Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are used to prevent malaria transmission. Both interventions use insecticides to kill mosquitoes that bite and rest indoors. Adding IRS to ITNs may improve malaria control simply because two interventions can be better than one. Furthermore, IRS may improve malaria control where ITNs are failing due to insecticide resistance. Pyrethroid insecticides are the predominant class of insecticide used for ITNs, as they are more safe than other insecticide classes when in prolonged contact with human skin. While many mosquito populations have developed some resistance to pyrethroid insecticides, a wider range of insecticides can be used for IRS. This review is an update of the previous Cochrane 2019 edition. 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; CENTRAL; MEDLINE; and five other databases for records from 1 January 2000 to 8 November 2021, on the basis that ITN programmes did not begin to be implemented as policy before the year 2000. We included cluster-randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before-after studies (CBAs) comparing IRS plus ITNs with ITNs alone. We included studies with at least 50% ITN ownership (defined as the proportion of households owning one or more ITN) in both study arms. Two review authors independently assessed studies 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 studies to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach. Eight cRCTs (10 comparisons), one CBA, and one ITS study, all conducted since 2008 in sub-Saharan Africa, met our inclusion criteria. The primary vectors in all sites were mosquitoes belonging to the Anopheles gambiae s.l. complex species; five studies in Benin, Mozambique, Ghana, Sudan, and Tanzania also reported the vector Anopheles funestus. Five cRCTs and both quasi-experimental design studies used insecticides with targets different to pyrethroids (two used bendiocarb, three used pirimiphos-methyl, and one used propoxur. Each of these studies were conducted in areas where the vectors were described as resistant or highly resistant to pyrethroids. Two cRCTs used dichloro-diphenyl-trichlorethane (DDT), an insecticide with the same target as pyrethroids. The remaining cRCT used both types of insecticide (pyrethroid deltamethrin in the first year, switching to bendiocarb for the second year). Indoor residual spraying using 'non-pyrethroid-like' insecticides Six studies were included (four cRCTs, one CBA, and one ITS). Our main analysis for prevalence excluded a study at high risk of bias due to repeated sampling of the same population. This risk did not apply to other outcomes. Overall, the addition of IRS reduced malaria parasite prevalence (RR 0.61, 95% CI 0.42 to 0.88; 4 cRCTs, 16,394 participants; high-certainty evidence). IRS may also reduce malaria incidence on average (rate ratio 0.86, 95% CI 0.61 to 1.23; 4 cRCTs, 323,631 child-years; low-certainty evidence) but the effect was absent in two studies. Subgroup analyses did not explain the qualitative heterogeneity between studies. One cRCT reported no effect on malaria incidence or parasite prevalence in the first year, when a pyrethroid-like insecticide was used for IRS, but showed an effect on both outcomes in the second year, when a non-pyrethroid-like IRS was used. The addition of IRS may also reduce anaemia prevalence (RR 0.71, 95% CI 0.38 to 1.31; 3 cRCTs, 4288 participants; low-certainty evidence). Four cRCTs reported the impact of IRS on entomological inoculation rate (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). Studies also reported the adult mosquito density and the sporozoite rate, but we could not summarize or pool these entomological outcomes due to differences in the reported data. Three studies measured the prevalence of pyrethroid resistance before and after IRS being introduced: there was no difference 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 EIR were limited so no conclusion was made (very low-certainty evidence). in communities using ITNs, the addition of IRS with 'non-pyrethroid-like' insecticides was associated with reduced malaria prevalence. Malaria incidence may also be reduced on average, but there was unexplained qualitative heterogeneity, and the effect may therefore not be observed in all settings. When using 'pyrethroid-like' insecticides, there was no detectable additional benefit of IRS in communities using ITNs.

Pryce J ，Medley N ，Choi L 《Cochrane Database of Systematic Reviews》

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

Choi L ，Pryce J ，Garner P 《Cochrane Database of Systematic Reviews》

Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa.

Pyrethroid long-lasting insecticidal nets (LLINs) have been important in the large reductions in malaria cases in Africa, but insecticide resistance in Anopheles mosquitoes threatens their impact. Insecticide synergists may help control insecticide-resistant populations. Piperonyl butoxide (PBO) is such a synergist; it has been incorporated into pyrethroid-LLINs to form pyrethroid-PBO nets, which are currently produced by five LLIN manufacturers and, following a recommendation from the World Health Organization (WHO) in 2017, are being included in distribution campaigns. This review examines epidemiological and entomological evidence on the addition of PBO to pyrethroid nets on their efficacy. To compare effects of pyrethroid-PBO nets currently in commercial development or on the market with effects of their non-PBO equivalent in relation to: 1. malaria parasite infection (prevalence or incidence); and 2. entomological outcomes. We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, CAB Abstracts, and two clinical trial registers (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) up to 25 September 2020. We contacted organizations for unpublished data. We checked the reference lists of trials identified by these methods. We included experimental hut trials, village trials, and randomized controlled trials (RCTs) with mosquitoes from the Anopheles gambiae complex or the Anopheles funestus group. Two review authors assessed each trial for eligibility, extracted data, and determined the risk of bias for included trials. We resolved disagreements through discussion with a third review author. We analysed data using Review Manager 5 and assessed the certainty of evidence using the GRADE approach. Sixteen trials met the inclusion criteria: 10 experimental hut trials, four village trials, and two cluster-RCTs (cRCTs). Three trials are awaiting classification, and four trials are ongoing.  Two cRCTs examined the effects of pyrethroid-PBO nets on parasite prevalence in people living in areas with highly pyrethroid-resistant mosquitoes (< 30% mosquito mortality in discriminating dose assays). At 21 to 25 months post intervention, parasite prevalence was lower in the intervention arm (odds ratio (OR) 0.79, 95% confidence interval (CI) 0.67 to 0.95; 2 trials, 2 comparisons; moderate-certainty evidence). In highly pyrethroid-resistant areas, unwashed pyrethroid-PBO nets led to higher mosquito mortality compared to unwashed standard-LLINs (risk ratio (RR) 1.84, 95% CI 1.60 to 2.11; 14,620 mosquitoes, 5 trials, 9 comparisons; high-certainty evidence) and lower blood feeding success (RR 0.60, 95% CI 0.50 to 0.71; 14,000 mosquitoes, 4 trials, 8 comparisons; high-certainty evidence). However, in comparisons of washed pyrethroid-PBO nets to washed LLINs, we do not know if PBO nets had a greater effect on mosquito mortality (RR 1.20, 95% CI 0.88 to 1.63; 10,268 mosquitoes, 4 trials, 5 comparisons; very low-certainty evidence), although the washed pyrethroid-PBO nets did decrease blood-feeding success compared to standard-LLINs (RR 0.81, 95% CI 0.72 to 0.92; 9674 mosquitoes, 3 trials, 4 comparisons; high-certainty evidence). In areas where pyrethroid resistance is moderate (31% to 60% mosquito mortality), mosquito mortality was higher with unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs (RR 1.68, 95% CI 1.33 to 2.11; 751 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence), but there was little to no difference in effects on blood-feeding success (RR 0.90, 95% CI 0.72 to 1.11; 652 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence). For washed pyrethroid-PBO nets compared to washed standard-LLINs, we found little to no evidence for higher mosquito mortality or reduced blood feeding (mortality: RR 1.07, 95% CI 0.74 to 1.54; 329 mosquitoes, 1 trial, 1 comparison, low-certainty evidence; blood feeding success: RR 0.91, 95% CI 0.74 to 1.13; 329 mosquitoes, 1 trial, 1 comparison; low-certainty evidence). In areas where pyrethroid resistance is low (61% to 90% mosquito mortality), studies reported little to no difference in the effects of unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs on mosquito mortality (RR 1.25, 95% CI 0.99 to 1.57; 948 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence), and we do not know if there was any effect on blood-feeding success (RR 0.75, 95% CI 0.27 to 2.11; 948 mosquitoes, 2 trials, 3 comparisons; very low-certainty evidence). For washed pyrethroid-PBO nets compared to washed standard-LLINs, we do not know if there was any difference in mosquito mortality (RR 1.39, 95% CI 0.95 to 2.04; 1022 mosquitoes, 2 trials, 3 comparisons; very low-certainty evidence) or on blood feeding (RR 1.07, 95% CI 0.49 to 2.33; 1022 mosquitoes, 2 trials, 3 comparisons; low-certainty evidence). In areas where mosquito populations are susceptible to insecticides (> 90% mosquito mortality), there may be little to no difference in the effects of unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs on mosquito mortality (RR 1.20, 95% CI 0.64 to 2.26; 2791 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). This is similar for washed nets (RR 1.07, 95% CI 0.92 to 1.25; 2644 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). We do not know if unwashed pyrethroid-PBO nets had any effect on the blood-feeding success of susceptible mosquitoes (RR 0.52, 95% CI 0.12 to 2.22; 2791 mosquitoes, 2 trials, 2 comparisons; very low-certainty evidence). The same applies to washed nets (RR 1.25, 95% CI 0.82 to 1.91; 2644 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). In village trials comparing pyrethroid-PBO nets to LLINs, there was no difference in sporozoite rate (4 trials, 5 comparisons) nor in mosquito parity (3 trials, 4 comparisons). In areas of high insecticide resistance, pyrethroid-PBO nets have greater entomological and epidemiological efficacy compared to standard LLINs, with sustained reduction in parasite prevalence, higher mosquito mortality and reduction in mosquito blood feeding rates 21 to 25 months post intervention. Questions remain about the durability of PBO on nets, as the impact of pyrethroid-PBO nets on mosquito mortality was not sustained over 20 washes in experimental hut trials, and epidemiological data on pyrethroid-PBO nets for the full intended three-year life span of the nets is not available. Little evidence is available to support greater entomological efficacy of pyrethroid-PBO nets in areas where mosquitoes show lower levels of resistance to pyrethroids.

Gleave K ，Lissenden N ，Chaplin M ，Choi L ，Ranson H ... -  《Cochrane Database of Systematic Reviews》

Indoor residual spraying for preventing malaria.

Pluess B ，Tanser FC ，Lengeler C ，Sharp BL ... -  《Cochrane Database of Systematic Reviews》

Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa.

Gleave K ，Lissenden N ，Richardson M ，Choi L ，Ranson H ... -  《Cochrane Database of Systematic Reviews》