Introduction
Multiple species of flying and crawling insects, including mosquitoes, ticks, flies, midges, chiggers, and fleas, bite people. Although these insects are mostly a nuisance in North America, worldwide they transmit more than 100 bacterial, protozoan, parasitic, and rickettsial diseases to humans. A single bite from an infectious vector is sufficient to transmit disease. See the image below.
View Image | Boil-like lesion on the toe of a patient with botfly myiasis. |
Mosquitoes transmit more diseases to humans than any other biting insect. Mosquitoes are the vectors responsible for transmitting several forms of viral encephalitis, yellow fever, dengue fever, bancroftian filariasis, and epidemic polyarthritis to humans; more than 700,000,000 people are infected yearly. Malaria, which is transmitted by the bite of a mosquito infected with the single-cell protozoan Plasmodium, is responsible for 3,000,000 deaths annually.
In 1999, West Nile virus was detected for the first time in the Western hemisphere; 8 people died from the virus in the New York City area. By January 2005, the virus, carried by mosquitoes, had spread to all 48 states. More than 3000 cases of West Nile virus infection were reported to the US Centers for Disease Control and Prevention (CDC) in both 2006 and 2007.
Infected ticks can transmit Lyme disease, Rocky Mountain spotted fever, ehrlichiosis, Q fever, babesiosis, tularemia, STARI (Southern tick-associated rash illness) and tick paralysis.[1, 2]
Flies are the vectors responsible for transmitting African trypanosomiasis, leishmaniasis, onchocerciasis, and loiasis to humans.
Flea bites may transmit plague, and, in South America, kissing bugs transmit Chagas disease.
For patient education resources, see the Bites and Stings Center, as well as Insect Bites, Malaria, West Nile Virus, Plague, and Ticks. These guidelines may be helpful: The practice of travel medicine: guidelines by the Infectious Diseases Society of America.
Repellents
Despite the obvious desirability of finding an effective oral insect repellent, no such agent has been identified. Ingested garlic, brewer's yeast, and thiamine are not effective at repelling insects.[7] The quest to develop the perfect topical repellent has been an ongoing scientific goal for years but has yet to be achieved.
The ideal repellent would repel multiple species of biting arthropods; remain effective for at least 8 hours; cause no irritation to the skin or mucous membranes; possess no systemic toxicity; be resistant to abrasion and washoff; and be greaseless and odorless, making it cosmetically appealing. None of the currently available insect repellents meets all these criteria. Efforts to develop such a compound have been hampered by the multiplicity of variables that affect the inherent repellency of any chemical. All the repellents do not share a single mode of action, and different species of insects may react differently to the same repellent.
To be effective, an insect repellent must be volatile enough to maintain an effective repellent vapor concentration at the skin surface, but it must not evaporate so rapidly that it quickly loses its effectiveness. Multiple factors play a role in the effectiveness; these factors include the concentration, frequency, and uniformity of application; the user's activity level and overall attractiveness to blood-sucking arthropods; and the number and species of potentially biting organisms.
The effectiveness of any repellent is reduced by abrasion from clothing; evaporation and absorption from the skin surface; wash-off from sweat, rain, or water; a windy environment; and high ambient temperatures. (Each 10°C increase in temperature can lead to as much as a 50% reduction in protection time.) Moderate levels of physical activity have been shown to decrease the efficacy of N, N- diethyl-3-methylbenzamide (DEET) – based insect repellents by as much as 40%.[8]
The commercially available insect repellents do not cloak the user in a chemical veil of protection. Any untreated exposed skin can be readily bitten by hungry arthropods. Protection from both the nuisance and the health risks associated with insect bites is best achieved by avoiding infested habitats, wearing protective clothing, and applying adequate insect repellent.
Marketed insect repellents are divided by the US Environmental Protection Agency (EPA) into 2 categories: conventional manufactured chemical repellents and biopesticide repellents, which are derived from natural materials. In general, the chemical repellents have a broader spectrum of efficacy and a greater duration of action than the biopesticide repellents.
Conventional Repellents
DEET
Marketed products include OFF!, Cutter, Repel, Sawyer, Ben's (all in multiple formulations), and Ultrathon. Registered for use by the general public since 1957, DEET remains the criterion standard of currently available insect repellents. DEET, a broad-spectrum repellent, is effective against many species of crawling and flying insects, including mosquitoes, biting flies, midges, chiggers, fleas, and ticks.[9, 10, 11]
The EPA estimates that about 30% of the US population uses a DEET-based product every year. Worldwide use exceeds 200 million people annually.
Formulation of the available products
In the United States, DEET is sold in concentrations ranging from 5-40% and 100%. DEET is available in multiple formulations, including solutions, lotions, creams, gels, aerosol and pump sprays, and impregnated towelettes. EPA regulations require that the concentration of DEET in each product be disclosed on its label.
Most products contain unaltered DEET, but 2 manufacturers have developed extended-release formulations that have made it possible to lower the repellent concentration of their products without sacrificing the duration of action.[12]
The 3M Company manufactures a polymer-based 33% DEET cream, called Ultrathon, which is the standard issue repellent given to the US military. When tested under multiple different environmental and climatic field conditions, Ultrathon was as effective as 75% DEET, providing up to 12 hours of greater than 95% protection against mosquito bites. A 25% Ultrathon aerosol spray is also now available.
Sawyer Products makes a controlled-release 20% DEET lotion, which traps the chemical in a protein particle that slowly releases it to the skin surface. This formulation provides a repellency equivalent to a standard 50% DEET preparation, lasting about 5 hours. Studies show that this formulation can reduce the penetration of DEET through the skin.
How to choose a DEET-based repellent
As a general rule, higher concentrations of DEET provide longer-lasting protection. Mathematical models of the effectiveness and persistence of repellents show that the protection is proportional to the logarithm of the dose (ie, concentration of the product). This curve tends to form a plateau at higher repellent concentrations, providing relatively less additional protection for each incremental dose of DEET greater than 50%. Therefore, for casual use, the highest-available concentrations of DEET are not needed. Products with 5-35% DEET provide adequate protection under nearly all conditions. The American Academy of Pediatrics currently recommends that children older than 2 months can safely use DEET up to 30% concentration.
Products with higher DEET concentrations are best reserved for circumstances in which the wearer will be in an environment with a high density of insects (eg, a rain forest); when reapplication of repellent may be difficult; when traveling to an area where the risk of disease transmission from insect bites is high; and in circumstances where a rapid loss of repellent from the skin surface may occur, such as under conditions of high temperature, humidity, or rain.
Guidelines for safe and effective use of DEET insect repellents
For most uses, choose a repellent with 5-35% DEET.
Repellents can be safely applied to exposed skin or clothing. Repellents should not be applied under clothing. Repellents should be applied lightly, just covering the exposed areas of skin; do not spray repellents to the point of runoff.
The best way of applying insect repellents to the face is as follows: dispense it into the palms, rub them together, and apply a thin layer to the face. Contact with the eyes and mouth should be avoided.
Young children should not apply the repellents themselves. DEET should not be applied to a child's hands, thereby preventing any possible subsequent contact with mucous membranes.
To prevent irritation after the repellent is applied, it should be wiped from the palmar surfaces to prevent inadvertent contact with the eyes, mouth, and genitals.
The repellents should never be used over cuts; wounds; and inflamed, irritated, or eczematous skin.
The aerosol formulations should not be inhaled or sprayed into the eyes.
Contact with plastics (eg, watch crystals, eyeglass frames), rayon, spandex, and painted or varnished surfaces should be avoided because DEET can damage these surfaces.
Frequent reapplication is rarely necessary, unless the repellent seems to have lost its effectiveness. Reapplication may be necessary in hot, wet environments because of the rapid loss of the repellent from the skin surface or under conditions where the biting pressures are intense.
Simultaneous application of a DEET repellent and a sunscreen reduces the effectiveness of the sunscreen by as much as one third, requiring more frequent application of the sunscreen to maintain its effectiveness. In general, avoiding combination products that contain both insect repellent and sunscreen is probably better. While the proper use of sunscreens requires frequent reapplication, insect repellents should only be reapplied when their effectiveness seems to be waning. As such, the use of separate sunscreen and insect repellent products is better, keeping in mind that the combination reduces the effective sun protection factor (SPF) of the sunscreen.
Once indoors, the repellent-treated areas should be washed with soap and water. Washing the repellent from the skin surface is particularly important under circumstances where a repellent is likely to be applied for several consecutive days.
If a reaction to an insect repellent is suspected, then its use should be discontinued. The treated skin should be washed, and a physician should be consulted.
Pharmacology of DEET
The percutaneous penetration, absorption, metabolism, and rate of excretion of DEET continue to be the subject of numerous studies. Human studies show variable percutaneous penetration of DEET.
Depending on the applied dose, vehicle, anatomical site, and collection method, the reported penetration of DEET ranges from 5-56% of the topically applied dose. Because of its lipophilic nature, DEET is rapidly absorbed within 2 hours after application and is eliminated from the plasma within 4 hours after being rinsed off the skin. Absorbed DEET is almost completely metabolized, with 99% eliminated through urine, mostly within 12 hours.
The chemical does not accumulate in the stratum corneum; no evidence of any systemic bioaccumulation exists.
Toxicity
In 1998, Fradin summarized the published reported cases of potential DEET toxicity from 1961-1999.[13] After more than 8 billion applications in 50 years of worldwide use, DEET continues to show a remarkable safety profile.[14, 15, 16]
Over the last 50 years, fewer than 50 significant cases of DEET toxicity have been reported in the medical literature. In most of these cases, the associated signs and symptoms resolved without sequelae. Most of these cases had long-term, excessive, or inappropriate use of DEET repellents. In addition, the details of exposure were poorly documented, making causal relationships difficult to establish.
In the cases where toxicity was reported, no correlation was found between adverse effects and age, gender, or concentration of the DEET product used. Of the 6 reported deaths, 3 resulted from the deliberate ingestion of DEET repellents.
The reports of greatest concern involved 18 cases of encephalopathy, 14 in children younger than 8 years. Of these children, 3 died; 1 child had an ornithine carbamoyl transferase deficiency, which might have caused a predisposition to DEET-induced toxicity. The other children recovered without sequelae.
Initial repeat-insult patch tests with DEET have not exhibited an irritant effect. However, 12 cases of bullous contact dermatitis were subsequently reported, only in military personnel, all of whom had applied a 35% DEET formulation to their antecubital fossae and slept overnight with the repellent on their skin.
In 1980, to meet newer, more stringent EPA safety requirements, more than 30 new animal studies were conducted on DEET to assess its acute, chronic, and subchronic toxicity. In animal studies, no evidence of mutagenicity or oncogenicity was present, and no developmental, reproductive, or neurologic toxicity associated with DEET exposure was found. Animal studies in rats and mice showed that DEET was not a selective neurotoxin. The results of these studies neither led to any product changes to comply with EPA safety standards nor indicated any new toxicity under normal usage.
Released in 1998, the EPA's re-registration eligibility decision (RED) confirmed the agency's conclusion that "normal use of DEET does not present a health concern to the general U.S. population."
According to EPA guidelines, thoughtful product selection and careful application of the repellent greatly reduce the risk of adverse effects. Judicious use of low-concentration DEET products is most appropriate when applying the repellent to children's skin.
Piperidine (Picaridin)
Piperidine-based repellents have been sold in Europe for several years, and they were introduced to the US market in 2005. Derived from pepper, this repellent is labeled for use against ticks, mosquitoes, and flies. The repellent is cosmetically pleasant and does not harm plastics or fabric. The limited data available on this product suggests that it has low potential for toxicity. The manufacturer claims DEET-like efficacy against mosquitoes, lasting 2-8 hours, depending on the species of mosquito and concentration of the active ingredient used.[17, 18, 11]
This repellent is currently sold as Cutter Advanced Insect Repellent (7% and 15% picaridin formulations) and as Avon Skin-So-Soft Bug Guard Plus Picaridin (10% picaridin). In April 2005, the CDC added picaridin to its approved list of insect repellents, joining DEET, as well as a botanical repellent, p -menthane, 3,8-diol (PMD). See Eucalyptus below in Biopesticide Repellents.
Skin-So-Soft bath oil
Avon Corporation's Skin-So-Soft bath oil received considerable media attention several years ago when some consumers reported it to be effective as a mosquito repellent.
Studies have shown that Skin-So-Soft bath oil has a minimal repellent effect, and it is at least 10 times less effective than 12.5% DEET.[19] The limited mosquito repellent effect of Skin-So-Soft oil may be due to its fragrance or to other components of its formulation, which may possess some repellent activity. The product's manufacturer has never marketed the bath oil as an insect repellent.
Skin-So-Soft bath oil has been found to be somewhat effective against biting midges, but this effect is presumed to be a result of its trapping insects in an oily film on the skin surface.
Biopesticide Repellents
IR3535
IR3535 (3-[N- butyl-N- acetyl]-aminopropionic acid) is structurally similar to the amino acid alanine and has been classified by the EPA as a biopesticide. It has been been available in Europe for 20 years and has been sold in the United States since 1999. This repellent is currently available through the Avon Corporation as Skin-So-Soft Bug Guard Plus IR3535, at concentrations of 7.5-15%, and as Bullfrog's Mosquito Coast, with 20% IR3535.
IR3535 is labeled for use against mosquitoes, ticks, and biting flies.[11]
The literature shows variable responses to IR3535-based repellents, depending on the testing methods and the species of insect. Data initially submitted by the manufacturer to the EPA revealed a protection time against mosquitoes of 2.7-4 hours and protection against ticks for as long as 4 hours. However, when tested by the United States Department of Agriculture (USDA) Laboratories in the late 1970s, IR3535 provided only 6-75 minutes of complete protection against mosquito bites, and 25% IR3535 was 1/8-1/100 as effective as 25% DEET when tested against mosquitoes.
In one laboratory comparative study of the efficacy of insect repellents against mosquito bites, Avon Corporation's IR3535-based 7.5% repellent provided an average complete protection time of only about 23 minutes (range, 10-60 min).[20] Arm-in-cage studies showed a mean protection time of 90-170 minutes against Aedes aegypti and 3.5 to 6.5 hours against Culex quinquefasciatus.[21] A 2008 study showed protection times up to 10 hours against mosquitoes, and up to 12 hours against black-legged ticks.[22]
Plant-Based Repellents
Thousands of plants have been tested as sources of insect repellents. Although none of the plant-derived chemicals tested to date demonstrates the broad effectiveness and duration of the protection of DEET, a few do show repellent activity.[23, 24]
Plants whose essential oils reportedly have repellent activity include citronella, neem, cedar, verbena, pennyroyal, geranium, lavender, pine, cajeput, catnip, cinnamon, rosemary, basil, thyme, allspice, garlic, and peppermint.
Unlike synthetic insect repellents, plant-derived insect repellents have been relatively poorly studied. When tested, most of the essential oils yield short-lasting protection, lasting from a few minutes to as long as 2 hours.
Citronella
Marketed products include Natrapel, Buzz Away, Herbal Armor, and Green Ban. Oil of citronella is the plant-derived active ingredient found in many natural or herbal insect repellents marketed in the United States. Oil of citronella has a lemony scent and is extracted from the grass plants Cymbopogon nardus and Cymbopogon winterianus. It has been registered for use in the United States since 1948.[25]
Conflicting data exist on the efficacy of citronella-based products. This data variation is attributed to differences in study methodology, location, and species of the biting insects tested. One comparative laboratory study demonstrated that marketed citronella-based insect repellents protected against mosquito bites for an average of less than 20 minutes. In general, citronella-based repellents provide considerably shorter protection times than DEET repellents; therefore, they require more frequent reapplication to maintain their effectiveness.
In 1997, the EPA concluded that citronella-based insect repellents must carry the following statement on their labels: "For maximum repellent effectiveness of this product, repeat applications at one hour interval."
Citronella products are not intended to be used as tick repellents.
Soybean oil
The marketed product is called Blocker. Released in the United States in 1997, this natural repellent combines soybean oil, geranium oil, and coconut oil in its formulation. This product has been available in Europe for several years.
In tests, this repellent usually provides longer-lasting protection than citronella-based repellents. In some studies, Blocker provided complete protection against mosquito bites for as long as 3.5 hours, and against blackflies for as long as 10 hours.
The product is not labeled for use against ticks.
Eucalyptus
Marketed products include Repel Oil of Eucalyptus Repellent, OFF! Botanical, and Travel Medicine's FiteBite. In Europe, the product is sold as Mosiguard Natural.
Distillation of the essential oil of the lemon eucalyptus tree leaves behind a derivative known as PMD. PMD appears to offer greater repellency than any of the other currently marketed plant-derived repellents.[26] This repellent has been popular in China since 1978, is currently available in Europe, and was brought to the US market in 2002. In April 2005, the CDC added PMD to its list of approved repellents, joining DEET and picaridin-based repellents.
A 2006 study of PMD concluded that the repellent worked as well as 30% DEET in cage studies, but for a briefer period of time. In a 6-hour field study, 20% PMD prevented bites as well as a 20% DEET formulation. As with most repellents, lower concentrations of PMD will provide shorter durations of protection.[27]
PMD-based repellents show low toxicity, but care must be taken to keep them out of the eyes because PMD can cause significant eye irritation.
Insecticides
Marketed products include Duranon, Permethrin Tick Repellent, Cutter Outdoorsman Gear Guard, and Permanone Sprays.
Pyrethrum is a powerful, rapidly acting insecticide. It was originally derived from the crushed dried flowers of the daisy Chrysanthemum cinerariifolium. Permethrin is a synthetic pyrethroid. Rather than work as a repellent, its predominant effect is as a contact insecticide. Permethrin is toxic to the nervous system of insects, leading to death or knockdown of insects that encounter it. The chemical is effective against mosquitoes, flies, ticks, fleas, human lice, and chiggers. Permethrin has low mammalian toxicity, is poorly absorbed by the skin, and is rapidly metabolized by skin and blood esterases.[28, 29]
Permethrin sprays should be applied directly to clothing or other fabrics (eg, tent walls, mosquito nets) but not to the skin. To apply to clothing, spray each side of the fabric (outdoors) for 30-45 seconds, just enough to moisten it. The clothing should then be allowed to dry for 2-4 hours before being worn. The spray is nonstaining; nearly odorless; resistant to degradation by heat or sun; and retains its potency for at least 2 weeks, even after several launderings. Buzz Off is a brand of outdoor adventure clothing that can be purchased with permethrin already bound into the fabric.
The combination of permethrin-treated clothing and the application of a DEET-based repellent to the skin creates a formidable barrier against biting insects and is capable of nearly eliminating mosquito bites, even in areas of intense biting pressure.
Permethrin-sprayed clothing readily kills Dermacentor occidentalis ticks, the cause of Rocky Mountain spotted fever, as well as Ixodes dammini ticks, the vector of Lyme disease.
Permethrin-containing yard foggers may be set off just prior to an outdoor event to temporarily reduce the local population of biting insects. However, care should be taken to keep these sprays away from food and to avoid ornamental fishponds because of potential toxicity.
Burning coils that contain either synthetic or natural pyrethroids can reduce biting insect populations in an indoor environment, but some concerns have been raised about the safety of these products.
Relief From Insect Bites
Cutaneous responses to arthropod bites are polymorphic and range from the common localized wheal-and-flare reactions (type I hypersensitivity) to the delayed bite lesions (type IV hypersensitivity). Rarely, systemic Arthus-type reactions and even anaphylaxis may occur.
Bite reactions are the result of sensitization to salivary antigens, which leads to the formation of both specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies. Immediate-type reactions are mediated by IgE, IgG, and histamine, while cell-mediated immunity is responsible for the delayed reactions.
Several modalities exist to alleviate the itch of insect bites.
Topical corticosteroids are useful to reduce the associated erythema, itching, and induration of insect bites. In cases of extensive and intensely itching bites, a short and rapidly tapered course of oral prednisone (or its equivalent) is effective in reducing the uncomfortable symptoms of extensive bite reactions.
Applications of diphenhydramine or benzocaine (an ester-type topical anesthetic) should be avoided because of the risk of these compounds inducing allergic contact sensitivity. Pramoxine-containing lotions can also help reduce itching.
Oral antihistamines, such as cetirizine and levocetirizine, are effective in reducing the itching and swelling associated with insect bites.[30, 31] In individuals who are highly sensitive, nonsedating antihistamines may be successfully taken prophylactically to reduce the subsequent cutaneous reactions to arthropod bites.
After Bite (an over-the-counter solution of 3.6% ammonium) has been found to relieve the type I hypersensitivity symptoms associated with mosquito bites.[32]
Author
Mark S Fradin, MD, Adjunct Clinical Associate Professor, Department of Dermatology, University of North Carolina at Chapel Hill
Disclosure: Nothing to disclose.
Specialty Editors
Abdul-Ghani Kibbi, MD, Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon
Disclosure: Nothing to disclose.
Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Disclosure: Nothing to disclose.
Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio
Disclosure: Nothing to disclose.
Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator
Chief Editor
Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York
Disclosure: Nothing to disclose.
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