Head Lice: An Update on Diagnosis & Treatment

INTRODUCTION

Throughout the history of mankind Pediculus humanus capitis (or here referred to as head lice) has defined itself as a consistent and ever present problem that requires intervention to rid the host of infestation; especially because these parasites use the human as their only means of survival. This insect has managed to biologically specialize and evolve to co-exist with humans even as humans have evolved. The history of lice can be physically traced back thousands of years by examination of both Peruvian and Egyptian mummies, which show the presence of head lice on the preserved human specimens.^1,2 The lice have long been known to improve their longevity by infesting humans via head-to-head contact (hair-to-hair) contact, and now information clearly indicates that they can cause infestation via transference with inanimate objects (fomites) as well.^1,3

Head lice are tiny insects that use the human scalp and hair as an arena for their reproduction, gestation, and growth stages while feasting on the host’s blood supply for their nutrition. These 6-legged, blood-sucking parasites live in 5 stages, starting as a nit, growing through 3 phases of nymphs (also known as instars) and finally maturing as adults when their sex organs are fully defined and reproduction can occur.^4.5 They do not fly or jump, they do however move through various means, most often by “walking.”

Lice are commonly referred to as cooties and the eggs they lay are known as nits. An infestation is referred to as pediculiasis and the disease state known as pediculosis. The removal process itself can be done by application or ingestion of chemicals known as pediculicides. If the pediculicide kills the nymph or adult lice, it is known to be a lousicide, and if it can exterminate the egg, it is known as an ovicide.⁵

EPIDEMIOLOGY AND IMPACT

Age, sex, race, and socioeconomic status do not exclude any particular group from potential infestation. Yet, a brilliant number of variables and factors play into the identification and diagnosis of a head lice infestation, which can ultimately negatively affect the reliability of reporting. Essentially the epidemiology of head lice is poorly understood and, even though it has been studied for well over 100 years and many strong claims have been made, much of the findings have come under scrutiny as a result of poor quality evidence.⁶ When considering the unreliability of those data reported, it is important to consider why underreporting of infestations may occur. There are a variety of reasons infestations may not be reported; one of which is social stigmas because of the potential for school absences and other hardships.⁵

Most available sources indicate that in the United States (U.S.), alone, there are more than 12 million cases of infestation annually.⁷ The socioeconomic status of these cases shows no boundaries, but it stands to reason that the poor, homeless, and children do account for the vast majority of the cases because these groups traditionally find themselves with more opportunity for head-to-head contact as a result of close living conditions, cohabitation, and simply the increased population in a given geographical area.³

Age is a factor that plays a substantial role in the occurrence of infestations, with children representing an abundantly large percentage of the population with lice. In the U.S., preschool and elementary school children between 3 and 11 years of age make up the largest group. Their household contacts and caretakers are highly susceptible to infestations.^4,6,7 A study from India found school children in the first, second, and third grades have the highest rate of head lice infestations, which drops a percentile with each subsequent higher grade.⁸

A different study showed that the length of a person’s hair can act as a variable in infestation rates, with lice and nits appearing significantly more often in children with long (68.9%) and medium-length (63.9%) hair than in children with short hair (44.0%) (P <0.01).⁹

When it comes to gender, studies vary as to whether or not there is a statistical difference in incidence between boys and girls.⁹ Although not designed to evaluate gender specifically, one study found a significant disparity, with girls being 7.4 times more likely to have lice (26.7% versus 3.6%) and 13 times more likely to be infested with nits (23.8% versus 1.8%) than boys (n = 280).⁸ Some of the factors affecting this outcome may include hair length, grooming standards and methods, and use of hair accessories. The hair shaft itself is also a consideration, since the shape, fiber diameter, and texture of the hair shaft can significantly alter louse-laying behaviors and deter louse movement. Kinky hair seems to represent less opportunity for infestation than straight hair because it is likely handicapping the free movement of the louse along the hair shaft.^1,6

Things that can further influence the incidence of infestations are the scents, oils and condition of the scalp itself. There are natural attractants or repellents secreted in human sweat which may be detected by the lice.⁸ The louse is attracted to the odor of ammonium that is found in lice feces, and so the presence of lice itself can act as an aggregation attractant.³ Additional considerations for determining the attractiveness of lice to individuals are the density of hair, hair-color, and the blood-type grouping. All are contributing factors that can potentially play a role, alone or in combination.⁸

The ambient environmental temperature and humidity (corresponding with seasonal changes) are also factors to consider; although this arena is considered difficult to measure because of the contributing variables, such as population movements, school sessions, and endemic areas.¹⁰ Evidence shows that fomite transmissions occur more easily in warmer, more humid, areas (such as tropical environments); this is likely because the temperature of the inanimate object and the human scalp may be similar. Conversely, in colder climates fomite transmission, from objects NOT in direct contact with the scalp, seems to be relatively nonexistent. However, it is reasonable to assume that children in these cooler climates are more likely to be wearing something on their heads, such as hats, caps, hoods, and scarves, which can effectively increase the incidence of transmission.^10,11

In a very interesting study in Germany, pharmacist consultations and the retail movement of lice treatment packages were monitored for a period just shy of 5 years. The study found that pharmacists were consulted about head lice 2.5 times weekly, with the number of consultations varying greatly throughout the year; the study statistically concluded that the consultations had no clear isolated peak incidence. The attempt to isolate and predict a distinct pattern of infestations may have been diluted to represent a longer period of time rather than a clear, peaked time period because they were influenced by social variations or the willingness of parents to deal with the problem stemming from private-, family-, or leisure-related factors. However, logical stepwise evaluation of the German data suggests an increase in infestations could be expected after children return from summer travels (particularly late summer). During travel, children are exposed to a much larger demographic reservoir of potentially infested heads. After returning to school, the transmission commences and continues until the infestation is identified, which may be as long as 4 weeks; as the weeks pass, the demand for treatment products also grows. Data indicate that infestation rates stay relatively low throughout the year, with intermittent spikes arising after various holidays from school.¹⁰

The impact of head lice infestations typically lends itself to a very unique perception and negative connotation, contributing to a well-established social stigma and attitude toward those infested. In some cases, this may spread to their circle of family, friends, and even their institution. As a result, head lice infestation can cause substantial social distress, discomfort, anxiety, and embarrassment, that may lead to the unnecessary absence from school and work.^12,13 It’s completely understandable that in the U.S., with our current cultural perceptions of head lice, that people avoid announcing and discussing infestations and this may negatively impact their decision on “what to do,” resulting in a poor outcome for all parties.

There is also an act of blame that almost unconsciously accompanies infestations, where the parents frequently seek to ascribe blame to the person(s) transmitting the lice, a quick response that precipitates unproductive outcomes. Because it is not accurately viable to determine the identity of the original or subsequent donor, it is significantly more rational to encourage all parties to focus their energies on education and treatment.⁵

DIAGNOSIS (SIGNS AND SYMPTOMS)

Head lice most commonly present as pruritus of the head, which may start anywhere from 1 to 4 weeks after the initial infestation and stands as the defining symptom for those infested. The pruritus can cause loss of sleep, distracted concentration, and the possibility of secondary infections.^1,14

Once the symptom occurs, differential diagnosis begins. Historically, visual identification of nits and/or lice has been used for diagnosis of a head lice infestation and this still stands as the gold standard today.¹⁵ However, it has been a well-studied “art” to determine the best practices and techniques for diagnosing infestations because not all methods are equally successful. It is the diagnosis of head lice that presents the most substantial deviations in epidemiological research, and the reasons for this may include poor methodologies, inaccurate inspections, and the mistaken acceptance of artifacts, just to mention a few.

Determining an accurate screening and diagnosis process involves detailed knowledge of the organism, it’s characteristics and physical makeup. Head lice live on the scalp and on the hair shaft. They have nervous system attributes that enable them to detect environmental hazards, such as wind, combing, chemicals, and the act of a finger scratching the scalp.³ They most commonly take residence near the ears and nape of the neck.^14,15 It is crucial to perform the inspection under bright lighting, and the use of a magnifying glass can also improve accuracy. The American Academy of Pediatrics (AAP) guidelines indicate that the nit must be within 1 cm of the scalp in order to be considered viable.¹⁵ The CDC is more stringent, saying viable eggs are usually found within 6 mm of the scalp.⁴ A definite diagnosis of head lice should be limited to the observation of viable nits or live nymphs/adult lice. The presence of nits alone decreases the likelihood an accurate diagnosis and may simply provide evidence of a past infestation.⁹

The overwhelmingly consistent complication with diagnosis is the mistaken acceptance of dead, hatched, or nonvital nits as active nits. In fact, investigation of samples submitted for a study indicated that only 53% of the samples submitted were viable louse or nits. These samples contained hatched eggs, dead embryos, other arthropods, dandruff, scabs, and hair plugs (plugs of epidermal cells adherent to hairs). Ironically, the study also found that laypersons do a better job of diagnosis than medical professionals (including dermatologists) but, in general, both groups consistently fail to identify the difference between inactive nits and active (live) infestations.¹⁴ One study found that 139 of 280 children would have been unnecessarily treated for pediculosis had the method of diagnosis been based solely on a visual method.⁹

Even though visually identifying the nits remains as the standard for diagnosis, Research has repeatedly demonstrated that visual identification through the use of a comb is substantially more effective than simple visual examination using hands or other tools. In the comprehensive review of combing versus visual inspection, Mumcuoglu et al found combing to be 4 times more efficient and twice as fast. It is recommended the examiner use a comb and go over the entire scalp, inspecting the teeth of the comb after each and every stroke through the hair, looking for the physical presence of live lice; this process should take at least 5 minutes.¹⁴ Ultimately, the only time when noncombing visualization is deemed equally effective as the combing method is when the infestation is very heavy. A study in 1990 found that 78% of the infested children had 10 or less lice on their scalp, 18.7% had 11 to 20, and 3.2% had >20 lice present, indicating 97% of those infested had 20 or less lice.⁹

If the suspected host presents with nits only, the examiner should strongly consider their proximity to the scalp (if seen before combing out) and the magnified visual appearance of the nit, if possible. An active nit shell will have a darkened core, indicating it has not hatched (though not confirming viability). If it is more toward transparent, then the likelihood increases that it is a hatched shell. If the patient presents with nit-only, the patient should be examined for the next few consecutive days and then 1 week later to identify the presence of live lice. If no living lice are detected, then the patient should be considered negative for head lice infestation.⁹ This screening technique should be applied to all individuals within an infested person’s immediate circle of contact, including family members, classmates, and best friends, especially if they’ve had close contact recently.³

Differential Diagnosis

It is important to clarify that, although all lice are considered obligate blood sucking parasites, human pubic lice (Phthirus pubis) belong to a different family entirely.¹⁶ This is true, as well, for human scabies infections, which are caused by Sarcoptes scabiei, species hominis. These microscopic scabies are actually mites which burrow into the upper layer of the skin and lay their eggs, leaving behind a trail of feces which creates an intense pruritis.¹⁷

LOUSE LIFE CYCLES

There are 5 total stages to the life cycle of head lice, i.e., 1 for nits, 3 for nymphs, and 1 for the adult.

Nits

The nits (or eggs) are hard to see because they are only 0.8 mm in length and they are quite often mistaken for artifacts such as hair castings, dandruff, dirt, and hair-care product droplets. They are oval in appearance and usually possess a yellow to white color.¹⁸ They typically take 7 days to hatch, but they have a hatching window of 6 to 12 days.^4,14,19 The adult louse produces a protective coating to cover the nit and hold it to the hair shaft (or alternative fabric) as a method to increase the chances of the egg’s survival. This material is a proteinaceous substance that hardens within seconds to form a resilient mechanical-like clamp or holdfast to keep the nit in place as the fixative substance hardens. This holdfast can retain the empty eggshell in position for months after the young louse has emerged, not disrupted by the normal riggers associated with typical hair washing and grooming techniques. This sheath may be slid across the hair shaft without any residue or damage left behind.^6,20 As the hair grows, the nit moves away from the base of the scalp, where they can be seen easily, however this does NOT indicate an active infestation, but rather a prior infestation, and should not prompt unqualified and unnecessary treatments.^13,20

By scanning electron microscopy, egg of Pediculus humanus capitis with nit sheath casing surrounding both egg and hair shaft is noted. The only area of the egg not coated by the nit sheath is the domed operculum, through which respiration occurs.6 Image used with written approval from Dr. Burkhart, 2010.

In the case of fomite infestation, if an ambient temperature (82° to 90° F) and humidity (70% to 90% relative humidity) of the inanimate object exists, the nits can survive and hatch after 10 days away from the host.¹

Nymphs

After the nit hatches, a nymph is born as an immature adult with smaller stature and undeveloped sex organs. Most live lice are considered nymphs, 1 to 2 mm in length (the size of a pin head) which is 1/3 the length of the adult.¹ They are very difficult to see without the aid of a magnifying glass. Nymphs will move through 3 different stages (instars) to mature into adults, which is generally from 9 to 12 days after hatching^3,21,22 (the CDC states 7 days).⁴ Both nymphs and adults require a blood supply for sustenance; they feed at least once daily,²³ and they must feed every 24 to 48 hours to live.^4,22

Adults

The typical adult louse is the size of a sesame seed and its color is tan to grayish-white; although, when in dark hair, the louse will appear darker.^4,22 Larger and faster than the nymphs, the adult louse has fully developed sex organs and is capable reproducing. The female louse has a sperm depository, or spermatheca, so that a single mating is all that is required for a lifetime of fertility. Its lifespan is roughly 30 days and, during this time, the females typically lay 5 to 10 eggs a day and, with an infestation of 20 lice, in vivo studies have shown that more than 2600 eggs may be laid on the scalp during the 30 day life cycle.¹ The female creates a glue substance and lays the egg in the glue, using her vaginal musculature and movement of the posterior anatomy to attach the egg firmly to the top of the hair shaft. Glue is also applied to the hair shaft and done exquisitely as to not cover the minute operculum (respiratory hole) used by the larva. This process takes only 16 seconds to occur.⁶

Photo credit to John Van Dyke, ISU.

ETIOLOGY AND TRANSMISSION OF HEAD LICE

It has been a widely held belief, for great lengths of time, that the transmission of head lice was solely a result of head-to-head contact. The theory of fomite transmission (the use of an inanimate object or material to allow for the infestation to be transmitted) was a consideration, but remained unjustified in the medical literature. A study in 2005, and then another in 2007,¹ confirmed that fomite transmission does occur, but exactly how this interaction transpires is still a mystery.³ To ultimately improve public health considerations and treatment methodologies, clearly there are many nuances to consider in the transmission of head lice.

Lice move in a variety of ways. They do not show evidence of propelling themselves by jumping or flying, instead they walk. Both nymphs and adults move on their own, but the adults typically move the quickest, at 6 to13 cm/min (the CDC recorded their movements at 30 cm/min); however this speed is reduced when the hair is wet.^3,15 The movements are generally on the scalp as well as up and down the hair shaft and cross-migrating to other hairs at hair-to-hair junctions or bridges (essentially defining head-to-head transmission methodology). Close proximity between heads offers an increased opportunity for hair-to-hair contact and it should always be monitored and considered with the highest regard.^8,15

Another means of movement for the louse is defined as a “flee response.” That is when impending peril is perceived; such as light, odor, or agitation of the hair, the louse traverses to the end of the hair, ready to drop off (cliff jumping if you would), essentially, allowing the louse to flee the area. Once airborne, the ambient conditions have a direct affect on the louse’s direction and travel.¹ Air movement, such as that produced by hair dyers, can dislodge nits, nymphs, and adult lice from the hair shaft. This creates a zone of uncontrolled flight that establishes another transmission opportunity.¹ Once the louse is on the fabric or other fomite, whether it be by fleeing, dislodging from the hair shaft, or simply walking, they can lay eggs and, if left undisturbed, those eggs can hatch in approximately 10 to 14 days³

HEAD LICE AS VECTORS OF DISEASE AND OTHER SECONDARY COMPLICATIONS

The concept as to whether or not head lice are actual vectors for disease has been highly debated. The medical literature from as early as 1935 indicate that physicians suspected lice of transmitting various diseases, helping to exacerbate epidemic activity.^2,24 More recently, in 2009, Weiss, took a broad anthropological look at the full genomic history of lice. He stated that body lice, and occasionally head and pubic lice, transmit bacterial diseases: typhus (Rickettsia prowazekii), trench fever (Bartonella quintana) and relapsing fever (Borellia recurrentis). The lice themselves actually succumb to the typhus infection, yet they pass the Rickettsia in their feces, which the human then scratches into the skin.²⁵ Further studies indicate that lice do transmit coagulase-positive Staphylococcus aureus and group A Spyogenes, by carrying these organisms on their external surfaces.¹ Thus the itching and subsequent scratching which leads to excoriation of the skin could introduce the pathogen and create a secondary skin infection such as impetigo and pyoderma.¹⁴

In light of this evidence, it has been well-established that body lice are indeed vectors of disease. Very recently, in March of 2010, Li et al brought forth evidence to establish that head and body lice are essentially the same species. The mitochondrial and nuclear genes of the 2 are indistinguishable and that very limited mutations actually exist, suggesting the 2 are actually conspecific.²⁶. Further studies have revealed the ability of head lice to successfully colonize in clothing, as well as produce a body louse variant; all indicating that an infection has the potential to generate an epidemic situation. It has even been confirmed that head lice and body lice can interbreed despite their various genetic differences (morphological and physiological).²⁶

TREATMENT

“The greatest harm associated with head lice results from the well-intentioned but misguided use of caustic or toxic substances to eliminate the lice.” RJ Pollack⁵

When investigating treatments for head lice, it is most important to consider the overwhelming evidence suggesting treatment be initiated only when viable eggs or live lice are identified. There are many methods used to treat head lice infestations; some are tested more thoroughly than others. There are countless reports of resistance to products, which may prompt patients to investigate the use of products considered less toxic. This section will review pharmaceutical treatment options, as well as evaluate the natural treatment methods available on the retail market today.

Although household contacts should be checked for infestation, the CDC strongly recommends treatment only for those diagnosed with an active infestation, although they also suggest it prudent to prophylactically treat those sleeping in the same bed as the infested individual. It is generally best to treat all infested individuals at the same time.⁷

Cleaning

Treatment guidelines for delousing must take into consideration the passive transmission of lice via clothing such as hats, scarves, coats, headphones, hair adornments, towels, combs and brushes of the infected individuals; this extends to upholstery, bedding, pillows, carpet, and stuffed animals, with which the person may have been in recent contact.

Cleaning should be done to all objects that have come in direct contact with the infested individual during the 2 days prior to treatment. Lice will not survive if exposed to 5 minutes of heat at 53.5°C (128.3°F) and live nymphs and adults cannot survive longer than 2 days away from a host. Items that should be washed and dried (with heat) include such things as caps, scarves, hoods, pillows, sheets, clothing, towels and stuffed animals. Accessory items such as combs, brushes, and adornments should be placed in hot water (130°F) for 5 or more minutes. If the item in question cannot be washed or cleaned, it should be quarantined for 2 weeks (stored in a sealed plastic bag) because newly hatched nymphs can only last that long away from the actual host.^5,7

Upholstery, carpet, furniture, car interiors, and other items that the person may have had extended, close contact with, should be cleaned with a standard carpet vacuum. After delousing, vacuuming the surrounding surfaces/floors with a hand-held vacuum (even after as many as 5 passes) was essentially a failure at removing nits. However, a standard carpet vacuum worked successfully in removing nits and lice from the field in simply one pass.³ Extensive household cleaning will ultimately result in a cleaner living environment, but the expense and time associated with doing so is unlikely to change the incidence of reinfestation. In the case of a child’s car seat, it is recommended to clean the seat cover, but vacuuming should be sufficient.^5,7 It is very important that children always wear protective helmets, even if the helmet must be borrowed. The risk of a potential head injury far outweighs any risk from a head lice infestation.¹⁵ Avoid the use of pesticide/chemical laden sprays and bombs; the potential of health risks and toxicity associated with contact (inhaled or topical) of these insecticides far outweigh the benefits to using them.^5,7,12 Likewise, chemical repellents pose an unnecessary risk to those exposed and study results do not favor their use.⁸

Resistance

It has been well-established in the medical literature that head lice are resistant to the most commonly used chemical/drug/toxic treatments. One of these well-known chemicals with established resistance is permethrin, a very common synthetic insecticide, acaricide, and insect repellent.^19,27-29

Patients should be instructed to read package inserts and instructions about the various products, carefully, to ensure proper treatment application before declaring the products ineffective. As of today, no product made or found is considered to be 100% effective at killing the eggs (ovacidal). Retreatment is often recommended, 10 days after initial treatment, to focus on the nymphs that may have hatched. It is important to frequently reinspect the individual for active infestations.⁵ Lack of efficacy following a treatment may also be an indication of poor treatment application, or it may be a result of the long length and thick volume of the hair, which can complicate effective application.^30-32 It is important to note, insecticides do not cause mutations which lead to resistance, but rather the insect itself can, by chance, demonstrate an ability to avoid, detoxify, or eliminate toxins from its body and, thereby, perpetuate a sense of resistance.³³ The best treatment option is to ensure manual removal of all nits.¹⁹

TREATMENT AGENTS

Because no product is completely ovicidal, it is crucial to identify any remaining nits following treatment. A pediculicide can certainly kill nymphs, adults, and to some degree affect eggs; but they typically have no prominent residual activity when applied to the hair and, therefore, do not protect against reinfestation. Thus, suggesting retreatment should be initiated 7 to 10 days later, if live infestations persist.⁸

OTC items for the treatment of lice include natural and chemical-based pediculicides, as well as numerous other products that treat head lice through various means and measures, such as repellents and devices (combs, blow-dryers, etc).

Nonpyrethroid Insecticides (Rx Only)

Malathione 0.5%, an organophosphate and alcohol-type lotion, is considered to be pediculicidal and partially ovicidal. It should applied to dry hair, up to 2 ounces, and left on for 8 to12 hours. Subsequently, the hair should be shampooed and rinsed and the treatment reapplied after 7 days.^15,34,35 The Medical Letter^® recognizes malathione as highly effective and declares it to be a first-line choice.³⁶ Complications with use include toxicity and flammability (consider hair dryers, curling irons, etc), as well as its notable odor. It is indicated for people 6 years of age and older and it is contraindicated in infants and neonates. Side effects are minimal, with local irritation to the skin and conjunctivitis when exposed to the eyes most commonly reported. This product can be used routinely and safely during pregnancy.^15,34,35

Benzyl alcohol 5% is a non-neurotoxic water-soluble lotion. It is designed suffocate the lice by effectively blocking their spiracles, which are the external entry point to their breathing apparatus. This product was introduced to the U.S. market in 2010 and it represents a significant breakthrough in pediculicide treatment. Benzyl alcohol could be seriously considered as a first- line, alternative treatment to the current chemical pesticide products.³⁷ Photos of the benzyl alcohol applications clearly showed the product effectively stunned the lice and kept them from closing the spiracle, which allowed the ingredients in the lotion (mineral oil among other inactive ingredients) to infiltrate the spiracle and effectively cause asphyxiation.³⁷

Benzyl alcohol 5% is well tolerated with low systemic exposure; localized skin reactions, such as pruritus, erythema, and ocular irritation, account for the majority of adverse reactions associated with use.³⁷ This medication can be administered to infants as young as 6 months of age, as indicated by the dosing chart provided in the manufacture’s package insert.³

In addition to its mechanism of action, the recommended application of 5% benzyl alcohol lotion is also different from other pesticides because the volume of product used is much larger. The amount to be applied is adjusted according to the amount of hair that needs treatment (see Table 1). Administration calls for the sufficient and effective saturation of the entire scalp and all hair shafts. The product is applied to dry hair, left on for 10 minutes, and rinsed; this process is repeated for 7 days. This product can be used routinely and safely during pregnancy.³⁸ Due to the potentially large volume of product required for application, cost may ultimately be a factor in the value of this product.

Lindane (gamma-hexachlorocyclohexane), an organochloride product, carries the substantial risk of neural toxicity. As a result, the Food and Drug Administration (FDA) recommended additional safeguards for its use because safer treatments are available. The FDA continues to allow lindane to remain on the market because they determined that the benefits outweigh the risks when it is used appropriately; however a black box warning was issued for the lindane shampoo in 1995.³⁹ In conjunction with this warning, it is important to instruct patients about the proper use of lindane shampoo, including the amount to apply and how long to leave it on the scalp. The State of California banned lindane, in January of 2002, as an environmental hazard.^37,41,42 It should not be used as a first-line therapy, rather consider lindane products only after persistent failures with all other treatment methods. The package insert suggests that lindane be avoided in patients with skin conditions such as contact dermatitis and psoriasis because of increased systemic absorption, as well as in patients with a known history of uncontrolled seizures and in those who are pregnant.⁴⁰

Sulfamethoxazole with trimethoprim is prescribed off-label because it is theorized to be an agent capable to kill the bacterial flora necessary for the synthesis of B vitamins in the intestinal track of lice.⁴³ However, the effect of antibiotics on the propagation of lice has yet to be determined conclusively; therefore, their use in treating lice should be opposed pending further testing as to not contribute to declining antibiotic sensitivities in general.⁵

Ivermectin is an oral antiparasitic agent that is commonly used to treat infestations caused by certain worms. However, studies have shown oral ivermectin to be substantially effective for the treatment of head lice.⁴⁴ Generally, oral ivermectin is considered safe in children as young as 2 years of age, but complications have been observed in older patients with comorbidities. Its use should be reserved for patients who have clearly been defined as resistant to established head lice treatment options because of concerns regarding the increasing prevalence of a worldwide resistance to ivermectin for the treatment of scabies.⁴⁵ Further studies are required to truly establish the safety and efficacy of ivermectin.

Pyrethroid Insecticides (OTC Only)

According to studies conducted worldwide, there has been an increase in the resistance to pyrethroid insecticides. Contributions to this effect may include slow pediculicidal action, ineffective formulations, and a sublethal residue which is left on the hair and scalp.^{12,27,28,32,46} This resistance needs to be considered when deciding on a therapy, although the pyrethroids are still considered first-line therapy by many sources including the Medical Letter.^32,36

Pyrethrins 0.33%are naturally occurring nondipyridyl biocide substances extracted from the chrysanthemum plant. They act by interfering with the sodium transport in lice, causing neurotoxicity and eventual paralysis of the muscles that the lice use to breath.^12,47 Pyrethrins are often combined with piperonyl butoxide (4%), which acts to prevent pyrethroid breakdown, making the medication maintain effectiveness for a longer period of time.⁴³ The products are available as shampoos, gels, foams, and other varieties of topical application. They have been broadly identified as the treatment of choice in newly identified head lice infestations.³²

It is widely believed that nondipyridyl insecticides (including the pyrethrins and pyrethroids) rarely produce adverse reactions other than mild skin, eye, and/or gastrointestinal (GI) irritation with topical applications.⁴⁷ They are contraindicated in patients with sensitivities or allergic reactions to ragweed and chrysanthemum, however this is somewhat clinically contested.^34,43 Patients should be instructed to follow product directions carefully, and rinse hair with cool water after use to decrease the systemic absorption that results from vasodilatation of surface capillaries. Since nondipyridyl insecticides are not considered ovicidal, a second application is recommended after 7 to 10 days. They are safe for children as young as 2 years of age, however, are only to be used by pregnant women when absolutely necessary because of the risk of harm to the fetus.⁴³ Some of the more common products, available in the U.S. containing the combination treatment pyrethrins 0.33% with piperonyl butoxide 4% include A-200, Pronto, R&C, Rid, Triple X, Bio-Sentry, and End-Lice.

Permethrin 1% (available as Nix brand in the U.S.) is basically a synthetic analog of pyrethrin, thus making it a pyrethroid, with similar efficacy and resistance. Unlike pyrethrin, permethrin does show residual activity, lasting for more than 2 weeks; this indicates both pediculicidal and ovicidal activity. One application may be all that is necessary, but a second application has been shown to increase effectiveness to a 95% cure rate.¹²

Patients should read permethrin application instructions carefully and take additional care to ensure the hair is not too wet when applying, thereby diluting the distribution of the drug. Permethrin is also available in a prescription strength of 5%, however, studies indicate lice that show resistance to permethrin 1% are also resistant to the 5% formulation, making use of the higher concentration unwarranted.³² The side-effect profile is similar to that of pyrethrin and is generally well tolerated, with only mild local irritations reported.⁴⁷ Permethrin is safe for use in children as young as 2 years of age and in those who are pregnant where it has been commonly reported to be used.⁴³ Permethrin is available OTC as Nix.

ALTERNATIVE MEDICINES

If the number of natural, nontoxic head lice treatment products being offered on the consumer-driven market indicate anything, it would have to be that people remain very concerned about the use of insecticide products, even though studies indicate the low toxicity of products currently available for use in the U.S. The use of organic and natural products has proliferated the U.S. market and demand for these products continues to increase, while concerns for safety and effectiveness remain paramount.

Botanicals

The vast majority of alternative medicine products come from the botanical (plant-based) treatment arm of nontoxic (natural) products. This group has a significant number of supporting research studies, indicating the products have promise. The complementary medicine database, Natural Standard, has reviewed many of the studies and offers a large list of alternative methods used to treat lice. Within their data search, American pawpaw, hibiscus, tea tree oil, and tumeric show positive scientific evidence for effectiveness, however, the evidence is defined as unclear or conflicting. Other items known to have traditional or theoretical (not scientific) use include acacia, aconite, American hellebore, anise, burdock, cinnamon, clove, English ivy, fenugreek, gumweed, lavender, mastic, noni, peppermint, rosemary, scotch broom, tansy, and thyme.⁴⁸

McCage et al conducted small trials (n = 21 in pilot studies) and a final clinical trial (n = 16) where they observed that the combination of pawpaw placed in shampoo and combined with thymol and tea tree oil (plants known to deplete energy source adenosine 5‘-triphosphate [ATP]) was 100% effective for removing head lice and nits. This combination product is currently available as PawPaw Lice Remover Shampoo (with lice comb).⁴⁹

Mumcuolglu et al found a natural remedy containing oils of coconut, anise, and ylang-ylang to be nearly identical in its effectiveness against lice versus a control pediculicide mixture containing malathion, permethrin, piperonyl butoxide, isododecane and propellant gas, in a spray formulation (92.3% versus 92.2%, respectively).¹⁴

Another study demonstrated the effectiveness of eucalyptus essential oil against head lice. Toloza et al describes eucalyptus as a “good and safe alternative due to its low toxicity to mammals and easily biodegradable in their testing against permethrin-resistant lice.” Regarding potential eucalyptus oil toxicity, the oil is listed in the Generally Recognized as Safe category by the FDA and classified as a “safer and non-toxic compound” by the U.S. Environmental Protection Agency, 1993.⁵⁰

Another botanical study looked at a formulation of the Australian herb quassia amara, formulated in homeopathic potencies and mixed with a low potency homeopathic natrum muriaticum and oils of peppermint, tea tree lemongrass, and lavender for effectiveness against lice. In vitro application, with 2-hour and overnight exposure on adult lice, resulted in 73% and 100% kill rates for the exposures respectively.⁵¹ Similarly impressive was the nit kill rates of 98.3% and 100% during those same time periods. In an in vivo study involving 100 children, the formula showed a 99% effectiveness rate and no significant adverse reactions.⁵² This quassia amara combination treatment is available in the U.S. as Quit Nits Advance Treatment.

Heat Devices

In early research, as far back as 1941, air which is heated and blown (similar to hair drying) has been shown to be a potential nontoxic approach to killing lice and, even more effectively, killing their eggs. In an in vivo study, delivery of large volumes of hot air resulted in 98% mortality of eggs and 80% mortality of hatched lice on infested children, suggesting that heat could be considered effective and safe. Of notable interest is that it requires only 30 minutes of treatment duration.⁵³ The handheld product showing the highest effectiveness during the 2006 testing was released in May of 2010 as the LouseBuster.

Suffocation

Multiple trials have employed a scanning electron microscope to evaluate the spiracles (breathing apparatus of lice) and noted that the lice had the ability to open and close the spiracles in a survival capacity that would basically allow them to avoid asphyxiation when they were submerged. When mayonnaise was applied, it seemed that the lice were resurrected after rinsing off the mayonnaise. The lice somehow resisted asphyxiation even after overnight application. This is believed to be the result of the organism’s ability to close the spiracle before the mayonnaise was able to clog it and ensure suffocation.³⁷

Prior to the release of the study data involving benzyl alcohol lotion, the concept of suffocation as a treatment option for head lice infestation was virtually nonexistent (see Nonpyrethroid Insecticides: Rx-Only above); most data surrounding the theory of suffocation were anecdotal and theoretical. The idea of using a product to coat the nits and restrict oxygen transfer to the developing larvae seemed attractive because there would be no transdermal absorption and, therefore, no potential for systemic toxicity, but the research was difficult to cultivate. In most other suffocation studies, treatments were focused on the domed operculum, or permanent opening in the egg’s shell, where respiration occurs.⁶ Thus the hope of finding an inexpensive, nontoxic product (such as mayonnaise, vinegar, isopropyl alcohol, olive oil, melted butter, or petroleum jelly) that could effectively treat head lice was the basis of many nonclinical attempts and theories.

That was until 2004, when an independent study by Dr. Dale Pearlman was published in Pediatrics. He wrote of a Nuvo-Method for Treating Head Lice involving the application of an unnamed nontoxic, dry-on, suffocation-based, pediculicide lotion, which turned out to be very successful in the treatment of lice (96% cure rate with a 94% remission rate). The study had 2 arms: one arm included mechanical nit removal in addition to the application of the lotion (n = 91) and the other involved the lotion application alone (n = 40). The results concluded that there was no statistically significant difference between the 2 groups, indicating that suffocation alone could cure infestations.⁵⁴ Dr. Pearlman’s methods and the validity of his results were challenged. As a result, in 2005, he disclosed his use of OTC Cetaphil lotion to conduct his research and he still stands by his results today.^30,55 In an effort to allow individuals to replicate the precise instructions for the novel treatment application of Cetaphil lotion, Dr Pearlman has published the details of his procedure at www.Nuvoforheadlice.com. An abbreviated version of the instructions is as follows: apply the lotion (in a specific application methodology), wait 2 minutes, comb out excess lotion with a nit comb, blow dry hair, wait 8 hours, shampoo, and then mechanically remove nits.⁵⁶

Recent in vitro experimentation has demonstrated that lice were irreversibly immobilized after being submerged for 5 minutes in 4% dimethicone (a commonly used nontoxic ingredient found in cosmetic and hair-care products). While similar in application to suffocation methods, this therapy was theorized to be effective as a result of applying a coating to the insects’ bodies and thereby disrupting their ability to manage water.³⁰ A similar product is available as Lice MD: Lice and Egg Treatment, and dimethicone is an ingredient in Quit Nit Everyday Preventative Spray.

Haircuts (Shaving)

While it is often joked about, haircuts can improve outcomes with head lice control. While it does not stop infestations, it does make nit combing more effective and easy to do and thus likely substantially influences positive outcomes. While this option may be satisfactory for boys, the shaving of girl’s heads can be more emotionally detrimental, resulting in low self- esteem and more embarrassment than having head lice. Thus, for girls, it should realistically not be considered.¹⁸

MANUAL DELOUSING/ WET COMBING/ BUG BUSTING

Manually removing the nits and lice from the scalp and hair shaft is deemed a necessary step in nearly every lice treatment. It is suggested as an adjunct to nearly every pediculicide therapy (natural and botanical), as well as after suffocation methods. Manual delousing can also be used as a stand-alone therapy, especially when treatment with pesticides is not indicated, such as in children less than 2 years of age or when cost is prohibitive. Spears et al suggests that the removal of viable eggs at the time of treatment for pediculosis will, in theory, improve the efficacy of treatment by stopping recruitment of newly hatched lice onto the head;¹⁹ essentially, stating that the removal of eggs is a critical strategy in the treatment of head lice. The meticulous process of tediously running a comb through an infested person’s hair is an essential, safe, and reliable step to be considered in treatments, although this process remains unpleasant for anyone involved.

When a study evaluated different styles of combs, it was overwhelmingly evident that a rectangular, metal comb performed better than the typical plastic combs, which were molded with cylindrical teeth embedded into a plastic handle. The metal combs, with rectangular teeth, removed 3 to 4 times more eggs than the plastic combs (depending on whether the egg was hatched, dead, or alive).¹⁹ One comb, in particular, named the LiceMeister (National Pediculosis Association), is described as a premium lice removal comb.⁵⁷ Following testing, it was concluded that, while the the LiceMeister comb was 4 times more effective, it was 10-times more expensive than plastic combs, which could substantially influence consumer purchasing. It was recommended that if the infestation is one of recent occurrence (meaning few nits have developed), then a plastic comb may work fine. However, this would require more repetitive combing to remove the newly hatched nymphs that were not removed as eggs. Thus, with more eggs and longer established lice infestations, it is recommended to consider metal combs when treating infestations.¹⁹

The specific technique for nit removal is essentially the same as that for diagnosis: combing clean, wet hair and moving smoothly from root to tip, while wiping the comb clean on a disposable towel after each completed stroke is most effective. The combing should be continued until no lice are found. Combing is repeated once every 3 to 4 days for several weeks and should continue for 2 weeks after any session during which an adult louse is found.^6,19 One study indicated that it can take as many as 9 hours for a parent to thoroughly search and remove all nits from a child’s scalp, however taking 5 to 30 minutes each session is more realistic.^6,14,29 If possible, the use of 2 people for combing can help to decrease the chance of missed nits.

Conditioners

The use of conditioners will help smooth out the hair shaft and improve the outcome of the manual lousing process according to many researchers. There are related products specifically designed to remove the chemical bond the nit has on the hair shaft via an ungluing or enzymatic decomposition method. However, this is based on a scientifically flawed theory because it is believed the nit is attached by a mechanical means, with a cement-like clamp, rather than by a chemical means that can be biochemically decomposed (see Louse Life Cycles). Furthermore, the inner portion of the sheath is very similar in composition to that of the hair shaft, thus any product that theoretically decomposes the glue, would essentially also destroy the hair. However sound in theory, keep in mind that these concepts are continuing to be evaluated and warranted of further analysis.^6,20

Related experiments were conducted by Burgess, a well-written author in the research of head lice, investigating the commercial products Step 2 and Clear Lice Egg Remover. These products were found not effective in disabling the eggs’ fixative mechanism. Similarly, RID Egg & Nit Comb-Out Gel, which uses cabbage and pineapple extracts because of their ability to enzymatically break down the silk gum sericin protein, was found to be no more effective than daily-use hair conditioners. It was also found that soaking the eggs in vinegar, which has been widely embraced as a means to facilitate nit removal, was no more effective than soaking them in water. The study ultimately suggested that any product that can lubricate the hair will, in the end, slick the hair shaft adequately to facilitate optimal lice and nit removal.^20,58

Prevention/Repellency

There are many products marketed that suggest repellency as a means to prevent spreading and reinfestation. Residual repellency, or the action of the insecticide, essentially lays the foundation for the development of resistance. However, in the natural arena, it appears that repellency may be possible, even while maintaining a high safety profile.

A study using a citronella-based spray repellent on children with lice-infested hair was found to be substantially more effective when compared with a placebo-control group treated with only the inert ingredients (12.4% and 33.7% of children showing infestations at 4 months, respectively). Even though it was anticipated that the citronella spray would work as effectively when applied every 2 to 3 days, once-daily application of the repellant was ultimately suggested because the application was quick and the quantity of drug small (1 to 3 pumps once-daily). Aside from a slight odor (which could affect daily compliance), only 1% of the subjects spoke of burning or itching scalp sensitivities from the product. It is not known if this product is currently available in the U.S.⁸

Tea tree oil was also found to be an effective repellent against head lice (as was peppermint oil). It was also observed that the application of these oils caused the hair shaft to remain slippery, decreasing the louse’s ability to transfer (or walk) from hair to hair. More importantly, this also seemed to cause a decrease in the louse’s ability to blood feed (as was also shown with lavender oil).⁵⁹ In addition, based on studies involving the use of eucalyptus oil in head lice treatment, a popularly marketed product in the U.S. called Quit Nit Everyday Preventative Spray is a natural and safe product for repellency; it contains eucalyptus oil (in a 1x HPUS homeopathic dilution) as well as geranium, lavender ,and sandalwood essential oils.⁵⁰

Research evidence indicates successful outcomes from the use of botanical repellents with a high safety standard. Despite this, some medical professionals will remain cautious regarding the effectiveness or safety of these products.⁶⁰ It is probably wisest to advise patients that when considering botanical repellents, which typically demonstrate a well-tolerated profile of adverse reactions and proven efficacy, one should consider cost-effectiveness and make recommendations accordingly.

STRATEGIES FOR PHARMACISTS

There is ample opportunity for pharmacists to intervene in the education, diagnosis, and treatment, of patients concerned with a head lice infestation. As commonly acknowledged, pharmacists’ opinions are met with a high standard of respect by consumers, especially when the information they are seeking involves an immediate health-related issue, the need for either prescription medication or OTC items. The esteemed nature of the profession should compel pharmacists to offer suggestions based on scientific evidence, rather than simply an anecdotal or personal opinion. Pharmacists can influence choices and help to establish a degree of social etiquette regarding a particular disease state or condition, especially where there is a stigma involved, as with head lice infestations. The hysteria, misdiagnosis, and poor treatment outcomes that shroud these infestations help fuel harmful personal, community, and school ideologies about treating head lice.

Sharing Helmets

While the public should be educated about sharing things such as hair brushes, hats, towels, and similar products, when the risk of acquiring lice is weighed against the risk of a child not wearing a protective helmet, there is simply one answer: Wear the helmet! While there is risk of acquiring head lice from the helmet of an infested child, if sharing that helmet is necessary, then all logic should dictate that the child should wear the helmet.

No-Nit School Policies

The controversial approach by school districts in the U.S. to evoke no-nit policies in schools is repeatedly and emotionally challenged by parents, communities, and science alike. The decision to isolate children by either sending them home or quarantining them is often fueled by misinformation and misdiagnosis. As always, the diagnosis of infestations should be based solely on the objective identification of live lice and viable eggs. It is impractical and harmful to establish these no-nit policies when there is gross misdiagnosis occurring.^5,61 Yet, the National Pediculosis Association, which emphatically supports no-nit policies, is steadfast in their realistic approach to treating head lice, first considering the safety of all children. An algorithm for managing presumed head lice infestations in schools can be found on the Harvard School of Public Health (HSPH) Web site.⁵

Valid Diagnosis

While perhaps not necessary in every case, there may be some patients who request information for sources to accurately identify lice infestations based on entomological identification (other than submitting specimens for diagnosis to a clinical laboratory). Currently, the HSPH Web site is a valuable resource to access this information.⁵

Rational Approaches

The aspect of injecting rational and creative thinking into specific scientific arenas isn’t always a wise proposition. However, when discussing rational approaches to treating head lice, understanding all the new information and conflicting information, there are some simple takeaway’s that pharmacists should embrace:

1. Suggest inspection and treatment of head lice to be done with a metal comb (when cost effective), which should include all family members who have had close contact in the preceding 2 days. This should be under good lighting and, when possible, while using a magnifying glass.
2. Launder and dry all bedding, towels, hats, shirts and clothing. When an item cannot be laundered, consider drying alone, or quarantine these items for 14 to 18 days.
3. Vacuum all carpet, upholstery, and floors with a carpet vacuum.
4. Treat ONLY when live infestations are confirmed.

CONCLUSION

The evolution of Human head lice has plagued society for thousands of years. The knowledge and scientific pursuit of understanding and treating these parasites has been engaged widely throughout the world with references and publications abound. Yet, still no one treatment alone has proven to be 100% effective. In light of recent evidence indicating the fomite transfer of head lice, along with the very recent evidence indicating that body lice and head lice may essentially be cospecies, science is ready to validate head lice as an effective vector of disease. The risk:benefit associated with bombing houses and using topical sprays to eliminate lice is not currently supported; this may change as we learn more about the potential dangers associated with lice infestations.

According to our most recent study data and demographic information, patients are requesting more natural and safer treatment options, and they are doing the research themselves. In answer to this, the Centers for Disease Control and Prevention (CDC) and other social and collegiate entities should continue with their research as a means to provide confident, reliable information to both medical professionals and the public, enabling them to choose safe, non-toxic, and effective treatment options for head lice.

Of notable mention would be the ideas and purposes behind the National Pediculosis Association (NPA) (www.headlice.org), which acts as a independent, self-sustaining, nonprofit organization, yet provides a forum for rational, safe choices in all things related to head lice. The NPA endorses caution, peace of mind, and preparedness in their approach to head lice. While not a anti-chemical organization, they endeavor to suggest safe approaches toward treating children with head lice infestations. They suggest that in the face of pesticide toxicity and resistance, alternative approaches which are defined as much safer and still effective should be considered as fundamental first-line rational approaches toward the treatment of head lice in contrast to the continued offering of drug studies, which are now even suggesting the oral dosing of pesticides in children in attempts to control these topical infestations.

Lastly, it may be valuable for the pharmacist to acknowledge and perhaps develop supportive programs to coincide with the National Head Lice Prevention Month each September. The NPA can offer suggestions on how to promote this event.⁶²

REFERENCES

1. Burkhart CN, Burkhart CG. Fomite transmission in head lice. J Am Acad Dermatol. 2007;56(6):1044-1047.
2. HeadLice.Org. Zinsser, Lice And History: Lice & Disease. The National Pediculosis Association, Inc. Web site. www.headlice.org/faq/disease/zinsser.htm. Accessed July 3, 2010.
3. Laboratory Identification of Parasites of Public Health Concern (DPDx). Parasites and Health: Pediculosis. Centers for Disease Control and Prevention (CDC) Web Site.www.dpd.cdc.gov/dpdx/HTML/HeadLice.htm. Accessed July 3,2010.
4. Takano-Lee M, Edman JD, Mullens BA, Clark JM. Transmission potential of the human head louse, Pediculus capitis (Anoplura: Pediculidae). Int J Dermatol. 2005;44(10):811-816.
5. Pollack RJ. Head lice: Information and Frequently Asked Questions. Harvard School of Public Health Web site. www.hsph.harvard.edu/headlice.html#what. Accessed July 3, 2010.
6. Burkhart CN, Burkhart CG. Head lice: scientific assessment of the nit sheath with clinical ramifications and therapeutic options. J Am Acad Dermatol. 2005;53(1):129-133.
7. Centers for Disease Control and Prevention (CDC). Epidemiolgy & Risk Factors. CDC Web site. www.cdc.gov/lice/head/epi.html. Updated May 16, 2008. Accessed July 3, 2010.
8. Mumcuoglu KY, Magdassi S, Miller J, et al. Repellency of citronella for head lice: double- blind randomized trial of efficacy and safety. Isr Med Assoc J. 2004;6(12):756-759.
9. Mumcuoglu KY, Friger M, Ioffe-Uspensky I, et al. Louse comb versus direct visual examination for the diagnosis of head louse infestations. Pediatr Dermatol. 2001;18(1):9-12.
10. Bauer E, Jahnke C, Feldmeier H. Seasonal fluctuations of head lice infestation in Germany. Parasitol Res. 2009;104(3):677-681.
11. Burgess IF. Human lice and their control. Annu Rev Entomol. 2004;49:457-481.
12. Nutanson I, Steen CJ, Schwartz RA, Janniger CK. Pediculus humanus capitis: an update. Acta Dermatovenerol Alp Panonica Adriat. 2008;17(4):147-154, 156-157,159.
13. Williams LK, Reichert A, MacKenzie WR, et al. Lice, nits, and school policy. Pediatrics. 2001;107(5):1011-1015.
14. Mumcuoglu KY, Miller J, Zamir C, et al. The in vivo pediculicidal efficacy of a natural remedy. Isr Med Assoc J. 2002;4(10):790-793.
15. Frankowski BL. American Academy of Pediatrics guidelines for the prevention and treatment of head lice infestation. Am J Manag Care. 2004;10(suppl 9):S269-S272.
16. Bonilla DL, Kabeya H, Henn J, et al. Bartonella quintana in body lice and head lice from homeless persons, San Francisco, California, USA. Emerg Infect Dis. 2009;15(6):912-915.
17. Centers for Disease Control and Prevention (CDC). Scabies. CDC Web site. www.cdc.gov/scabies/. Updated November 10, 2008 Accessed July 3, 2010.
18. Centers for Disease Control and Prevention (CDC). Diagnosis. CDC Web site. www.cdc.gov/lice/head/diagnosis.html. Updated May 28, 2008. Accessed July 3, 2010.
19. Speare R, Canyon DV, Cahill C, Thomas G. Comparative efficacy of two nit combs in removing head lice (Pediculus humanus var. capitis) and their eggs. Int J Dermatol.2007;46(12):1275-1278.
20. Burgess IF. Do nit removal formulations and other treatments loosen head louse eggs and nits from hair? Med Vet Entomol. 2010;24(1):55-61.
21. Mumcuoglu KY, Miller J, Gofin R, et al. Epidemiological studies on head lice infestation in Israel. I. Parasitological examination of children. Int J Dermatol. 1990;29(7):502-506.
22. Directors of Health Promotion and Education (DHPE). Head Lice. DHPE Web site. www.dhpe.org/infect/lice.html. Accessed July 3, 2010
23. Abrams TW. Department of Health and Human Services: Warning Letter to Kurt Orlofski, CEO of Morton Grove Pharmaceuticals , Inc (Lindane Shampoo). U.S. Food and Drug Administration (FDA) Web site.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementA ctivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/uc m054144.pdf. Accessed July 3, 2010
24. Murray ES, Torrey SB. Virulence of Rickettsia prowazeki for head lice. Ann N Y Acad Sci. 1975;266:25-34.
25. Weiss RA. Apes, lice and prehistory. J Biol. 2009;8(2):20.
26. Li W, Ortiz G, Fournier PE, et al. Genotyping of human lice suggests multiple emergencies of body lice from local head louse populations. PLoS Negl Trop Dis. 2010;4(3):e641.
27. Hemingway J, Miller J, Mumcuoglu KY. Pyrethroid resistance mechanisms in the head louse Pediculus capitis from Israel: implications for control. Med Vet Entomol.1999;13(1):89-96.
28. Mumcuoglu KY, Hemingway J, Miller J, et al. Permethrin resistance in the head louse Pediculus capitis from Israel. Med Vet Entomol. 1995;9(4):427-432, 447.
29. Roberts RJ. Clinical practice. Head lice. N Engl J Med. 2002;346(21):1645-1650.
30. Burgess IF, Brown CM, Lee PN. Treatment of head louse infestation with 4% dimeticone lotion: randomised controlled equivalence trial. BMJ. 2005;330(7505):1423.
31. Mumcuoglu KY. Effective treatment of head louse with pediculicides. J Drugs Dermatol. 2006;5(5):451-452.
32. Pollack RJ, Kiszewski A, Armstrong P, et al. Differential permethrin susceptibility of head lice sampled in the United States and Borneo. Arch Pediatr Adolesc Med.1999;153(9):969-973.
33. HeadLice.Org. Resistant Lice? The National Pediculosis Association, Inc. Web site. http://headlice.org/faq/treatments/pest.htm. Accessed July 3, 2010.
34. Centers for Disease Control and Prevention (CDC). Treatment. CDC Web site.www.cdc.gov/lice/head/treatment.html. Updated October 7, 2008. Accessed July 3, 2010.
35. Ovide [package insert]. Hawthorne, NY: TaroPharm, a division of Taro Pharmaceuticals U.S.A., Inc; 2005.
36. Centers for Disease Control and Prevention (CDC). Parasites and Health: Pediculosis: Treatment. CDC Web site. http://www.dpd.cdc.gov/dpdx/HTML/HeadLice.htm. Accessed July 5, 2010.
37. Meinking TL, Villar ME, Vicaria M, et al. The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (Pediculosis humanus capitis). Pediatr Dermatol. 2010;27(1):19-24.
38. Ulesfia [package insert]. Atlanta, GA : Sciele Pharma, Inc. A Shionogi Company; 2009.
39. U.S. Food and Drug Administration (FDA). FDA Public Health Advisory: Safety of Topical Lindane Products for the Treatment of Scabies and Lice. FDA Web site.www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ ucm110845.htm Updated April 30, 2009. Accessed July 4, 2010.
40. Lindane [package Insert]. Morton Grove, IL: Morton Grove Pharmaceuticals, Inc.; 2005.
41. CA Law Health and Safety Code 111246. http://leginfo.ca.gov/calaw.html. Accessed July 20, 2010.
42. Morewitz HA. Nuvo A Brief History of Head Lice. Nuvo for Head Lice Web site. http://www.nuvoforheadlice.com/history.htm. Accessed July 3, 2010.
43. Diamantis SA, Morrell DS, Burkhart CN. Treatment of head lice. Dermatol Ther. 2009;22(4):273-278.
44. Strycharz JP, Yoon KS, Clark JM. A new ivermectin formulation topically kills permethrin-resistant human head lice (Anoplura: Pediculidae). J Med Entomol. 2008;45(1):75-81.
45. Chosidow O, Giraudeau B, Cottrell J, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice. N Engl J Med. 2010;362(10):896-905.
46. Meinking TL. Clinical update on resistance and treatment of Pediculosis capitis. Am J Manag Care. 2004;10(suppl 9):S264-S268.
47. Simpson WM Jr, Schuman SH. Recognition and management of acute pesticide poisoning. Am Fam Physician. 2002;65(8):1599-1604.
48. Natural Standard Database. NaturalStandard.com Web site.http://naturalstandard.com/monographs/efficacycharts/conditionset-189-lice.asp. Accessed July 20, 2010.
49. McCage CM, Ward SM, Paling CA, et al. Development of a paw paw herbal shampoo for the removal of head lice. Phytomedicine. 2002;9(8):743-748.
50. Toloza AC, Lucía A, Zerba E, et al. Eucalyptus essential oil toxicity against permethrin- resistant Pediculus humanus capitis (Phthiraptera: Pediculidae). Parasitol Res.2010;106(2):409-414.
51. Found J. Quit Nits Advance Proof of Concept in vitro Trial Results. 2004, Data on file Wild Child (WA) Pty Ltd., a Hyland’s, Inc. company: Los Angeles, California.
52. Hormigos AGG, Sadaba B, Azanza JR. A study of effectiveness and tolerance of Quit Nits Advance after the topical administration to 100 children With Pediculosis. 2010. Data on file Wild Child (WA) Pty Ltd., a Hyland’s, Inc. company: Los Angeles, California.
53. Goates BM, Atkin JS, Wilding KG, et al. An effective nonchemical treatment for head lice: a lot of hot air. Pediatrics. 2006;118(5):1962-1970.
54. Pearlman DL. A simple treatment for head lice: dry-on, suffocation-based pediculicide. Pediatrics. 2004;114(3):e275-e279.
55. Pearlman D. Cetaphil cleanser (Nuvo lotion) cures head lice. Pediatrics. 2005;116(6):1612.
56. Pearlman D. Nuvo Method for Treating Head Lice. Nuvo for Head Lice Web site. www.Nuvoforheadlice.com. Accessed July 3, 2010.
57. HeadLice.Org. Alternative Treatments. The National Pediculosis Association, Inc, Web site. http://headlice.org/faq/treatments/alternatives.htm Accessed July 3, 2010.
58. Natural Standard Website. http://naturalstandard.com/monographs/monoframeset.asp?monograph=/monographs/herbssu pplements/quassia.asp%3Fprintversion%3Dtrue page. Updated July 14, 2010. Accessed July 15, 2010.
59. Canyon DV, Speare R. A comparison of botanical and synthetic substances commonly used to prevent head lice (Pediculus humanus var. capitis) infestation. Int J Dermatol. 2007;46(4):422-426.
60. Pollack RJ. Head lice: Information and Frequently Asked Questions. Harvard School of Public Health Web site. http://www.hsph.harvard.edu/headlice.html#malathion. Accessed July 3, 2010.
61. Pollack RJ, Kiszewski AE, Spielman A. Overdiagnosis and consequent mismanagement of head louse infestations in North America. Pediatr Infect Dis J. 2000;19(8):689-693.
62. HeadLice.Org. Press Release: National Head Lice Prevention Month. The National Pediculosis Association, Inc. Web site. www.headlice.org/news/2009/national-head-lice- prevention-month-08112009.html. Accessed July 5, 2010.