Head Louse Resistance to Pediculicides: A Growing Menace

Note: This article expands on a presentation given by the author in Anchorage in 2004 at the invitation of the Environmental Protection Agency to the Commission for Environmental Cooperation North American Task Force on Lindane.

Head lice are perfectly evolved human predators. They establish and maintain residence on the human head. They copulate and reproduce on the host. The host’s blood provides their sustenance. Their success in this ecological niche exceeds perhaps any other macroorganism that preys on humans. Their prevalence far exceeds other parasites such as pinworm or hookworm. Sales of nonprescription products for head lice and school-related expenses cost U.S. citizens an estimated $350 million yearly.¹

Potential Treatment Modalities
Potential therapies for pediculosis can be separated into four broad groups: topical pesticides (also known as pediculicides), physical methods, suffocating methods, and miscellaneous approaches. These potential therapies must be examined closely in light of an emerging and little-appreciated phenomenon: an alarming trend for head lice to develop resistance to pesticides.

The Phenomenon of Resistance
Pharmacists are well aware of the phenomenon of resistance. Pathogenic microorganisms have become resistant to many antibiotics, forcing manufacturers to develop novel chemical structures in the hope that resistance will not develop. It should come as no surprise that rapidly reproducing insects such as head lice will inevitably develop resistance to the pesticides used to combat them.^2,3 The problem of resistance has been characterized as “a growing problem” that is “daunting.”^4,5 One of the dangers is that patients will resort to multiple treatments with pesticides, re-exposing children needlessly to potentially toxic chemicals.
Resistance to Lindane. Lindane users have experienced seizures, lethargy, slurred speech, and neck and extremity stiffness.^6,7 Reports of resistance have accelerated since the 1970s.^8,9 The mechanism for development of resistance is hypothesized to be alterations in amino acids located at the nerve sheath sodium channel; this phenomenon may also confer resistance to pyrethrins and permethrin.¹

Resistance to Malathion
Malathion is an odorous, flammable pesticide that must remain on hair until it is dry, perhaps 8-12 hours later. It can sting and irritate skin. Although the product marketing claims to have a residual effect, the manufacturer suggests that patients undergo a second exposure if lice remain after 7-9 days. Malathion has had a checkered marketing history in the U.S., having been known as Prioderm and Ovide. It was discontinued, but re-marketed in 1999.⁶ Treatment failures were reported as early as 1990, with early reports emanating from Australia and England, where it is a nonprescription product.^10,11,12 Early reports cited a failure rate of 8%, but reports from 1999 gave the figure as 64%.^13,14,15 In 2001, a Cochrane Review concluded that resistance was widespread in the United Kingdom; resistance in the United States has not been widely reported, but may eventually develop with continued use, given its emergence in other countries.^8,16,17

Resistance to Synergized Pyrethrins
Pyrethrins are chrysanthemum derivatives that must be synergized with piperonyl butoxide, a petroleum derivative, to retain efficacy. They cannot be used in patients allergic to ragweed. Reports of resistance to this nonprescription pesticide began in 1986, growing in scope until in 1997 the Medical Letter reported that treatment failures had become common.^18,19,20 In 1999, researchers reported that synergized pyrethrin’s efficacy was questionable in light of the accelerating number of anecdotal reports of resistance.²¹ As case reports of resistance continued to accumulate, dermatologists suggested that multiple resistance had appeared, and that those patterns would undoubtedly be seen throughout the world.^22,23
Resistance to Permethrin. Permethrin was a prescription product (Nix) in the U.S. from 1986-1990, when it became an OTC. Permethrin also has a residual effect. The first reports of resistance to permethrin emerged in 1990, with reports coming from Israel, the Czech Republic, and Britain in 1995.^10,19,24-26 In 1997, the Medical Letter stated that resistance was increasing.²⁰ It was reported in Washington State in 1998.²⁷ In 1999, it was reported to be virtually useless in the U.K.; even very high concentrations had no effect on resistant lice.^14,27,28 Allegations of resistance continued to accumulate; resistance figures as high as 87% were quoted for the U.K.^{16,17,22,29-31} A 1999 study indicated possible resistance in the United States; this was demonstrated again in 2003.^21,32 Resistance of head lice to permethrin has prompted researchers to explore other chemicals.³³ Permethrin resistance may develop through several mechanisms. If the kdr (knock-down resistance) gene is involved, no strength of permethrin will be effective, which eliminates consideration of the 5% prescription concentration (e.g., Elimite).

Resistance as a Cumulative Phenomenon
Resistance is the development of mechanisms to survive potentially deadly onslaughts. Once these successful mutations are incorporated into the DNA of the living being, they will continue to be passed to succeeding generations. The numbers of resistant organisms can only stabilize or grow in the face of continual challenge by the provocative agent. Thus, any figure for the percentage of resistant members of a population is outdated; the actual percentage of resistant louse strains can only stabilize or increase. Given the dynamic nature of organism adaptation, increase is the only logical conclusion, meaning that any figure for percentage is of necessity lower than reality.

Survey of Pharmacists
A survey of pharmacists discovered that 81.7% of respondents had encountered patients with apparent treatment failures after use of synergized pyrethrins and 78.6% following use of permethrin.³⁴ Treatment failures occurred once or twice weekly in 58.1% of pharmacists’ practices, often causing patients to treat themselves more frequently or in higher doses with pesticides.

Manufacturer Explanations of Resistance
The manufacturers of topical pesticides for lice state that they have reports of efficacy. However, lab-bred lice are different from free-living lice in the U.S. at large. Data from specially-bred lab lice populations cannot necessarily be extrapolated to the hardier lice typically found on human heads.³⁵

Manufacturers also blame the victim of resistance through suggesting the victim failed to apply the pesticide for a second time, that too little product was used, that the victim was re-exposed, by stating that the victim did not remove nits, or by stating that the victim did not clean the environment.

What is the Future of Pesticides?
At this time, no pesticide is proven to be resistance-free. To the contrary, each available pesticide has been implicated in causing resistance, which is widespread in some cases. Continued use of pesticides will undoubtedly select for resistance lice, just as continual use of antibiotics selects for resistant strains of organisms.

Physical Methods
Physical methods of head louse treatment have the greatest potential for safely and effectively halting an infestation. However, the proper techniques and products must be chosen to realize the full benefit. One of the possibilities is individual louse removal. This involves use of a bright light, magnifying glass, and blunt scissors to clip away any hair that has a nit. Live lice are removed and placed in a bag. The method is time-consuming and may miss lice and/or nits. A better method of diagnosis is the use of a nit detection/removal comb. Combing has the potential to compensate for ineffective pesticides through removal of nits.^34,36 However, in the opinion of one expert, “Unfortunately, the free plastic combs included in many product packs are as ineffective as the products.” Preliminary research has demonstrated that the LiceMeister Comb (National Pediculosis Association) is superior to other plastic and metal combs due to its unique construction, having 32 closely spaced, rigid, stainless steel teeth.²⁹ In contrast to the use of pesticides, combing with the LiceMeister presents no risk of pesticide absorption or toxicity, presents no danger to the environment, and can simultaneously detect and treat an infestation.

Suffocating Methods
In desperation, frustrated parents and caregivers may turn to alternate louse control methods that are of unknown safety and/or efficacy. Some are unpleasant for victims. They include covering the head with olive oil, petrolatum (left on overnight under a shower cap), full-fat mayonnaise (also left on overnight), hair styling gel, salad dressings (overnight covered with plastic wrap), baby oil, or mineral oil. Removal of the normal amount of oil from one’s hair with shampoo is fairly simple; removal of a jar of petrolatum is infinitely harder. Washing the hair several times with harsh shampoos may leave the scalp more irritated than the louse infestation itself.

Miscellaneous Methods
Numerous unproven methods have been marketed, including homeopathic products containing diluted salt water (Licefreee!), one containing dimethicone (Rid Pure Alternative) and others containing herbs such as rue, tea tree oil, paw paw, sage, rosemary, thyme, pennyroyal, and essential oils. One product claims to make nits visible by means of a “neon” aerosol, which is noxious to breathe when sprayed. Desperate patients may resort to potentially deadly alternatives such as gasoline, kerosene, lantern oil, and industrial strength diazinon. The first three often explode, killing and maiming users. The latter caused irreversible brain damage when applied to the head of a child. Pharmacists must advise against unproven and unsafe methods whenever they are asked about their use.

Advice to Patients: What To Do About Head Lice?

Head lice on your children—it’s more than embarrassing. Control of these parasites can be difficult, time-consuming and frustrating, especially if you use the wrong products.

What to Avoid
You should avoid most products commonly sold for head lice. First are the shampoos. Some are prescription, and you can buy others in any pharmacy. Head lice in certain areas have become resistant to them. In other words, some head lice have developed the ability to live through the shampoos. This means that they cannot work, even if you use them exactly as recommended. Never use them in higher doses or more often than recommended, as they may be dangerous to your children. You should avoid them altogether.

There are also sprays to treat the environment, pillows, beds, and mattresses. Any head lice away from the head will die shortly since they cannot get the blood they need to survive. You can vacuum thoroughly if you wish, but you should not use sprays. Your child might breathe them in all night if you cover the mattress and pillows with them. They are of unknown safety.

Also avoid products that promise to kill or remove lice, but contain nothing more than diluted table salt in water (labeled as natrum muriaticum), neon paint, dimethicone and others containing herbs such as rue, tea tree oil, paw paw, sage, rosemary, thyme, pennyroyal, and essential oils. None of these is yet proven safe and effective.

Avoid so-called “suffocating treatments” that force you to cover the head with olive oil, salad dressing, full-fat mayonnaise, petrolatum, and other thick, gooey or oily substances. You may be forced to leave them on overnight underneath several layers of plastic wrap. Removal of these greasy oils can involve several courses of regular shampoo, which can irritate the scalp. These methods have never been proven to kill head lice in any case.

Never resort to potentially deadly treatments such as gasoline, kerosene and lantern oil. These have all exploded in flash fires in people’s homes, killing them and causing severe burns. Never use any type of garden or pet insecticide, and never use any industrial strength chemicals.

What to Use
Evidence suggests that combing can safely and effectively stop head lice. However, most plastic or metal combs do not do the job as promised. Existing evidence points to one comb that is superior to others because of its construction. Known as the LiceMeister Comb, it is the only comb which has a set of metal teeth in a permanently sealed handle. It is inexpensive, and can be re-used, since it can be boiled between uses. When you comb through a child’s (or adult’s) hair according to the directions provided, this comb can treat lice by removing the live lice and their eggs. It is available from your pharmacy and by contacting www.headlice.org/licemeister/. This is the address of the National Pediculosis Association, the only nonprofit health and information organization dedicated to stopping the use and abuse of dangerous chemicals on children’s heads.

“What About Public Lice?”

Pharmacists are often asked to help treat pubic lice. It is vital to remember that nonprescription permethrin (Nix) has not been found effective for pubic lice, and is not labeled for this. The only other nonprescription alternative is synergized pyrethrins. However, as one would expect, resistance is also an issue, as evidence by one case report. A 43-year-old male with adult lice and nits in the pubic area was treated with synergized pyrethrins, but the infestation persisted.37 While 5% permethrin cream was eventually successful in this case, resistance may eventually emerge to this product also.
 

W. Steven Pray, Ph.D., D.Ph.
Bernhardt Professor of Nonprescription Drugs and Devices
College of Pharmacy Southwestern Oklahoma State University
Weatherford, OK 73096

e-mail steve.pray@swosu.edu for more details

REFERENCES

1. Jones KN, English JC III. Review of common therapeutic options in the United States for the treatment of pediculosis capitis. Clin Infect Dis. 2003; 36 (11):1355-1361.
2. Burgess IF. Human lice and their control. Annu Rev Entomol. 2004;49:457-481.
3. Wendel K, Rompalo A. Scabies and pediculosis pubis: An update of treatment regimens and general review. Clin Infect Dis. 2002; 35 (Suppl 2): S146-S151.
4. Heukelbach J, Feldmeier H. Ectoparasites—The underestimated realm. Lancet. 2003; 363 (9412):889-891.
5. Ko LJ, Elston DM. Pediculosis. J Am Acad Dermatol. 2004; 50(1):1-14.
6. Anon. Malathion for treatment of head lice. Med Lett. 1999; 41(1059):73-74.
7. Kassirer JP, Kopelman RI. Lest we become smug. Hosp Pract. 1990; 25(7):33-35, 39, 47.
8. 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. 2002; 138(2):220-224.
9. Meinking TL, Taplin D. Advances in pediculosis, scabies, and other mite infestations. Adv Dermatol. 1990; 5:131-150.
10. Goldsmid JM. Head louse treatment: Is there an insecticide resistance problem? (Letter) Med J Aust. 1990; 153(4):233-234.
11. Kyle DR. Comparison of phenothrin shampoo and malathion lotion in the treatment of head louse infection. J Roy Soc Hlth. 1990; 110(2):622-63.
12. Burgess I. Malathion lotions for head lice—a less reliable treatment than commonly believed. Pharm J. 1991;247:630-632.
13. Chosidow O, Chastang C, Brue C, et al. Controlled study of malathion and d-phenothrin lotions for Pediculus humanus var capitis-infested schoolchildren. Lancet. 1994; 344(8939-8940):1724-1727.
14. Downs AMR, Stafford KA, Coles GC. Head lice: Prevalence in schoolchildren and insecticide resistance. Parasit Today. 1999; 15(1):1-4.
15. Downs AMR, Stafford KA, Harvey I, Coles GC. Evidence for double resistance to permethrin and malathion in head lice. Br J Derm. 1999; 141(3):508-511.
16. Downs AM, Stafford KA, Hunt LP, et al. Widespread insecticide resistance in head lice to the over-the-counter pediculocides in England, and the emergence of carbaryl resistance. Br J Dermatol. 2002; 146(1):88-93.
17. Dodd CS. Interventions for treating headlice. Cochrane Database Syst Rev. 2001(2); CD 001165:1-1-44.
18. Rasmussen JE. Pediculosis: Treatment and resistance. Adv Dermatol. 1986; 1:109-125.
19. 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.
20. Anon. Drugs for head lice. Med Lett. 1997; 39(992):6-7.
21. 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.
22. Bailey AM, Prociv P. Persistent head lice following multiple treatments: Evidence for insecticide resistance in Pediculus humanus capitis. Australas J Dermatol. 2000; 41(4):250-254.
23. de Berker D, Sinclair R. Getting ahead of head lice. Austral J Dermatol. 2000; 41(4):209-212.
24. Rupes V, Moravec J, Chmela J, et al. A resistance of head lice (Pediculus capitis) to permethrin in Czech Republic. Centr Eur J Pub Hlth. 1995; 3(1):30-32.
25. Anon. Concern over development of resistance to pyrethroid head lice treatments. Pharm J. 1995; 255:490.
26. Burgess IF, Peock S, Brown CM, Kaufman J. Head lice resistant to pyrethroid insecticides in Britain. (Letter) BMJ. 1995; 311(7007): 752
27. Bell TA. Treatment of Pediculus humanus var. capitis infestation in Cowlitz County, Washington, with ivermectin and the LiceMeister Comb. Pediatr Infect Dis J. 1998; 17(10): 923-924.
28. Dawes M, Hicks NR, Fleminger M, et al. Evidence based case report: Treatment for head lice. BMJ. 1999; 318(7180):385-386.
29. Picollo MI, Vassena CV, Mougabure Cueto GA, et al. Resistance to insecticides and effect of synergists on permethrin toxicity in Pediculus capitis (Anoplura: Pediculidae) from Buenos Aires. J Med Entomol. 2000; 37(5):721-725.
30. Dodd C. Treatment of head lice. BMJ. 2001; 323(7321):1084.
31. Meinking TL, Clineschmidt CM, Chen C. et al. An observer-blinded study of 1% permethrin creme rinse with and without adjunctive combing in patients with head lice. J Pediatr. 2002; 141(5):665-670.
32. Yoon KS, Gao JR, Lee SH, et al. Permethrin-resistant human head lice, Pediculus capitis, and their treatment. Arch Dermatol. 2003; 139(8): 994-1000.
33. Mougabure Cueto G, Gonzalez AP, Vassena CV, et al. Toxic effect of aliphatic alcohols against susceptible and permethrin-resistant Pediculus humanus (Anoplura: Pediculidae). J Med Entomol. 2002; 39(3): 457-460.
34. Pray WS. Pediculicide resistance in head lice: A survey. Hosp Pharm. 2003: 38(3):241-246.
35. Burgess IF. Shampoos for head lice treatment—Comparative in vitro tests. Pharm J. 1996; 257: 188-190.
36. Burgess IF. Human lice and their management. Adv Parasitol. 1995; 36:271-342.
37. Speare R. A case of pubic lice resistant to pyrethrins. Aust Fam Physician. 2001; 30(6):572-574.

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