Efficacy of Olyset Duo, a bednet containing pyriproxyfen and permethrin, versus a permethrin-only net against clinical malaria in an area with highly pyrethroid-resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial.

BACKGROUND: Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets containing permethrin, a pyrethroid, and pyriproxyfen, an insect growth regulator, versus permethrin-only (standard) LLINs against clinical malaria in children younger than 5 years in Banfora, Burkina Faso. METHODS: In this two-group, step-wedge, cluster-randomised, controlled, superiority trial, standard LLINs were incrementally replaced with LLINs treated with permethrin plus pyriproxyfen (PPF) in 40 rural clusters in Burkina Faso. In each cluster, 50 children (aged 6 months to 5 years) were followed up by passive case detection for clinical malaria. Cross-sectional surveys were done at the start and the end of the transmission seasons in 2014 and 2015. We did monthly collections from indoor light traps to estimate vector densities. Primary endpoints were the incidence of clinical malaria, measured by passive case detection, and the entomological inoculation rate. Analyses were adjusted for clustering and for month and health centre. This trial is registered as ISRCTN21853394. FINDINGS: 1980 children were enrolled in the cohort in 2014 and 2157 in 2015. At the end of the study, more than 99% of children slept under a bednet. The incidence of clinical malaria was 2·0 episodes per child-year in the standard LLIN group and 1·5 episodes per child-year in the PPF-treated LLIN group (incidence rate ratio 0·88 [95% CI 0·77-0·99; p=0·04]). The entomological inoculation rate was 85 (95% CI 63-108) infective bites per transmission season in the standard LLIN group versus 42 (32-52) infective bites per transmission season in the PPF-treated LLIN group (rate ratio 0·49, 95% CI 0·32-0·66; p<0·0001). INTERPRETATION: PPF-treated LLINs provide greater protection against clinical malaria than do standard LLINs and could be used as an alternative to standard LLINs in areas with intense transmission of Plasmodium falciparum malaria and highly pyrethroid-resistant vectors. FUNDING: EU Seventh Framework Programme.