Mosquitoes vector more diseases to humans than any other blood-feeding arthropod. They transmit malaria to 300 to 500 million people each year, resulting in as many as 3 million deaths per year.¹⁴⁸ In addition, about 30,000 international travelers visiting malaria-endemic countries contract the disease yearly.⁷⁴ Mosquitoes vector multiple arboviruses to humans, including several forms of encephalitis, epidemic polyarthritis, yellow fever, and dengue fever (see Chapter 48). Mosquitoes also transmit the larval form of the nematode that causes lymphatic filariasis.

Only female mosquitoes bite, requiring a blood-protein meal for egg production. Male mosquitoes feed solely on plant juices and flower nectar. Mosquitoes feed every 3 to 4 days, consuming up to their own weight in blood with each feeding. Certain species of mosquitoes prefer to feed at twilight or nighttime; others (such as the now-widespread Asian tiger mosquito, Aedes albopictus) bite mostly during the day. Some mosquito species are zoophilic (preferring to feed on animals, including birds, reptiles, various mammals, and amphibians), whereas others are anthropophilic (preferring human blood). Members of the genera Anopheles, Culex, and Aedes are the most common biters of humans. In some mosquitoes, seasonal switching of hosts provides a mechanism for transmitting disease from animal to human.

Mosquitoes rely on visual, thermal, and olfactory stimuli to help them locate a blood meal.* For mosquitoes that feed during the daytime, host movement and dark-colored clothing may initiate orientation toward an individual. Visual stimuli appear to be important for in-flight orientation, particularly over long ranges, whereas olfactory stimuli become more important as a mosquito nears its host. Carbon dioxide and lactic acid are the best-studied attractants. Carbon dioxide serves as a long-range attractant, luring mosquitoes at distances of up to 36 m (118.1 feet).^56,^57,¹⁵²At close range, skin warmth and moisture serve as attractants.^15,²⁹ Volatile compounds, derived from sebum, eccrine and apocrine sweat, and/or the cutaneous microflora bacterial action on these secretions, may also act as chemoattractants.^65,^87,^103,^143,¹⁷⁰ Floral fragrances found in perfumes, lotions, soaps, and hair-care products can also lure mosquitoes.⁴⁸ One study has shown that alcohol ingestion increases the likelihood of being bitten by mosquitoes.¹⁴⁹ Mosquitoes are more attracted to individuals infected with transmittable malaria than to uninfected people or to treated individuals who are no longer infected.⁸⁹

There can be significant variability in the attractiveness of different individuals to the same or different species of mosquitoes ^22,^32,⁸¹—a point that travelers should keep in mind when visiting new areas. In some studies, men have been bitten more than women, and adults more than children.^81,¹¹³ Other studies have shown that repellents based on N,N-diethyl-3-methylbenzamide (DEET) (previously called N,N-diethyl-m-toluamide) may protect women more poorly than they do men.⁶⁰ Heavyset people are more likely to attract mosquitoes, perhaps due to their greater relative heat or carbon dioxide output.¹²⁸ Of note is that some studies have failed to confirm these findings.²²

Mosquito bites commonly produce small local wheal reactions and associated itching. More dramatic reactions, including generalized urticaria, angioedema, and anaphylaxis have been reported in highly sensitive individuals. Rare “skeeter syndrome” has been documented in five young children who had dramatic localized redness, swelling, warmth and induration develop within hours of a mosquito bite. This entity mimics cellulitis but resolves spontaneously and is associated with significantly elevated serum levels of IgE and IgG to mosquito salivary gland antigens.¹⁵¹ Antihistamines may be useful when taken prophylactically to reduce the intensity of mosquito bite reactions: Compared with placebo, levocetirizine was shown in one study to reduce the size of the 24-hour bite papules by 71% and the accompanying pruritus by 56%.⁷⁵

During the day, many mosquito species tend to rest in cool, dark areas, such as on dense vegetation, or in hollow tree stumps, animal burrows, and caves. To complete their life cycle, mosquitoes also require standing water, which may be found in tree holes, woodland pools, marshes, drainage ditches, or puddles. To minimize the chances of being bitten by mosquitoes, campsites should ideally be situated as far away from these sites as possible.

Blackflies (Family Simuliidae)

At 2 to 5 mm (0.1 to 0.2 inch) in length, blackflies ^20,^39,^59,^79,¹⁰⁴ (Figure 47-1, B) are smaller than mosquitoes. They have short antennae, stout humpbacked bodies, and broad wings. Blackflies are found globally wherever there are fast-running, clear rivers or streams, which they require for larval development. In temperate regions, adults are most prevalent in late spring and early summer and are most likely encountered near larval habitats, where they are difficult to avoid. However, unlike most mosquitoes, blackflies tend to bite during the daytime. They primarily use visual cues to locate a host. Dark moving objects are particularly attractive, but carbon dioxide and body warmth also serve as attractants. Only the female bites, taking up to 5 minutes to feed. Blackflies may be present at high densities, inflicting numerous bites on their victims.

Blackflies are particularly attracted to the eyes, nostrils, and ears of their hosts. They often crawl under clothing or into the hair to feed. The insect’s mouthparts tear the skin surface, producing a pool of blood from which the fly feeds. Blood loss from the bite site often continues after the blackfly has departed. The resulting intensely pruritic, painful, and edematous papules are typically slow to heal. Rare systemic reactions, including fever, urticaria, anaphylaxis, and even death have been reported following blackfly bites. Although these flies are not known to transmit disease to humans in North America, in the tropics, blackflies are vectors of the parasite Onchocerca volvulus, which causes the disease river blindness.

Biting Midges (Family Ceratopogonidae)

Also known as no-see-ums, sand gnats, sand fleas, and sand flies, biting midges ^20,^39,^59,^79,¹⁰⁴ are small, slender flies (<2 mm [0.1 inch] body length) with narrow wings (Figure 47-1, C). Their small size makes them difficult to see, and they can pass readily through common window screens. Biting midges occur from low to high latitudes worldwide. They breed most commonly in salt marshes, but larvae also develop in moist organic matter associated with freshwater wetlands and irrigated pastures. Despite their inconspicuous size, female midges are aggressive biters, frequently attacking in swarms and inflicting multiple painful and pruritic bites within minutes. Midges often crawl into the hair before biting. Depending on the species, midges may bite during the day or at nighttime. Their activity is greatest during calm weather, declining as wind speed increases. They may be avoided by moving to open areas with greater airflow or into shelters with no-see-um netting. Biting midges are not known to transmit diseases to humans in temperate regions but vector filarial and microbial parasites in tropical regions.

Tabanids (Family Tabanidae)

The family Tabanidae (Figure 47-1, D) includes horseflies, deerflies, greenheads, and yellow flies.^20,^39,^59,^79,¹⁰⁴ These insects are relatively large (10 to 20 mm [0.4 to 0.8 inch]) robust fliers, with numerous species worldwide. Tabanids breed in aquatic or semiaquatic environments, with a life cycle of over 1 year. They are able to fly for miles and rely primarily on vision to locate a host by movement. Dark-colored clothing may increase the likelihood of being bitten. These flies are most active on warm, overcast days. Only the females bite, using scissor-like mouthparts to create within the skin a bleeding slash, which is slow to heal. Despite their size, these flies usually bite painlessly, but the resulting reaction can include intense itching, secondary infection, and, rarely, systemic reactions, such as urticaria or anaphylaxis. Because the adult fly usually lives only about 1 month, and only one generation emerges per year, the potential season for being bitten is relatively short in higher latitudes and altitudes. In the United States, deerflies have been shown to be capable of transmitting tularemia to humans; in Africa, the deerfly may vector the filarial parasitic worm, Loa loa.

Sand Flies (Family Psychodidae)

Sand flies * are tiny (2 to 3 mm [0.1 inch]), hairy, and long-legged flies, with multisegmented antennae and a characteristic V-shape to the wings when at rest. (Figure 47-1, E ). Only female sand flies are blood feeders, feeding mostly during calm, windless nights and resting during the day in animal burrows, tree holes, or caves, which should be avoided. Larvae develop in moist organic matter within such habitats. Most sand fly bites occur on the face and neck, but all exposed skin may be attacked.

In tropical and subtropical climates, sand flies have been shown to vector multiple cutaneous, mucocutaneous, and systemic diseases, including bartonellosis and three forms of leishmaniasis. Visceral leishmaniasis is endemic in the tropical and subtropical regions of Central and South America, Africa, Asia, the Mediterranean, and Southern Europe. The only sand fly–transmitted disease in the United States has been cutaneous leishmaniasis, reported in Texas and Oklahoma.

Tsetse Flies (Family Glossinidae)

Tsetse flies ^20,^39,^59,^79,¹⁰⁴ are found only in tropical Africa. They are 7 to 14 mm (0.3 to 0.6 inch) long, yellowish-brown, with wings that fold over their backs, giving them the appearance of honeybees at rest (Figure 47-1, F ). Both sexes bite, feeding in daytime on a wide variety of mammals, including humans. Light-colored, thickly-woven, loose-fitting clothing may deter biting. Tsetse flies seem to rely primarily on vision and movement to identify their hosts. Their bites are painful and may cause petechiae or pruritic wheals. Tsetse flies vector African trypanosomiasis (sleeping sickness).

Stable Flies (Family Muscidae)

Stable flies ^59,⁷⁹ resemble common houseflies, and are most often encountered in coastal areas. Unlike a housefly, which rests with its body parallel to the surface, a stable fly rests with its head held higher than its posterior (Figure 47-1, G). Both male and female stable flies are vicious daytime biters, requiring a blood meal every 48 hours in order to survive. If disturbed, they will attempt to feed multiple times, preferring to bite the lower extremities. Horses and cattle are the preferred hosts, but hungry stable flies readily bite humans. These flies have knife-like mouthparts that they use to puncture flesh before pumping up the blood. Stable flies breed in decaying vegetation (e.g., wet hay bales, beach seaweed) and herbivore manure and are frequently found congregated on sunny walls. Moving away from these breeding habitats will reduce the likelihood of being bitten. Stable fly bites are generally self-limited. They are not known to transmit disease to humans.

Kissing Bugs (Family Reduviidae)

Kissing or Chagas bugs * (triatomine or assassin bugs) are large (10 to 30 mm [0.4 to 1.2 inches] adult length) insects with cone-shaped heads, overlapping wings, and an alternating pattern of dull orange and dark brown stripes on the lateral abdomen (Figure 47-1, H ). Kissing bugs get their name from a tendency to bite around the human mouth, but they also bite other parts of the body. Both male and female kissing bugs bite, requiring a blood meal in order to mature through each of five nymphal growth stages. They are nocturnal feeders, attracted to their hosts by warmth, carbon dioxide, and odor. During the day, they rest in trees or indoors in crevices of house walls and ceilings. Kissing bug bites are initially painless, but frequent exposure to the bites can produce erythema, edema, and pruritus at the bite sites. Kissing bugs are the vector for Trypanosoma cruzi, the causative agent of Chagas’ disease, which has been reported in Central and South America, as well as in the southwestern United States. Chagas’ disease symptoms are more severe with long-term repeated inoculations and are also more harmful in South America than farther north. Kissing bugs often feed on rodents that may live within thatch roofing material. Avoiding sleeping under thatch roofing in Chagas-endemic areas may reduce the probability of infection.

Fleas (Family Pulicidae)

Adult fleas ^20,^39,^59,^79,¹⁰⁴ are small (2 to 6 mm [0.1 to 0.2 inch]), wingless insects with powerful legs that enable adults to jump distances of up to 30 cm (11.9 inches) (Figure 47-1, I ). Hungry adult fleas of both sexes feed on humans and other warm-blooded mammals and birds. Different flea species are associated with specific hosts, and they may be especially abundant around rodent and bird nests, which serve as both adult and larval habitats and should be avoided. Fleas usually move actively on the host, probing and biting several times, resulting in grouped lesions of pruritic papules. Fleas are capable of transmitting sylvatic plague and murine typhus.

Chigger Mites (Family Trombiculidae)

Trombiculid mites ^20,^39,^59,^79,¹⁰⁴ (Figure 47-1, J ) may be found worldwide. Commonly known as chiggers, redbugs, or harvest mites, these reddish-yellow insects are readily encountered in damp, grassy, and wooded areas, especially along the margins of forests, where they may number in the thousands. Only the tiny (less than 0.2 mm [0.1 inch]) larval stages are parasitic, feeding on mammals, birds, reptiles, and amphibians. Chiggers are most active in the summer and early autumn. They usually infest humans by crawling up the shoes and legs, preferring to attach to skin at areas where the clothing fits tightly, such as at the tops of socks or around the elastic edges of underwear. Chiggers do not burrow into the skin or actively suck blood. Rather, they pierce skin with their mouthparts and secrete a proteolytic salivary fluid that dissolves host tissue, which they in turn suck up. If undisturbed, chiggers may feed for several days, before dropping off. In humans, this rarely occurs, because the larvae usually cause enough irritation that they are dislodged by scratching. The host response to chigger bites is brisk, often leading to intensely pruritic, bright-red 1- to 2-cm (0.4- to 0.8-inch) nodules.

Chiggers are especially abundant in warm, moist temperate climates (e.g., the southeastern United States) and tropical areas of high mammal density, including livestock pastures and natural parks and reserves, where moist grassy or understory areas can be found. These areas may seem like attractive camping areas but should be avoided. In Asia, chiggers may serve as vectors of scrub typhus. Rickettsialpox is also transmitted by a mite bite.

Ticks (Families Ixodidae and Argasidae)

(See Chapter 51.)

Ticks,* like mites, are arachnids rather than insects. There are hard ticks (family Ixodidae) and soft ticks (family Argasidae) (Figure 47-1, K and L). Hard ticks are so named because of the presence of a sclerotized plate, or scutum, that covers part of the body. Both types of ticks may be found worldwide, but hard ticks are more commonly encountered in North America. Hard ticks are usually found in weedy or shrubby areas, along trails, and at forest boundaries, where mammalian hosts, such as deer, are plentiful. Soft ticks are more resistant to desiccation than are hard ticks. Soft ticks thrive in hot and dry climates and are commonly found in animal burrows or caves.

After hatching, both genders of ticks pass through three developmental stages—larval, nymph, and adult—all of which blood-feed. Ticks are unable to fly or jump. Soft ticks are nocturnal and feed rapidly, in just a few minutes. Hard ticks most commonly “quest” for hosts during the day, often climbing vegetation and waiting still for hours or days, forelegs outstretched, until they detect the vibration or carbon dioxide plume of a passing host. When they encounter fur or skin, they climb onto the host and then crawl in search of an appropriate location on which to attach and feed. The attachment bite is usually painless. Hard ticks may remain and feed on a single host for days.

People in suspected tick habitats should check clothing frequently for the presence of ticks. If multiple ticks are seen on clothing, they are most easily removed by permanently trapping them on a piece of cellophane duct tape or by rolling a sticky tape type of lint remover across them; hundreds of small ticks can be easily removed by this method. Tape can be stuck onto the inner thigh area of pants for storage between episodes of tick removal. Laundering infested garments cannot be relied on to kill nymphs, unless the clothing is subjected to the hot cycle of the dryer.²¹

Attached ticks are more difficult to remove. Tick mouthparts are barbed, and some species of tick also secrete a cement that firmly anchors the tick into the skin. Erythema, pruritus, and edema are commonly seen at the site of a tick bite. Improper partial removal of the mouthparts may initiate a long-lasting foreign body reaction, leading to secondarily infected lesions that are slow to heal, or granuloma formation that may persist for months. (For a discussion of the best method for tick removal, see Chapter 51.)

After the tick is removed, the bite site should be cleansed with soap and water, or an antiseptic, and hands should be washed. It may be prudent to save the tick, in case later identification becomes necessary. Laboratory studies of Borrelia burgdorferi (Lyme disease)–infected ticks show that duration of attachment is directly correlated with the risk for transmission of the spirochete.* Prompt removal of attached ticks (ideally within 24 hours of attachment) will greatly reduce the likelihood of disease transmission.¹²⁵

In the United States, soft ticks of the single genus Ornithodoros are capable of transmitting to humans the Borrelia spirochete that causes relapsing fever. Three genera of hard ticks transmit disease to man: Ixodes (which vectors Lyme disease, babesiosis, tick paralysis, and Russian spring–summer encephalitis), Dermacentor (vectors tularemia, Rocky Mountain spotted fever, ehrlichiosis, Colorado tick fever, and tick paralysis), and Amblyomma (vectors tularemia, ehrlichiosis, and tick paralysis).^107,¹⁵⁵ Larval, nymph, and adult ticks may all transmit disease during feeding. Transovarial transmission also enables female ticks to directly infect their offspring.

Personal Protection

Personal protection against bites may be achieved in three ways: avoiding infested habitats, using protective clothing and/or shelters, and applying insect repellents.

Habitat Avoidance

As discussed in the sections above, knowing where to find biting arthropods’ breeding and resting places can help reduce exposure and the chance of being bitten. Mosquitoes and other nocturnal bloodsuckers are particularly active at dusk, making this a good time to be indoors. To avoid the usual resting places of biting arthropods, campsites should ideally be situated in areas that are high, dry, and open, devoid of rodent burrows and nests, and as free from vegetation as possible. Areas with standing or stagnant water should be avoided, because these are ideal breeding grounds for mosquitoes. Attempts should be made to avoid unnecessary use of lights, which attract multiple insects.

Physical Protection

Physical barriers can be extremely effective in preventing insect bites, by blocking arthropods’ access to the skin. Long-sleeved shirts, socks, long pants, and a hat will protect all but the face, neck, and hands. Tucking pants into the socks or boots makes it much more difficult for ticks or chigger mites to gain access to the skin. Rubber boots are commonly worn, particularly in tropical areas, to reduce chigger and tick contact while walking and hiking. Light-colored clothing is preferable, because it makes it easier to spot ticks and is less attractive to mosquitoes and biting flies. Ticks will find it more difficult to cling to smooth, closely woven fabrics (e.g., nylon).¹⁴⁶ Loose-fitting clothing, made out of tightly woven fabric, with a tucked-in T-shirt undergarment is particularly effective at reducing bites on the upper body. A light-colored, full-brimmed hat will protect the head and neck. Deerflies tend to land on the hat instead of the head; blackflies and biting midges are less likely to crawl to the shaded skin beneath a hat brim.

Mesh overgarments, or garments made of tightly woven material, are available to protect against insect bites. Head nets, hooded jackets, pants, and mittens are available from a number of manufacturers, in a wide range of sizes and styles (Box 47-2). Mesh garments are usually made of either polyester or nylon and, depending on the manufacturer, are available in either white or dark colors. With a mesh size of less than 0.3 mm (0.01 inch), many of these garments are woven tightly enough to exclude even biting midges and immature ticks. As with any clothing, bending or crouching may still pull the garments close enough to the skin surface to enable insects to bite through. Shannon Outdoors addresses this potential problem with a double-layered mesh that reportedly prevents mosquito penetration. Similarly, Outdoor Research manufactures head nets with a lightweight spring-steel hoop positioned to prevent the netting from collapsing against the face. Although mesh garments are effective barriers against insects, some people may find them uncomfortable during vigorous activity or in hot weather.

BOX 47-2 Manufacturers of Protective Clothing, Protective Shelters, and Insect Nets

Lightweight insect nets and mesh shelters are available to protect travelers, sleeping indoors or in the wilderness (Figure 47-2). The effectiveness of insect nets or shelters may be enhanced by treating them with a permethrin-based contact insecticide (discussed below), which can provide weeks of efficacy following a single application.

FIGURE 47-2 A to C, Protective shelters. D, Bed net.

Repellents

For many people, applying a topical insect repellent may be the most effective and easiest way to prevent arthropod bites. The quest to develop the “perfect” insect repellent has been an ongoing scientific goal for years and has yet to be achieved. The ideal agent would repel multiple species of biting arthropods, remain effective for at least 8 hours, cause no irritation to skin or mucous membranes, possess no systemic toxicity, be resistant to abrasion and washing off, and be greaseless and odorless. No presently available insect repellent meets all of these criteria. Efforts to find such a compound have been hampered by the multiplicity of variables that affect the inherent repellency of any chemical. Repellents do not all share a single mode of action, and different species of insects may react differently to the same repellent.¹³³

Many chemicals that are effective repellents evaporate or absorb into the skin too quickly to be of great usefulness. To be effective as an insect repellent, a chemical must be volatile enough to maintain an effective repellent vapor concentration at the skin surface but not evaporate so rapidly that it quickly loses its effectiveness. Multiple factors play a role in effectiveness, including concentration, frequency and uniformity of application, the user’s activity level and overall attractiveness to blood-sucking arthropods, interaction between the individual user and the repellent formulation, and the number and species of the organisms trying to bite. The effectiveness of any repellent is reduced by abrasion from clothing; evaporation and absorption from the skin surface; being washed off by sweat, rain, or water; physical activity; and a windy environment.* Each 10° C (18° F) increase in ambient temperature can lead to as much as 50% reduction in protection time.⁸³ Recent formulation developments improve the duration of effectiveness and the cosmetic properties of repellent active ingredients, such that a well-formulated mediocre active ingredient may outperform a poorly formulated stronger active ingredient. Insect repellents do not “cloak” the user in a chemical veil of protection; any untreated exposed skin can be readily bitten.¹⁰² Individuals not wearing insect repellent may be bitten with increased frequency when standing next to someone who is wearing insect repellent.¹¹¹

Chemical Repellents

DEET

DEET has been the gold standard of insect repellents for many decades. Only in the past 5 years have other repellents come to market that show comparable broad-spectrum efficacy (discussed later). DEET has been registered for use by the general public since 1957. It is effective against many species of crawling and flying insects, including mosquitoes, biting flies, midges, chiggers, fleas, and ticks. The U.S. Environmental Protection Agency (EPA) estimates that about 30% of the U.S. population uses a DEET-based product every year; worldwide use exceeds 200 million people annually.^167,¹⁶⁸ Decades of empirical testing of more than 20,000 other compounds has not yet led to the release of a clearly superior repellent.* The mechanism of action of DEET is only partially understood. One recent study demonstrated that DEET blocks a specific olfactory sensory neuron in mosquitoes, effectively masking odors that would normally attract the mosquito to a host.⁴⁰ Another study, in contrast, found that a single olfactory neuron in mosquitoes responds to DEET and induces avoidance behaviors.¹⁵⁹

DEET may be applied directly to skin, clothing, mesh insect nets or shelters, window screens, tents, or sleeping bags. Care should be taken to avoid inadvertent contact with plastics (such as watch crystals, glasses frames or lenses, other optics, equipment, and fishing line), rayon, spandex, leather, or painted and varnished surfaces, because DEET may damage these. DEET does not damage natural fibers like wool and cotton.

In the United States, DEET is sold in concentrations from 5% to 100%, in various formulations, including lotions, solutions, sprays, and impregnated wipes (Table 47-1). As a general rule, higher concentrations of DEET will provide longer-lasting protection. Duration of efficacy of DEET increases only slowly above 35% concentrations, and the longest-lasting (extended duration) formulations all use concentrations no higher than 35%. Higher-concentration and extended-duration DEET formulations are probably best reserved for circumstances in which the wearer will be in an environment with a very high density of insects (e.g., tundra in early summer, or salt marsh), where there is a high risk for disease transmission from insect bites, or under circumstances where there may be rapid loss of repellent from the skin surface, such as under conditions of high temperature and humidity or rain. Under these circumstances, reapplication of the repellent will likely be necessary to maintain its effectiveness.

TABLE 47-1 DEET-Containing Insect Repellents

For most uses, however, there is no need to use the highest concentrations of DEET. Most manufacturers, responding to consumer demand, offer a large variety of low-concentration DEET products. Persons averse to applying DEET directly to their skin may get long-lasting repellency by applying DEET only to their clothing. DEET-treated garments, stored in a plastic bag between wearings, maintain their repellency for several weeks.³²

Sequential application of a DEET-based repellent and a sunscreen can reduce the efficacy of the sunscreen. In a study of 14 patients who applied a 33% DEET repellent, followed by a sun protection factor (SPF) 15 sunscreen, the sunscreen’s SPF was decreased by a mean of 33%.¹⁰⁹ One study showed that the efficacy of a polymer-based DEET repellent was not decreased by the subsequent application of sunscreen 5 minutes later.¹¹⁵ Another study, however, showed that reapplication of sunscreen 2 hours after DEET repellent was applied significantly decreased the protection time of the DEET repellent.¹⁷² There has been some concern that DEET and the sunscreen oxybenzone act synergistically to enhance the percutaneous absorption of the other chemical.⁷⁷ Combination sunscreen-DEET products are available and will deliver the SPF as stated on the label. However, these products are generally not the best choice, because it is rare that the need for reapplication of sunscreen and repellent is exactly the same. For these reasons, in 2000 Health Canada decided to discontinue approval of combination sunscreen and insect repellent products, pending further safety data. Likewise, the EPA in 2007 also issued a request for information regarding proper regulation of combination products, given the conflicting issues regarding proper application frequency.¹⁶⁵

3M and Sawyer Products currently manufacturer extended-release formulations of DEET that make it possible to deliver long-lasting protection without relying on high concentrations of DEET. 3M’s product, Ultrathon, was originally developed for the U.S. military but is also available to the general public. This acrylate polymer 35% DEET formulation, when tested under multiple different environmental/climatic field conditions, was as effective as 75% DEET in ethanol, providing up to 12 hours of greater than 95% protection against mosquito bites.* Sawyer Products’ controlled-release 20% DEET lotion traps the chemical in a protein particle that slowly releases it to the skin surface, providing repellency equivalent to a standard 50% DEET preparation, lasting about 5 hours.⁴⁶ Sixty percent less of this encapsulated DEET is absorbed when compared with a 20% ethanol-based preparation of DEET.⁴⁵ In vitro experiments confirm that microencapsulation of DEET can reduce its cutaneous absorption.⁷⁸ Sawyer Products also markets a controlled-release 30% DEET lotion in which the chemical is slowly released from a lipid sphere (liposome). This nongreasy formulation has low odor and can provide more than 10 hours of protection. Liposomal preparations of DEET can help to retain potency of the repellent on the skin surface, while minimizing percutaneous absorption.¹³⁴

Given its use by millions of people worldwide for 50 years, DEET continues to show a remarkable safety profile. In 1980, as part of the EPA registration standard for DEET,¹⁶⁸ over 30 additional animal studies were conducted to assess acute, chronic, and subchronic toxicities; mutagenicity; oncogenicity; and developmental, reproductive, and neurologic toxicities. The results of these studies neither led to any product changes to comply with current EPA safety standards nor indicated any new toxicities under normal usage. The EPA’s reregistration eligibility decision,¹⁶⁷ released in 1998, confirmed that the agency believes that “normal use of DEET does not present a health concern to the general U.S. population.”

Case reports of potential DEET toxicity have been extensively reviewed.^8,^50,^119,^157,¹⁶⁹ Fewer than 50 cases of significant toxicity from DEET exposure have been documented in the medical literature over the last four decades; over three-quarters of these resolved without sequelae. Many of these cases involved long-term, excessive, or inappropriate use of DEET repellents; the details of exposure were frequently poorly documented, making causal relationships difficult to establish. These cases have not shown a correlation between concentration of the DEET product used and the risk for toxicity.

The reports of DEET toxicity that raise the greatest concern involve 18 cases of encephalopathy, 14 in children under age 8 years.* Three of these children died, one of whom had ornithine carbamoyl transferase deficiency, which might have predisposed her to DEET-induced toxicity.^69,⁷⁰ The 11 surviving children recovered without sequelae. The EPA’s analyses of these cases concluded that they “do not support a direct link between exposure to DEET and seizure incidence.”¹⁶⁷ Animal studies in rats and mice show that DEET is not a selective neurotoxin.^117,^136,¹⁶⁸ Even if a link between DEET use and seizures does exist, the observed risk, based on DEET use patterns, would be less than 1 per 100 million users.¹⁶⁷ Other studies have confirmed that children are not at greater risk for developing adverse effects from DEET when compared with older individuals.^3,^8,^88,¹⁶⁹

A review of adverse events reported to the DEET Registry from 1995 to 2001 concluded that individuals with underlying neurologic disorders were not predisposed to a greater risk for DEET toxicity. There was no evidence that using higher concentrations of DEET increases the risk for adverse events.¹¹⁹

Very limited studies have investigated DEET safety during pregnancy. One followed 450 Thai women who used 20% DEET daily during the second and third trimesters of pregnancy to reduce the risk for contracting malaria.¹⁰⁶ Of these women, 4% had detectable levels of DEET in umbilical cord blood at the time of delivery. However, no differences in survival, growth, or neurologic development could be detected in the infants born to mothers who used DEET when compared with an equal number of mothers treated with a daily placebo cream during their pregnancies.

The EPA has issued guidelines to ensure safe use of DEET-based repellents ¹⁶⁷ (Box 47-3). Careful product choice and common-sense application will greatly reduce the possibility of toxicity. Current recommendations of the American Academy of Pediatrics are that children over the age of 2 months can safely use up to 30% DEET.¹⁷³ When required, reapplication of a low-strength repellent can compensate for their inherent shorter duration of protection.

BOX 47-3

Guidelines for Safe and Effective Use of DEET Insect Repellents

• When only short-term protection is needed, repellents with 10% DEET or less may provide adequate protection.

• Use just enough repellent to lightly cover the exposed skin; do not saturate the skin.

• Repellents should be applied only to exposed skin and clothing. Do not use under clothing.

• To apply to the face, dispense into palms, rub hands together, and then apply thin layer to face.

• Young children should not apply repellents themselves.

• Avoid contact with eyes and mouth. Do not apply to children’s hands, to prevent possible subsequent contact with mucous membranes.

• After applying, wipe repellent from the palmar surfaces to prevent inadvertent contact with eyes, mouth, and genitals.

• Never use repellents over cuts, wounds, or inflamed, irritated, or eczematous skin.

• Do not inhale aerosol formulations or get them in eyes. Do not apply when near food.

• Frequent reapplication is rarely necessary, unless the repellent seems to have lost its effectiveness. Reapplication may be necessary in very hot, wet environments because of rapid loss of repellent from the skin surface.

• Once inside, wash treated areas with soap and water. Washing the repellent from the skin surface is particularly important when a repellent is likely to be applied for several consecutive days.

• If you suspect you are having a reaction to an insect repellent, discontinue its use, wash the treated skin, and consult a physician.

Modified from U.S. Environmental Protection Agency, Office of Pesticide Programs, Prevention, Pesticides and Toxic Substances Division: Reregistration Eligibility Decision (RED): DEET, (EPA-738-F-95-010), Washington, DC, 1998, EPA.

Questions regarding the safety of DEET may be addressed to the EPA-sponsored National Pesticide Information Center, available every day from 6:30 AM to 4:30 PM PST at 800-858-7378 or via their website at http://npic.orst.edu/.

Picaridin

The piperidine derivative, Picaridin (also known as KBR 3023 and Icaridin), is the newest repellent active ingredient to become available in the United States. Picaridin-based repellents have been sold in Europe since 1998, under the brand names Autan and Bayrepel.

Picaridin is a synthetic repellent developed by the Bayer Corporation using molecular modeling techniques. From more than 800 screened substances, KBR 3023 showed the best repellent efficacy against a variety of arthropods,¹⁶ along with a very favorable safety profile, low percutaneous absorption, and good aesthetic qualities.¹³⁵

In 2005, the first picaridin-based repellent was brought to the market in the United States. It is currently available in concentrations ranging from 5% to 20% (Table 47-2). This nearly odorless, nongreasy repellent is effective against mosquitoes, biting flies, and ticks. The 7% repellent provides protection against mosquito bites for up to 4 hours. At 20%, picaridin repellents offers comparable efficacy with DEET against mosquitoes, giving up to 8 or more hours of protection.* Picaridin is superior to DEET as a tick repellent.¹² The chemical is aesthetically pleasant and, unlike DEET, shows no detrimental effects on contact with plastics. The EPA found picaridin to have a very low toxicity risk, with low dermal absorption. In 2005, the Centers for Disease Control and Prevention (CDC) released a statement adding picaridin to the list of approved repellents that could be used effectively to prevent mosquito-borne diseases.

TABLE 47-2 Biopesticide Repellents

IR3535 (ethyl-butylacetylaminoproprionate)

IR3535 is an analog of the amino acid β-alanine and has been sold in Europe as an insect repellent for 20 years. In the United States, this compound is classified by the EPA as a biopesticide, effective against mosquitoes, ticks, and flies. IR3535 was brought to the U.S. market in 1999 and is sold by Avon Products, Inc and Sawyer Products in concentrations from 7.5% to 20%, with and without sunscreen (see Table 47-2). Depending on the species of mosquito and the testing methodology, this repellent has demonstrated widely variable effectiveness, with complete protection times ranging from 23 minutes to over 10 hours.^6,^7,^23,^27,⁵¹ IR3535 can provide up to 12 hours of protection against black-legged ticks.²³ Higher concentrations of IR3535 give longer protection times. In general, IR3535 does not match the efficacy of high-concentration DEET.^6,^7,^51,⁵² IR3535 is most effective at 20% concentrations. It is nongreasy, nearly odorless, will not dissolve plastics, and has a very good safety profile. In 2008, the CDC released a statement adding IR3535 to the list of approved repellents that could be used effectively to prevent mosquito-borne diseases.

Botanical 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 DEET, many show repellent activity and some may be superior against certain important vectors such as anopheline mosquitoes. Plants with essential oils that have been reported to possess repellent activity include citronella, eucalyptus, neem, cedar, verbena, pennyroyal, geranium, catnip, lavender, pine, cajeput, cinnamon, vanilla, rosemary, basil, thyme, allspice, garlic, and peppermint.* Unlike DEET-based repellents, botanical repellents have been relatively poorly studied. When tested, most of these essential oils tended to show short-lasting protection, lasting minutes to 2 hours, after which insufficient material remains on the skin to be repellent. A summary of readily available plant-derived insect repellents is shown in Table 47-3.

TABLE 47-3 Botanical Insect Repellents

Citronella

Oil of citronella was initially registered as an insect repellent by the EPA in 1948. It is the most common active ingredient found in “natural” or “herbal” insect repellents marketed in the United States. Originally extracted from the grass plant Cymbopogon nardus, oil of citronella has a lemony scent.

Conflicting data exist on the efficacy of citronella-based products, varying greatly depending on the study methodology, location, and species of biting insect tested. One citronella-based repellent was found to provide no repellency when tested in the laboratory against Aedes aegypti mosquitoes.²⁶ Another study of the same product, however, conducted in the field, showed an average 88% repellency over a 2-hour exposure. The product’s effectiveness was greatest within the first 40 minutes after application and then decreased with time over the remainder of the test period.¹⁵⁸ All Terrain Company produces citronella-based lotion in which the essential oil has been encapsulated into a beeswax matrix, which slowly releases it to the skin surface, prolonging its efficacy. In laboratory testing against A. aegypti, this product provided complete protection for the first 2 hours and 77% protection 4 hours after application.⁶⁷

Many citronella repellents on the market incorporate geranium oil and/or soybean oil to increase the repellent effect of the product. In general, studies show that citronella-based repellents are less effective than DEET repellents. Citronella provides a shorter protection time, which may be partially overcome by frequent reapplication of the repellent. In 1997, after analyzing available data on the repellent effect of citronella, the EPA concluded that citronella-based insect repellents must contain the following statement on their labels: “for maximum repellent effectiveness of this product, repeat applications at one-hour intervals.”¹⁶⁶

Citronella candles have been promoted as an effective way to repel mosquitoes from one’s local environment. One study compared the efficacy of commercially available 3% citronella candles, 5% citronella incense, and plain candles to prevent bites by Aedes species mosquitoes under field conditions.⁹⁷ Subjects near the citronella candles had 42% fewer bites than did controls who had no protection (a statistically significant difference). However, burning ordinary candles reduced the number of bites by 23%. There was no difference in efficacy between citronella incense and plain candles. The ability of plain candles to decrease biting may be due to their serving as a “decoy” source of warmth and carbon dioxide. In contrast, in a field study, candles with 5% geraniol placed 1 m from volunteers reduced the mosquito biting pressure by an average of 56% and the sand fly pressure by 62%, compared with paraffin control candles.¹¹⁴ These efficacies are, unfortunately, far too low to offer useful protection from mosquito-borne diseases.

The citrosa plant (Pelargonium citrosum “Van Leenii”) has been marketed as being able to repel mosquitoes through the continuous release of citronella oils. Unfortunately, when tested, these plants offer no protection against bites.^28,¹⁰⁵ In experimental hut trials in Africa, potted live plants of Ocimum americanum, Lantana camara, and Lippia uckambensis repelled an average of 40%, 32%, and 33% of mosquitoes, respectively.¹⁴⁷

BiteBlocker

BiteBlocker is a “natural” repellent that was released to the United States market in 1997, after being sold in Europe for several years.¹⁶³ BiteBlocker’s present formulation combines derivatives of soybean oil, geranium oil, and castor oil. Studies conducted at the University of Guelph showed that this product was capable of providing over 97% protection against Aedes species mosquitoes under field conditions, even 3.5 hours after application. During the same time period, a 6.65% DEET-based spray afforded 86% protection, whereas Avon’s Skin-So-Soft citronella-based repellent gave only 40% protection.⁹⁴ A second study showed that BiteBlocker provided a mean of 200 ± 30 (SD) minutes of complete protection from mosquito bites.⁹⁵ A laboratory study using three different species of mosquitoes showed that BiteBlocker provided an average protection time of about 7 hours.⁷ Another study showed that BiteBlocker could give about 10 hours of protection against biting black flies; in the same test, 20% DEET only protected for about 6.5 hours.⁹⁶

BioUD (2-Undecanone)

HOMS is the sole distributor in the United States of another repellent, BioUD (2-Undecanone). This repellent was derived from the wild tomato plant and registered by the EPA in 2007 as a biopesticide for use against mosquitoes and ticks. In field studies against mosquitoes, 7.75% BioUD provided repellency comparable with 25% DEET.¹³ BioUD repelled the American dog tick Dermacentor variabilis from human skin for over 2.5 hours and was still effective 8 days after application to cotton fabric.¹³ Laboratory testing demonstrated that BioUD was two to four times more effective than 98% DEET at repelling Amblyomma americanum, D. variabilis, and Ixodes scapularis.¹¹ BioUD was significantly better than either IR3535 or PMD (see below) at repelling A. americanum.¹⁴

Lemon Eucalyptus

A derivative (p-menthane-3,8-diol, or PMD) isolated from oil of the lemon eucalyptus (or pine) plant has a strong lemony scent and has shown promise as an effective “natural” repellent.³³ PMD evaporates more slowly from the skin surface than do molecularly similar botanical insect repellents like citronella, and it offers longer-lasting protection. PMD has been very popular in China for years and is currently sold in Europe as Mosi-Guard and in the United States as Repel Lemon Eucalyptus Insect Repellent and Cutter Lemon Eucalyptus Insect Repellent. Tests of this repellent have shown mean complete protection times ranging from 4 to 8 hours, depending on the mosquito species and testing methodology used.* Several studies suggest that PMD-based repellents are superior to DEET against malaria-vectoring Anopheles mosquitoes.²² PMD-based repellents can cause significant ocular irritation, so care must be taken to keep them away from the eyes and that they are not used in children younger than 3 years. In 2005, the CDC added this repellent to the approved list of products that can be effectively used to prevent mosquito-borne disease.

Efficacy of DEET Versus Botanical Repellents

Limited data are available from studies that directly compare plant-derived repellents with DEET-based products. Available data proving the efficacy of “natural” repellents are often sparse, and there is no uniformly accepted standard for testing repellent products. As a result, different studies often yield varied results, depending on how and where the tests were conducted.

Studies comparing “natural” repellents to low-strength DEET products, conducted under carefully controlled laboratory conditions with caged mosquitoes, typically demonstrate dramatic differences in effectiveness between currently marketed insect repellents.^7,⁵¹ Citronella-based insect repellents usually provide the shortest-duration protection, often lasting only a few minutes. Low-concentration DEET lotions (under 7%) typically prove to be more effective than citronella-based repellents in their ability to prevent mosquito bites and can generally be expected to provide about 1.5 to 2 hours of complete protection.^51,⁶⁸ Reapplication of these low-concentration DEET products can compensate for their shorter durations of action. Because DEET repellents show a clear dose–response relationship, higher concentrations of DEET can be used to provide proportionately longer complete protection times—up to 6 to 8 hours after a single application. BiteBlocker and oil of eucalyptus repellents offer the best protection of the “botanical” repellents, but some consumers may object to their odor; the aesthetic qualities of IR3535 and picaridin may be better choices for those sensitive individuals. BioUD also shows promise as an effective alternative to DEET in repelling both mosquitoes and ticks.

Alternative Repellents

There has always been great interest in finding an oral insect repellent. Oral repellents would be convenient and would eliminate the need to apply creams to the skin or put on protective clothing. Unfortunately, no effective oral repellent has been discovered. For decades, lay literature has made the claim that Vitamin B₁ (thiamine) works as a systemic mosquito repellent. When subjected to scientific scrutiny, however, thiamine has unanimously been found not to have a repellent effect on mosquitoes.^84,¹⁷⁴ The U.S. Food and Drug Administration (FDA), prompted by misleading consumer advertising, issued the following statement in 1983: “There is a lack of adequate data to establish the effectiveness of thiamine or any other ingredient for OTC [over the counter] internal use as an insect repellent. Labeling claims for OTC orally administered insect repellent drug products are either false, misleading, or unsupported by scientific data.”⁴⁷ Tests of over 100 ingested drugs, including other vitamins, failed to reveal any that worked well against mosquitoes.¹⁵⁶ Ingested garlic has also never proved to be an effective insect deterrent.¹³¹

Insecticides

Permethrin

Pyrethrum is a powerful, rapidly acting insecticide, originally derived from the crushed dried flowers of the daisy Chrysanthemum cinerariifolium.²⁵ Permethrin is a synthetic pyrethroid. It does not repel insects but instead works as a contact insecticide, causing nervous system toxicity, leading to death, or “knockdown,” of the insect. The chemical is effective against mosquitoes, flies, ticks, fleas, lice, and chiggers. Permethrin has low mammalian toxicity, is poorly absorbed by the skin, and is rapidly metabolized by skin and blood esterases.^71,¹⁷⁶

Permethrin should be applied directly to clothing or to other fabrics (tent walls ¹³⁸ or mosquito nets⁹⁸), not to skin. Permethrins are nonstaining, nearly odorless, and resistant to degradation by heat or sun, and they will maintain their effectiveness for at least 2 weeks, through several launderings.^140,¹⁴⁵

The combination of permethrin-treated clothing and skin application of a DEET-based repellent creates a formidable barrier against biting insects.^64,^86,¹⁵⁰ In an Alaskan field trial against mosquitoes, subjects wearing permethrin-treated uniforms and a polymer-based 35% DEET product had greater than 99.9% protection (one bite per hour) over 8 hours; unprotected subjects sustained an average of 1188 bites per hour.⁹³

Permethrin-sprayed clothing also proved very effective against ticks.¹² One hundred percent of Dermacentor occidentalis ticks (which carry Rocky Mountain spotted fever) died within 3 hours of touching permethrin-treated cloth.⁹⁰ Permethrin-sprayed pants and jackets also provided 100% protection from all three life stages of Ixodes dammini ticks, the vector of Lyme disease.¹⁴⁶ In contrast, DEET alone (applied to the skin), provided 85% repellency at the time of application; this protection deteriorated to 55% repellency at 6 hours, when tested against the lone star tick A. americanum.¹⁵³ Ixodes scapularis ticks, which may transmit Lyme disease, also seem to be less sensitive to the repellent effect of DEET.¹⁴¹

Permethrin-based insecticides available in the United States are listed in Table 47-4. To apply to clothing, spray each side of the fabric (outdoors) for 30 to 45 seconds, just enough to moisten it. Allow to dry for 2 to 4 hours before wearing it. Permethrin solution is also available for soak-treating large items, such as mesh bed nets, or for treating multiple garments simultaneously.

TABLE 47-4 Permethrin Insecticides

Reducing Local Mosquito Populations

Consumers may still find advertisements for small ultrasonic electronic devices that are meant to be carried on the body and claim to repulse mosquitoes by emitting “repellent” sounds, such as that of a dragonfly (claimed to be the “natural enemy” of the mosquito), male mosquito, or bat. Multiple studies, conducted both in the field and laboratory, show that these devices do not work.^9,^31,^49,^73,⁹² Although most studies have shown that DEET-impregnated wristbands offered no protection against mosquito bites,^51,⁷³ in one study wearing impregnated anklets, wristbands, shoulder strips, and pocket strips provided up to 5 hours of complete protection.⁷⁶

Likewise, mass-marketed backyard bug “zappers,” which use ultraviolet light to lure and electrocute insects, are also ineffective: mosquitoes continue to be more attracted to humans than to the devices.¹¹⁶ One backyard study showed that of the insects killed by these devices, only 0.13% were female (biting) mosquitoes.⁵⁴An estimated 71 to 350 billion beneficial insects may be killed annually in the United States by these devices.⁵⁴ Newer technology, using more specific bait, such as a warm, moist plume of carbon dioxide, as well as other known chemical attractants (e.g., octenol), may prove to be a more successful way to lure and selectively kill biting insects. Although the manufacturers of these machines accurately claim that these machines can lure and kill thousands of mosquitoes, it remains to be proven that an individual unit can actually kill enough mosquitoes to reduce the local biting pressures. Pyrethrin-containing “yard foggers” set off before an outdoor event can temporarily reduce the number of biting arthropods in a local environment. These products should be applied before any food is brought outside and should be kept away from animals or fish ponds. Burning coils that contain natural pyrethrins or synthetic pyrethroids (such as D-allethrin or D–trans allethrin) can also temporarily reduce local populations of biting insects.^73,^100,¹⁷⁵ Concerns have been raised about the long-term cumulative safety of using these coils in an indoor environment.^1,¹²¹