Update on pharmacotherapy of head lice

September 2004

With a new academic year upon us, this month’s Pharmacology Consult will review the therapy of head lice infection. Head lice infestation is a common problem among school children, and while several drug therapies are available, the potential for head lice to develop resistance to these therapies has created new difficulties in selecting the most effective therapy for a child.

Resistance

The potential for head lice to develop resistance to the commonly used pediculicides complicates selection of an effective agent for treatment. While resistance is well documented in the literature, methods to assess resistance have not been standardized. This increases the difficulty for clinicians in selecting effective treatments, as the prevalence and patterns of resistance in a specific geographical area are unlikely to be well defined. When caregivers complain that over-the-counter (OTC) therapies failed to eradicate their child’s head lice infestation, clinicians must evaluate if resistance is truly present, or if the therapies were not applied properly or reinfestation has occurred.

Several recent studies have evaluated head lice resistance to common therapies. Meinking evaluated the pediculicidal and ovicidal activity of five common products (Ovide [malathion, Medicis], RID [synergized pyrethrin, Pfizer], A-200 [synergized pyrethrin, Hogil], lindane and Nix [permethrin, Insight]) on head lice taken from children in Panama. These head lice had been previously tested and found to be sensitive to permethrin. These results were compared with a previous study of the same pediatric population in 1984, and the authors additionally sought to evaluate whether changes in product formulation had contributed to product efficacy. Overall, malathion was the most pediculicidal and ovicidal agent, and lindane was the least effective. A-200, Nix and RID were evaluated as effective at killing most lice and their eggs. Meinking again evaluated the above commonly available pediculicides in a study employing similar methodology, yet using lice from children from a south Florida population, where lice had been reported to be resistant to permethrin and lindane. Ovide was found to be the most effective pediculicide, killing 100% of lice tested in 20 minutes. The next most effective product, A-200, killed 60% of lice tested in 20 minutes. RID, despite containing the same active ingredient as A-200 (synergized pyrethrin), was effective at killing only 8% of lice in 20 minutes. Nix killed 8% of tested lice in 20 minutes. Lindane was the least effective product evaluated, killing only 2% of lice in 20 minutes. It is important to keep in mind that Nix, RID and A-200 are labeled for 10-minute application times, which suggests a likelihood of product failure when used in a population of head lice as tested in this study. The researcher attributes differences between A-200 and RID to recent changes in formulation, namely the absence in RID of benzyl alcohol, which may contribute to product efficacy. When compared to Meinking’s previous study published in 2001, killing power for all tested products, with the exception of Ovide, was decreased (P <.05), providing evidence for the development of resistance.

Yoon compared the pediculicidal activity of Ovide with that of Nix in permethrin-resistant lice by in vitro analysis. This study confirmed resistance through DNA sequencing by assessing for the presence of resistance-type mutations, T929I and L932F. These point mutations have been associated with resistance to permethrin and increased nerve insensitivity. Lice were sampled from children in Ecuador (where pediculicides are not used), Florida (documented permethrin resistance) and Texas. Lice collected from children in Florida displayed a slower killing response to permethrin as compared with lice from Ecuador and were found to have knockdown resistance-type mutations when tested. Lice collected in Texas were slightly resistant to permethrin and displayed a 13% rate of resistant genotypes. Lice did not exhibit resistance to Ovide, which killed permethrin-resistant lice at a 10-fold increased rate as compared with Nix.

When clinicians are faced with treatment failures, prior to jumping on the “resistance bandwagon,” other reasons for treatment failure should be considered. Clinicians should assess if the product used was applied appropriately. For example, hair conditioners should not be applied prior to using Nix, as this may reduce its ovicidal activity. Infection control practices should be reviewed, as treatment failure may be due to reinfestation. An inaccurate diagnosis may also cause one to assume that products failed. A recent study (Pollack, 2000) found that of samples of suspected lice submitted to a laboratory for microscopic evaluation, more than 35% were not lice (ie, dandruff, particulate matter), and of 364 louse-derived samples submitted, only 53% were a live louse or viable egg.

Treatment recommendations

The above studies indicate that resistance to the commonly used OTC pediculicides and lindane is well documented. However, how widespread resistance is throughout the country is not well known, nor are standardized methods to assess resistance. Anecdotal reports of treatment failure primarily guide clinicians when concerns of resistance arise. Because many unknowns exist regarding resistance, it is still reasonable to continue to use OTC products such as Nix, A-200 or RID as first-line therapy. Permethrin and synergized pyrethrin function to interfere with louse neuronal sodium transport, resulting in respiratory paralysis. They have a low toxicity profile for humans. It is important for clinicians to review the appropriate use of these products in addition to reviewing infection control practices to prevent reinfestation.

If resistance is suspected, malathion should be used as second-line therapy. Studies evaluating malathion have shown it to have quick and very effective pediculicidal and ovicidal activity. Resistance to malathion has not been documented in the United States, although it has been documented in the United Kingdom. This may be a reflection of the relatively low use of malathion in this country, as it has only recently become commercially available again. Malathion has been available in the United Kingdom for a longer period. When Ovide is used, it is important that caregivers are made aware of its potential dangers, as it contains a high amount of alcohol and thus is potentially flammable. Lindane has little if any role in the treatment of head lice. Studies have documented its poor pediculicidal and ovicidal activity, and it is potentially neurotoxic. While the majority of cases of significant toxicity have involved inappropriate use (eg, multiple applications), lindane can be absorbed and has the potential for significant toxicity. It should not applied to infants. California has recently banned the use of lindane.

Other treatments are available, such as systemic ivermectin (Stromectol, Merck) or trimethoprim-sulfamethoxazole. While some evidence of efficacy exists for these products, they are not FDA-approved for this use; they involve systemic administration and thus an increased potential for adverse effects. Published treatment reviews generally do not recommend these therapies as first- or second-line treatments. Other, unconventional therapies are also available, including occlusives (eg, petroleum jelly) or natural therapies. These options have not been evaluated in controlled trials. It is interesting to note that lice may live for prolonged periods without oxygen; thus, even though smothered in petroleum jelly for one hour and perhaps appearing to be dead, they can regain full motor function once rinsed off.

Household contacts

Household and close contacts of infested children should be examined and treated if determined to have live lice. The 2003 Red Book states that affected children should not be sent home early from school or excluded, and children may return to school the day after treatment. No-nit policies in schools are not necessary. Because fomites (eg, headgear, towels) are not a major source of lice transmission, specific disinfection efforts are not always necessary.

Conclusions

Evidence exists for the development of resistance by lice to the active ingredients in OTC pediculicides. Standardized means of measuring and reporting resistance, however, do not exist. Thus, true assessments of resistance in specific geographic areas are difficult to measure. OTC pediculicides should continue to be used as first-line therapy. Clinicians should stress the appropriate use of the chosen product and review infection control practices to prevent reinfestation. Malathion should be used when first-line treatment failure does occur. Lindane should not be used. The role of alternative therapies is yet to be defined.

For more information:

• Burkhart CG. Relationship of treatment-resistant head lice to the safety and efficacy of pediculicides. Mayo Clinic Proceedings. 2004;79:661-666.
• Meinking TL. Comparative efficacy of treatments for pediculosis capitis infestations, update 2000. Arch Dermatol. 2001;137:287-292.
• Meinking TL. Comparative in vitro pediculicidal efficacy of treatments in a resistant head lice population in the United States. Arch Dermatol. 2002;138:220-224.
• Yoon KS. Permethrin-resistant human head lice, pediculus capitis, and their treatment. Arch Dermatol. 2003;139:994-1000.
• Committee on School Health and the Committee on Infectious Diseases of the American Academy of Pediatrics. Head lice. Pediatrics. 2002;110:638-643.
• Pollack RJ. Overdiagnosis and consequent mismanagement of head louse infestations in North America. Pediatr Infect Dis J. 2000;19:689-693.

• Edward A. Bell, PharmD, BCPS, is an associate professor of pharmacy practice at Drake University College of Pharmacy, and a clinical specialist at Blank Children's Hospital, Des Moines, Iowa.