Impact of multi-active ingredient long-lasting insecticidal nets for malaria vector control in sub-Saharan Africa: a systematic review and meta-analysis

Abstract

Strong selective pressures on mosquitoes arise from an over-reliance on a narrow range of insecticides and the continuous increase in insecticide resistance. This increased resistance weakens the effectiveness of conventional single-ingredient vector control interventions, thus undermining the efforts to reduce malaria transmission. This study aimed to assess the comparative efficacy of multi-active ingredients interventions, which include pyrethroid combinations with pyriproxyfen, chlorfenapyr, and piperonyl butoxide (PBO), versus single-active ingredients approaches in reducing malaria prevalence and key entomological outcomes in malaria-endemic regions. A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. Studies were selected based on specific inclusion criteria, including randomised controlled trials conducted in sub-Saharan Africa and interventions focused on multi-active ingredient (MAI) approaches. Data on malaria prevalence, vector density, sporozoite rate, and entomological inoculation rate (EIR) were extracted. Random- and fixed-effects models were applied to evaluate the pooled effects, and heterogeneity was assessed using a diagnostic plot. Publication bias was examined using funnel and forest plots. Four studies met the inclusion criteria, which comprise a total of 135,706 households for pyrethroid-only ITNs, 117,652 for pyrethroid-pyriproxyfen, 118,518 for pyrethroid-chlorfenapyr, and 63,331 for pyrethroid-PBO interventions. Chlorfenapyr-pyrethroid combinations showed the most substantial reduction in malaria prevalence (adjusted odds ratio (aOR) 0.53; 95% CI: 0.30–0.67) and entomological inoculation rate (aOR 0.13; 95% CI: 0.07–0.31). Although pyriproxyfen and PBO combinations also reduced vector density and sporozoite rates, chlorfenapyr exhibited the highest efficacy, especially in regions with established pyrethroid resistance. Publication bias was observed, resulting in a slight overestimation of the effectiveness of MAI-LLINs interventions. MAI-LLINs approaches, particularly chlorfenapyr-pyrethroid interventions, have demonstrated superior effectiveness compared to single-active-ingredient (SAI) LLIN interventions in reducing malaria transmission metrics in sub-Saharan Africa. While the results underline the potential of MAI-LLINs strategies, further research and collaborative studies are needed to optimise MAI-LLINs deployment, assess long-term impacts on resistance, and ensure cost-effectiveness in resource-limited settings.