WHO) only recommended pyrethroids until 2018, but mosquito vectors are becoming resistant to this insecticide. For IRS, a range of insecticides are recommended. Adding IRS to ITNs may improve control, simply because two interventions may be better than one; it may improve malaria control where ITNs are failing due to pyrethroid resistance; and it may slow the emergence and spread of pyrethroid resistance.ObjectivesTo summarize the effect on malaria of additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, in communities currently using ITNs.Search MethodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the WHO International Clinical Trials Registry Platform; ClinicalTrials.gov; and the ISRCTN registry up to 18 March 2019.Selection CriteriaCluster-randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before-and-after studies (CBAs) comparing IRS plus ITNs with ITNs alone.Data Collection And AnalysisTwo review authors independently assessed trials for eligibility, analyzed risk of bias, and extracted data. We used risk ratio (RR) and 95% confidence intervals (CI). We stratified by type of insecticide: 'non-pyrethroid-like', as this could improve malaria control better than adding IRS insecticides that have the same way of working as the insecticide on ITNs ('pyrethroid-like'). We used subgroup analysis of ITN usage in the trials to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach.Main ResultsSix cRCTs (eight comparisons) met our inclusion criteria conducted since 2008 in sub-Saharan Africa. Malaria transmission in all sites was from mosquitoes belonging to the Anopheles gambiae s.l. complex species; two trials in Benin and Tanzania also reported the vector Anopheles funestus. Three trials used insecticide with targets different to pyrethroids (two used bendiocarb and one used pirimiphos-methyl); two trials used dichloro-diphenyl-trichlorethane (DDT), an insecticide with the same target as pyrethroids; and one trial used both types of insecticide (pyrethroid deltamethrin in the first year, switching to bendiocarb for the second-year). ITN usage was greater than 50% in three trials, and less than 50% in the remainder.Indoor residual spraying using 'non-pyrethroid-like' insecticides Adding IRS with a non-pyrethroid-like insecticide had mixed results. Overall, we do not know if the addition of IRS impacted on malaria incidence (rate ratio 0.93, 95% CI 0.46 to 1.86; 2 cRCTs, 566 child-years; very low-certainty evidence); it may have reduced malaria parasite prevalence (0.67, 95% CI 0.35 to 1.28; 5 comparisons from 4 cRCTs, 10,440 participants; low-certainty evidence); and it may have reduced the prevalence of anaemia (RR CI 0.46, 95% 0.18 to 1.20; 3 comparisons from 2 cRCTs, 2026 participants; low-certainty evidence). Three trials reported the impact on EIR, with variable results; overall, we do not know if IRS had any effect on the EIR in communities using ITNs (very low-certainty evidence). Trials also reported the adult mosquito density and the sporozoite rate, but we could not summarize or pool these entomological outcomes due to unreported data. ITN usage did not explain the variation in malaria outcomes between different studies. One trial reported no effect on malaria incidence or parasite prevalence in the first year, when the insecticide used for IRS had the same target as pyrethroids, but showed an effect on both outcomes in the second year, when the insecticide was replaced by one with a different target.Two trials measured the prevalence of pyrethroid resistance before and after IRS being introduced: no difference was detected, but these data are limited.Indoor residual spraying using 'pyrethroid-like' insecticidesAdding IRS using a pyrethroid-like insecticide did not appear to markedly alter malaria incidence (rate ratio 1.07, 95% CI 0.80 to 1.43; 2 cRCTs, 15,717 child-years; moderate-certainty evidence), parasite prevalence (RR 1.11, 95% CI 0.86 to 1.44; 3 cRCTs, 10,820 participants; moderate-certainty evidence), or anaemia prevalence (RR 1.12, 95% CI 0.89 to 1.40; 1 cRCT, 4186 participants; low-certainty evidence). Data on the entomological inoculation rate (EIR) were limited, and therefore we do not know if IRS had any effect on the EIR in communities using ITNs (very low-certainty evidence).Authors' ConclusionsFour trials have evaluated adding IRS using 'non-pyrethroid-like' insecticides in communities using ITNs. Some of these trials showed effects, and others did not. Three trials have evaluated adding IRS using 'pyrethroid-like' insecticides in communities using ITNs, and these studies did not detect an additional effect of the IRS. Given the wide geographical variety of malaria endemicities, transmission patterns, and insecticide resistance, we need to be cautious with inferences to policy from the limited number of trials conducted to date, and to develop relevant further research to inform decisions.

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