The Immune Home: Domestic Enclaves, Diffuse Protections

This essay tracks a paradigm shift in the use of chemicals to control malaria: away from insecticidal approaches, focused on killing mosquitoes within private domestic dwellings, and toward the creation of protective communal atmospheres. An ongoing study of the efficacy of spatial repellents to reduce malaria transmission in rural Tanzania provides an opportunity to rethink the oikographic assumptions of malaria control—and of many global health interventions—and to foreground the specific relationalities of peri-domestic spaces. Yet a sense of moral ambivalence permeates this inquiry, as malaria prevention becomes untethered from any long-lasting material improvement in the house. We reflect on the power of chemicals to reveal chronic forms of neglect and, just possibly, conjugate new, if diffuse, forms of communitas.

To Kill or to Repel Mosquitoes? Exploring Two Strategies for Protecting Humans and Reducing Vector-Borne Disease Risks by Using Pyrethroids as Spatial Repellents

Although control efforts are improving, vector-borne diseases remain a global public health challenge. There is a need to shift vector control paradigms while developing new products and programmes. The importance of modifying vector behaviour has been recognised for decades but has received limited attention from the public health community. This study aims to: (1) explore how the use of spatial repellents at sublethal doses could promote public health worldwide; (2) propose new methods for evaluating insecticides for use by the general public; and (3) identify key issues to address before spatial repellents can be adopted as complementary vector control tools. Two field experiments were performed to assess the effects of an insecticidal compound, the pyrethroid transfluthrin, on Aedes albopictus mosquitoes. The first examined levels of human protection, and the second looked at mosquito knockdown and mortality. For the same transfluthrin dose and application method, the percent protection remained high (>80%) at 5 h even though mosquito mortality had declined to zero at 1 h. This result underscores that it matters which evaluation parameters are chosen. If the overarching goal is to decrease health risks, sublethal doses could be useful as they protect human hosts even when mosquito mortality is null.

Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in western Kenya compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program)

Background: Spatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round. Methods: This trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial. Sixty clusters will be randomly assigned in a 1:1 ratio to receive spatial repellent or placebo. A total of 6120 children aged ≥ 6 months to 10 years of age will be randomly selected from the study clusters, enrolled into an active cohort (baseline, cohort 1, and cohort 2), and sampled monthly to determine time to first infection by smear microscopy. Each cohort following the implementation of the intervention, will be split into two groups, one to estimate direct effect of the spatial repellent and the other to estimate degree of diversion of mosquitoes and malaria transmission to unprotected persons. Malaria incidence in each cohort will be estimated and compared (primary indicator) to determine benefit of using a spatial repellent in a high, year-round malaria transmission setting. Mosquitoes will be collected monthly using CDC light traps to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches will assess behavioral effects of the intervention. Discussion: Findings will serve as the first cluster-randomized controlled trial powered to detect spatial repellent efficacy to reduce malaria in sub-Saharan Africa where transmission rates are high, insecticide treated nets are widely deployed, and mosquitoes are resistant to insecticides. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of spatial repellents in malaria control programs. Trial registration: ClinicalTrials.gov NCT04766879. Registered February 23, 2021.

INSECTICIDE EFFICACY OF SPATIAL REPELLENT COMPOUND-METOFLUTHRIN AGAINST SUSCEPTIBLE AND RESISTANT STRAINS OF AEDES AEGYPTI

Spatial repellents (SR), include pyrethroid insecticides that are highly volatile at low temperatures and with high lethal activities against mosquitoes, mainly Aedes vectors of arboviral diseases. Of these SR, metofluthrin is widely used in various devices for repellent consumer products. This article reports the susceptibility status of Ae. aegypti Puerto Rico permethrin-resistant laboratory strain (PR) and Orlando susceptible laboratory strain (ORL) to metofluthrin and permethrin using the CDC glass bottle bioassay. The time-mortality relationships showed that the permethrin-resistant PR strain is highly resistant to both permethrin and metofluthrin compared to the susceptible ORL strain. The resistant ratio (RR) based on the killing time (KT) (KT50 -PR/KT50 -ORL) was 30- and 5- folds for permethrin and metofluthrin, respectively. The results also showed that the PR strain is less resistance to metofluthrin than to permethrin, with a three-fold RR (KT50 -PR-per/KT50 -PR-met). These results indicate the potential risk of developing cross-resistance of metofluthrin in permethrin-resistant mosquitoes. Integrated vector management in mosquito control should be considerate of how consumer products and field operations interact to accelerate cross resistance to pyrethroids.

Spatial Repellents Protect Small Perimeters from Riceland Mosquitoes in a Warm-Humid Environment

ABSTRACT Recent experiments suggest spatial repellents may significantly reduce biting pressure from host-seeking riceland mosquitoes, such as Anopheles quadrimaculatus, in a warm-humid open-field habitat. However, little is known regarding efficacy of these formulations in partially enclosed spaces where US military personnel may be sheltered or concealed in an operational environment. In this study we investigated the capability of 3 spatial repellents—metofluthrin, linalool, and d-cis/trans allethrin—to reduce mosquito incursion into small open-top enclosures of US military camouflage netting. We found that metofluthrin was more effective in partially enclosed spaces compared with the open field, whereas both linalool and d-cis/trans allethrin provided superior protection in the open. These findings support strategic selection of spatial repellents depending on the environment immediately surrounding the host.

Predicting the impact of outdoor vector control interventions on malaria transmission intensity from semi-field studies

Background Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments. Methods We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area. Results Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors. Conclusions The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC.

Functional assessment of biodegradable cotton nonwoven substrates permeated with spatial insect repellants for disposable applications

Arboviral diseases and malaria transmitted by mosquitoes are major health concerns worldwide responsible for millions of deaths annually. Spatial repellents have been used as preventative measures via direct application to the skin or disposable devices worn outside of clothing. Naturally derived, plant-based repellents are safe, effective alternatives to synthetic repellents and may be applied to disposable substrates including adhesive patches. Many disposables are composed of synthetic petrochemical-based polyester and polypropylene nonwoven fabrics, contributing to growing concern surrounding microplastic pollution. Sustainable and biodegradable substrates including those made from cotton are cost effective and environmentally friendly. Therefore, we explored the utilization of cotton-based substrates for the application of natural spatial and synthetic contact insect repellents. Cotton fibers used in the study were commercially available greige cotton, scoured and bleached greige cotton and reginned greige cotton motes, a value-added byproduct of the ginning process. Synthetic polyester and polypropylene were used for comparison. Thermogravimetric/derivative thermogravimetric analysis (TG/DTG) in combination with modulated differential scanning calorimetry (mDSC) were used to discern vaporization properties of repellents from the substrates. Retention times of repellents on the substrates were analyzed using a Fourier-transform infrared spectroscopy–focal plane array detector and compared with the TG/DTG and mDSC data. Mosquito landing assays confirmed the feasibility of using cotton-based substrates treated with plant-based spatial repellents as an effective and environmentally friendly alternative to synthetic materials.

Behavioral response of insecticide-resistant mosquitoes against spatial repellent: A modified self-propelled particle model simulation

Rapidly increasing pyrethroid insecticide resistance and changes in vector biting and resting behavior pose serious challenges in malaria control. Mosquito repellents, especially spatial repellents, have received much attention from industry. We attempted to simulate interactions between mosquitoes and repellents using a machine learning method, the Self-Propelled Particle (SPP) model, which we modified to include attractiveness/repellency effects. We simulated a random walk scenario and scenarios with insecticide susceptible/resistant mosquitoes against repellent alone and against repellent plus attractant (to mimic a human host). Simulation results indicated that without attractant/repellent, mosquitoes would fly anywhere in the cage at random. With attractant, all mosquitoes were attracted to the source of the odor by the end. With repellent, all insecticide-susceptible mosquitoes eventually moved to the corner of the cage farthest from the repellent release point, whereas, a high proportion of highly resistant mosquitoes might reach the attractant release point (the human) earlier in the simulation. At fixed concentration, a high proportion of mosquitoes could be able to reach the host when the relative repellency efficacy (compare to attractant efficacy) was <1, whereas, no mosquitoes reached the host when the relative repellency efficacy was > 1. This result implies that repellent may not be sufficient against highly physiologically insecticide resistant mosquitoes, since very high concentrations of repellent are neither practically feasible nor cost-effective.