Protopopoff 2018.

Methods	Study design: cRCT with 4 intervention arms using a 2 × 2 factorial design arm 1: standard LLIN (Olyset Net) arm 2: standard LLIN (Olyset Net) + IRS arm 3: pyrethroid net + synergist PBO (Olyset Plus) arm 4: pyrethroid net + synergist PBO (Olyset Plus) + IRS Therefore, there were 2 comparisons for this review: arm 1 versus arm 2, and arm 3 versus arm 4 Unit of allocation: clusters comprised from 40 villages Number of units: 48 clusters randomized into 4 arms equally Outcome assessment/surveillance type: cross‐sectional surveys of children aged 0.5–14 years were done to determine the prevalence of Plasmodium spp infection. The main endpoint for assessment of the IRS was 9 months postintervention. Up to 3 children from 55 households with eligible participants per cluster were randomly selected for each survey. Length of follow‐up: originally planned for 18 months (1 January 2015 to 30 June 2016) but was subsequently extended to 24 months (1 January 2014 to 31 December 2016) Adjustment for clustering: yes
Participants	Number of participants: at the primary endpoint for assessment of the IRS, the number of children recruited were 933 in arm 1, 877 in arm 2, 883 in arm 3, and 969 in arm 4 Population characteristics: total population in core and buffer areas ranged from 31,138 to 38,081 total population in the core area of the clusters between 14,845 and 16,358 Withdrawal and loss to follow‐up: a fresh cohort was recruited for each cross‐sectional survey and ITT analysis was conducted.
Interventions	IRS: Active ingredient and dosage: pirimiphos‐methyl at the recommended dosage 1 g/m² Formulation: 30% capsule suspension (Actellic 300CS) Frequency of spraying: once in February 2015 Coverage: per cluster (%): 94% (95% CI 92% to 96%) in arm 2 and 94% (95% CI 87% to 97%) in arm 4 Buffer size between clusters: minimum outer buffer zone of 300 m. Only the inner core area was used for the measurement of study outcomes ITN: Active ingredient and dosage: permethrin 2% w/w (Olyset Net) and permethrin 2% (Olyset Plus) and PBO 1% w/w Coverage: 9 months postintervention, coverage defined as household owning ≥ 1 LLIN (study LLIN or any other LLIN) was 98% (95% CI 96% to 99%) in arm 2 and 98% (95% CI 95% to 99%) in arm 4 Compliance: at 9 months postintervention, compliance defined as residents declaring to use an LLIN the previous night (study LLIN or any other LLIN) was 76% (95% CI 70% to 80%) in arm 2 and 77% (95% CI 70% to 83%) in arm 4 Control: ITN only as above Coverage: at 9 months postintervention, coverage defined as household owning ≥ 1 LLIN (study LLIN or any other LLIN) was 97% (95% CI 93% to 99%) in arm 1 and 98% (95% CI 97% to 99%) in arm 3 Compliance: at 9 months postintervention, compliance defined as residents declaring to use a LLIN the previous night (study LLIN or any other LLIN) was 80% (95% CI 75% to 85%) in arm 1 and 78% (95% CI 73% to 82%) in arm 3 Cointerventions: none reported
Outcomes	Prevalence of Plasmodium spp infection Proportion of children with moderate‐to‐severe anaemia (defined as haemoglobin < 8 g/dL) EIR defined as the mean number of infective mosquito bites per household per month Adult mosquito density per night per household
Location profile	Study location: Northwest Tanzania, Muleba Distract, Kagera Region, the study area comprised 29,365 households and a population of 135,900 people Malaria endemicity: perennial with peaks after the rainy season. Rainfall occurs in 2 seasons: the "short rains" in October–December (mean monthly rainfall 160 mm) and the "long rains" in March–May (mean monthly rainfall 300 mm) EIR: not measured at baseline Population proximity/density: not reported Plasmodiumspp:P falciparum
Vector profile	Primary (and secondary) vector species:An gambiae s.s. (An arabiensis and An funestus) Vector behaviour (nature, stability, adult habitat, peak biting times, exophilic/endophilic, exophagic/endophagic, anthropophilic/zoophilic): not reported Phenotypic resistance profile:An gambiae s.l. had high levels of resistance to pyrethroids. Genotypic resistance profile: the Vgsc gene mutation was found in all tested An gambiae s.l. with co‐occurrence of Vgsc‐1014F and Vgsc‐1014S in 22 (9%) of 234 An gambiae s.l. mosquitoes. No mutation was found in the 247 An arabiensis tested. Method of mosquito collection: mosquito surveillance was done from March 2015 to December 2016, in each cluster by a project field assistant for 1 night per month in 7 randomly selected houses per cluster using CDC Miniature Light Trap Model 512 (John W Hock Company, USA).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	During each survey, we randomly sampled 55 households with children aged 6 months to 14 years from the core area of each cluster using the census lists.
Allocation concealment (selection bias)	Low risk	The inhabitants of each cluster to the type of LLINs received. The 2 types of nets were of similar colour and shape, and only distinguishable by label codes and coloured thread inserted during manufacture. Additionally, field staff who took blood samples in the cross‐sectional surveys were masked to the study arms the clusters were assigned to. It was not possible to blind either the investigators or the participants to the treatment allocation of IRS but we do not feel this would impact the outcome.
Blinding of participants and personnel (performance bias) Incidence of malaria	Low risk	This outcome was not measured.
Blinding of participants and personnel (performance bias) Prevalence of malaria	Low risk	Field staff who took blood samples in the cross‐sectional surveys were masked to the study arms the clusters were assigned to. It was not possible to mask either the investigators who assessed the blood samples or the participants to the treatment allocation of IRS but we do not consider this would impact the outcome which was assessed by RDT (an objective test).
Blinding of outcome assessment (detection bias) Incidence of malaria	Low risk	This outcome was not measured.
Blinding of outcome assessment (detection bias) Prevalence of malaria	Low risk	Field staff who took blood samples in the cross‐sectional surveys were masked to the study arms the clusters were assigned to. It was not possible to blind either the investigators or the participants to the treatment allocation of IRS but we do not feel this would impact the outcome which was assessed by RDT (an objective test).
Incomplete outcome data (attrition bias) All outcomes	Low risk	A new cohort of children was used for each cross‐sectional survey.
Selective reporting (reporting bias)	Low risk	The study protocol reported each outcome as stated in the clinical trials register (note: retrospectively registered).
Recruitment bias	Low risk	Cohort of children were randomly selected.
Baseline imbalance	Low risk	Baseline data was displayed. No significant differences at baseline for outcomes the study assessed.
Loss of clusters	Low risk	No clusters were lost.
Incorrect analysis	Low risk	Adjustment for clustering was done.
Comparability with RCTs randomizing participants	Low risk	Because the intervention is expected to have community level impact as well as individual impact, cRCTs are the most appropriate study design to capture this.
Other bias	Low risk	No other biases.