The emergence of mosquitoes that can avoid indoor-deployed interventions, such as treated bed nets and indoor residual spraying, threatens the mainstay of malaria control in Zambia. Furthermore, the requirement for high coverage of these tools poses operational challenges. Spatial repellents are being assessed to supplement these vector control tools, but limitations exist in the residual effect of the repellent and the need for external power or heat for diffusion of the volatiles. A semi-field evaluation of a novel controlled release spatial repellent device (CRD) was conducted in Macha, Zambia. These devices emanate metofluthrin with no need for external power. Devices were deployed in huts within the semi-field system (SFS). Female Anopheles gambiae sensu stricto released within the SFS were trapped overnight by light traps and collected by aspiration the next morning inside and outside of huts to determine the extent of mosquito repellency and the impact on host-seeking and survival. Experiments studied the impact of number of devices as well as the presence of hut occupants. The study was complemented with numerical methods based on computational fluid dynamics to simulate spatial distribution of metofluthrin. Presence of CRDs was associated with significant reductions in indoor counts of mosquitoes, regardless of whether huts were occupied or not. Repellency ranged from 15 to 60% compared to huts with no devices. Reducing the number of devices from 16 to 4 had little impact on repellency. When huts were occupied, indoor mosquito host-seeking was higher in the presence of CRDs, whilst survival was significantly reduced. This study demonstrated that deployment of as few as four CRDs within a hut was associated with reduced indoor mosquito densities. As would be expected, presence of occupants within huts, resulted in greater indoor catches (both with and without devices). The increased indoor mosquito host-seeking and mortality in huts when devices were present may be explained by the excito-repellency activity of metofluthrin. These semi-field experiments provide preliminary data on the utility of CRD spatial repellents to reduce indoor densities of An. gambiae mosquitoes. Studies will further investigate the impact of CRDs on mosquito behaviour as well as epidemiological protective efficacy.

Repellents serve an important role in bite protection. Tick repellents largely rely on biomechanisms that induce responses with direct contact, but synthetic pyrethroids used as spatial repellents against insects have received recent attention for potential use in tick protection systems. An in vitro vertical climb assay was designed to assess spatial repellency against Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis adult, female ticks. Climbing behavior was assessed with and without the presence of two spatial repellents, transfluthrin and metofluthrin. Repellency parameters were defined to simulate the natural questing behavior of ambushing ticks, including measures of detachment, pseudo-questing duration, climbing deterrence, and activity. Significant effects were observed within each parameter. D. variabilis showed the greatest general susceptibility to each repellent, followed by A. americanum, and I. scapularis. The most important and integrative measure of repellency was climbing deterrence–a measure of the spatial repellent’s ability to disrupt a tick’s natural propensity to climb. Transfluthrin deterred 75% of D. variabilis, 67% of A. americanum, and 50% of I. scapularis. Metofluthrin was slightly more effective, deterring 81% of D. variabilis, 73% of A. americanum, and 72% of I. scapularis. The present study poses a novel paradigm for repellency and reports a preliminary assessment of spatial repellent effect on tick behavior. Further research will assess spatial repellency in a more natural setting, scale exposure conditions, and incorporate host cues.

Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC₅₀) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC₅₀ = 0.87 ± 0.05 µg/cm²). Higher concentrations were required to repel D. variabilis (EC₅₀ = 252 ± 12 µg/cm²) and A. americanum (EC₅₀ = 2313 ± 179 µg/cm²). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues.

U.S. military troops are exposed to mosquito-borne pathogens when deployed to endemic regions. Personal protective measures such as permethrin-treated uniforms and dermal repellents are the cornerstones of mosquito-borne disease prevention for the U.S. military. These measures have limitations and additional personal protection tools, such as spatial repellent devices to decrease the risk of vector-borne pathogen transmission, are required. Novel spatial repellent controlled-release devices formulated with metofluthrin were evaluated in an outdoor setting in the northern Amazon of Peru to evaluate performance under field conditions. The metofluthrin emitting devices lowered the number of mosquitoes captured in protected human landing collections (HLC) compared to blank devices, although there were effect differences between Anopheles spp. and species in other mosquito genera. A computational-experimental model was developed to correlate HLC and active ingredient (AI) concentrations as a function of time and space. Results show a strong correlation between the released AI and the decrease in HLC. This model represents the first effort to obtain a predictive analytical tool on device performance using HLC as the entomological endpoint.