US Pharm. 2006;6:72-77.     

Whether preparing for a backyard barbecue or an Amazon adventure, people need to take some simple steps to avoid insect bites--practices that could protect them from potentially life-threatening diseases carried by insects. The insects and other arthropods that transmit disease to humans include mosquitoes, ticks, flies, chiggers, fleas, and lice. From West Nile virus to malaria, these tiny vectors transmit a host of diseases both here in the United States and abroad. Therefore, it is important to be aware of the behavioral, physical, and chemical defenses available.

Travel-Related Diseases
In 2004, approximately 763 million people worldwide traveled across international borders; most of them were simply vacationing.1 Many travel destinations are developing nations, where insect-borne diseases are more likely to occur. The Centers for Disease Control and Prevention (CDC) receives reports of more than 1,000 cases of malaria every year in people returning to the U.S. from other countries. 2 In fact, the most common cause of fever in someone returning from a trip to the tropics is dengue fever--a viral disease in the family of yellow fever--and malaria.3 However, travelling to Africa is not the only way to encounter a potentially deadly mosquito-borne disease. West Nile virus is transmitted by the Culex mosquito in all but a couple of states in the U.S. In 2005, there were nearly 3,000 cases, with 116 deaths. 4 Although most people who use an insect repellent do so for mosquito protection, they should also be aware of other arthropod-borne diseases such as Lyme disease (tick bite), murine typhus (flea bite), and African sleeping sickness (Tsetse fly bite). The CDC's Travelers' Health Web site (www.cdc.gov/travel) can provide patients and health professionals with a vast amount of information on diseases associated with travel. With a few exceptions, if you don't get an insect bite, you can't get the disease it carries.

Why People Get Bites
Mosquitoes are specially equipped to find us during the day or night. They use a combination of visual, chemical, and olfactory senses to locate a blood meal. From a distance, mosquitoes that bite during the day can detect motion and bright colors. Carbon dioxide, which we exhale and release from our skin, makes a powerful attractant from up to 36 meters.5 Although we can't stop breathing, people should avoid wearing strong perfumes and colognes or using scented soaps, which may also attract mosquitoes. As the mosquito closes in, it can still detect carbon dioxide, but it can also sense body heat and lactic acid, all of which are increased with physical activity. Other factors that may increase a person's chance of being bitten include being male, overweight, or an adult.5 The type of mosquito and the availability of a primary host other than people determine how aggressive a biter of humans they may be. Many mosquitoes in South America, Africa, and Asia are aggressive biters--they are less deterred by typical insect avoidance methods than our domestic ones are. Thus, a higher level of insect precaution compliance is needed with international travel.

PERSONAL PROTECTIVE MEASURES
Behavior Modification
If possible, people should avoid typical insect habitats. These habitats may vary by geographic location, time of the day, season, temperature, and urban versus rural environments. Heavily forested areas or locations surrounding bodies of standing water, such as a brackish lake, are more likely to be mosquito breeding grounds. Ticks prefer low-lying brush in heavily wooded areas where they can sit and wait for a leg to brush up against their perch. Since ticks do not jump or fly, they need this close contact to attach to clothes where they can crawl to a bare part of a leg and attach. Thus, visual inspection for attached ticks and then prompt removal effectively minimizes the chance of acquiring a tick-borne infection.

The abundance of insects can be affected by the temperature and season. Typically, mosquitoes are more common during summer and fall months in temperate climates and following the rainy season in the tropics. However, it takes only one bite by a mosquito carrying yellow fever or malaria, for example, to transmit these deadly diseases. Thus, all relevant insect precautions should be taken even when mosquito populations are less intense.

Some mosquitoes are active at night and some during the day. For example, peak biting times of the Aedes mosquito, which carries yellow fever, dengue fever, and chikungunya viruses, are dawn and dusk. The Anopheles mosquito carries malaria and bites only at night between dusk and dawn. Knowing when certain mosquito-borne diseases are more likely to be transmitted can help determine the appropriate intervention. In some countries, such as Cambodia, both malaria and dengue fever occur, necessitating the use of insect precautions day and night.

Insects may have a predisposition for rural areas or for the city life. Dengue fever is an example of a disease spread by an urban mosquito that has adapted its breeding grounds to places like old tires, tin cans, or even puddles. Malaria, however, is mainly found in rural areas of the tropics and subtropics, but there are notable exceptions, such as India, where it occurs in rural and urban locations. When traveling to malarious areas, it is important to know the cities to be visited, as some have done a good job of mosquito breeding site cleanup, rendering the city free of malaria. For example, in Nairobi, Kenya, there is no malaria, but virtually everywhere else in Kenya it exists.

General advice for behavior modifications to avoid insect bites would include staying indoors in a well-screened air-conditioned room during peak biting times, avoiding outdoor exposure at dusk, and not wearing bright clothing or perfumes.

Physical Barriers
Seek to put distance between you and the blood-sucking insect looking for a meal. To protect against flying insects, wear long-sleeved shirts and pants, as well as a hat. For ticks, make sure to wear boots or other shoes that cover your ankles, and tuck your pants into your shoes or socks. To decrease the chance of a mosquito biting through your clothes, permethrin can be applied to clothing, or permethrin-treated clothes can be purchased. Permethrin is a synthetic pyrethroid compound used for its insecticide and insect repellent properties and is often referred to as a "knock-down" insecticide. It is odorless, colorless, and won't affect the material on which it is applied. This is the same chemical in products available over the counter for killing head lice, so it is relatively safe. To treat clothing before going out, apply a 0.5% spray to the surface of the clothing, or soak clothing in a higher concentration. The treated clothes, either sprayed or soaked, should protect for two weeks or two washings and up to four weeks or six washings, respectively. When staying in regions where insects bite at night, people should sleep under bed netting. In addition, mosquito bed nets can be soaked in permethrin or purchased presoaked.

Insect Repellents
Whenever there is a risk of contracting arthropod-borne disease, insect repellents should be applied to exposed intact skin, never under clothing. Other general recommendations for safe use of insect repellents are to apply it to an adult's hands and then to the face with the hands, rather than spraying directly; never let young children apply it to themselves; and wash off repellent when it is no longer needed. Natural and synthetic repellents are available with variable efficacy and safety.

The CDC officially endorses two ingredients  with proven efficacy, DEET and picaridin, for domestic and international use. For domestic mosquitoes, the CDC also sanctions the use of Environmental Protection Agency (EPA)–registered repellents containing PMD (p-menthane 3,8-diol), the active ingredient of oil of lemon eucalyptus (for use in ages >= 3 years).6 See Table  for a comparison of select repellents.  




DEET: The insecticide commonly known as DEET (now called N,N -diethyl-3-methylbenzamide, formerly known as N,N-diethyl-meta-toluamide ) was developed for the military and was subsequently marketed to the public in 1957. It is the most frequently used insect repellent in the world, with an estimated 38% of the U.S. population applying it annually.7 Although the mechanism is not fully understood, it appears to interfere with an insect's chemoreceptors for lactic acid. This broad-spectrum insect repellent is relatively safe for adults and children and is the preferred insect repellent, according to the CDC.8 DEET is an organic solvent and in higher concentrations can dissolve synthetic material such as plastic and rayon. The EPA considers it safe to humans and the environment. The American Academy of Pediatrics considers it safe in concentrations between 10% and 30%.9 DEET is available over the counter in concentrations ranging from 5% to 100%. Above 50% concentration, little more protection is gained, just increased duration of action. The optimal concentration for four to six hours of protection is 20% to 35%. To increase the duration of action to eight to 12 hours without having to increase the concentration beyond 20% to 30%, sustained-release formulations are available.

When insect repellent is applied during the day, people are often outside in the sun, where sunscreen is also necessary. DEET repellents should be applied more than an hour after the application of sunscreen, as DEET can reduce the effect of the sun protection factor (SPF) an average of 33%.10 Combination DEET and sunscreen products should be avoided, as they have not been clinically evaluated. It is estimated that for every 10°C increase in outside temperature, 50% of an insect repellent's duration of action is lost to evaporation.5 Thus, frequent reapplication of DEET may be necessary, especially if one is swimming or sweating excessively.

Picaridin: Picaridin, also known as Bayrepel or KBR 3023, is a relatively new, piperidine-based insect repellent in the U.S. It is touted as less irritating, less smelly, and less damaging to clothing than DEET. Both DEET and picaridin, however, are reported by the EPA to have a low potential for toxicity to humans or the environment.11 Picaridin is marketed in the U.S. in a concentration of 7%, but field testing with this compound was done on a 19.2% concentration, roughly equivalent to DEET 20%.12 Thus, if you are recommending picaridin, you should emphasize that it needs to be reapplied more frequently than every four hours, especially in the tropics, due to the low concentration available in the U.S.

Miscellaneous: Although not originally introduced to   repel insects, Avon's Skin-So-Soft product was subsequently found to do so. The main ingredient is butylacetylaminopropionate, or IR3535, an amino acid analog. IR3535 is registered with the EPA as a pesticide against mosquitoes, ticks, and biting flies, but it has a short duration of action. There is little clinical data on IR3535, but in one large clinical study, it protected for only about 23 minutes.13

Botanicals: Unlike the previous three synthetic insect repellents, the following are derived from plant sources. Oil of lemon eucalyptus, also known as PMD, was recently endorsed by the CDC against carriers of West Nile virus and other domestic mosquitoes.6 This pleasant-smelling menthol-like repellent at 30% is approximately equivalent to the protection of DEET 20% but does not last as long; it must be applied more often than every four hours.

Citronella is a popular ingredient in everything from sprays to candles and coils that are burned. Although it smells nice, it offers less than an hour of protection per application; when used as the candle or coil, it gives the same effect as does burning a regular candle.7

The only other product clinically tested to have protection against mosquitoes is a soybean oil–based product marketed as Blocker. It provides protection similar to a 4.75% DEET or about 1.5 hours. 13

No other products have shown any clinically proven efficacy, including vitamin B1 (thiamine) and garlic. In 1985, the FDA responded to the increased anecdotal accounts of vitamin B1's effectiveness as an insect repellent by issuing a statement refuting any claims of efficacy and prohibiting manufacturers from doing the same for any oral product.14

Treating the Bite
The main objective in caring for mosquito bites is to reduce inflammation and itching that might lead to superinfection of the bite site. Topical corticosteroids work fairly well at reducing itching and inflammation. Oral antihistamines, particularly cetirizine, also work well at reducing the redness and itching.15 An ammonium solution marketed as Afterbite was shown to be effective, at least temporarily, in nearly everyone who used it.16

Conclusion
Although yellow fever and malaria have been eradicated in the U.S. in the last century, other potentially deadly mosquito-borne diseases such as West Nile virus and dengue fever have recently emerged here. Thus, the need to protect against mosquitoes and other biting arthropods both in the U.S. and abroad is great. Counseling patients on the importance of personal protective measures will help to ensure safe and enjoyable outdoor experiences. 

References
1. Hill DR. The burden of illness in international travelers. N Engl J Med 2006;354:115-117.
2. Shah S, Filler S, Causer LM, et al. Malaria surveillance--United States, 2002. MMWR Surveill Summ 2004;53:21-34.
3. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354:119-130.
4. 2005 West Nile Virus Activity in the United States. February 14, 2006. CDC Division of Vector-borne Infectious Diseases. Available at: www.cdc.gov/ncidod/ dvbid/westnile/surv&controlCaseCount 06_detailed.htm. Accessed April 10, 2006.
5. Fradin MS. Insect protection. In: Keystone J, Kozarsky P, Freedman D et al., eds. Travel Medicine. Mosby, 2004;61-69.
6. Updated Information Regarding Mosquito Repellents. April 22, 2005. Centers for Disease Control and Prevention. Available at: www.cdc.gov/ncidod/dvbid/westnile/RepellentUpdates.htm. Accessed April 3, 2006.
7. Fradin, MS. Mosquitoes and mosquito repellents: clinician's guide. Ann Intern Med 1998;128:931-940.
8. Centers for Disease Control and Prevention. Protection against mosquitoes and other arthropods. In: Arguin PM, Kozarsky PE, Navin AW, eds. Health Information for International Travel 2005-2006 (Yellow Book). Atlanta: US Department of Health and Human Services, Public Health Service; 2005.
9. Flake ZA, Hinojosa JR, Brown M, et al. Clinical inquiries. Is DEET safe for children? J Fam Pract 2005;54:468-469.
10. Montemarano AD, Gupta RK, Burge JR, et al. Insect repellents and the efficacy of sunscreens. Lancet 1997;349:1670-1671.
11. Environmental Protection Agency: New Pesticide Fact Sheet: Picaridin. 2005.
12. Frances SP, Waterson DGE, Beebe NW et al. Field evaluation of repellent formulations containing DEET and picaridin against mosquitoes in Northern Territory, Australia. J Med Entomol 2004;41:414-17.
13. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002;347:13-18.
14. FDA. Drug products containing active ingredients offered over-the-counter (OTC) for oral use as insect repellents. Federal Register 1985;50,116 (21 CFR Part 310):25170-25171. Available at www.fda.gov/cder/otcmonographs/Insect_Repellent/insect_repellant_final_conclusions_19850617.pdf.
15. Reunala T, Brummer-Korvenkontio H, Karppinen A, et al. Treatment of mosquito bites with cetirizine. Clin Exp Allergy 1993;23:72-75.
16. Zhai H, Packman EW, Maibach HI. Effectiveness of ammonium solution in relieving type I mosquito bite symptoms: a double-blind, placebo-controlled study. Acta Derm Venereol 1998;78:297-298.

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