Abstract: IRS versus no IRS Stable malaria (entomological inoculation rate (EIR) > 1): In one RCT in Tanzania IRS reduced re-infection with malaria parasites detected by active surveillance in children following treatment; protective efficacy (PE) 54%. In the same setting, malaria case incidence assessed by passive surveillance was marginally reduced in children aged one to five years; PE 14%, but not in children older than five years (PE -2%). In the IRS group, malaria prevalence was slightly lower but this was not significant (PE 6%), but mean haemoglobin was higher (mean difference 0.85 g/dL). In one CBA trial in Nigeria, IRS showed protection against malaria prevalence during the wet season (PE 26%; 95% CI 20 to 32%) but not in the dry season (PE 6%; 95% CI -4 to 15%). In one ITS in Mozambique, the prevalence was reduced substantially over a period of 7 years (from 60 to 65% prevalence to 4 to 8% prevalence; the weighted PE before-after was 74% (95% CI 72 to 76%). Unstable malaria (EIR < 1): In two RCTs, IRS reduced the incidence rate of all malaria infections;PE 31% in India, and 88% (95% CI 69 to 96%) in Pakistan. By malaria species, IRS also reduced the incidence of P. falciparum (PE 93%, 95% CI 61 to 98% in Pakistan) and P. vivax (PE 79%, 95% CI 45 to 90% in Pakistan); There were similar impacts on malaria prevalence for any infection: PE 76% in Pakistan; PE 28% in India. When looking separately by parasite species, for P. falciparum there was a PE of 92% in Pakistan and 34% in India; forP. vivax there was a PE of 68% in Pakistan and no impact demonstrated in India (PE of -2%). IRS versus Insecticide Treated Nets (ITNs) Stable malaria (EIR > 1): Only one RCT was done in an area of stable transmission (in Tanzania). When comparing parasitological re-infection by active surveillance after treatment in short-term cohorts, ITNs appeared better, but it was likely not to be significant as the unadjusted CIs approached 1 (risk ratio IRS:ITN = 1.22). When the incidence of malaria episodes was measured by passive case detection, no difference was found in children aged one to five years (risk ratio = 0.88, direction in favour of IRS). No difference was found for malaria prevalence or haemoglobin. Unstable malaria (EIR < 1): Two studies; for incidence and prevalence, the malaria rates were higher in the IRS group compared to the ITN group in one study. Malaria incidence was higher in the IRS arm in India (risk ratio IRS:ITN = 1.48) and in South Africa (risk ratio 1.34 but the cluster unadjusted CIs included 1). For malaria prevalence, ITNs appeared to give better protection against any infection compared to IRS in India (risk ratio IRS:ITN = 1.70) and also for both P. falciparum (risk ratio IRS:ITN = 1.78) and P. vivax (risk ratio IRS:ITN = 1.37). Historical and programme documentation has clearly established the impact of IRS. However, the number of high-quality trials are too few to quantify the size of effect in different transmission settings. The evidence from randomized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria settings, but randomized trial data from stable malaria settings is very limited. Some limited data suggest that ITN give better protection than IRS in unstable areas, but more trials are needed to compare the effects of ITNs with IRS, as well as to quantify their combined effects. Ideally future trials should try and evaluate the effect of IRS in areas with no previous history of malaria control activities.

Plain-language summary: Six studies were identified for inclusion (four cluster RCTs, one CBA and one ITS). Four of these studies were conducted in sub-Saharan Africa, one in India and one in Pakistan. IRS reduced malaria transmission in young children by half compared to no IRS in Tanzania (an area where people are regularly exposed to malaria), and protected all age groups in India and Pakistan (where malaria transmission is more unstable and where more than one type of malaria is found). When compared with ITNs, IRS appeared more protective (according to the outcome chosen) in one trial conducted in an area of stable malaria transmission, but ITN seemed to be more protective than IRS in unstable areas. Unfortunately, the level of evidence is very limited and no firm conclusions should be drawn on the basis of this review. In conclusion, although IRS programmes have shown impressive success in malaria reduction throughout the world, there are too few well-run trials to be able to quantify the effects of IRS in areas with different malaria transmission, or to properly compare IRS and ITN.  High-quality and long-duration trials on a large scale, done in areas where there has been little or no mosquito control are still urgently required. New trials should include an IRS arm and an ITN arm, and should also assess the combined effect of ITN and IRS, a very important question in view of malaria elimination.