Prevention of Arthropod and Insect Bites: Repellents and Other Measures

Prevention of arthropod and insect bites: Repellents and other measures - UpToDate 19/08/2019 23)32
Author: Nancy L Breisch, PhD

Section Editor: David B Golden, MD
Deputy Editor: Anna M Feldweg, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2019. | This topic last updated: Feb 11, 2019.
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.
Repellents are not effective against stinging insects, such as Hymenoptera species (yellow
jackets, wasps, bees, hornets, imported fire ants, and harvester ants) or 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.
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'.)
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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 nearly 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 other than those discussed previously, including
sandalwood, geranium, soybean, and others, have been used alone or in combination for
repelling mosquitoes and ticks. The majority of studies of these alternative plant-based
repellents show that the protection they offer is far inferior to DEET, PMD, or picaridin
[35,46,47]. 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 near 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 die if they remain in contact. 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 [52], 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 [53,54].
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 [55]. 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 [56].
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 [57].
PROTECTION AGAINST SPECIFIC PESTS
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 [19,39,58]. 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) [59].
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 'Tick removal'.)
Other insects — Biting flies, chiggers, midges, and fleas are deterred by DEET [6,7,60]. PMD
repels biting flies and gnats. DEET and picaridin exert repellent and deterrent effects on the
sand fly, P. papatasi.
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 5th to 6th
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 10th to 12th 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
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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.
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Prevention of arthropod and insect bites: Repellents and other measures - UpToDate 19/08/2019 23)32

Author: Nancy L Breisch, PhD

Specific agents — The most effective insect repellents are:

Picaridin — Picaridin (Saltidin [brand name], icaridin, KBR 3023), a plant-derived

Picaridin has an excellent tolerability profile in contrast to DEET. Picaridin is odorless,

BioUD (2-undecanone) — BioUD is a tomato-derived arthropod repellent registered by

Metofluthrin — Metofluthrin is a synthetic pyrethroid insecticide that, in vapor form, also

Citronella — Citronella is a plant-based repellent that lacks the broad spectrum of

Vitamin supplements and herbal remedies — No controlled scientific study of

The combination of permethrin-treated clothing and a DEET-based repellent on any exposed

Experimentally, efficacy of 5% permethrin lotion as a topical repellent has been investigated in

PROTECTION AGAINST SPECIFIC PESTS

INFORMATION FOR PATIENTS

a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

● For most patients requiring an insect repellent, we suggest DEET (N,N-diethyl-3-

● A product containing 10 to 35 percent DEET is adequate in most circumstances, with

● Less studied repellents include PMD (P-menthane-3,8-diol), BioUD (2-undecanone), and

• For environments in which there is a high concentration of biting arthropods and/or a

and 'Permethrin-treated clothing' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

1. Bohbot JD, Fu L, LE TC, et al. Multiple activities of insect repellents on odorant

3. Insect repellents. Med Lett Drugs Ther 2003; 45:41.

4. Schofield S, Tepper M, Gadawski R. Laboratory and Field Evaluation of the Impact of

10. Insect repellents. Med Lett Drugs Ther 1989; 31:45.

13. Briassoulis G, Narlioglou M, Hatzis T. Toxic encephalopathy associated with use of

15. Morton R, Brooks M, Eid N. Hypersensitivity pneumonitis in a child associated with

16. AAP news: Use of DEET on children. Available online. http://www.aappublications.org/c

22. Badolo A, Ilboudo-Sanogo E, Ouédraogo AP, Costantini C. Evaluation of the sensitivity

24. Costantini C, Badolo A, Ilboudo-Sanogo E. Field evaluation of the efficacy and

50. Day JF. Repellent Wars. http://entomology.ifas.ufl.edu/pestalert/arbovirus/repellentwars.

52. Kasai S, Komagata O, Itokawa K, et al. Mechanisms of pyrethroid resistance in the

Permethrin-Treated Military Fabrics. J Med Entomol 2014; 51:1220.

Topic 4085 Version 20.0

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