What was the aim of this review?
Indoor residual spraying (IRS) is the regular application of chemical insecticides to household walls. The insecticide lasts for at least four months, killing mosquitoes that land on them. Insecticide-treated nets (ITNs) are bed nets treated with insecticides, preventing mosquitoes from biting people and reducing the mosquito population. Both interventions help to control malaria by reducing the number of people being bitten by mosquitoes infected with malaria. Implementing IRS in communities that are using ITNs may be better for malaria control than using ITNs alone for three reasons: two interventions may be better than one; it may improve malaria control where mosquitoes have become resistant to the pyrethroid insecticides used in ITNs; and the combination of ITNs and IRS may also help to slow the emergence of pyrethroid resistance (where pyrethroids are no longer effective at killing mosquitoes).
Pyrethroids were the only class of insecticides approved for use in ITNs until 2018, but growing resistance to pyrethroids impairs their effectiveness. The addition of IRS could counteract this reduction in ITN effectiveness. We could expect that IRS insecticides that have a different way of working to pyrethroids (‘non-pyrethroid-like') could restore effectiveness better than those that have the same way of working (‘pyrethroid-like'). The aim of this review was to summarize the impact of pyrethroid-like or non-pyrethroid-like IRS on malaria, when implemented in communities that are using ITNs.
When IRS was conducted with a non-pyrethroid-like insecticide, some studies and outcomes suggested an impact, but this was not consistent. Factors such as the number of people using nets did not explain the differences between studies. When a pyrethroid-like insecticide was used for IRS, data were limited but there was no additional effect demonstrated.
What was studied in the review?
We searched for trials that evaluated the impact on malaria transmission when IRS, using a World Health Organization (WHO)-recommended dosage, was implemented in communities that were using either ready-treated ITN products or standard nets treated with insecticide at a WHO-recommended dose. We considered effects on both human health outcomes and on mosquito populations.
What were the main results of the review?
In total, we identified six trials matching our inclusion criteria, from which eight comparisons were drawn. Three trials (providing four comparisons) used a non-pyrethroid-like IRS throughout the study, and two trials (providing two comparisons) used a pyrethroid-like IRS throughout. One further trial used a pyrethroid-like IRS in the first study year and switched to a non-pyrethroid-like IRS in the subsequent years, therefore providing two different comparisons. All six trials were conducted in sub-Saharan Africa.
Adding non-pyrethroid-like IRS in communities using ITNs gave mixed results, with some trials detecting substantial effects but one trial detecting no effect. Overall, the results from the four included trials found that there may be a reduction in malaria parasite prevalence and anaemia prevalence (low-certainty evidence). We do not know if there is an impact on the malaria incidence or on the number of infected bites received per person per year (very low-certainty evidence).
When adding pyrethroid-like IRS in communities using ITNs, the data from three trials indicate there is probably no effect on malaria incidence or parasite prevalence (moderate-certainty evidence), and there may be little or no effect on the prevalence of anaemia. Data on the number of infected bites received per person per year were too limited to draw a conclusion (very low-certainty evidence).
How up to date is the review?
We searched for relevant trials up to 18 March 2019.
Four 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.
Insecticide-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.
To summarize the effect on malaria of additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, in communities currently using ITNs.
We 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.
Cluster-randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before-and-after studies (CBAs) comparing IRS plus ITNs with ITNs alone.
Two 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, ‘pyrethroid-like’ and ‘non-pyrethroid-like’; the latter 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.
Six 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' insecticides
Adding 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).