US Pharm. 2012;37(3):32-36.
Head lice (Pediculus humanus capitis) are ectoparasites, meaning that they live on or within the skin rather than inside the body. Annually, approximately 6 to 12 million U.S. children aged 3 to 11 years become infested with head lice.1 Lice infestations are a substantial economic burden on the health care system. Although difficult to assess, the annual direct and indirect costs of infestations, including treatment, lost wages, and school-system expenses, are estimated to be $1 billion.2,3
Preschool-age and school-age children are most commonly infested, with household members also at increased risk.2 Not only is lice infestation a nuisance, but if it is left untreated, it may result in a secondary bacterial infection. Infestation has nothing to do with hygiene practices or hair length, nor do lice transmit disease.2 Despite these facts, the social stigma, embarrassment, and anxiety resulting from infestation can be considerable for both the child and the parent(s).2,4
Background
Louse saliva, which contains vasodilators and anticoagulants, is injected into the host while the louse is feeding on the host’s blood. The host usually develops a sensitivity to the saliva, resulting in pruritus; however, it may take 4 to 6 weeks for the sensitivity and itching to manifest.2
The adult head louse is tan to grayish-white and 2 to 3 mm long (about the size of a sesame seed), with six legs. The female louse can live 3 to 4 weeks, and upon maturation she can lay up to 10 eggs per day. The eggs, which are cemented to the base of the hair shaft approximately 4 mm from the scalp, are pigmented to match the hair color of the host, rendering them difficult to see. Eggs farther than 1 cm from the scalp likely are not viable. Once hatched, the eggs are easier to see, as the empty casings appear white. The term nit denotes the empty casing; however, some experts also use the term to describe the viable egg containing the nymph.2
The life cycle of head lice consists of three phases: 1) egg without an eyespot (the eyespot signifies a developed nervous system), 2) egg from time laid to time hatched, and 3) nymph (newly hatched louse) to mature egg-laying louse. From the time of laying, an egg takes an average of 4 days to develop an eyespot and 8.5 days to hatch. It takes a nymph an average of 9.7 days to develop into a mature egg-laying adult.4 Once mature, the female louse can mate and lay eggs in approximately 1.5 days. Eggs cannot hatch at room temperature; they need body heat to incubate.2 Even under optimal conditions, 10% to 30% of eggs fail to hatch.5
Transmission
Lice usually cannot survive away from the host for 24 hours. Lice do not hop or fly; they can only crawl. However, there have been some reports of lice being ejected from the scalp as a result of static buildup from brushing dry hair. Transmission usually occurs from direct head-to-head contact, and rarely from contact with the infested individual’s brush, comb, or hat.2
Diagnosis
Since lice avoid light and crawl quickly, it is difficult to detect a live louse on the scalp. A quicker, more efficient way to diagnose head lice infestation is to use a nit comb.2 Compared with direct visualization, using a nit comb reduces the number of false negatives.3 Some experts believe that the use of a lubricant, such as oil, conditioner, or water, slows the lice down and facilitates diagnosis.2
Usually it is easier to see eggs at the nape of the neck or behind the ears.2 A diagnosis of lice infestation should not be based on detection of nits alone. When diagnosis is made by the detection of nits alone, up to 66% of children are treated unnecessarily. Treatment should not be administered if living lice cannot be found.3
Prevention
Preventing head lice is difficult, especially in young children. Avoiding head-to-head contact is the surest way to prevent transmission. Children should be taught not to share personal items such as combs, brushes, and hats. Prompt treatment of infested individuals can aid in prevention.2
Treatment
The optimal treatment would be readily available, easy to use, effective and safe, affordable, and non–resistance-promoting.2 Prophylactic treatment is not recommended.3 OTC and prescription-only medications are approved for use in the U.S.2 These products, which are pediculicidal (kills live lice only) or ovicidal (kills lice and eggs), act either on the louse’s nervous system or as occlusive agents.6
Many reports exist of resistance to the OTC agents; however, in the case of treatment failure, improper use by the patient should be suspected first. Some experts recommend removing nits with a nit comb after treatment.2
Based on life cycle, pediculicidal agents that act on the nervous system ideally should be applied twice. The first application kills all hatched lice. Nine days later (rather than 7 days, as some manufacturers recommend), a second application kills all newly hatched eggs not killed with the first application. If the second application is done on day 7, some eggs laid just before the first application have not yet hatched, based on the average hatching time of 8.5 days.4
Indicated Medications
See TABLE 1 for application instructions.
Permethrin 1% (Nix): Available OTC, permethrin is the least toxic of the pediculicides. The American Academy of Pediatrics (AAP) considers permethrin the first-line treatment of choice. It causes hyperstimulation of the nervous system of lice, resulting in paralysis and death.4 Widespread resistance to permethrin has been reported, but the prevalence is unknown.2 Resistance tends to vary geographically.4
Permethrin leaves a residue on the hair that can kill any nymphs remaining after the first application. The use of conditioners and hair products with silicone-based additives may hinder permethrin’s adherence to the hair shaft and impair the residual effect. Adverse effects include pruritus, erythema, and edema.2
Pyrethrins With Piperonyl Butoxide (PBO) (RID): This product is available OTC. Pyrethrin is extracted from the chrysanthemum flower and then formulated with PBO. Individuals who are allergic to ragweed may react to pyrethrins, although this is rare.2 PBO works synergistically by inhibiting the louse enzymes that catabolize pyrethrins, thus extending pyrethrins’ action.4
Pyrethrins with PBO are not completely ovicidal, and 20% to 30% of eggs will remain viable and hatch. This warrants a second treatment, ideally on day 9. Unlike permethrin, pyrethrins with PBO have no residual activity.2
Resistance to pyrethrins with PBO has been demonstrated; however, the prevalence is unknown. Resistance seems to differ from community to community and from country to country.2
Malathion (Ovide): Available by prescription only, malathion was reintroduced in 1999 after being removed from the market two different times based on concerns about its long application time, flammability, and odor.2 Malathion is an organophosphate that inhibits cholinesterase activity, resulting in increased acetylcholine concentrations.7 The excess cholinergic activity causes hyperstimulation of the louse nervous system and prevents feeding.4
Malathion is highly ovicidal, and a single application is sufficient for most patients.2 Superior activity over 1% permethrin has been demonstrated.8,9 Because of the increased permeability of infant scalps, malathion is contraindicated in neonates and infants.7 Malathion has not been studied in children aged less than 6 years, and it is contraindicated in children aged 24 months and younger.2 The drug is Pregnancy Category B.7
Resistance has been reported in the United Kingdom, but the UK formulation differs from that used in the U.S. The U.S. formulation contains terpineol, dipentene, and pine needle oil, all of which are pediculicidal, and the combination of these ingredients with malathion is thought to have delayed resistance in the U.S.2
The U.S. formulation contains 78% isopropyl alcohol, which renders it highly flammable. Patients should be counseled to avoid high temperatures and open flames (e.g., hair dryers, cigarettes) while the hair is still wet.7
Adverse effects include a slight stinging sensation; however, because inadvertent transdermal absorption has occurred in agricultural use, the patient should be monitored for signs of excessive cholinergic activity, including increased sweating, salivary and gastric secretions, gastrointestinal and uterine motility, and bradycardia.7
Benzyl Alcohol (Ulesfia): Approved by the FDA in April 2009, benzyl alcohol is available only by prescription. Benzyl alcohol is not neurotoxic or ovicidal; it is an occlusive agent and kills lice by asphyxiation.2,10 Because lice can close their respiratory spiracles when they are submerged in water or other occlusive agents, it is difficult to suffocate them.11 The benzyl alcohol in Ulesfia prevents the lice from closing the spiracles and allows the vehicle (containing mineral oil and inactive ingredients) to penetrate and obstruct them, resulting in asphyxiation.10
Ulesfia is approved for children older than 6 months and is Pregnancy Category B. The most common adverse effects include ocular irritation, application-site irritation, application-site anesthesia, and hypoanesthesia.10
Spinosad (Natroba): Spinosad, an ovicidal agent, was approved by the FDA in January 2011. Spinosad is indicated for use in patients aged 4 years and older.12,13 The drug is derived through the fermentation of Saccharopolyspora spinosa, a soil Actinomycete bacterium.12,14 The mechanism of action (MOA) is hyperexcitability of the louse nervous system that results in paralysis and death.12
In two clinical studies evaluating the efficacy of spinosad and permethrin under actual-use conditions (in the home), spinosad without nit combing was superior to permethrin with nit combing (study 1, 84.6% vs. 44.9%; study 2, 86.7% vs. 42.9%) for complete lice eradication 14 days after the last treatment. Most spinosad patients required only one application (63.8% and 86.2% in studies 1 and 2, respectively); most permethrin patients required two treatments (60.3% and 64.5% in studies 1 and 2, respectively).13 These data suggest that spinosad is more effective and convenient than permethrin.
This product contains benzyl alcohol and is classified as Pregnancy Category B. The most common adverse reactions (≥1%) are application-site erythema, ocular irritation, and application-site irritation.12
Lindane: This product is indicated for the treatment of head lice. With gross misuse, lindane causes neurotoxicity in humans, and seizures have been reported in children. The AAP does not recommend the use of lindane, and the drug has been banned in California.2
Off-Label Medications
Ivermectin (Stromectol): Ivermectin is an anthelmintic agent structurally similar to macrolide antibiotics, but with no antibacterial activity. A single dose of 200 mcg/kg given orally and repeated 10 days later has been shown to be effective against head lice.2 A recent study found a dose of 400 mcg/kg given on days 1 and 8 to be more effective than malathion.15
A neurotoxic drug, ivermectin causes central nervous system (CNS) hyperstimulation, resulting in paralysis and death.16 Although ivermectin does not readily cross the blood–brain barrier, young children may be susceptible to CNS adverse effects.2,16 Children weighing less than 15 kg should not receive ivermectin.16
On February 7, 2012, the FDA approved a topical ivermectin lotion for the treatment of lice in patients aged 6 months and older.17
Sulfamethoxazole/Trimethoprim (SMZ/TMP) (Bactrim): This agent is used off-label to treat head lice. Although the MOA is unknown, SMZ/TMP is thought to eradicate symbiotic bacteria in the louse gut.2 In one study, SMZ/TMP (10 mg/kg/day in 2 divided doses) administered for 10 days with permethrin 1% was superior to both SMZ/TMP and permethrin alone at 2 weeks (95%, 83%, and 79.5%, respectively) and 4 weeks (92.5%, 78%, and 72%, respectively).18
Occlusive Agents
There is anecdotal evidence that substances such as mayonnaise, margarine, herbal oils, and olive oil act as occlusive agents and are effective.2 Dimethicone products have been clinically shown to have ovicidal properties. The product kills eggs by obstructing their aeropyle (similar to obstructing the louse’s respiratory spiracles).19 Available OTC, LiceMD is formulated with dimethicone.2
Nonpharmacologic Treatment
Shaving the head is an effective means of eradicating lice; however, for cosmetic reasons, it is an undesirable option.2 Wet combing with nit combs is an attractive alternative to insecticides for some parents. Combing may be facilitated by using shampoo or conditioner as a lubricant; however, evidence is insufficient to conclude that this is an effective method for eradicating lice.20
School Screening and the “No Nits” Policy
The No Nits policy is based on the premise that all nits are viable eggs. Based on this logic, all children with live lice or nits are immediately dismissed from school or other institutions (e.g., day care). This can cause considerable distress for both the child and the parent(s).3 The economic burden resulting from the No Nits policy can be hefty, including loss of wages and/or the cost of a babysitter.6
Children at higher risk for developing an active infestation have five or more nits within one-quarter inch of the scalp; however, only about one-third of these cases actually convert to an active infestation.2,5 One study reported that only 31% of children with visible nits had active lice infestation, and only 18% of those with nits alone went on to develop an active infestation within 14 days.5
Because of the low conversion to active infestation, as well as the low risk of transmitting lice in the school setting, the AAP recommends abandoning the No Nits policy.2,5 The AAP advises that children with signs or symptoms be checked by the school nurse. Since an active infestation has probably existed for at least a month before the child experiences signs or symptoms, the AAP recommends that the child remain in class but be discouraged from coming in close contact with others. The child’s parents should be notified that day so that appropriate treatment may be administered promptly. Sending home a child who has a serious infestation should be left to the discretion of the school nurse. Any children likely to have had head-to-head contact with the afflicted individual should be checked for lice.2 Infested children should be allowed to return to school immediately after the initial treatment.3
Conclusion
Lice infestation is common, and the patient or caregiver may seek help from the pharmacist first. The pharmacist is poised to recommend products and to counsel regarding their proper use. See TABLE 2 for counseling points.
REFERENCES
1. CDC. Head lice. www.cdc.gov/parasites/lice/head/index.html. Accessed February 1, 2012.
2. Frankowski BL, Bocchini JA Jr. Head lice. Pediatrics. 2010;126:392-403.
3. Mumcuoglu KY, Meinking TA, Burkhart CN, Burkhart CG. Head louse infestations: the “no nit” policy and its consequences. Int J Dermatol. 2006;45:891-896.
4. Lebwohl M, Clark L, Levitt J. Therapy for head lice based on life cycle, resistance, and safety considerations. Pediatrics. 2007;119:965-974.
5. Williams LK, Reichert A, MacKenzie WR, et al. Lice, nits, and school property. Pediatrics. 2001;107:1011-1015.
6. Gur I, Schneeweiss R. Head lice treatments and school policies in
the US in an era of emerging resistance: a cost-effectiveness analysis. Pharmacoeconomics. 2009;27:725-734.
7. Ovide (malathion) product information. Hawthorne, NY: TaroPharma; July 2005.
8. Meinking TL, Vicaria M, Everdam DH, et al. Efficacy of a reduced
application time of Ovide lotion (0.5% malathion) compared to Nix crème
rinse (1% permethrin) for the treatment of head lice. Pediatr Dermatol. 2004;21:670-674.
9. Meinking TL, Vicaria M, Eyerdam DH, et al. A randomized,
investigator-blinded, time-ranging study of the comparative efficacy of
0.5% malathion gel versus Ovide Lotion (0.5% malathion) or Nix Crème
Rinse (1% permethrin) used as labeled, for the treatment of head lice. Pediatr Dermatol. 2007;24:405-411.
10. Ulesfia (benzyl alcohol) product information. Atlanta, GA: Shionogi Pharma, Inc; June 2010.
11. 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;27:19-24.
12. Natroba (spinosad) product information. Carmel, IN: ParaPRO LLC; January 2011.
13. Stough D, Shellabarger S, Quiring J, Gabrielsen AA Jr. Efficacy
and safety of spinosad and permethrin creme rinses for pediculosis
capitis (head lice). Pediatrics. 2009;124:e389-e395.
14. Spinosad (Natroba) topical suspension for head lice. Med Lett Drugs Ther. 2011;53:50-51.
15. Chosidow O, Giraudeau B, Cottrell J, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice. N Engl J Med. 2010;362:896-905.
16. Stromectol (ivermectin) product information. Whitehouse Station, NJ: Merck & Co, Inc; May 2010.
17. Sklice (ivermectin) product information. Swiftwater, PA: Sanofi Pasteur Inc; February 2012.
18. Hipolito RB, Mallorca FG, Zuniga-Macaraig ZO, et al. Head lice
infestation: single drug versus combination therapy with one percent
permethrin and trimethoprim/sulfamethoxazole. Pediatrics. 2001;107:e30.
19. Heukelbach J, Sonnberg S, Becher H, et al. Ovicidal efficacy of
high concentration dimeticone: a new era of head lice treatment. J Am Acad Dermatol. 2011;64:e61-e62.
20. Tebruegge M, Runnacles J. Is wet combing effective in children with pediculosis capitis infestation? Arch Dis Child. 2007;92:818-820.
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