Identification of an arthropod molecular target for plant-derived natural repellents.

Arthropods maintain ecosystem balance while also contributing to the spread of disease. Plant-derived natural repellents represent an ecological method of pest control, but their direct molecular targets in arthropods remain to be further elucidated. Occupying a critical phylogenetic niche in arthropod evolution, scorpions retain an ancestral genetic profile. Here, using a behavior-guided screening of the Mesobuthus martensii genome, we identified a scorpion transient receptor potential (sTRP1) channel that senses Cymbopogon-derived natural repellents, while remaining insensitive to the synthetic chemical pesticide DEET. Scrutinizing orthologs of sTRP1 in Drosophila melanogaster, we further demonstrated dTRPγ ion channel as a chemosensory receptor of natural repellents to mediate avoidance behavior. This study sheds light on arthropod molecular targets of natural repellents, exemplifying the arthropod­plant adaptation. It should also help the rational design of insect control strategy and in conserving biodiversity.

Efficacy of Unregulated Minimum Risk Products to Kill and Repel Ticks.

Human-biting ticks threaten public health in the United States. Registration by the Environmental Protection Agency of products to kill host-seeking ticks or repel ticks contacting humans is indicative of their safety and effectiveness. Unregulated minimum risk products, exempt from Environmental Protection Agency registration and often based on botanical oils, are proliferating in the marketplace, but there is concern about their effectiveness to kill and repel ticks. Evaluations of such products are limited in the published literature. A review showed considerable variability among minimum risk products to kill host-seeking blacklegged ticks, with effectiveness similar to chemical pesticide products for some minimum risk products but minimal impact on the ticks for other products. Evaluations of minimum risk tick repellents have typically focused on individual active ingredients rather than formulated products, which often combine multiple active ingredients. Consumers should be aware that effectiveness to kill and repel ticks can differ among unregulated minimum risk products.

An Overview of Tsetse Fly Repellents: Identification and Applications.

Tsetse flies are vectors of the parasite trypanosoma that cause the neglected tropical diseases human and animal African trypanosomosis. Semiochemicals play important roles in the biology and ecology of tsetse flies. Previous reviews have focused on olfactory-based attractants of tsetse flies. Here, we present an overview of the identification of repellents and their development into control tools for tsetse flies. Both natural and synthetic repellents have been successfully tested in laboratory and field assays against specific tsetse fly species. Thus, these repellents presented as innovative mobile tools offer opportunities for their use in integrated disease management strategies.

Tritrophic Interactions Mediated by Zoophytophagous Predator-Induced Host Plant Volatiles.

The zoophytophagous mirid predator Nesidiocoris tenuis and the ectoparasitoid Stenomesius japonicus are important biological control agents for several agricultural pests including the invasive leafminer, Phthorimaea absoluta, a destructive pest of Solanaceous crops especially tomato in sub-Saharan Africa. However, little is known about how feeding by N. tenuis can influence the tritrophic interactions in the tomato plant. Here, we tested the hypothesis that N. tenuis phytophagy would influence the tritrophic olfactory interactions between the host plant tomato and pest, predator, and parasitoid. In olfactometer assays, P. absoluta females and N. tenuis adults were both attracted to constitutive volatiles released by the tomato plant. Whereas females of P. absoluta avoided volatiles released by N. tenuis-infested plants, S. japonicus females and N. tenuis adults were attracted to the induced volatiles. In coupled gas chromatography-electroantennographic detection (GC-EAD) recordings of intact and N. tenuis-infested plant volatiles, antennae of P. absoluta and S. japonicus females both detected eight components, whereas N. tenuis adults detected seven components which were identified by GC-mass spectrometry (GC-MS) as terpenes and green leaf volatiles (GLVs). Dose-response olfactometer bioassays revealed that the responses of P. absoluta, N. tenuis, and S. japonicus varied with the composition and concentration of blends and individual compounds tested from N tenuis-induced volatiles. Females of P. absoluta showed no preference for an eight-component blend formulated from the individual repellents including hexanal, (Z)-3-hexenyl butanoate, and δ-elemene identified in the volatiles. On the other hand, S. japonicus females were attracted to an eight-component blend including the attractants (E)-2-hexenal, (Z)-3-hexenol, methyl salicylate, ß-phellandrene, and (E)-caryophyllene. Likewise, N. tenuis adults were attracted to a seven-component blend including the attractants ß-phellandrene, δ-elemene, and (E)-caryophyllene identified in the volatiles. Our findings suggest that there is potential for the use of terpenes and GLVs to manage the insects in the tritrophic interaction.

Sequential Isolation of Essential Oils Repellent to the Red Palm Weevil Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae).

The push-pull approach using semiochemicals in pest control requires both an attractant and a repellent. Many previous studies have arbitrarily tested one or more known insect repellents or plant essential oils (EOs) hoping to find repellents of an insect pest. We used a comprehensive approach that synergistically tests in the field numerous natural volatiles from commercial EOs to identify repellents of the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae), a worldwide pest of palms and date palms. Volatiles from 79 EOs in slow-release devices were divided into five groups and tested in traps with attractive pheromone compared to traps with pheromone alone. EO-treatment groups exhibiting repellency due to significant trap shutdown, were further subdivided into subgroups of four EOs each and tested further. Two groups of four EOs (cypress, desert wormwood, elemi, and Eucalyptus citriodora) and (niaouli, nutmeg, oregano, and orange sweet), or their corresponding mixtures of major volatiles, caused pheromone trap reductions of up to 92%. Further tests showed that seven of the eight EOs are similarly repellent as the corresponding subgroup. This systematic approach of successively testing sub-fractions of EOs in the field for trap shutdown should be useful to identify repellents of other insect pests of crops.

Association between early-life mosquito repellents exposure and ADHD-like behaviours.

BACKGROUND: Limited research has explored the impact of mosquito repellents exposure during early life on ADHD symptoms. This study aimed to explore the associations of exposure to mosquito repellents from pregnancy to 3 years old and the prevalence of ADHD-like behaviours among children aged 3-9 years, and further identify the sensitive exposure period. METHODS: A cross-sectional study was conducted, including 12 275 children in Hefei City, China. Exposure was self-reported via primary caregivers. ADHD-like behaviours were measured by the Swanson, Nolan and Pelham, version IV scale (SNAP-IV), and Conners' Parent Rating Scale (CPRS). Cross-over analysis, binary logistic regression and linear regression were employed. RESULTS: After adjusting for confounding variables, early-life exposure to mosquito repellents was associated with a higher risk of ADHD-like behaviours (OR = 1.81, 95% CI = 1.49-2.19). By comparing the strength of the association for each subgroup, we found exposure during 1-3 years old was a sensitive period (OR = 1.89, 95% CI = 1.25-2.87) by the cross-over analysis. Furthermore, we found a dose-response relationship in which the likelihood of ADHD-like behaviours increased with children's early-life mosquito repellents exposure dose. CONCLUSIONS: Early-life exposure to mosquito repellents is linked with an elevated risk of ADHD-like behaviours in children, with a sensitive period identified during 1-3 years old.

An updated review on the safety of N, N-diethyl-meta-toluamide insect repellent use in children and the efficacy of natural alternatives.

N, N-diethyl-meta-toluamide (DEET) has been considered the 'gold standard' for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA-approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents.

Encapsulation of carvacrol and thymol with yeast cell wall and its repellent activity against Amblyomma sculptum and Rhipicephalus sanguineus (Sensu Lato).

The main way to avoid contact with ticks and consequently tick-borne disease is the use of synthetic repellents. The search of new repellent compounds to increase the possibilities of use in strategies controls are necessary. The present study evaluated the repellent activity of two natural terpenes carvacrol and thymol in each one two different formulation (encapsulated and nonencapsulated with yeast cell wall) against the ticks Amblyomma sculptum and Rhipicephalus sanguineus sensu lato nymphs. Nymphs of A. sculptum and R. sanguineus s.l. of a single generation were used. The vertical filter paper repellency assay were performed with different concentration of both terpenes encapsulated and nonencapsulated in yeast cell wall. The repellent concentration 50% (RC50) were calculated to each compound formulation. Both carvacrol and thymol (encapsulated and nonencapsulated), had a repellent activity against A. sculptum and R. sanguineus s.l nymphs. Amblyomma sculptum was more sensitive to nonencapsulated carvacrol (RC50 values: 0.0032 to 0.0082 mg/cm2 after 1 and 15 min) (P < 0.05), while R. sanguineus s.l. was more sensitive to encapsulated carvacrol (RC50 values: 0.00008 to 0.0035 mg/cm2 after 1 and 15 min) (P < 0.05). Among tick species, R. sanguineus s.l. was more sensitive for most compounds than A. sculptum (P < 0.05). Although with distinct repellent activities, carvacrol and thymol encapsulated can be a promising alternative to synthetic repellents against A. sculptum and R. sanguineus s.l.

Insect repellents: An updated review for the clinician.

Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. The use of insect repellents (IRs) to prevent systemic infections constitutes a fundamental public health effort. Cost effectiveness, availability, and high efficacy against arthropod vectors are key characteristics of an ideal IR. Currently, numerous IRs are available on the market, with N,N-diethyl-3-methylbenzamide (DEET) being the most widely used. DEET has an excellent safety profile and remarkable protection against mosquitoes and various other arthropods. Other Environmental Protection Agency-registered IR ingredients (eg, permethrin, picaridin, IR3535, oil of lemon eucalyptus, oil of citronella, catnip oil, and 2-undecanone) are alternative IRs of great interest because some of these ingredients have efficacies comparable to that of DEET. These alternative IRs possess low toxicity and favorable customer experiences in use (eg, cosmetically pleasant, naturally occurring). This review summarizes the currently available Environmental Protection Agency-registered IRs, including their origins, mechanisms of action, side effect profiles, and available formulations. This review will enable the clinician to select the best IR option to meet a patient's needs and provide the greatest protection from arthropod bites and their sequelae.

Matricaria chamomilla Essential Oils: Repellency and Toxicity against Imported Fire Ants (Hymenoptera: Formicidae).

Matricaria chamomilla flower essential oils (EOs) blue Egyptian (EO-1), chamomile German CO2 (EO-2), and chamomile German (EO-3) and the pure compound α-bisabolol were evaluated against red imported fire ants (RIFA), Solenopsis invicta Buren, black imported fire ants, S. richteri Forel (BIFA), and hybrid imported fire ants (HIFA) for their repellency and toxicity. A series of serial dilutions were tested starting from 125 µg/g until the failure of the treatment. Based on the amount of sand removed, EO-1 showed significant repellency at dosages of 7.8, 7.8, and 31.25 µg/g against RIFA, BIFA, and HIFA, respectively. EO-3 was repellent at 3.9, 7.8, and 31.25 µg/g against BIFA, RIFA, and HIFA, whereas α-bisabolol was active at 7.8, 7.8, and 31.25 µg/g against BIFA, HIFA, and RIFA, respectively. DEET (N, N-diethyl-meta-toluamide) was active at 31.25 µg/g. Toxicity of EOs and α-bisabolol was mild to moderate. For EO-1, LC50 values were 93.6 and 188.11 µg/g against RIFA and BIFA; 98.11 and 138.4 µg/g for EO-2; and 142.92 and 202.49 µg/g for EO-3, respectively. The LC50 of α-bisabolol was 159.23 µg/g against RIFA. In conclusion, M. chamomilla EOs and α-bisabolol offer great potential to be developed as imported fire ant repellents.

Volatile allosteric antagonists of mosquito odorant receptors inhibit human-host attraction.

Odorant-dependent behaviors in insects are triggered by the binding of odorant ligands to the variable subunits of heteromeric olfactory receptors. Previous studies have shown, however, that specific odor binding to ORco, the common subunit of odorant receptor heteromers, may allosterically alter olfactory receptor function and profoundly affect subsequent behavioral responses. Using an insect cell-based screening platform, we identified and characterized several antagonists of the odorant receptor coreceptor of the African malaria vector Anopheles gambiae (AgamORco) in a small collection of natural volatile organic compounds. Because some of the identified antagonists were previously shown to strongly repel Anopheles and Culex mosquitoes, we examined the bioactivities of the identified antagonists against Aedes, the third major genus of the Culicidae family. The tested antagonists inhibited the function of Ae. aegypti ORco ex vivo and repelled adult Asian tiger mosquitoes (Ae. albopictus). Binary mixtures of specific antagonists elicited higher repellency than single antagonists, and binding competition assays suggested that this enhanced repellence is due to antagonist interaction with distinct ORco sites. Our results also suggest that the enhanced mosquito repellency by antagonist mixtures is due to additive rather than synergistic effects of the specific antagonist combinations on ORco function. Taken together, these findings provide novel insights concerning the molecular aspects of odorant receptor function. Moreover, our results demonstrate that a simple screening assay may be used for the identification of allosteric modifiers of olfactory-driven behaviors capable of providing enhanced personal protection against multiple mosquito-borne infectious diseases.

Skin microbiome alters attractiveness to Anopheles mosquitoes.

BACKGROUND: Some people produce specific body odours that make them more attractive than others to mosquitoes, and consequently are at higher risk of contracting vector-borne diseases. The skin microbiome can break down carbohydrates, fatty acids and peptides on the skin into volatiles that mosquitoes can differentiate. RESULTS: Here, we examined how skin microbiome composition of women differs in relation to level of attractiveness to Anopheles coluzzii mosquitoes, to identify volatiles in body odour and metabolic pathways associated with individuals that tend to be poorly-attractive to mosquitoes. We used behavioural assays to measure attractiveness of participants to An. coluzzii mosquitoes, 16S rRNA amplicon sequencing of the bacteria sampled from the skin and gas chromatography of volatiles in body odour. We found differences in skin microbiome composition between the poorly- and highly-attractive groups, particularly eight Amplicon Sequence Variants (ASVs) belonging to the Proteobacteria, Actinobacteria and Firmicutes phyla. Staphylococcus 2 ASVs are four times as abundant in the highly-attractive compared to poorly-attractive group. Associations were found between these ASVs and volatiles known to be attractive to Anopheles mosquitoes. Propanoic pathways are enriched in the poorly-attractive participants compared to those found to be highly-attractive. CONCLUSIONS: Our findings suggest that variation in attractiveness of people to mosquitoes is related to the composition of the skin microbiota, knowledge that could improve odour-baited traps or other next generation vector control tools.

Malaria prevention interventions beyond long-lasting insecticidal nets and indoor residual spraying in low- and middle-income countries: a scoping review.

BACKGROUND: Significant progress in malaria prevention during the past two decades has prompted increasing global dialogue on malaria elimination. Recent reviews on malaria strategies have focused mainly on long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with little emphasis on other prevention methods. This article is a scoping review of literature on malaria prevention methods beyond LLINs and IRS in low- and middle-income countries (LMICs). METHODS: This scoping review found articles published between from 1994 to 2020. Studies were obtained from a search of the PubMed, the Cochrane Library and Social Science abstracts. Grey literature and manual search of secondary references was also done. The search strategy included all study designs but limited only to English. Three independent reviewers performed the selection and characterization of articles, and the data collected were synthesized qualitatively. RESULTS: A total of 10,112 studies were identified among which 31 met the inclusion criteria. The results were grouped by the 3 emerging themes of: housing design; mosquito repellents; and integrated vector control. Housing design strategies included closing eves, screening of houses including windows, doors and ceilings, while mosquito repellents were mainly spatial repellents, use of repellent plants, and use of plant-based oils. Integrated vector control included larvae source management. Evidence consistently shows that improving housing design reduced mosquito entry and malaria prevalence. Spatial repellents also showed promising results in field experiments, while evidence on repellent plants is limited and still emerging. Recent literature shows that IVM has been largely ignored in recent years in many LMICs. Some malaria prevention methods such as spatial repellents and IVM are shown to have the potential to target both indoor and outdoor transmission of malaria, which are both important aspects to consider to achieve malaria elimination in LMICs. CONCLUSION: The scoping review shows that other malaria prevention strategies beyond LLINs and IRS have increasingly become important in LMICs. These methods have a significant role in contributing to malaria elimination in endemic countries if they are adequately promoted alongside other conventional approaches.

Potent Ant Deterrents Emitted from Nematode-Infected Insect Cadavers.

Most known species of entomopathogenic nematodes (EPNs) are generalist obligate parasites of insects. They kill their hosts within days after infection and mortality is mainly caused by toxins produced by bacteria that co-infect the hosts and serve as food for the nematodes. EPNs can infect a very broad spectrum of insects and these insects can therefore be expected to have evolved strategies to avoid infection. Indeed, ants are known to avoid feeding on EPN-infected insect cadavers, most likely because they are repelled by semiochemicals that emanate from the cadavers. The source and nature of these repellents are so far unknown. In a series of behavioral and chemical analytical experiments we identified hexadecanal and 2-heptadecanone as two compounds that are emitted by insect larva that are infected by the EPN Steinernema feltiae, but not by uninfected larvae. When spiking honey water with the two semiochemicals, they were confirmed to be highly deterrent to the ant Lasius niger. The environmentally benign hexadecanal and 2-heptadecanone could be employed to ward off ants and possibly other pests. Additional experiments are needed to fully determine their application potential.

Host-Guest Inclusion Complexes of Natural Products and Nanosystems: Applications in the Development of Repellents.

Repellents are compounds that prevent direct contact between the hosts and the arthropods that are vectors of diseases. Several studies have described the repellent activities of natural compounds obtained from essential oils. In addition, these chemical constituents have been pointed out as alternatives to conventional synthetic repellents due to their interesting residual protection and low toxicity to the environment. However, these compounds have been reported with short shelf life, in part, due to their volatile nature. Nanoencapsulation provides protection, stability, conservation, and controlled release for several compounds. Here, we review the most commonly used polymeric/lipid nanosystems applied in the encapsulation of small organic molecules obtained from essential oils that possess repellent activity, and we also explore the theoretical aspects related to the intermolecular interactions, thermal stability, and controlled release of the nanoencapsulated bioactive compounds.

Insecticide-treated eave ribbons for malaria vector control in low-income communities.

Supplementary tools are required to address the limitations of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), which are currently the core vector control methods against malaria in Africa. The eave ribbons technology exploits the natural house-entry behaviours of major malaria vectors to deliver mosquitocidal or repellent actives around eave spaces through which the Anopheles mosquitoes usually enter human dwellings. They confer protection by preventing biting indoors and in the peri-domestic outdoor spaces, and also killing a significant proportion of the mosquitoes. Current versions of eave ribbons are made of low-cost hessian fabric infused with candidate insecticides and can be easily fitted onto multiple house types without any additional modifications. This article reviews the evidence for efficacy of the technology, and discusses its potential as affordable and versatile supplementary approach for targeted and efficient control of mosquito-borne diseases, particularly malaria. Given their simplicity and demonstrated potential in previous studies, future research should investigate ways to optimize scalability and effectiveness of the ribbons. It is also important to assess whether the ribbons may constitute a less-cumbersome, but more affordable substitute for other interventions, such as IRS, by judiciously using lower quantities of selected insecticides targeted around eave spaces to deliver equivalent or greater suppression of malaria transmission.

A retail audit of mosquito control products in Busia County, western Kenya.

BACKGROUND: Approximately 70% of Kenya's population is at risk for malaria. The core vector control methods in Kenya are insecticide-treated mosquito nets (ITNs) and indoor residual spraying, with supplementary larval source management. In 2015, 21% of ITNs were accessed through the private retail sector. Despite the private sector role in supplying mosquito control products (MCPs), there is little evidence on the availability, sales trends, and consumer preferences for MCPs other than ITNs. This study, a component of a larger research programme focused on evaluating a spatial repellent intervention class for mosquito-borne disease control, addressed this evidence gap on the role of the private sector in supplying MCPs. METHODS: A cross-sectional survey was deployed in a range of retail outlets in Busia County to characterize MCP availability, sales trends, and distribution channels. The questionnaire included 32 closed-ended and four open-ended questions with short answer responses. Descriptive analysis of frequency counts and percentages was carried out to glean insights about commercially available MCPs and the weighted average rank was used to determine consumer preferences for MCPs. Open-ended data was analysed thematically. RESULTS: Retail outlets that stocked MCPs commonly stocked mosquito coils (73.0%), topical repellents (38.1%), aerosol insecticide sprays (23.8%) and ITNs (14.3%). Overall, retailers reported the profits from selling MCPs were adequate and they overwhelmingly planned to continue stocking the products. Of respondents who stocked MCPs, 96.8% responded that sales increased during long rains and 36.5% that sales also surged during short rains. ITNs and baby-size nets were often delivered by the wholesaler. Retailers of aerosol sprays, mosquito coils, and topical repellents either collected stock from the wholesaler or products were delivered to them. Other commercially available MCPs included insecticide incense sticks, electric mosquito strikers, insecticide soaps, electrically heated insecticide mats, and electric insecticide emanators, indicating a well-established market. CONCLUSIONS: The wide range of MCPs in local retail outlets within the study area suggests the need and demand for mosquito control tools, in addition to ITNs, that are affordable, easy to use and effective. The presence of a wide range of MCPs, is a promising sign for the introduction of a spatial repellent intervention class of products that meets consumer needs and preferences.

The Effect of Long-lasting Permethrin Impregnated Socks on Tick Bite in Korea.

BACKGROUND: The risk of tick-borne diseases is decreased by increasing awareness and knowledge through prevention education. The aim of the present study was to evaluate the effect of long-lasting permethrin impregnated (LLPI) socks for tick bites. METHODS: A randomized open label study was conducted to determine the effectiveness of LLPI socks for prevention of tick bites among 367 adults living in a rural area. Participants completed questionnaires at the start of follow-up (July 2014) and at the end of follow-up (December 2014), and tick bites were reported. RESULTS: A total of 332 subjects completed the follow-up survey. The tick bite rate of the two groups was not significantly different (3.6% vs. 3.1%). But the tick bite rate of lower extremities of subjects wearing LLPI socks was significantly lower compared to that of subjects wearing general socks. CONCLUSION: The tick bite rate was not different between the two groups, but the tick bite rate of lower extremities of LLPI was significantly lower than general groups. Further study is needed to investigate the effect of LLPI clothes with larger populations.

Properties of Mosquito Repellent-Plasticized Poly(lactic acid) Strands.

Poly(lactic acid) (PLA) is an attractive candidate for replacing petrochemical polymers because it is fully biodegradable. This study investigated the potential of PLA as a sustainable and environmentally friendly alternative material that can be developed into commercially viable wearable mosquito repellent devices with desirable characteristics. PLA strands containing DEET and IR3535 were prepared by twin screw extrusion compounding and simultaneously functioned as plasticizers for the polymer. The plasticizing effect was investigated by thermal and rheological studies. DSC studies showed that the addition of DEET and IR3535 into PLA strands reduced the glass transition temperature consistent with predictions of the Fox equation, thus proving their efficiency as plasticizers. The rheology of molten samples of neat PLA and PLA/repellents blends, evaluated at 200 °C, was consistent with shear-thinning pseudoplastic behaviour. Raman studies revealed a nonlinear concentration gradient for DEET in the PLA strand, indicating non-Fickian Type II transport controlling the desorption process. Release data obtained at 50 °C showed initial rapid release followed by a slower, near constant rate at longer times. The release rate data were fitted to a novel modification of the Peppas-Sahlin desorption model.

Who's afraid of DEET? Fearmongering in papers on botanical repellents.

DEET (N,N-Diethyl-meta-toluamide) is considered the gold standard in mosquito repellents, not only for its effectiveness, but also for its safety. DEET has been more extensively studied for safety than any other repellent, and is accepted as completely safe when used correctly (i.e. not consumed or bathed in). Researchers studying botanical repellents, however, often paint DEET as far more toxic than it really is, falsely claiming it is a menace to the public health or even the environment. These claims are unfounded, and often the only evidence given by such publications are references to other publications also studying botanical repellents. Such publications are biased, and may be attacking DEET's excellent safety record to justify their existence and the need for their research. The inconvenient yet undisputable fact is that no botanical repellent has been proven to be as safe as DEET, and the majority never had any safety testing whatsoever. The automatic assumption that botanical repellents are safer than DEET is the 'appeal to nature fallacy,' which also drives most of the market for "natural" repellents, yet natural repellents have side effects and even a body count. Finding a botanical repellent that works as well as DEET and is equally safe is a legitimate research goal on its own, and need not be justified by fear-mongering and irrational chemophobia. Researchers studying these alternatives should strive for integrity, raising the real issue of the lack of safety testing for botanical repellents rather than denying the proven safety of DEET.