Treatment of head lice: what’s new?

Octoboer 2002

With a new school year under way, a review of the treatment of head lice infestation is timely. While no new controlled trials have recently been published, the AAP has recently published a committee statement on the diagnosis and management of head lice infection (Pediatrics, September 2002). This clinical report is “must” reading for any clinician treating children infested with head lice. While the treatment section provides no new findings, the various treatment options are summarized. Perhaps even more useful is the discussion of school control measures.

Available agents and guidelines

Four agents are FDA-approved for the treatment of head lice infection: permethrin 1%, pyrethrins, malathion and lindane (table). Permethrin 1% and pyrethrin-based products are available over-the-counter (OTC), while malathion and lindane are available only by prescription. Other products have been advocated as alternative therapies, but they are not as well studied and do not have FDA-approval for the treatment of head lice (table). These products include trimethoprim-sulfamethoxazole, ivermectin, permethrin 5% and crotamiton. Other nontraditional agents have also been suggested: products described as “natural,” and occlusive agents (eg, petrolatum). Efficacy data for these therapies remain scanty.

Complicating a discussion of which agent is most effective is a general lack of controlled trials comparing one agent to another and the increasing concern over the potential for resistance by head lice. While resistance has been widely reported, resistance to these therapies has not been well defined. How the term “resistance” is used and defined, and its clinical implications, requires further study.

Permethrin 1% continues to be commonly recommended as first-line therapy and as the most effective agent available OTC. The AAP report describes permethrin as the treatment of choice, based upon expert opinion and a published systematic literature review (Vander Stichele). This published review employed defined criteria to screen the literature (through early 1995). Seven trials met the inclusion criteria and were evaluated. Permethrin was the only agent to demonstrate efficacy with cure rates above 90% in more than two studies. Malathion, which had been removed from the commercial market and now has recently been reintroduced, was assessed by the study authors as effective, albeit with limited evidence (one study). Pyrethrin products were assessed as insufficiently effective.

In another systematic review, the Cochrane Infectious Disease Group (Cochrane Database of Systematic Reviews) published its findings in 2001 of a review of randomized trials of pediculicides for the treatment of head lice. Four trials met the inclusion criteria; these trials tested permethrin, malathion and pyrethrins. It was concluded that all of these agents are comparatively effective, although caution was also expressed that this effectiveness may not include concerns over potential resistance factors.

In 2000 guidelines for treatment of head lice were published by the Working Group on the Treatment of Resistant Pediculosis (Hansen). These guidelines were based upon presentations made to the Working Group members. Either permethrin or pyrethrin-based products are recommended as first-line therapy. With both agents a second course of therapy eight to 10 days after the initial treatment is recommended to treat nits or newly hatched lice. It is further recommended to use a prescription agent as initial therapy if local resistance is a concern. These recommendations do not, however, account for the general lack of understanding and standardization of resistance patterns. Malathion is recommended by the Working Group as second-line therapy, or initially in areas where resistance is a concern. This recommendation is based upon one double-blind trial (68 patients) and an in vitro study published in 1986 comparing the pediculicidal and ovicidal activity of pyrethrins, lindane and malathion. In the latter study malathion was found to be most ovicidal. This in vitro study was similarly conducted again in Panama and the results published in 2001. Malathion was again found to be the most ovicidal and acted the quickest to kill live lice. However, permethrin 1% killed all lice after one hour to exposure (as compared with 100% killing at 10 minutes for malathion) and was only slightly less ovicidal than malathion. The Working Group guidelines assess lindane as a “last resort” therapy, because of its potential toxicity and reduced efficacy. Systemic therapies (ivermectin, trimethoprim-sulfamethoxazole) are not recommended by the Working Group, although an explanation is not given.

Lindane has generally been relegated to last on the list of alternative agents for consideration of use. Lack of efficacy and concerns over resistance are commonly found in published reports. Several in vitro studies have found lindane the least ovicidal and least effective in killing lice. The AAP document recommends that lindane be used only very cautiously. Lindane’s toxicity profile includes central nervous system involvement (seizures). These toxicities have occurred mostly when lindane has been used inappropriately (eg, excessive dosing or contact time). Lindane should not be used on premature infants or children with seizure disorders.

Malathion was reintroduced several years ago into the commercial market. In clinical and in vitro studies malathion has been found to be very effective at killing live lice and eggs. As with the other pediculicides reviewed here, resistance towards malathion has been reported. Its true incidence is not well defined. The potential for significant toxicity is greater with malathion than approved OTC treatments. Malathion is formulated as a solution in 78% isopropanol and thus may be irritating to open wounds or mucous membranes. Additionally, this relatively high alcohol content poses a significant flammable risk. When malathion is used it is imperative that these concerns and its appropriate use be discussed with the patient and caregivers.

Other therapies, both topical and systemic, have been advocated for the therapy of head lice infection that has failed treatment with the above agents: ivermectin, trimethoprim-sulfamethoxazole, permethrin 5% or crotamiton. None of these products have FDA approval for this use, and evidence for their efficacy is based on anecdotal experience or few studies. In one randomized, unblinded study, trimethoprim-sulfamethoxazole combined with permethrin 1% was found to be more effective than either trimethoprim-sulfamethoxazole or permethrin alone.

Ivermectin and trimethoprim-sulfa- methoxazole both have the potential for significant systemic adverse effects. The AAP document cautions against using ivermectin in children with weights less than 15 kg, as it may affect neural transmission centrally. Permethrin 5% (Elimite) contains the same active ingredient as the OTC product, at a five-fold increased concentration. Recommendations for its use are based upon anecdotal experience. A recent susceptibility study of head lice, using a graded array of permethrin concentration “disk assays” found a flat dose-response curve, implying that increased concentrations of permethrin may be no more effective.

Treatment failures

It may be easy for clinicians to blame treatment failures on “resistance.” However, before resistance is accepted as the cause, it is useful to consider other potential causes. Appropriate use of the initial product should be verified. The approved products described above are applied differently. For example, hair conditioners or shampoos with conditioners should not be used prior to applying permethrin 1% products, as the conditioner may coat and protect nits. Use of pyrethrin-based products necessitates a second application in seven to 10 days, to treat nits and new hatched lice. Permethrin has residual activity, with package labeling indicating that one treatment should be sufficient. Many experts, however, recommend a second treatment, especially if live lice are seen, because of growing concerns over resistance and because of permethrin’s lack of total ovicidal activity. Thus, it is important for clinicians to assess the patient’s use of the product before concluding that the lice are resistant. Reinfestation, despite adequate killing of the initial infestation, may be another cause of treatment failure. It is additionally possible that particulate matter in the child’s hair may be misdiagnosed as head lice infestation. An interesting study published in 2000 evaluated submitted samples of suspected lice or eggs. The researchers microscopically evaluated samples submitted by clinicians, the lay public or teachers. Over 35% of submitted samples were determined to be debris (eg, dandruff, scabs), and of 364 louse-derived specimens, only 53.3% included a live louse or a viable egg. Thus, many children may be treated unnecessarily and withheld from school unnecessarily. Resistance still may be an important cause of treatment failure. However, it is important to consider that resistance among head lice to the above products has not been well studied, defined or characterized. Certainly, the incidence and degree of resistance by head lice is not comparable to our understanding of bacterial resistance to antibiotics.

Conclusions

Despite the commonality of head lice infection and discussions of its treatment, relatively good data on optimal treatment regimens are scarce. The approved agents available OTC continue to be generally recommended first-line, for they have been shown to be effective. When used, it is important that these products be applied properly and their package instructions followed. A second application in seven to 10 days may be necessary. Permethrin-based products may be more effective than pyrethrin-based products. The AAP currently recommends permethrin-based products as first-line therapy. Malathion may be the agent most likely to be effective as second-line therapy. This product must be used cautiously. Although resistance to these therapies has been commonly reported, its true incidence and definition have not been well documented. Other than the potential for resistance, other causes of treatment failure may be present and should be investigated. The recently published AAP document contains useful information on nit removal and its implications for school attendance.

For more information:

• Frankowski BL, Weiner LB. Head lice. Pediatrics. 2002;110(3):638-643.
• Vander Stichele RH. Systematic review of clinical efficacy of topical treatments for head lice. Br Med J. 1995;311(7005):604-608.
• Cochrane Infectious Disease Group of The Cochrane Database of Systematic Reviews. Interventions for treating head lice. The Cochrane Library. 2001;1-45.
• Hansen RC. Guidelines for the treatment of resistant pediculosis. Contemp Pediatrics. 2000;20:4-10.
• Pollack RJ. Overdiagnosis and consequent mismanagement of head louse infestations in North America. Pediatr Infect Dis J. 2000;19:689-693.
• Pollack RJ. Differential permethrin susceptibility of head lice sampled in the United States and Borneo. Arch Pediatr Adolesc Med. 1999;153:969-973.
• Hipolito RB. Head lice infestation: single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole. Pediatrics. 2001:107:575.