BACKGROUND: Spatial repellents (SRs) have been widely used for the prevention of mosquito bites, and preliminary findings suggest efficacy against both malaria (1) and Aedes-borne viruses (2) but their effectiveness in reducing mosquito-borne diseases under operational use has never been evaluated. SRs have the potential of being critical tools in the prevention of mosquito-borne diseases in contexts where typical vector control strategies, such as insecticide-treated nets (ITNs) and indoor residual spraying, are inaccessible or underutilized such as among displaced persons or in emergency relief settings.
METHODS: Children will be enrolled in 3 separate cohorts to establish the effectiveness of SRs in reducing malaria infection in different distribution channels. One cohort will estimate the direct effect of the SR distributed through a reference channel (study personnel distribution). The two remaining cohorts will estimate the protection of the SR distributed through a voucher channel and the Village Health Team channel. Cohorts will be followed twice a month (approximately every 15 days): during the first scheduled household visit in the month, a blood sample will be taken for malaria rapid diagnostic test (Monthly Visit #1); and, during the second scheduled household visit, a blood sample will only be taken if the participant has a recent history of fever (Monthly Visit #2). The incidence of malaria in each cohort will be estimated and compared to the reference cohort to determine the benefit of using a SR in an area with high, year-round transmission of malaria.
CONCLUSIONS: This study will address the knowledge gap of whether or not SRs are effective in reducing human malaria disease in humanitarian assistance and emergency response settings in sub-Saharan Africa where underlying transmission rates are historically high and ITNs may or may not be widely deployed. This research will inform policy makers on whether to recommend SRs as a means to further reduce malaria transmission for such operational programs.
BACKGROUND: ClinicalTrials.gov NCT06122142. Registered on November 8, 2023.

OBJECTIVE: The flea Ctenocephalides felis (Siphonaptera: Pulicidae), parasitizes dogs and cats globally, acting as a vector for various pathogens affecting both animals and humans. Growing interest in environmentally friendly, plant-based products prompted this study. The aim of the study was to determine the chemical composition of essential oils (EOs) from Copaifera reticulata, Citrus paradisi, Lavandula hybrida and Salvia sclarea, assessing their insecticidal and repellent properties, determining lethal concentrations (LC50 and LC90), and evaluating residual efficacy in vitro against Ctenocephalides felis felis.
METHODS: Gas Chromatography with Flame Ionization Detector analyzed EO composition. In vitro tests involved preparing EO solutions at various concentrations. Ten specimens from each life stage (egg, larva, pupa, adult) were used for insecticidal activity assessment. Adulticidal activity was assessed using 10 cm2 filter paper strip, each treated with 0.200 mL of the test solution. Immature stages activities were evaluated using 23.76 cm2 discs of the same filter paper, each treated with 0.470 mL of the test solution. Mortality percentage was calculated using (number of dead insects × 100) / number of incubated insects. Probit analysis calculated LC50 values with a 95% confidence interval.
RESULTS: Major EO constituents were β-caryophyllene (EOCR), linalool (EOLH), linalyl acetate (EOSS), and limonene (EOCP). LC50 values were obtained for all stages except for the essential oil of C. paradisi. All oils showed repellent activity at 800 μg/cm2. OECR exhibited greater residual efficacy.
CONCLUSIONS: Each EO demonstrated superior insecticidal activity against specific C. felis felis stages.

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With growing interest in natural compounds as alternative mosquito repellents, assessing the toxicity and structure of potential repellent naturals like thymol (monoterpene phenol) and geraniol (monoterpene alcohol) is vital for understanding their stability and human impact. This study aimed to determine the structural, toxicity, and binding profiles of thymol and geraniol using computational predictions, xTB metadynamics, quantum mechanics, and principal component analysis. Toxicity studies using Protox-II, T.E.S.T, and SwissADME indicated that thymol and geraniol belong to toxicity class 4 and 5, respectively, with low toxicity predictions in other endpoints. Overall pharmacokinetic profile was generated via pkCSM. Off-target predictions via SwissTarget Predictions, LigTMap, Pharmapper, and SuperPred showed that these molecules can bind to 614 human proteins. The degradation of thymol and geraniol were performed using xTB metadynamics and the outcomes showed that the degradants for both compounds were stable and had lower toxicity profile. Nine tautomers were generated via quantum mechanics for thymol and four for geraniol, with RMSD ranging from 3.8 to 6.3 Å for thymol and 3.6 to 4 Å for geraniol after superimpositions. DFT studies found that HOMO-LUMO values and electronegativity parameters of thymol and geraniol did not differ significantly from their isomers. Binding affinity studies against 614 proteins, analysed via PCA and violin plots, highlighted the probable range of binding. These multifaceted in-silico findings corroborate the stability and potential utility of thymol and geraniol as safer alternatives in repellent applications.

Encapsulation of essential oils (EOs) is an important strategy that can be applied to intensify the stability and efficiency of these compounds in integrated pest management. The present study aimed to investigate the sub-lethal activity of polymer-based EOs nanoparticles against red flour beetle, Tribolium castaneum adults as an important critical pest of stored products. Chitosan nanoparticles (CSNPs) containing garlic and cinnamon essential oils (GEO and CEO) prepared using the ionic cross-link technique. Stability of nano-formulations evaluated over temperature and storage time. The fumigant effect (LC10, LC20, LC30) and contact toxicity (LC10, LC15, LC25) determined. In addition, the contact toxicities of EOs and their nanoparticles on nutritional indices evaluated. An olfactometer used to assess the repellent activity of EOs and EOs loaded in CSNPs (EOs@CSNPs) in sub-lethal fumigant concentrations. Characterization results showed GEO loaded in CSNPs has particle size of 231.14 ± 7.55 nm, polydispersity index (PDI) value of 0.15 ± 0.02, encapsulation efficiency (EE) percentage of 76.77 ± 0.20 and zeta potential of - 18.82 ± 0.90 mV, in which these values for the CEO loaded in CSNPs (CEO@CSNPs) changed to 303.46 ± 0.00 nm, 0.20 ± 0.05, 86.81 ± 0.00% and - 20.16 ± 0.35 mV, respectively. A lower PDI value for both CSNPs showed an appropriate NPs size distribution. Furthermore, NPs size and encapsulation efficiency did not change in various temperatures and during four months which confirm good stability of the EOs@CSNPs. In LC30 of GEO@CSNPs, the maximum repellency was determined as 66.66 ± 3.33. Among nutritional indices, in LC25 of GEO@CSNPs, the relative growth rate (RGR) (0.011 ± 0.003 mg.mg-1.day-1), relative consumption rate (RCR) (0.075 ± 0.004 mg.mg-1.day-1) and feeding deterrence index (FDI) (54.662 ± 1.616%) were more affected, so GEO@CSNPs was more effective than CEO@CSNPs. The results of repellent and anti-dietary activities of EOs and EOs@CSNPs confirmed the higher repellency and adverse effectivity on nutritional indices of Tribolium castaneum pest treated with EOs@CSNPs compared to free EOs. In conclusion, the NPs form of GEO and CEO can be a novel and efficient carrier for improving the repellent and anti-nutritional activities of EOs.

Essential oils (EOs) are natural products currently used to control arthropods, and their interaction with insect odorant-binding proteins (OBPs) is fundamental for the discovery of new repellents. This in silico study aimed to predict the potential of EO components to interact with odorant proteins. A total of 684 EO components from PubChem were docked against 23 odorant binding proteins from Protein Data Bank using AutoDock Vina. The ligands and proteins were optimized using Gaussian 09 and Sybyl-X 2.0, respectively. The nature of the protein-ligand interactions was characterized using LigandScout 4.0, and visualization of the binding mode in selected complexes was carried out by Pymol. Additionally, complexes with the best binding energy in molecular docking were subjected to 500 ns molecular dynamics simulations using Gromacs. The best binding affinity values were obtained for the 1DQE-ferutidine (-11 kcal/mol) and 2WCH-kaurene (-11.2 kcal/mol) complexes. Both are natural ligands that dock onto those proteins at the same binding site as DEET, a well-known insect repellent. This study identifies kaurene and ferutidine as possible candidates for natural insect repellents, offering a potential alternative to synthetic chemicals like DEET.

The ubiquitous use of mosquito repellents in homes across Asia, Africa, and South America is related with human exposure to indoor volatile organic compounds (VOCs). There are three primary types of mosquito repellents: those in the form of coils, mats, and liquids. The repellent mechanisms of these products are distinct, resulting in the generation of varying types of VOCs during the repellent process. In this study, the emission characteristics of commercial coil-, mat-, and liquid-type mosquito repellents were observed in a laboratory chamber using real-time measurement. A previously developed personal passive sampler, ePTFE PS, was used to quantify personal exposure to indoor VOCs while 86 volunteers habitually used those three representative types for 3 h in their residence. Notable increase of indoor benzene was observed for coil- and mat-type mosquito repellents, while α-pinene concentration increased significantly following the use of liquid-type mosquito repellent. The average incremental cancer risks for benzene were 10-6 to 10-4 for adults following the use of coil- and mat-type mosquito repellents. The average non-cancer risks for all chemicals were <1 after the use of three types of mosquito repellents. Considering the potential human health risks associated with byproducts (e.g., particulate matter or carbon monoxide from incomplete combustion) emitted after mosquito coil use, further research on this topic is warranted.

BACKGROUND: Spatial repellents can provide personal and household protection against biting vector mosquitoes by volatizing repellents into the air within a given area. Mosquito Shield™ is a transfluthrin passive emanator undergoing evaluation for malaria control. Studies evaluating its entomological impact against different local malaria vector populations would help guide its deployment in endemic countries.
METHODS: A two-arm single-blinded small-scale household randomised entomological trial was conducted to assess the impact of Mosquito Shield™ on the human landing rate of wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) vector mosquitoes in houses in the Ganhoua village of the Zakpota District of central Benin. From a total of 30 houses, 15 were randomly allocated to receive Mosquito Shield™, while the remainder received a placebo product. The trial lasted through the life of the Mosquito Shield™ product (32 days). Mosquito sampling was performed by human landing catches at baseline and at 6 timepoints post-intervention (days 0-1, 7-8, 14-15, 21-22, 28-29 and 31-32). Collections were performed for 2 nights at each sampling time point. WHO cylinder bioassays were conducted during the trial with F1 An. gambiae s.l. mosquitoes that emerged from larvae from the study area to assess the intensity of resistance to pyrethroids in the wild vector population.
RESULTS: The vector population in the study area showed a high intensity of resistance to pyrethroids. Baseline An. gambiae s.l. human landing rates were similar in houses in both study arms before product application (11.53/person/night vs 11.67/person/night, p > 0.05). A total of 5736 mosquitoes were collected in the placebo control arm and 3862 in the Mosquito Shield™ arm post-intervention. Overall An. gambiae s.l. post-intervention human landing rates were significantly lower in houses in the Mosquito Shield™ arm (18.13/person/night) compared to the houses in the placebo control arm (26.84/person/night, IRR = 0.658, p < 0.001). Over the lifespan of the product, Mosquito Shield™ provided a significant protective efficacy of 34.2% (22.1-44.4%, p < 0.001) against wild pyrethroid-resistant An. gambiae s.l. vectors compared to the placebo. Human landing rates of other nuisance vector mosquito species (Culex and Mansonia) were also reduced in houses treated with Mosquito Shield™ compared to the placebo.
CONCLUSIONS: Mosquito Shield™, a transfluthrin passive emanator, provided significant protection against pyrethroid-resistant malaria vectors to households in Benin. The spatial repellent shows potential to reduce malaria transmission by pyrethroid-resistant An. gambiae s.l. vector mosquitoes and cover gaps in malaria control when deployed to complement existing vector control interventions.

Cambodia\'s goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence.

With high aphid-repellent activity but low stability, (E)-β-farnesene (EβF), the major component of the aphid alarm pheromone, can be used as a synergist to insecticides. Some EβF analogues possess both good aphid-repellent activity and stability, but the synergistic effect and related mechanism are still unclear. Therefore, this study investigated the synergistic effect and underlying mechanism of the EβF and its analogue against the aphid Myzus persicae. The results indicated that EβF and the analogue showed significantly synergistic effects to different insecticides, with synergism ratios from 1.524 to 3.446. Mechanistic studies revealed that EβF and the analogue exhibited effective repellent activity, significantly upregulated target OBP genes by 161 to 731%, increased aphid mobility, and thereby enhanced contact with insecticides. This research suggests that the EβF analogue represents a novel synergist for insecticides, with the potential for further application in aphid control owing to its enhanced bioactivity and the possibility of reducing insecticide doses.