Infectious Disease · Medical Literature
Field evaluation of 3-(N-acetyl-n-butyl) aminopropionic acid ethyl ester - IR3535 as a spatial repellent to control malaria: A Randomised, Before-After-Control-Intervention trial.
Abstract
Malaria remains a major public health challenge in sub-Saharan Africa. Increasing mosquito resistance to insecticides can significantly limit current vector control strategies. Spatial repellents represent a promising complementary tool by disrupting mosquito human-seeking behaviour. This trial aimed to evaluate the efficacy of IR3535 as a spatial repellent in Tambai, a high-transmission rural area in central Mozambique. This was a randomised, Before-After-Control-Intervention trial. Four Tambai blocks were randomly selected, with 40 households randomly assigned to receive IR3535 spraying and 40 assigned to as a no-repellent control group. Plasmodium falciparum malaria prevalence was estimated in children under 5 years of age using polymerase chain reaction, before, at year one and at year two. Data were first analysed using frequentist methods and subsequently using spatiotemporal Bayesian models, incorporating INLA-based models to assess the impact of repellent intervention on mosquito density and diversity, sporozoite rates, and malaria prevalence in the repellent and control groups. A total of 5716 mosquitoes were collected, 57.2% were Anopheles and 42.7% were Culex sp.. An. funestus s.l. females, were the most prevalent mosquito both indoor (92.7%) and outdoor (82.5%), followed by An. gambiae and An. tenebrosus. The total number of An. funestus s.l. females was lower in the repellent group compared with the control group [indoors: 765 vs 1,432; outdoors: 175 vs 293], as was the average number of mosquitoes collected per household [indoors: 18.6 vs 35.0; outdoors: 4.3 vs 7.1]. Spatiotemporal analysis revealed evidence of repellent-associated reduction in mosquito densities, with species-specific and indoor-outdoor differences, highlighting An. funestus s.l. dominance and spatial-temporal clustering patterns. P. falciparum prevalence among children under five declined from 72.6% (95% CI = 64.1-80.2) at baseline to 51.3% (95% CI = 43.5-59.1) at year one and 43.3% (95% CI = 35.7-51.1) at the end of the study, with similar reductions in both repellent and control groups. Sporozoite rates were slightly lower in the repellent group, particularly outdoors, however, these differences could not be directedly attributed to the repellent. Our findings indicate that the use of IR3535 as a spatial repellent reduces indoor and outdoor malaria vector densities, which may contribute to reduced malaria transmission. ClinicalTrials.gov NCT04419766.
Clinical relevance
This trial addresses a critical gap in malaria vector control in sub-Saharan Africa, where escalating insecticide resistance threatens the efficacy of standard tools such as indoor residual spraying and insecticide-treated nets. It evaluates IR3535 — a non-toxic, non-insecticidal spatial repellent — as a complementary strategy capable of disrupting mosquito host-seeking behavior both indoors and outdoors in a high-transmission, rural Mozambican setting. Clinicians and public health practitioners should attend to these findings because spatial repellents offer a resistance-agnostic mechanism that could meaningfully augment existing malaria prevention programs in hyperendemic regions.
Key findings
1. Entomological burden: A total of 5,716 mosquitoes were collected over two years; 57.2% were Anopheles spp. and 42.7% were Culex spp., with An. funestus s.l. being the dominant vector both indoors (92.7%) and outdoors (82.5%). 2. Indoor vector density reduction: Total An. funestus s.l. females collected indoors were substantially lower in the repellent group versus control (765 vs. 1,432), representing approximately a 47% reduction in absolute counts. 3. Outdoor vector density reduction: Outdoor An. funestus s.l. female counts were also lower in the repellent group compared to control (175 vs. 293), corresponding to approximately a 40% reduction in absolute counts. 4. Per-household mosquito burden: Average mosquitoes collected per household were lower in the repellent group indoors (18.6 vs. 35.0) and outdoors (4.3 vs. 7.1), indicating roughly 47% and 39% reductions, respectively. 5. Malaria prevalence trajectory (PCR-confirmed, children <5 years): Baseline P. falciparum prevalence was 72.6% (95% CI: 64.1–80.2%), declining to 51.3% (95% CI: 43.5–59.1%) at year one and 43.3% (95% CI: 35.7–51.1%) at year two — with similar reductions observed in both the repellent and control groups, precluding attribution of prevalence decline to the intervention alone. 6. Sporozoite rates: Sporozoite rates were slightly lower in the repellent group, particularly outdoors; however, spatiotemporal Bayesian (INLA-based) analysis could not directly attribute these differences to the IR3535 intervention, underscoring the limits of the BACI design in a setting with concurrent secular trends.
Practice implications
IR3535 spatial repellent applied via household spraying (indoors and outdoors) demonstrates meaningful reductions in Anopheles vector densities — particularly An. funestus s.l. — and should be considered as an adjunct, not a standalone, malaria vector control strategy in high-transmission settings with documented insecticide resistance; it does not exert selective pressure on resistance genes, making it uniquely suitable where pyrethroid resistance is prevalent. Given that P. falciparum prevalence reductions were observed in both intervention and control arms, future trials in this population must employ larger cluster-randomized designs with adequate allocation to disentangle intervention effects from secular trends and community-level transmission dynamics. Monitoring should include longitudinal entomological surveillance (species-specific indoor vs. outdoor mosquito densities and sporozoite rates) alongside PCR-confirmed malaria prevalence in children under five to accurately capture the incremental benefit of spatial repellent deployment.