Volatile pyrethroid spatial repellents for preventing mosquito bites: a systematic review and meta-analysis

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BACKGROUND: Volatile pyrethroid spatial repellents (VPSRs) can prevent mosquito-borne diseases including malaria and dengue fever, but the use of varied evaluation methods has resulted in a lack of clarity regarding their protective efficacy (PE) against contact with mosquitoes. This systematic review and meta-analysis consolidates the entomological evidence base on the PE of VPSRs against Anopheles, Aedes, and Culex mosquitoes and different test methods used. METHODS: We identified studies completed between January 2000 and September 2023 by searching through databases, conference abstracts, and personal correspondences. Included studies were semi-field or field studies that measured the PE of VPSRs using human landing catch (HLC) of mosquito landings on human legs and/or mosquito trap density, the number of mosquitoes captured using traps per set time period, compared to control groups. The systematic review summarised study-level data using a generalised linear mixed model with random effects. The meta-analysis pooled individual mosquito-level data and weather data on temperature, humidity, and wind from satellites, analysing PE subgrouped by product format, active ingredient, mosquito capture method used, mosquito species, and indoor vs outdoor setting. Risk of bias was assessed using a SYRCLE tool adapted for mosquito studies. Additional studies published from October 2023 to July 2025 were summarised. PROSPERO registration: CRD42021268852. FINDINGS: 58 eligible publications showed that VPSRs provided an average of 56% (95% CI 50, 62%) PE from mosquito bites. Meta-analysis of individual mosquito-level data from 50 (86%) of eligible studies involving 1,703,120 mosquitoes showed that PE was highest when measured using HLC, with similar results seen in semi-field (58%, 95% CI 54, 62%) and field studies (50%, 95% CI 40, 59%). Differences between indoor (54%, 95% CI 18, 68%) and outdoor settings (56%, 95% CI 51, 60%) were unclear. Species-level differences were observed with low PE seen in Anopheles funestus (31%, 95% CI 19, 43%); the potential for cross-resistance to solid-state pyrethroids is unclear. Efficacy was not sensitive to combined weather effects. INTERPRETATION: VPSRs offer protection from contact with mosquitoes, with semi-field studies reflecting field data and species-level differences observed. HLC provided the best quality data. Additional field studies that evaluate outdoor protection in malaria-endemic settings are needed, especially in West African, South American, and Southeast Asian settings. FUNDING: National Institutes of Health (National Institute of Allergy and Infectious Diseases (K01AI156182)) and "Accelerate to Eliminate Malaria" program.

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