Trying To Keep Ahead of Lice: A Therapeutic Challenge

C. E. Malcolm, MD, CCFP¹ and J. N. Bergman MD, FRCPC²
1. University of British Columbia Student Health Services, Vancouver, Canada
2. Department of Dermatology and Skin Science, University of British Columbia, and The Pediatric Allergy Dermatology Centre (PADC), Vancouver, Canada

ABSTRACT

Pediculosis capitis, or head lice, is a world-wide public health concern affecting persons of all ages and socioeconomic backgrounds. It is caused by Pediculus humanus capitis, an obligate ectoparasite that lives on human hair and feeds on the blood from the skin. Upon diagnosis, treatment should be initiated, since established infestations with head lice generally do not spontaneously resolve. Chemical pediculicides are currently the standard treatment, however, issues of resistance have made it necessary to explore new alternatives. If an infestation is resistant to these drugs, then the physician should consider treating with an agent from a different class of pediculicides or, potentially, with newer nonpediculicides.

Key Words: pediculosis capitis, head lice, pediculicide

In the US, the number of head lice infestations annually is estimated between 6–12 million among children 3–12 years of age.¹ The social, economic and educational impact of head lice infestations is considerable. In the US, the total direct costs for treatment and indirect costs for lost wages, educational programs, and school and nursing home monitoring programs have been estimated at more than $1 billion annually.²

Infestation is most common in school-aged children with girls being more commonly affected than boys. African-American children are less often affected; this variation is thought to be the result of differences in the hair shaft structure, which may be oval shaped and thus more difficult for a louse to grasp.¹ Transmission of head lice most commonly occurs through close physical contact, especially head-to-head contact, but fomites, such as hats also play a role. Louse transfer has been found to be optimal when hairs are relatively stationary and parallel, suggesting that louse transmission is more likely to occur while children are at rest, than during periods of vigorous play.³

Head lice infestation is caused by the obligate ectoparasite Pediculus humanus capitis, a wingless, elongated, dorsoventrally flattened insect. The adult louse feeds 4–5 times/day and can normally only survive for 1–2 days away from the scalp. Eggs are glued to the hair in egg castings, or nits, close to the scalp and can survive up to 10 days away from the human host. Lice typically lay nits within 1–2mm of the scalp and for practical purposes, nits within 1cm of the scalp should be counted as a sign of active infestation.⁴

Clinical Presentation

Although some children with infestation are asymptomatic, the most common symptom is pruritus, which occurs due to sensitization to either louse salivary or fecal antigens and may be so intense that excoriations and secondary bacterial infection may occur.⁵

Many children with an active infestation will, on exam, have nits attached to their hair and some live lice on their scalp. The diagnostic gold standard for head lice is finding a live louse or nymph on the scalp or a viable egg attached to the hair.⁵ Nits alone are not proof of active infection because some of these represent hatched empty shell casings or nonviable eggs that may retain a viable appearance for weeks after death. Microscopic examination of the nit, or use of a hand lens, may aid in this determination.⁴ Since lice move rapidly, not finding a louse does not completely rule out infestation. The use of louse combs increases the diagnostic yield.³ If head lice is diagnosed, then it should be treated, since established infestations, in general, do not spontaneously resolve.

Treatment

The ideal treatment agent for lice would be free of harmful chemicals, readily available without a prescription, easy to use, and inexpensive.⁵ Chemical pediculicides are currently the standard treatment.

Prior to the emergence of resistance, the treatment of choice in North America was permethrin 1% due to its safety and efficacy. Unfortunately resistance to permethrin and lindane is common in populations where these pediculicides have been heavily used.³ To illustrate this, the insecticidal activity of pyrethroids in the mid 1980s was 100%, but by 2000 it had decreased to only 28%.⁶ Conversely Meinking, et al., in a recent study, showed 1% lindane was the slowest and least effective pediculicide with no lice eradicated after 10 minutes (the recommended application time), and killing only 17% of lice after 3 hours.⁷ Malathion (Ovide^®, Taro Pharmaceuticals), which had not been used extensively in the US, has performed well in permethrin-resistant populations.³ Lice resistance to both pyrethrin and malathion has been documented in the UK (Downs, et al. showed a 64% failure rate for malathion).⁸ The pattern of resistance in an area generally follows the pattern of pediculicide use, and this geographic variation in sensitivities further reinforces the belief that lice adapt to toxins and develop resistance with ongoing exposure.

Treatment Failures

While treatment failures may be due to drug resistance, it is important to recognize many treatment failures are a result of reinfestation from an untreated classmate, inadequate quantity of pediculicide applied, or improper duration of product application.4 A recent paper suggested that a second treatment of the prescribed standard pediculicides (except permethrin) should be administered ideally 10 days after the start of treatment to kill all active stages of the louse.⁹ However, in practice many physicians retreat in 7 days instead of 10. Resistance should be suspected after the second treatment if live lice are still present 2-3 days after a product has been used correctly and no other cause for failure can be identified.1 If lice are present after 2 correctly applied treatments, resistance is certain.¹ Resistant infestations should be treated with an agent from a different class of pediculicides or with newer nonpediculicide agents.

Since permethrin resistance may be a relative phenomenon, some clinicians will use higher concentrations and longer durations of contact in an attempt to overcome this resistance. Whether increasing the permethrin concentration from 1% to 5% and leaving it on overnight affects the cure rate is unclear. Certainly this pattern of treatment may cause a higher rate of skin irritation, but longer contact with the same products is already used with other ectoparasites, such as scabies.

‘No nit’ policies exclude children from school unnecessarily and are not recommended.⁴ The presence of nits alone should not be the basis for exclusion of children from school. The child should be allowed to return to school or child care facilities after proper treatment.⁵

Myths and Facts

Myths about head lice are abundant and belief in these myths is often why treatments are not used properly and why people believe their lice treatment has failed. (See Table 1.)

Standard Pediculicides: Neurotoxic Agents

These agents are historically considered the standard treatment and have been the most effective treatment for head lice. This category of pediculicides is not recommended for children under 2 years of age and off-label use of these products for patients in this age range is based on clinical judgment.⁵ These products should be applied to the entire scalp. Because hair conditioner may coat the hair and protect the lice and nits, it should be avoided before product application.⁷

Permethrin

Permethrin 1% (Nix^®) is a poorly absorbed synthetic pyrethrin with pediculicidal and ovicidal activity. It blocks sodium channel repolarization of the louse neuron resulting in respiratory paralysis and death. By leaving a residue on the hair, it remains active for 2 weeks following application.⁵ After washing hair, rinsing with water, and towel drying, it is applied to the scalp and hair for 10 minutes and then rinsed out. To ensure a cure, many practitioners recommend a second treatment approximately 1 week later as any eggs not killed by first treatment will be hatching.

Permethrin-based Products

Permethrin-based products include over-the-counter (OTC) extracts of natural pyrethrins from chrysanthemums combined with piperonyl butoxide to increase stability and effect. These products are neurotoxic to lice but not ovicidal and even after two treatments viable lice and eggs may remain. These products are contraindicated in patients who are allergic to ragweed, chrysanthemums, or other permethrin products.⁵

Malathion

Malathion is an organophosphate cholinesterase inhibitor that causes respiratory paralysis of the louse. It is a fast acting pediculicide that presently has the highest ovicidal activity. It binds to the sulfur atoms of the hair, accounting for its residual effect. Malathion 0.5% can be applied for 10 minutes or overnight and repeated in 1 week. It has an unappealing odor and can cause stinging of the skin and eyes.⁵ This product should be used with caution, as its base is flammable and may lead to respiratory depression if ingested (although there are no reported cases).⁴ Currently significant resistance to this agent has not been reported in the US, but may occur with ongoing use as seen in other countries.⁸

Lindane

Lindane (gamma benzene hexachloride) 1% lotion is pediculicidal but it has limited ovicidal activity. This organochloride kills lice by causing CNS stimulation and respiratory paralysis. Given lindane’s increased side-effect potential including neurotoxicity and bone marrow suppression, it is considered a second-line treatment.5 Lindane remains on the market as an alternative when other treatments have failed. It is contraindicated in children under 2 years, pregnant women, and nursing mothers.

Oral Agents

Ivermectin

Ivermectin, an antihelminthic drug, has been suggested for off-label use in the treatment of head lice at a dosage of 200ìg/kg, repeated in 7-10 days to kill newly hatched nymphs.11 It is an effective pediculicide and the mechanism of action is thought to be on the symbiotic gram-negative bacteria that are required to digest blood. With the concern of possible neurotoxicity, the safety and efficacy of this agent for head lice remains to be established.³ No resistance has been reported to date and it may be used after failure with topical pediculicides. Treatment with this agent may benefit patients with extensive infestations or infestations with multiple types of ectoparasites.³ Oral ivermectin should not be used in children weighing less than 15kg.⁴ Topical ivermectin holds some promise but warrants further study.³

TMP/SMX

Oral TMP/SMX has been shown to be effective in small studies of off-label use.5 It presumably works by destroying the gut flora of the louse, thereby interfering with its ability to synthesize vitamin B and ultimately causing death.5 Combination therapy with topical agents may improve it's efficacy.

Non-neurotoxic Agents

Exoskeleton Integrity Dehydration Pediculicides

A new nonpesticide product containing isopropyl myristate 50% and ST-cyclomethicone 50% (Resultz™, Altana) works by dissolving the waxy exoskeleton of the louse, dehydrating them and eventually leading to their death. The first application is applied to dry hair, the scalp, and the nape of the neck; it is left in place for 10 minutes and then rinsed. A second application, 1 week later is recommended.

Based on safety and efficacy data, Health Canada has recently approved this nonprescription behind the counter product for the treatment of lice in persons aged 4 years and older. Phase II clinical trials document a higher success rate (no live lice) when compared with traditional pediculicides (57% Resultz™ vs. 22% with RID^®; 77.1% Resultz™ vs. 20% with permethrin 1%).¹⁷ Other Phase II studies have documented a 97% (28 of 29 patients) success rate.¹⁶ In studies to date, the product was well tolerated with mild local erythema or pruritus being the main side-effect (8 of 29 patients).¹⁶ Phase III clinical trials are pending. Isopropropyl myristate is a water-insoluble organic ester used as an emulsifier and emollient in low concentrations in cosmetic products such as oils, creams, lotions, makeup, lipstick, deodorants, sun screens, hair products, and nail lacquer removers.¹⁸

Dry-on Suffocation-Based Pediculicide

Nuvo^® Lotion, or dry-on suffocation-based pediculicide (DSP) (later found to be Cetaphil^® Gentle Skin Cleanser) was reported to have success rate of 96% when applied to the scalp, dried with a hair dryer (for approximately 30 minutes), and removed during the next day’s bath.¹² It was reported to work by suffocating the louses’ spiracles or breathing holes, causing death by suffocation. As reviewed in The Lancet13 and other sources,^14,15 the study did not use proper methods of diagnosing lice, was anecdotal, and was not a well-designed randomized control study. Nevertheless, the concept is novel and there may be a significant beneficial effect; therefore further studies are warranted.

Nit Agents

Further knowledge of the nit sheath, the glue by which the egg is attached to human hair, or the nit laying process may lead to the production of future treatment agents.¹⁹

Mechanical Removal

Mechanical nit removal as a treatment modality is not an appropriate method of lice eradication when used alone.20 Some authors believe that mechanical removal of nits after treatment with a pediculicide remains an important adjunct.³ Application of an 8% formic acid rinse or a 1:1 mixture of white vinegar and water followed by combing with a nit comb can aid in the removal of nits. Nit combing is the only treatment recommended for children < 2 years of age. It is labor intensive and somewhat painful.²¹

Environmental Interventions

Clothing, linen and towels should be decontaminated by hot water washing (60°C) or dry-cleaned. Combs and brushes should be treated with boiling water, alcohol, bleach, or soaked in a disinfectant solution (for example 2% Lysol^®).

All household members and close contacts should be examined and treated concurrently if infested; and the school should be notified. Bedmates should be treated prophylactically. Furniture disinfection is unnecessary since head lice generally die within 1–2 days when separated from a person.⁵

Alternative Treatments

Naturopathic products including herbal shampoos, occlusive agents (e.g., mayonnaise, margarine, and olive oil), kerosene or gasoline are largely unproven or ineffective.22 There is no evidence that the occlusive products suffocate lice and they have no pediculicidal or ovicidal effects.²² Kerosene or gasoline should never be used due to flammability and extreme hazard. Another "natural" remedy is Chick-Chack^®, containing coconut oil, anise oil, and ylang ylang oil.³ Published data is sparse and caution should be advised until more data is available.

Conclusion

Lice have developed resistance to some pediculicides and it is expected that with ongoing use these pediculicides will probably become less effective. These products can still be used effectively to treat nonresistant lice. Resistance should be suspected if live lice are still present 2–3 days after a product has been used correctly and no other cause for treatment failure can be identified. If lice are present after 2 correctly applied treatments, resistance is almost certain. Resistant infections should be treated with an agent from a different class of pediculicides or with newer non-neurotoxic agents. New products are presently in the process of being developed and tested. Over time these products may prove to be equal to or more effective/safe than the standard neurotoxic pediculicides, while at the same time minimize the problem of treatment resistant lice.

References

1. Hansen RC. Overview: the state of head lice management and control. Am J Manag Care 10(9 Suppl):S260-3 (2004 Sep).
2. Hansen RC, O’Haver J. Economic considerations associated with Pediculus humanus capitis infestation. Clin Pediatr 43(6):523-7 (2004 Jul-Aug).
3. Elston DM. Drugs used in the treatment of pediculosis. J Drugs Dermatol 4(2):207-11 (2005 Mar-Apr).
4. Frankowski BL. American Academy of Pediatrics guidelines for the prevention and treatment of head lice infestation. Am J Manag Care 10(9 Suppl):S269-72 (2004 Sep).
5. Leung AK, Fong JH, Pinto-Rojas A. Pediculosis capitis. J Pediatr Health Care 19(6):369-73 (2005 Nov-Dec).
6. Burkhart CG, Burkhart CN. Clinical evidence of lice resistance to over-the-counter products. J Cutan Med Surg 4(4):199-201 (2000 Oct).
7. Meinking TL, Serrano L, Hard B, et al. Comparative in vitro pediculicidal efficacy of treatments in a resistant head lice population in the United States. Arch Dermatol 138(2):220-4 (2002 Feb).
8. Downs AM, Stafford KA, Harvey I, Coles GC. Evidence for double resistance to permethrin and malathion in head lice. Br J Dermatol 141(3):508-11 (1999 Sep).
9. Mumcuoglu KY. Effective treatment of head louse with pediculicides. J Drugs Dermatol 5(5):451-2 (2006 May).
10. Hong CH. Treatment of head lice. Skin Therapy Lett - Pharm Ed 1(2):4-5 (2006 Sep-Oct).
11. Mazurek CM, Lee NP. How to manage head lice. West J of Med 172(5):342-5 (2000 May).
12. Pearlman DL. A simple treatment for head lice: dry-on, suffocation-based pediculicide. Pediatrics 114(3):e275-9 (2004 Sep).
13. Roberts RJ, Burgess IF. New head lice treatments: hope or hype? Lancet 365(9453):8-10 (2005 Jan).
14. Burkhart CG, Burkhart CN. Asphyxiation of lice with topical agents, not a reality…yet. J Am Acad Dermatol 54(4):721-2 (2006 Apr).
15. “Special” formula for head lice treatment-not so special, after all. Child Health Alert. 24:4 (2006).
16. Kaul N, Paulma KG, Maric A, et al. In vivo efficacy and safety of an experimental pediculicide rinse. Presented at: the 63rd Annual Meeting of the American Academy of Dermatology, New Orleans, Feb 2005.
17. Data on file – Altana Pharma.
18. National library of medicine/ NIH specialized Information Services. Household products database [online]. Available from: http://householdproducts.nlm.nih.gov/cgi-bin/household/brands?tbl=chem&id=94; accessed 2006 Nov 22.
19. Burkhart CN, Burkhart CG. Head lice: scientific assessment of the nit sheath with clinical ramifications and therapeutic options. J Am Acad Dermatol 53(1):129-33 (2005 Jul).
20. Meinking TL. Clinical update on resistance and treatment of pediculosis capitis. Am J Manag Care 10(9 Suppl):S264-8 (2004 Sep).
21. Roberts, RJ. Clinical practice. Head lice. New Engl J Med 346(21):1645-50 (2002 May).
22. West DP. Head lice treatment costs and the impact on managed care. Am J Manag Care 10(9 Suppl):S277-82 (2004 Sep).

1. Trying To Keep Ahead of Lice: A Therapeutic Challenge
2. Treatment of Acne Scarring
3. Update on Drugs and Drug News - December 2006 - January 2007