Prevention of arthropod and insect bites: Repellents and other measures

INTRODUCTION — The approach to protection against arthropod bites is influenced by the level of protection that is needed in a specific situation. For example, a combination of chemically-treated gear and clothing and a strong chemical repellent may be necessary in areas with high concentrations of disease-carrying arthropods (Centers for Disease Control and Prevention: Mosquitoes, ticks, and other arthropods). In contrast, milder repellents may be sufficient for preventing nuisance bites in areas with low levels of disease vectors. The phylum Arthropoda includes both insects and arachnids, although the terms "arthropod" and "insect" are used interchangeably in this topic review.

Repellents are variably useful in deterring mosquitoes, biting flies, fleas, midges, chiggers, and ticks.

The effectiveness and safety of the leading repellents and the use of permethrin will be discussed here. Additional measures to prevent mosquito-borne illness in tropical areas are presented separately. (See "Prevention of malaria infection in travelers", section on 'Mosquito bite prevention'.)

REPELLENTS — Among repellents for which a mechanism of action has been described, some act as agonists at olfactory receptors, binding the receptors and blocking recognition of suitable prey. Others antagonize olfactory receptors and actively reverse a normally attractive scent into a deterring scent. Due to highly divergent receptors, the same compound may act as an agonist in one species and an antagonist in another [1,2].

Proper application — Guidelines regarding the safe and effective use of insect repellents in order to maximize effectiveness and minimize side effects were issued by the United States Environmental Protection Agency (EPA). These are particularly important when using DEET-based repellents:

●Use just enough repellent to lightly cover but not saturate the skin.

●Repellents should be applied to exposed skin, clothing, or both but not under clothing.

●A thin layer can be applied to the face by dispensing repellent into the palms, rubbing hands together, and then applying to the face.

●Repellent should be washed from the palms after application to prevent contact with the eyes, mouth, and genitals.

●Do not use repellents over cuts and wounds or inflamed, irritated, or eczematous skin.

●Do not inhale aerosols, spray them in enclosed spaces or near food, or get them into the eyes.

●Do not apply insect repellent to the hands of small children, as it will inevitably be rubbed into the eyes.

●Frequent reapplication of repellent is unnecessary.

●The areas treated with repellent should be washed with soap and water once the repellent is no longer needed.

●If both sunscreen and repellent are being applied, sunscreen should be applied first, and repellent should be applied after. It is better to use separate sunscreen and repellent products, as sunscreen generally needs to be reapplied more frequently than repellent.

Protection is shortened by swimming, washing, sweating, wiping, exercise, and rainfall [3,4].

Specific agents — The most effective insect repellents are:

●DEET (N,N-diethyl-3-methylbenzamide)

●Picaridin (KBR 3023)

●PMD (P-menthane-3,8-diol)

●BioUD (2-undecanone)

●IR3535

●Metofluthrin

These agents are not equal in efficacy and provide varying degrees of protection against different arthropods.

DEET — DEET is effective against mosquitoes, biting flies, chiggers, fleas, and ticks. DEET has been in use for over 70 years and is considered the "gold standard" of insect repellents [5]. No other compound covers as broad a spectrum of arthropods or offers the extended duration of action of DEET [6-8]. In addition, there are microencapsulated formulations (eg, 3M Ultrathon [brand name]) that increase the period of evaporation (and hence repellency) while reducing absorption by the skin [9]. These products have made it possible to decrease the concentration of DEET without sacrificing its duration of action [3,10].

DEET is available in many products, in concentrations ranging from less than 10 percent to more than 75 percent [3]. The effectiveness of DEET plateaus at approximately 30 percent, but higher concentrations provide longer durations of protection. Products with concentrations around 10 percent are effective for periods of approximately two hours. A concentration of about 24 percent provides an average of five hours of protection [7]. Protection is shortened by swimming, washing, rainfall, sweating, and wiping [3].

A prudent approach is to select the lowest concentration effective for the amount of time spent outdoors. Products with 10 to 35 percent DEET are adequate in most circumstances. Higher concentrations should be reserved for situations in which insect infestation is high, elevated temperatures and humidity may limit evaporation, or time outdoors will exceed three to four hours.

Adverse effects — Serious adverse reactions to DEET are uncommon, and the rare reported cases resulted from oral ingestion or other massive exposures, usually in children. However, excessive absorption through the skin can cause dermatitis, allergic reactions, and rare neurotoxicity [11]. DEET is not carcinogenic.

DEET can damage some plastics as well as clothes made from synthetic fibers, such as spandex or rayon, and some patients dislike the oily and sticky skin sensation that DEET can cause.

Interference with sunscreens — Repellents containing DEET may reduce the efficacy of sunscreens applied simultaneously, although the labeling of combined products containing both components should have taken this into account, and the sunscreen component should provide the stated sun protection factor. These combination products are not recommended for use in children, as discussed in the following section.

Use in children — Used as directed, DEET appears to be safe for children older than two months of age [12]. However, adverse neurologic effects, such as encephalopathy, have been reported with massive exposure and chronic use [6]. Overall, fewer than 20 cases have been reported worldwide, and each developed in the setting of inappropriate use (oral ingestion or repeated exposure to high concentrations) with at least three fatalities [6,13]. Postmarketing surveillance has detected very low rates of adverse events in children [14]. Hypersensitivity pneumonitis in a child following the inhalation of a DEET-containing insect repellent has also been reported [15].

We agree with the recommendation by the American Academy of Pediatrics that children younger than two months of age should not use products with DEET. For older infants and children, repellents with 10 to 30 percent DEET should be safe and effective when used according to the directions on the product labels [16,17].

Products containing both DEET and sunscreen are not recommended for children, because reapplication (as may be necessary for the sunscreen component) will result in an excessive exposure to DEET. DEET-containing sunscreens should not be reapplied and should be washed off when back indoors or protection is no longer needed.

Pregnant women — The recommendations for DEET use in pregnant and lactating women do not differ from those for nonpregnant adults [12]. The Centers for Disease Control and Prevention (CDC) has advised pregnant women to take precautions to reduce their risk of acquiring arboviral infections (eg, Zika virus, West Nile virus) by avoiding mosquito bites through use of protective clothing including permethrin-treated and DEET-based repellents [18].

Topically-applied DEET does not pose hazards to the developing fetus, regardless of gestational age [19]. First trimester exposure of rats and rabbits to DEET did not result in an increased risk of malformations in offspring, although one study using a dose several-fold higher than the normal human dose reported an increase in low birth weight [20]. There are no human data for first trimester exposure. A double-blind, randomized, therapeutic trial of insect repellents for the prevention of malaria in 897 pregnant women did not find any adverse neurologic, gastrointestinal, or dermatologic effects in women who applied a median total DEET dose of 214 g per pregnancy (range = 0 to 345 g) [21]. No adverse effects were noted on fetal/infant survival, growth, or development up to one year of age. DEET was detected in four cord blood samples from a randomly selected subgroup of 50 DEET users.

Picaridin — Picaridin (Saltidin [brand name], icaridin, KBR 3023), a plant-derived piperidine compound, is effective against mosquitoes, ticks, and the sand fly, Phlebotomus papatasi [22-26]. This agent has been successfully used for years in Europe and Australia. In the United States, it is available in a 20 percent solution (Sawyer Picaridin Insect Repellent [brand name]) as well as in a 7 or 15 percent solution (as Cutter Advanced and Cutter Advanced Sport [brand names], respectively).

Higher concentrations of picaridin (eg, 20 percent) have similar efficacy to DEET when used for short periods [22-25]. However, DEET has a longer duration of action [23].

●Field trials comparing the efficacy of picaridin with DEET for protection against mosquitoes have been performed with varying concentrations of picaridin. These trials have demonstrated comparable potency between high strength picaridin and DEET up to about five hours after application [23,27].

●For ticks (which are harder to repel), one study showed equivalent potency only for the first hour, after which DEET was superior [25]. The manufacturer recommends application every three to four hours.

●Adverse effects – No toxicity in humans has been reported where it has been in long-term use, although hepatic toxicity has been reported in rats at very high doses [28,29]. Accidental ingestions generally do not cause serious harm [30].

Picaridin has an excellent tolerability profile in contrast to DEET. Picaridin is odorless, nonsticky, and nongreasy. It also does not irritate skin, stain fabrics, or degrade plastics.

No developmental or reproductive toxicity was observed in animal studies [31], but no studies in human pregnancy have been published. Based on available data, it is unlikely to cause a problem in pregnancy if used correctly.

PMD (P-menthane-3,8-diol) — PMD is the active ingredient in oil of lemon eucalyptus and in the most widely used Chinese insect repellent, Quwenling (brand name). It is a plant-derived ingredient that has been listed by the EPA as effective against mosquitoes, biting flies, and gnats [32]. In the United States, PMD is available as 65 percent PMD (Repel Lemon Eucalyptus Insect Repellent Lotion and Spray Lotion and Survivor Lemon Eucalyptus Insect Repellent [brand names]) and 10 percent PMD (Off! Botanical Insect Repellent [brand name]).

Studies of efficacy are limited and have yielded inconsistent results [33,34]. PMD is approximately one-half as effective as DEET, such that a 30 percent PMD product would protect as well as a 15 percent DEET product [35,36]. As an example, one comparative trial of 40 percent PMD and 25 percent DEET reported a mean protection time of 3.8 hours with PMD compared with 5.6 hours with DEET [37]. However, another study reported that 30 percent PMD provided a mean protection time of 5.5 hours compared with 2.2 hours for 15 percent DEET [38]. In a laboratory assay using a human hand as an attractant, a 30 percent PMD product was comparable with several DEET formulations in repellency to Aedes aegypti after four hours [34].

Adverse effects — Toxicity in animal studies was limited to eye irritation, with one study reporting skin irritation in a human subject. However, neither problem is common [36]. The CDC recommends avoiding eye contact and not using PMD on the faces and hands of small children [32,39].

Use in children — The compound has not been adequately tested in children younger than three years old and should not be used in this group [39].

BioUD (2-undecanone) — BioUD is a tomato-derived arthropod repellent registered by the United States EPA in April 2007 and assigned the lowest toxicity rating. Its active ingredient is 7.75 percent 2-undecanone. BioUD is available in the United States as BiteBlocker (brand name).

BioUD was found to repel mosquitoes similarly to products containing up to 30 percent DEET in one report [40]. Very high concentrations of BioUD and DEET appeared to have similar repellency against ixodid ticks, but this cannot necessarily be extrapolated to the lower concentrations intended for human use [41].

IR3535 — IR3535 is a synthetic repellent available in the United States as Avon Skin-So-Soft Bug Guard Plus IR3535 Expedition (brand name). There are limited studies comparing IR3535 with DEET or picaridin [24,35,42]. It appeared to be the least effective of the three in one study, although it compared favorably with DEET in another [24,42]. One study indicated a long duration of action [43]. However, until more definitive data are available, IR3535 should not be relied upon in malaria-endemic areas [44].

Metofluthrin — Metofluthrin is a synthetic pyrethroid insecticide that, in vapor form, also acts as a mosquito repellent. It is available in the United States as Off! Clip-on Mosquito Repellent (brand name), a unique spatial repellent device that disperses the vapor by means of a battery-powered fan. In a controlled wind tunnel test, the product was found to be highly effective in reducing the number of mosquitoes attracted to a human subject [45], and one field study reported that it provided a 70 to 79 percent reduction in mosquito bites [38].

Minimally effective and ineffective agents — Other agents marketed as insect repellents include citronella, various botanical oils, vitamin supplements, and herbal preparations.

Citronella — Citronella is a plant-based repellent that lacks the broad spectrum of activity and duration of action of DEET [6,7]. Frequent application may compensate for its limited duration of effectiveness, although animal studies have shown citronella-based repellents to be potential dermal sensitizers [7]. Citronella probably is not effective in repelling ticks.

Botanical oils — Various botanical oils, including cinnamon, peppermint, sandalwood, geranium, and soybean, have been used alone or in combination for repelling mosquitoes and ticks. Most of the studies evaluating these alternative plant-based repellents formulated in commercially available products have shown that the protection they offer is far inferior compared with DEET, PMD (the active ingredient in oil of lemon eucalyptus), or picaridin [35,46,47]. (See 'DEET' above and 'PMD (P-menthane-3,8-diol)' above and 'Picaridin' above.)

However, there is a growing public perception that products based on naturally occurring substances are preferable to synthetic products such as DEET, and the evaluation of various substances as pesticides and repellents is an extremely active field [48]. Although most available products have not performed well in testing, it is expected that a wider selection of effective alternatives will be available in the future [49].

Oral agents — Claims that ingestion of strong-smelling foods or other substances, such as garlic, onions, cruciferous vegetables, or mineral sulfur, can repel biting insects have not been substantiated.

Vitamin supplements and herbal remedies — No controlled scientific study of ingested vitamin or herbal remedies has ever shown these interventions to protect users from biting insects [50].

Repellent bracelets — Bracelets and wristbands impregnated with insect repellents are not effective, regardless of the repellent used [7,45].

Electronic devices — Electronic mosquito repellents are devices that emit high-pitched sounds that are generally inaudible to the human ear. A Cochrane review of 10 field studies concluded there was no evidence that the devices repelled mosquitoes to any degree [51], and one team of researchers stated that "we consider these devices as the modern equivalent of snake oil" [45].

PERMETHRIN-TREATED CLOTHING — Permethrin is a synthetic compound that is not a repellent but rather causes nervous system toxicity to insects. Its toxicity in humans is low [6]. For the prevention of insect bites, permethrin is applied to clothing or bedding but not to the skin. It is applied to the skin briefly in the treatment of head lice and scabies.

Permethrin is effective against mosquitoes, flies, ticks, and chiggers. Insects encountering permethrin-treated material either leave immediately or become unable to move normally if they remain in contact for even a short amount of time [52]. For some situations, permethrin-treated clothing alone, without an additional repellent applied to skin, is sufficient protection. Permethrin resistance is increasing among several mosquito species worldwide [53], although, despite this, most populations are still deterred or killed by it.

Permethrin is available as a spray for the treatment of clothing and gear (eg, Sawyer Permethrin Premium Insect Repellent [brand name], Repel Permethrin Clothing and Gear Insect Repellent [brand name], and others). Fabrics should be sprayed on both sides for 30 to 45 seconds and allowed to dry completely before wearing. One application maintains potency for at least two weeks, even after several washings [54,55].

Clothing and gear impregnated with permethrin (Insect Shield [brand name]) are also available. The United States Environmental Protection Agency has registered this technology and assigned the products a toxicity category IV (ie, practically nontoxic, not an irritant). Products made with this material carry no warnings about use in children or pregnant women. Both the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend its use (or DEET) during pregnancy as a key component for avoiding diseases transmitted by mosquito bites, particularly Zika virus [19].

These materials maintain their repellency through approximately 70 laundry cycles, according to the manufacturer's website. A study of protection from mosquito biting provided by permethrin-treated military uniforms (which are standard issue for United States and some allied forces) showed results varied by mosquito species, ranging from complete protection after 50 washes to 68 percent reduction in bites after 30 washes [56]. A randomized study comparing at-home treated clothing, commercially-treated clothing, and untreated clothing showed that subjects wearing treated clothing were 3.36 times less likely to have nymphal Ixodes scapularis ticks attach to their bodies than subjects wearing untreated clothing. In addition, ticks that did attach to subjects with treated clothing were more likely to be dead within 2.5 hours of attachment [57]. However, caution is warranted when relying on treated articles after prolonged use, as several studies have indicated a substantial loss of permethrin over the first 15 washes for treated consumer product clothing, reducing the extent of protection to suboptimal levels [58].

The combination of permethrin-treated clothing and a DEET-based repellent on any exposed skin may provide the best protection available against insect bites. This combination is particularly important for people with regular exposure to biting arthropods, as not all species of mosquitoes worldwide are repelled by DEET, but most populations are still deterred or killed by permethrin.

Experimentally, efficacy of 5% permethrin lotion as a topical repellent has been investigated in comparison with a 50 percent DEET spray against A. aegypti bites. Permethrin's repellency was significantly inferior to that of DEET [59].

PROTECTION AGAINST SPECIFIC PESTS — Repellents are variably useful in deterring mosquitoes, biting flies, fleas, midges, chiggers, and ticks. Currently registered repellents are not effective against stinging insects (bees, wasps, ants), spiders, or bedbugs.

Mosquitoes — In high-risk situations (such as in Zika-endemic regions for women who may become or are pregnant or are breastfeeding), the most effective protection against mosquitoes consists of permethrin-treated clothing and gear combined with DEET or picaridin (KBR 3023) applied to exposed skin [19,39,60]. We prefer a repellent containing at least 17 to 20 percent DEET for longer periods of exposure or in areas where disease risk is high.

If a DEET-containing repellent is not available in a high-risk area, the Centers for Disease Control and Prevention (CDC) has also suggested the use of other longer-acting, Environmental Protection Agency-registered repellents (picaridin, IR3535, or PMD [P-menthane-3,8-diol]), although these agents have not been as thoroughly studied. The CDC recommendations on insect repellents are available online. An evaluation of specific products available in the United States identified several brands of repellent that were reported to be effective against the mosquito species that carry Zika (Aedes) and West Nile (Culex) [61].

In areas with fewer mosquitoes and low risk of disease transmission, permethrin-treated clothing and gear alone or DEET or picaridin applied to exposed skin may be sufficient. Alternative repellents, such as IR3535, PMD, and BioUD (2-undecanone), may also be adequate in lower risk environments.

Ticks — The best protection against ticks consists of permethrin-treated clothing and gear combined with DEET applied to exposed skin [39]. Even DEET, which is considered the most effective agent, only repels ticks for short periods of time. (See 'Permethrin-treated clothing' above.)

Wearing clothing properly should keep ticks from gaining access to the skin (pant legs tucked into socks, etc), and light-colored materials are preferable, as ticks are more easily seen against these. Visual inspection of one's skin after any time spent outdoors is critical for effective prevention of tick-borne disease. (See "Prevention of Lyme disease".)

Ticks that are found already attached to the skin should be removed promptly. Tips for removing ticks safely and completely are reviewed elsewhere. (See "Evaluation of a tick bite for possible Lyme disease", section on 'Technique for tick removal'.)

Other insects

●Biting flies, chiggers, midges, and fleas are deterred by DEET [6,7,62].

●Biting flies and gnats are repelled by PMD.

●The sand fly, P. papatasi, is repelled and deterred by DEET and picaridin.

There are currently no repellents registered for use against bed bugs, although this is an active area of research [63].

Repellents are also not effective against stinging insects, such as Hymenoptera species (yellow jackets, wasps, bees, hornets, imported fire ants, and harvester ants), nor against spiders. Unlike bloodsucking arthropods, stinging insects and spiders do not seek out humans to feed. Rather, they sting/bite humans reflexively in self-defense or to defend the nest (some Hymenoptera) or egg sacs (some spiders), and it is not possible to chemically deter these extreme behaviors short of using an insecticide.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Insect bites and stings (The Basics)")

●Beyond the Basics topic (see "Patient education: Bee and insect stings (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●For most patients requiring an insect repellent, we suggest DEET (N,N-diethyl-3-methylbenzamide) (Grade 2B).

●A product containing 10 to 35 percent DEET is adequate in most circumstances, with higher concentrations reserved for situations in which insect infestation is high, the repellent may be partially washed off, or time outdoors will exceed three to four hours. Microencapsulated formulations are preferred, as these protect longer with lower concentrations of active repellent. (See 'DEET' above and 'Mosquitoes' above.)

●DEET should be used carefully and only as directed. It can be used safely by pregnant women and applied once daily to children older than two months of age. (See 'DEET' above and 'Other insects' above.)

●Twenty percent picaridin (KBR 3023) is a reasonable alternative for people who wish to avoid the unpleasant characteristics of DEET and are willing to accept a somewhat shorter-acting repellent. (See 'Picaridin' above.)

●Less studied repellents include PMD (P-menthane-3,8-diol), BioUD (2-undecanone), and IR3535. Available studies suggest these are less effective than DEET or picaridin, although they may be adequate in low-risk situations. (See 'Specific agents' above.)

●The approach to preventing arthropod bites depends upon the level of protection that is needed.

•For environments in which there is a high concentration of biting arthropods and/or a risk of disease transmission, we recommend the combination of permethrin-treated clothing and gear and a DEET-based repellent applied to any uncovered skin (Grade 1B). For protection from ticks, it is also important to keep them from crawling under clothing and to inspect the skin regularly. (See 'Mosquitoes' above and 'Ticks' above and 'Permethrin-treated clothing' above.)

•For environments in which there are lower concentrations of insects and less risk of disease, just one of these measures (ie, permethrin-treated clothing or a repellent) may be sufficient.