Published online May 1, 2007
PEDIATRICS Vol. 119 No. 5 May 2007, pp. 965-974 (doi:10.1542/10.1542/peds.2006-3087)
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REVIEW ARTICLE

Therapy for Head Lice Based on Life Cycle, Resistance, and Safety Considerations

Mark Lebwohl, MD, Lily Clark, MD and Jacob Levitt, MD

Department of Dermatology, Mount Sinai School of Medicine, New York, New York


   ABSTRACT
TOP
 ABSTRACT
LIFE CYCLE OF HEAD...
 GENERAL THERAPEUTIC...
 THERAPEUTIC OPTIONS
 CONCLUSIONS
 REFERENCES
 
The timing of head lice maturation most favorable to their survival in the presence of anti-lice agents is the maximum time as an ovum (12 days) and the shortest possible time of maturing from newly hatched nymph to egg-laying adult (8.5 days). Pediculicides that are not reliably ovicidal (pyrethroids and lindane) require 2 to 3 treatment cycles to eradicate lice. Ovicidal therapies (malathion) require 1 to 2 treatments. Treatment with an agent to which there is genetic resistance is unproductive. In the United States, lice have become increasingly resistant to pyrethroids and lindane but not to malathion. Treatment with malathion has favorable efficacy and safety profiles and enables the immediate, safe return to school. Nit combing can be performed adjunctively. No-nit policies should be rendered obsolete.

Key Words: head lice • malathion • resistance • life cycle

Abbreviations: MRSA—methicillin-resistant Staphylococcus aureus • GABA—{gamma}-amino butyric acid • FDA—US Food and Drug Administration • OTC—over-the-counter

Traditional pharmacological therapies for the human head louse, Pediculus humanus var. capitis, have focused on 1 or 2 courses of various ovicidal and pediculicidal topical therapies. Head lice, within the past 20 years, have developed resistance to nearly all first-line pharmacotherapy in the United States. The American Academy of Pediatrics recommends permethrin 1% as first-line treatment for head lice, a medicine for which resistance in the United States is extensively documented.1–4

Head lice infestations are not merely a nuisance. Untreated infection can lead to poor sleep and excoriation, which can occasionally become superinfected with methicillin-resistant Staphylococcus aureus (MRSA) or streptococcus.5–7 Social stigma, embarrassment, low self-esteem, and disgust often plague patients. Finally, from a purely functional aspect, many schools prevent children with nits from attending school. One study estimated that in 1998, 12 to 24 million days of school were lost secondary to no-nit policies.8 Such policies result in absenteeism, lost work for parents, missed education for the child, and needless anxiety. In addition, head lice carry a large economic burden. It is estimated that pharmacotherapy alone for head lice infestations costs the US economy up to $240 million per year. Estimates for combined direct and indirect costs may be as high as $1 billion per year.9


   LIFE CYCLE OF HEAD LICE
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 ABSTRACT
 LIFE CYCLE OF HEAD...
GENERAL THERAPEUTIC...
 THERAPEUTIC OPTIONS
 CONCLUSIONS
 REFERENCES
 
Until recently, the life cycle of the human head louse has been difficult to quantify because of environmental variance and the unavailability of in vitro rearing systems. From a practical perspective, one can view the life cycle of Pediculus humanus var. capitis as follows: (1) egg without an eyespot (the eyespot indicating a developed nervous system); (2) egg from lay to hatch; and (3) first nymphal (instar) stage to egg-laying adult. Table 1 summarizes the time spent in each stage of the life cycle.5,10 Most lice treatments are traditionally pediculicidal and inconsistently ovicidal. In the context of a nonovicidal therapy, without considering pediculicide resistance, a "worst-case" scenario for therapy (or best case scenario for lice survival) is a life cycle with the longest time spent as an egg (12 days) and the shortest time spent as a non–egg-laying adult (8.5 days).


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  		TABLE 1 Female Head Lice Life Cycle

 

   GENERAL THERAPEUTIC CONSIDERATIONS
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 LIFE CYCLE OF HEAD...
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Considerations in evaluating a lice therapy must include an understanding of a therapy's mechanism of action and resistance, prevalence of resistance, and safety. Application instructions also bear significance in light of the head lice life cycle. In the face of highly prevalent resistance to a particular molecule, therapy would likely be successful in only a small proportion of patients with lice infestations. Repeat treatments of resistant lice with preparations to which they are resistant will not kill the lice. In addition to wasting money, the patient is unnecessarily exposed to any associated toxicity of the therapy.

Putting aside the issue of resistance, a perfectly ovicidal and pediculicidal agent that acts on the louse nervous system requires 2 treatments separated at least 7 days apart. On day 0, all lice and eggs with eyespots would be killed. Those eggs without eyespots would develop eyespots by day 7 and thus be susceptible at that time. A solely pediculicidal agent would require 3 applications separated by 7 days (Fig 1). On day 0, all lice would be killed, leaving only newly laid eggs and eggs just about to hatch. Therapy on day 7 would kill those eggs that hatched. These nymphs would not have had time to mature to egg-laying adult. What would remain are those eggs that are 7 days old but did not hatch. Therapy anytime between days 13 and 15 would kill the nymphs from those eggs, precluding development to egg-laying adult.


Figure 1
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  		FIGURE 1 Worst-case scenario: treatment at day 0 kills all lice not in eggs. We are left with eggs laid just before therapy and eggs just hatched after therapy is washed away. For nonovicidal therapies, treatment must occur before each batch of hatched eggs matures to egg-laying adult. So, choosing day 7 gives a good buffer to the first deadline, which is day 8.5. We are left with eggs aged 7 and 12 days. We must treat before day 15.5 to kill day-7 hatchlings before they mature to egg-laying adult. We must treat after day 12 to assure that all eggs have hatched before the last treatment. One could, theoretically, choose days 0 and 8 and then days 12 to 16.5, but treatment at day 0, week 1, and week 2 is easier to remember.

 
Using average, rather than extreme, values for egg hatch (8.5 days10) and maturation time (9.7 days5,10) lowers the demand for treatment by a solely pediculicidal agent to days 0 and 9 (Fig 2). Indeed, so long as the average time to hatch is less than the average time to mature to egg-laying adult, only 2 treatments are theoretically necessary. The challenge is to identify the time interval after which all eggs should be hatched but before which new eggs are laid. The assurance of successful therapy is now at the mercy of favorable population statistics. Provided there is no resistance, enough lice may be killed to allow for stochastic extinction. These considerations become somewhat less relevant in the presence of resistant lice, which are not expected to respond regardless of treatment schedule.


Figure 2
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  		FIGURE 2 Average-times scenario: treatment at day 0 kills all lice not in eggs. We are left with eggs laid just before therapy and eggs just hatched after therapy is washed away. For nonovicidal therapies, treatment must occur before each batch of hatched eggs matures to egg-laying adult. In this case, all eggs will have hatched by day 8.5, but none will have matured to egg-laying adult until at least day 9.7. This leaves day 9 as the second and final therapy.

 

   THERAPEUTIC OPTIONS
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 ABSTRACT
 LIFE CYCLE OF HEAD...
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CONCLUSIONS
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Lindane ({gamma}-benzene hexachloride) noncompetitively inhibits the {gamma}-amino butyric acid (GABA) receptor, which typically binds GABA, an inhibitory neurotransmitter.11 The neuronal hyperstimulation that ensues causes paralysis of the louse and eventually death secondary to inability to feed. Lindane's efficacy has waned over the years, and it is inconsistently ovicidal.12 Because of its neurotoxicity, lindane carries a black box warning and is specifically slated as a second-line treatment by the US Food and Drug Administration (FDA). In addition, there is widespread resistance that renders this drug nearly obsolete for the treatment of lice.4,12–16,17 Lindane resistance is mediated by genetic mutations in the GABA receptor, resulting in decreased sensitivity of the receptor to GABA antagonists.18

Lindane is labeled for a single use and only a 4-minute application time. According to the package insert, longer application times and multiple applications are deemed too risky because of potential neurotoxicity. This risk is perhaps overstated, in light of the peculiar discrepancy in labeling between the shampoo and the lotion, which is indicated for total body (neck down) application for up to 12 hours. Such labeling may be arbitrary or may be because of concerns about increased absorption from the scalp. With respect to head lice life cycle, a single application would not reliably eradicate lice. Even in the circumstance of no resistance, one would require at least 2, if not 3, treatments to eliminate an infestation (as it is considered pediculicidal only). Two and 3 consecutive treatments are deemed unsafe by the FDA.

Permethrin and pyrethrins, in this article referred to collectively as "pyrethroids," are the principal over-the-counter (OTC) pediculicides available in the United States. (With respect to nomenclature, technically, pyrethrums are natural compounds originating from Chrysanthemum cineriaefolium, pyrethrins are the insecticidal component of pyrethrums, and pyrethroids are synthetic, rather than naturally occurring, forms of pyrethrins.19) They affect voltage-gated sodium channels, causing delayed repolarization of the neuron by impeding sodium channel closure.20 Like lindane, these insecticides paralyze the louse through hyperstimulation of the nervous system, preventing it from feeding. Pyrethrins are a chrysanthemum extract. In practice, these products are overwhelmingly safe. Rare cases of asthma exacerbations and even death have been reported in individuals with ragweed allergy after using pyrethrin-based products.19 This is clearly the exception rather than the rule. Piperonyl butoxide works synergistically with pyrethrins by inhibiting microsomal enzymes in the louse, preventing pyrethrin catabolism, thereby extending their action.21 Permetherin is a broad-spectrum synthetic pyrethroid that works similarly to pyrethrin.

Pyrethroid resistance is widespread. In the United States, it has been rigorously demonstrated in Massachusetts,2,3,23 Idaho,2 Florida,3,4,22 and Texas.22,23 The principal mechanism of pyrethroid resistance involves mutation of the {alpha}-subunit gene of the neuronal voltage gated sodium channel, conferring decreased sensitivity of the channel to pyrethroids (termed knock-down resistance, or the kdr allele).3,24,25 This mechanism indirectly renders piperonyl butoxide ineffective because this compound only serves to prevent degradation of a now ineffective pyrethroid. Additional resistance involves elevated glutathione S-transferase and monooxygenases, which serve to metabolize pyrethroids.26 If treatment failure is secondary to genetic resistance, as opposed to inappropriate application, using permethrin 5% should be no more efficacious than permethrin 1%.2,27

Genetic resistance to pyrethroids is widespread in both the Unites States and abroad, making these therapies increasingly less useful in treating head lice.2–4,22,23,28,29 At one point in time, efficacy rates for pyrethroids were high: in 1985, DiNapoli et al30 showed 96% efficacy and 62% efficacy of permethrin 1% and pyrethrins 0.3% with piperonyl butoxide 3% at 2 weeks after a single application; in 1986, Taplin et al17 showed 97% efficacy at 2 weeks with a single application of permethrin 1%; in 1986, Brandenberg et al14 showed 99% efficacy with permethrin 1% at 2 weeks with a single treatment; in 1987, Carson et al31 showed 100% efficacy and 93.5% efficacy of permethrin 1% and pyrethrins 0.3% with piperonyl butoxide 3% at 2 weeks (where pyrethrins were reapplied at day 7); and in 1994, Bainbridge et al32 showed 100% efficacy of both agents at 2 weeks using treatment at days 0 and 7. More recent data suggest that efficacy of these agents is waning. In 1999, Hipolito et al33 showed a 79.5% cure rate with permethrin 1% at 2 weeks using treatment at days 0 and 7. In 2004 and 2006, Meinking et al34,35 showed only 55% and 45% efficacy, respectively, with permethrin 1% at 2 weeks using treatment at days 0 and 7.

The best explanation for increased failure rates of permethrin is an increasing prevalence of resistant lice. A secondary explanation invokes the life-cycle analysis. According to the instructions for use of OTC pyrethroids, they are to be applied at days 0 and 7 to 10. Using the worst-case head lice life-cycle scenario, 3 applications would be required for these nonovicidal agents. Using the average life-cycle scenario, a second application would have to occur at day 9. It would seem that these product instructions are not consistent with the life cycle of the resistant head louse; however, in the absence of resistance, the products seem to be ovicidal and quite effective, sometimes with 1 treatment.

The instructions of OTC pyrethroid products place heavy emphasis on the adjunctive performance of nit combing in achieving efficacy. Of course, with perfect nit combing, pharmacologic therapy is not needed. Unfortunately, numerous studies and observations prove nit combing success rates to be far from perfect.5,36,37

Malathion (derived from Latin and Greek, meaning "bad sulfur," referring to this compound's smell) is an organophosphate insecticide. In the louse, malathion is converted to malaoxon, which irreversibly inhibits acetylcholinesterase. The excess cholinergic activity causes neuronal hyperexcitability, thereby preventing the ability to feed. Resistance to malathion, when it occurs, is thought to result from increased levels of carboxylesterases that metabolize malathion into nonmalaoxon intermediates and from decreased sensitivity of acetylcholinesterase to malathion and malaoxon.38–40 Additional mechanisms are esterase sequestration of malathion and elevated metabolism by cytochrome P450 monooxygenases, glutathione S-transferases, and phosphotriesterases.26 Malathion resistance has not been reported in the United States. It has proven to be the most efficacious head lice therapy, outperforming the pyrethroids and lindane in vitro and permethrin in the clinic.4,12,34,35 Malathion was reintroduced into the US market at the request of the Centers for Disease Control and Prevention in 1998 because of concerns of pediculicide resistance.41

Only 1 pharmaceutical preparation containing malathion exists in the United States. Its high degree of efficacy has been attributed not only to the presence of malathion 0.5%, but to the presence of a high concentration of isopropyl alcohol (78%) and terpineol (12%) in its excipients. Isopropyl alcohol has demonstrated clinical activity in head lice.42 It is a nonspecific toxin that likely denatures louse proteins in the egg and adult. It also may serve to dehydrate eggs.5 Terpineol is a tea tree oil extract that has been demonstrated to have ovicidal and pediculicidal activity.43 Terpineol both inhibits acetylcholinesterase and binds octopamine receptors, causing neuronal hyperactivity and death in insects.44,45

Efficacy is attributed to the triple action of malathion with isopropyl alcohol and terpineol, likely making this a resistance breaking formulation. The probability of simultaneously developing resistance to all 3 active agents is small. Similar approaches to infectious agents are found with multidrug antituberculosis regimens and highly active antiretroviral therapy for the human immunodeficiency virus. Of interest, British lice resistant to local malathion products were killed by the US formulation.46

Malathion, in its US formulation, is both ovicidal and pediculicidal.47 Approximately 80% of patients are cured with a single application, the remainder requiring a second application 1 week later.34 Because malathion is both ovicidal and pediculicidal, its labeling of 1 to 2 treatments separated by 7 to 9 days properly correlates with the head lice life cycle.

Unfortunately, many misconceptions abound regarding the safety of malathion in an isopropyl alcohol vehicle. Because malathion lotion is safe, the FDA has intended it for first-line use in head lice. In the United Kingdom, malathion is available OTC for the treatment of head lice. The United Kingdom Committee on Safety of Medicine takes the position that "there is no evidence to suggest that serious systemic adverse reactions are associated with topical malathion."48 Reports of accidental ingestion of malathion are exceedingly rare.49 Actually, between 1998 and 2003, malathion had fewer recorded symptomatic cases (<50) from unintentional ingestion than lindane (>700) or the pyrethroids (>300).50 The presence of a child-proof cap, a small orifice for egress of medication from the bottle, and an extremely unpleasant odor would seem to deter ingestion.

Concerns about flammability seem to be ill-founded, because there are no known reports of bodily injury resulting from the isopropyl alcohol catching fire.49 Appropriate precautions about avoidance of heat sources during use likely account for the lack of reports of flammability. Such precautions should not be misconstrued as a reason not to prescribe the product. With respect to malathion itself, a 59-mL bottle of malathion 0.5% lotion contains 295 mg of malathion. Transdermal absorption was minimal (between 0.2%–3.2%) when malathion 0.5% in isopropyl alcohol was applied to the scalp for 10 hours.51 This corresponds to a very small amount (9.44 mg at most) of malathion. Furthermore, no clinical effect was observed on plasma or erythrocyte cholinesterase activity levels when malathion in isopropyl alcohol was applied to intact or damaged skin.51

With respect to any malathion that is absorbed, it is rapidly metabolized by tissue A-esterases and carboxylesterases to inactive metabolites (mainly malathion monocarboxylic and dicarboxylic acid) that are subsequently excreted in the urine.52,53 Only with overwhelming doses of malathion does the liver metabolize malathion to its active metabolite, malaoxon.53 This is in contrast to other organophosphate insecticides, where metabolism in humans is not so efficient, resulting in poor selective toxicity.52 Of note, past reports of malathion toxicity rest largely with the use of agricultural grade malathion. In the 1970s, there were reports of "epidemic" malathion toxicity resulting in several deaths and several hundred ill. It was discovered that the material in question contained toxic impurities, including isomalathion, a potent noncompetitive inhibitor of carboxylesterase that prevented malathion detoxification.53,54 The malathion currently manufactured for topical application is extremely pure and of significantly lower concentration than that used in agriculture.

Resistance to first-line topical agents has encouraged some to search for alternative, off-label treatments for head lice. Two such therapies are oral ivermectin and oral trimethoprim/sulfamethoxazole.

Ivermectin causes an influx of chloride ions across neuronal membranes resulting in paralysis in many types of parasites.55 This therapy is only pediculicidal because for lice to be exposed, they must take a blood meal that contains the drug. Lice feed every 4 to 6 hours.5 Minimum blood levels of ivermectin required to kill a louse have not been delineated. Without this knowledge, rational dosing with respect to the head lice life cycle cannot be made. Dosing for head lice follows accepted dosing for scabies, which is 200 µg/kg.56 Head lice life cycle dictates 3 treatments to ensure lice eradication. Were blood levels to become subtherapeutic in 1 day (where 1 half-life is 18 hours), therapy at day 0 would eradicate all lice and any eggs hatched on days 0 and 1.5,57 Repeat treatment would be required on day 10 to prevent a day-2 hatchling from maturing to egg-laying. This leaves eggs that were laid just at the time of initial therapy to hatch at day 12. A third treatment anytime between days 13 and 20 would guarantee clearance of lice in the absence of resistance. Resistance to ivermectin has not been reported to date in head lice, and its mechanism is poorly understood in other arthropods. Ivermectin is contraindicated in children who weigh <15 kg as it can cross the blood brain barrier.1 Its use has been suggested to be efficacious for head lice infestations resistant to topical therapies; however, predictably, 1-time dosing was not effective.58

Trimethoprim/sulfamethoxazole is presumed to work by ridding lice of symbiotic bacteria in their gut.59 The lice presumably die from the lack of B vitamins that the bacteria synthesize; however, Meinking5,60 asserts that whereas body lice symbiotes are capable of B-vitamin synthesis, head lice symbiotes are not, calling into question this entire mechanism of action. One small study concluded that monotherapy with either trimethoprim or sulfamethoxazole is ineffective.61 Sulfamethoxazole carries the risk of Stevens Johnson syndrome, and in 1 trial for head lice, 3 (4%) of 76 patients experienced allergic rash.33 Dosing is 10 mg/kg per d based on trimethoprim,33 given in divided doses, because the drug's half-life is 10.1 hours.11 Trimethoprim/sulfamethoxazole is not ovicidal. The proposal of a rational dosing regimen based on the head lice life cycle is complicated by the lack of data on how long an individual louse would survive and be able to lay eggs during continuous exposure to trimethoprim/sulfamethoxazole blood meals. The efficacy of trimethoprim/sulfamethoxazole in treating head lice is controversial at best, with 1 large study showing no benefit62 and another showing significant benefit.33

Nonpharmacologic approaches involve occlusion therapy, nit combing, and hair removal. None has been proven, and many have been disproven, to be effective enough to be considered viable therapies. Vinegar, mayonnaise, petroleum jelly, olive oil, butter, isopropyl alcohol (70% by volume), and water submersion up to 6 hours fail as effective "occlusion therapy" to eliminate an infestation, being neither completely pediculicidal nor ovicidal.63 Lice do not have air sacs or lungs but, rather, obtain air by both diffusion and air in channels that tunnel throughout their bodies. When threatened with suffocation, lice can use spiracles to occlude air tunnels without suffocating and can survive for prolonged periods without air. Successful suffocation can only be achieved by blocking 100% of the louse's spiracles, as well as the entirety of its cuticle. In addition, lice have a pressure mechanism that allows them to open blocked spiracles.64

Hair removal (that is, shaving the head) has never been formally or rigorously proven but is anecdotally effective.65 Because the lice require hair shafts to lay eggs, removing the hair should theoretically prevent the lice from propagating. Although effective, the cosmetic result is less than desirable, especially for school-aged girls.65,66 Combing with a fine-toothed comb has relatively low cure rates as monotherapy. One large trial demonstrated that nit combing yielded a cure rate of 38%,36 whereas another large study reported a cure rate of 57%.67 The former faired worse than malathion applied at days 0 and 7,36 whereas the latter faired better compared with malathion or permethrin single-use therapy. The studies were performed in the United Kingdom, in areas where resistance to both permethrin and malathion exist.36 Viable nits are well camouflaged and often so close to the scalp that a nit comb cannot effectively reach them. Furthermore, those who claim efficacy with nit combing note it must be performed rigorously for many minutes over many days, which is not practical for most people.36,37,68 In any event, it is clear that nit combing has some merit but perhaps adjunctively rather than as monotherapy.

In addition to administering direct pharmacological and/or nonpharmacological therapy for head lice, some environmental treatments might be considered as a secondary measure. Head lice that have fallen off the scalp are believed to be too weak to reinfest; however, no study has either proven or disproven this presumption.37 Lice survival away from the host is 6 to 26 hours, at which point they die from dessication and/or starvation.5 Head lice have been found on pillow cases, albeit with relatively low incidence.69 In light of the above, routine house cleaning, including vacuuming of floors and furniture and laundering of linens and clothing, is recommended. Spraying of furniture and mattresses with permethrin spray is not recommended. Heat (hot wash and hot clothes dryer) killed head lice experimentally placed in pillowcases, whereas cold wash and hanging pillowcases out to dry did not kill head lice. Therefore, for those fomites (that is, hats, combs, brushes, stuffed animals, bed linens, clothing, etc) that are launderable, washing in water >50°C to 60°C or placing for 15 minutes in a hot clothes dryer is recommended.69,70 Grooming tools and toiletries should not be shared. Because nymphs will die if they do not feed immediately on hatching, it is unlikely that head lice will be propagated by a fomite harboring an egg. Put in another way, during the 12-day window during which an egg might hatch, it is more likely to be away from the host than on the host, such that a blood meal would be unavailable at the time of hatching. In light of the above argument, the extremist might store those items that are nonlaunderable in a closed plastic bag for 13 days, but this is not recommended.

The primary mode of head lice transmission is direct head-to-head contact.5,37,71 The prevention of new infestations and reinfestations must be considered as part of head lice management. In addition to and likely more important than the environmental measures taken above, is the identification of head lice in close contacts. Close contacts have been as narrowly defined as bedmates and as broadly defined as household members and classmates. Detection of head lice and nits, especially in light infestations and by those unfamiliar with head lice, is notoriously imperfect. Many infestations are missed by visual inspection, and many cases of head lice are asymptomatic.5 One method to improve detection is via the nit combing of wet hair and examining the threads of the comb.72

The American Academy of Pediatrics, in 2002, published the following guidance in this journal1: "If an index case is identified, all household members should be checked for head lice... ." The implication is that close contact, which in our opinion, include classmates, should be screened. On the basis of the findings of Williams et al,73 18 (31%) of 91 children with nits had concomitant lice, and 19 (18%) of 50 of those followed with nits alone converted to active infestation. On a theoretical level, if head lice is not a self-limiting infection, and if a child has not been previously treated for lice, then having "nits alone" would seem to imply that either the person screening is not trained in the detection of live lice or the screen was a false-positive. On the flip side, "progression to lice" must result either from hatching nits or reinfestation from a close contact.

The argument for not screening is that screening classmates would result in the exclusion of children from school. The issue here is not one of whether to screen or not to screen (and screening should take place), but what school policy should be with respect to a positive screen. Indeed, there is no way to identify which of the 18% of children with nits alone will develop an active infestation or which are false-positives for nits or false-negatives for live lice. On a theoretical basis, given the negligible risk and high efficacy, one approach is to treat all such patients simultaneously with malathion. Indeed, a study is warranted to validate this strategy with this agent. The alternative is to accept a continual, baseline lice prevalence in schools.

Because identification is imperfect, because head lice are known to exist in the close contacts of actively infected scalps, and because of the excellent safety profile of some available therapies, strong arguments can be made for the systematic treatment of close contacts regardless of screening. Indeed, the simultaneous treatment of contacts is the most reliable way to eliminate head lice outbreaks in households, schools, and communities and has been repeatedly validated.5,37,74 Although such a strategy is good in theory, many parents, nurses, and physicians may be averse to exposing those individuals not definitively infested to treatment. A compromise might be to encourage the treatment of household contacts and require at least careful screening of classmates of an index case by the school nurse.

A rigorous cost analysis of treatment with 1 or another agent is beyond the scope of this article. However, some general statements can be made. Malathion costs about $125 per bottle, lindane costs about $125 per bottle, and OTC permethrin costs approximately $10 to $15 per bottle. Looking at cost of therapy alone, permethrin is only 3 to 5 times cheaper than malathion considering the need for 2 to 3 bottles of the former, in the absence of OTC resistance. Malathion is covered by most Medicaid and managed care plans, and the copay is roughly equivalent to the out-of-pocket expense of an OTC. OTC failure, which is common, carries with it the economic burdens of additional physician visits (that often add to out-of-pocket costs), repeat purchases, lice transmissibility (raising treatment costs exponentially), missed work by parents (resulting in lost wages), and loss of state funding from schools because of student exclusion from school. The collective cost of OTC failure relative to that of malathion success would seem to exceed greatly the differential in product price. Most importantly, the child would be free from infection with malathion yet still have the infection with permethrin.

The out-of-pocket expense that families are willing to bear to eliminate head lice infestation is illustrated by professional nit-picking services available in some communities. They can charge up to $250/hour for the first 2 hours and $90/hour for each additional hour of nit picking. In addition, they offer a variety of nit combs, "chemical-free" anti-lice hair tonics, and informational materials that cost collectively up to $95.75 A household with >1 infested child could easily expend $1000 to avail themselves of these services.


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 LIFE CYCLE OF HEAD...
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REFERENCES
 
In light of the review of therapeutic modes of action, resistance considerations, and head lice biology, malathion, specifically in the formulation containing isopropyl alcohol and terpineol, is the favored first-line agent for head lice. A patient infected with head lice at any given time will have lice existing at different points in the life cycle. The only therapy that, when used according to the package insert, will ensure head lice eradication is malathion (Table 2). Regardless of adequate therapy, efforts are fruitless if the population in question is resistant, which is currently a concern for both lindane and pyrethroids and not for malathion as available in the United States.


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  		TABLE 2 Current FDA-Approved Pharmacologic Therapies for Head Lice

 
The use of malathion as a first-line treatment also has broader implications for school head lice policy in the United States. Currently, no-nit policies can exclude children from school unnecessarily, as is the case when only nonviable nits are present on the scalp.76 Conversely, insofar as nits represent the possibility of infestation and detection of active infestation is imperfect, the need for a more definitive demonstration of freedom from lice exists. A possible answer is to require index cases of head lice and their family members to be treated with malathion. Classmates could be screened for head lice and those found to have head lice treated promptly with malathion, preferably simultaneously and preferably at days 0 and 7. Rescreening after malathion treatment would not be necessary, because the examination is imperfect and the probability of treatment success is very high. As was done with Nix in the past, a child could return to school the following day with proof of treatment.5 Were the concern that a parent is neglectful or would not apply the product correctly, direct observational therapy could be used in the school. Such a practice would allow for the elimination of no-nit policies without risk of reinfestation in the school and with all the attendant pharmacoeconomic benefits: breaking the cycle of spread, decreasing absenteeism from schools, decreasing missed work by the parent, and eliminating repeated spends on ineffective modalities.


   FOOTNOTES
 
Accepted Jan 9, 2007.

Address correspondence to Jacob Levitt, MD, Department of Dermatology, Mount Sinai School of Medicine, 5 E 98th St, 5th Floor, New York, NY 10029. E-mail: tarony{at}aol.com

Financial Disclosure: Dr Levitt is vice president and a major shareholder of Taro Pharmaceutical Industries, Ltd, which manufactures and markets Ovide lotion. Drs Lebwohl and Clark have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
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 ABSTRACT
 LIFE CYCLE OF HEAD...
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 CONCLUSIONS
 REFERENCES
 

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