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A randomised, double-blind, comparative efficacy trial of three head lice treatment options: malathion, pyrethrins with piperonyl butoxide and MOOV Head Lice Solutionby Kerryn A Greive BA/BSc (Hons), PhD – Research and Development Manager, Ego PharmaceuticalsPhillip M Altman BPharm (Hons), MSc, PhD – Altman Biomedical ConsultingJames S Rowe BPharm, MSc, PhD, MPS, MRACI, C Chem – Scientific Director, Technical Consulting ServicesJohn A Staton MAIP (Dip), MAI Ex (Dip) – Commercial Director, Technical Consulting ServicesV M Jane Oppenheim BSc (Hons), PhD – Scientific Director, Ego Pharmaceuticals Abstract
Head lice are a growing source of parental and social concern. The introduction of pesticide based
head lice treatments several decades ago saw the infestation rate fall dramatically; today, due to growing
pesticide resistance, the head louse is staging a come back. New, effective, clinically proven head lice
treatments are urgently needed to control the growing head lice problem. MOOV Head Lice Solution is
the first herbal based head lice treatment to be registered by the TGA and has been clinically tested to
ICH-GCP standards. A randomised, double blind, comparative efficacy trial of MOOV Head Lice Solution
against malathion and pyrethrins with piperonyl butoxide was conducted using Queensland primary
school children who had active head lice infestations. MOOV Head Lice Solution achieved a cure rate
of 33/40 (82.5%), versus malathion 11/37 (29.7%, p<0.0001) and pyrethrins with piperonyl butoxide
13/36 (36.1%, p<0.0001) The 82.5% cure rate for MOOV Head Lice Solution was achieved without
the use of supportive combing, thus representing a significant reduction in time cost to caregivers. All
three treatment products were well tolerated by the subjects. MOOV Head Lice Solution is the first TGA
registered herbal based head lice treatment and is more than twice as effective as pesticide based head
lice treatments.
Introduction
Lice are most often found behind the ears or at the Head lice has been a community concern since back of the neck, and they attach their eggs to the hair the earliest civilisations, with evidence of head lice shaft close to the scalp.7 A head louse must feed on the infestations found on 5,000-year-old Egyptian host’s blood every three to six hours or it will dehydrate mummies.1 Today the head louse is making a come back after a number of relatively quiet decades.2,3 In Although distressing to parents and children alike, Australian schools head lice infestation rates of up to head lice are harmless and there is no evidence to support 35.1% have been published,4,5 with head lice the third cleaning bedding, clothing or furniture; lice found on most commonly reported outbreak in day care centres chairs, pillows and hats are dead, sick or elderly.7 Although an itchy scalp is often considered a good Although largely a condition of childhood and indicator of a head lice infestation, one study found most commonly affecting children aged 3-11 years,2 that 36.1% of children with an infestation and 20.6% a head louse infestation can be passed from child to of children without an infestation reported having an parent, student to teacher, sibling to sibling, or from itchy scalp.9 The majority of head lice infestations are any prolonged head to head contact.7 Head lice do not asymptomatic.7 It is therefore important that every discriminate on the basis of age, gender, race or social member of the household be checked – adults7 and class.8 Head lice are not concerned with hair type, colour children – if a family member has head lice.
The head lice cycle
parental frustration so great that drastic alternatives A louse egg that has been laid on a hair shaft is called such as kerosene and veterinary flea products21 are a ‘nit’. The nits are firmly attached with proteaceous being used on children in a desperate attempt to cure biological glue.8 There are currently no commercial recalcitrant head lice infestations. The lack of reliable products available that will dissolve this glue.8 The nit treatment products is becoming a health and safety risk will hatch six to 10 days after deposition. The louse will then go through three growth stages, each marked by an Heath departments in Australia have been exoskeleton moult. The first moult occurs two to three recommending wet combing as a method for treating days after hatching with subsequent moults around five head lice infestation.22-24 This method involves saturating and 10 days after hatching. Once the lice have moulted the hair with conditioner and combing it with a nit for the third time they are adults and able to mate and comb until no more head lice are found. This procedure reproduce. The female will begin to lay eggs one to two is repeated every two days until no head lice are found days after mating, and will continue to lay three to eight for 10 consecutive days of combing.22,23 This method eggs a day for the next 16 days. A louse will die around is laborious, time consuming and does not produce satisfying cure rates as a treatment on its own25 or One female louse can produce up to 128 lice in improve cure rates when used in conjunction with one generation, and over 8,000 in just two. A head traditional treatments.14 A family with several children lice infestation will consist of lice and eggs at all can spend many hours each night wet combing in an attempt to cure an infestation. When conducted by trained nurses in a clinical, controlled setting with a Unlike many conditions of childhood such as chicken standardised protocol, wet combing has a reported cure pox, a past head lice infestation offers no protection from rate of 50-60%.18,26 A home based trial using parents to the next infestation. It is common for a cycle of cure perform the wet combing achieved a cure rate of only and reinfestation to be seen, i.e. the infestation is cured 38% and concluded that wet combing as the first line during school holidays, and reinfestation occurs within treatment for head lice is inappropriate.25 This conclusion is supported by the Cochrane review that concluded physical methods such as wet combing were ineffective Treatments for head lice
On the market today are a host of products that There is a clear need for an effective, natural and quick claim to cure a head lice infestation. An international head lice treatment that can deliver the results parents review of head lice treatments from the Cochrane need without a significant lifestyle impact. MOOV Head Collaboration11 concluded that although permethrin, Lice Solution AUST R 128237, is a natural-based head synergised pyrethrin and malathion were once effective, lice treatment that utilises eucalyptus oil in an optimised the emergence of drug resistant lice means that there is base, and is the first herbal based head lice treatment to no direct contemporary evidence for the effectiveness of these compounds. While malathion, permethrins and piperonyl butoxide/pyrethrins have been the mainstay In order to demonstrate the clinical efficacy of of the battle against head lice, their residual nature and MOOV Head Lice Solution a double blind, randomised, misapplication has led to a dramatic increase in resistance comparative clinical trial was conducted. This trial was in head lice populations.12 This resistance has been found conducted according to the International Conference in Australia13 and across the world.14-19 on Harmonisation Good Clinical Practice (ICH-GCP) guidelines, and addressed the protocol criticisms outlined The increasingly poor performance of traditional head in the TGA Head Lice Review20 and the Cochrane lice products has led to a surge in the commercialisation of herbal or natural based head lice treatments. While herbal based head lice treatments are appealing, a 2003 review20 by the Therapeutic Goods Administration of Australia (TGA) found no published clinical trials This phase four clinical trial was a multi-centred, supporting the efficacy or safety of the herbal head lice randomised, three-parallel group, comparative, double products on the Australian market. This was supported blind study designed according to ICH-GCP guidelines. by the Cochrane review which concluded that there The protocol was registered (NCT00381082) and was no evidence for herbal treatments.11 This has been approved by the Human Research Ethics Committee recognised in the wider scientific community.7 of the University of Queensland (Clearance no. 2003000184). The parents of the children involved The poor efficacy of traditional products and the provided written informed consent. The children gave unproven nature of herbal products is resulting in verbal consent to participate in the trial at the start of the trial at any time, and adverse events were monitored each treatment day. The trial was conducted in 2004 and involved Queensland primary school children from seven Per protocol assessment
The three products tested were registered with the To be considered per protocol, the subject must have TGA for the treatment of head lice: Banlice Mousse received two treatments of Banlice or KP24, each seven AUST R 46708 containing 16.5mg/g piperonyl butoxide days apart, or three treatments with MOOV, each seven and 1.65mg/g pyrethrins; KP24 Medicated Foam AUST days apart. In addition, all primary school aged siblings R 18867 containing 1.0% malathion (maldison); and of the subject who were found to be infested must have MOOV Head Lice Solution AUST R 128237 containing received at least one treatment with either Banlice or KP24, or two treatments with MOOV in the context of Banlice Mousse and KP24 Medicated Foam were purchased from a pharmacy wholesaler, while MOOV Head Lice Solution was supplied by Ego Efficacy assessment
A ‘cure’ was defined as the absence of live lice as Although Banlice and KP24 claimed that only one diagnosed by wet combing of the hair. The primary treatment was required to effect a cure, both were efficacy endpoint was the cure rate seven days after the applied twice using the manufacturers’ directions, with last application, i.e. day 14 for Banlice and KP24, and a week between applications, i.e. at day 0 and day 7. day 21 for MOOV. Wet combing is considered the best The use of two applications for Banlice and KP24 was in technique for diagnosing a head louse infestation.27,28 For accordance with the recommendations of the TGA Head this study the wet comb technique was standardised and MOOV Head Lice Solution was applied three Despite the difference in appearance of the three times with a week between applications as per the treatments, double blinding was maintained. The manufacturer’s directions, i.e. at day 0, day 7 and day treatments were randomly assigned to the subjects. 14. As head lice eggs can take up to 10 days to hatch, the One group of personnel applied the treatments, while use of three applications was designed to ensure that any a second group carried out the efficacy assessments. lice hatching from eggs laid immediately before the first Although it was not possible to blind the treatment application would be kil ed by the third application. personnel, the subjects were unaware that three different treatments were involved. The efficacy assessors were Subjects were screened for head lice using visual physically removed from the treatment areas, and were inspection and dry combing. Those children meeting the unaware of which treatment the subjects had received.
entry criteria were randomised to receive one of the three Safety assessment
The entry criteria were: primary school children; Safety was assessed by comparing the adverse events presence of live head lice, not just eggs; available for reported by the three treatment groups.
trial duration; parent or guardian wil ing to abstain from using any other head lice product, including head louse combs, on their child for the duration of the trial; parent or guardian gave written informed consent.
Efficacy
The exclusion criteria were: history of allergies or During the study period, September to November adverse reactions to head lice products or the specific 2004, 822 subjects were examined, of which 237 components being tested; treatment for head lice in the had live head lice. Of these 237 subjects, 152 met the four weeks before day 0; presence of scalp disease; more inclusion and exclusion criteria and were enrolled; 113 than one fixed place of residence. In addition, if a subject were assessed as per protocol for the purposes of safety had primary school aged siblings, those siblings had to and efficacy analysis. Of the 113, 36 were treated with be screened, and enrolled if they had head lice.
Banlice, 37 were treated with KP24 and 40 with MOOV. Reasons for a subject being deemed not per protocol During the trial, subjects were free to wash their hair were: an infested primary school aged sibling not treated with ordinary shampoo and conditioner and to comb with the minimal application of Banlice, KP24 or MOOV with standard combs. Head louse combs, other head (20); use of alternative head lice treatments during the lice products, hair dyes or bleaches were not permitted trial (12); subject did not undergo the entire treatment/ during the trial. Subjects were free to withdraw from assessment, i.e. due to non-attendance at school (7).
The cure rates were determined one week after the combing, efficacy was determined one week after the final product application: day 14 for KP24 and Banlice, final application, subjects were randomised, the study day 21 for MOOV. KP24 had a cure rate of 29.7%, was double-blinded and adequately powered to allow Banlice had a cure rate of 36.1% and MOOV had a cure statistical analysis. In addition, the siblings of the enrolled subjects were examined for head lice.
MOOV Head Lice Solution achieved an 82.5% TABLE 1: Cure rates for the primary efficacy endpoint cure rate, while Banlice and KP24 achieved cure rates of 36.1% and 29.7% respectively. MOOV Head Lice Solution is not only significantly more effective than Banlice (p<0.0001) and KP24 (p<0.0001), it is twice as Banlice and KP24 have promoted their ability to kill head lice and eggs in one application. In accordance with † Significantly better than either comparator (p<0.0001) the recent recommendations from the TGA20 Banlice and KP24 were applied twice in this study, with seven days Using chi-squared tests with a Bonferroni adjustment to allow for multiple comparisons, it was found that MOOV Head Lice Solution was applied three times, MOOV was significantly more effective in curing head each application being seven days apart. Head lice eggs lice infestations than either Banlice (p<0.0001), or KP24 can take up to 10 days to hatch, so by including a third application in the treatment regimen, any lice that hatch from an egg laid immediately before the first application will be killed by the third application. This reduces Of the 152 subjects enrolled, 23 adverse events were the likelihood of the primary head lice infestation reported: 18 for MOOV, three for Banlice, two for KP24. continuing. While MOOV Head Lice Solution kills eggs The adverse events related to scalp sensations experienced and lice, the survival of only a few out of thousands by the subjects during product application, i.e. itching, of eggs is sufficient for the infestation to continue. By a hot sensation, stinging and burning. All the adverse incorporating a third application into the regimen, it events resolved completely within five minutes of the ensures that the infestation is eradicated.
products being washed from the hair.
Transient, mild to moderate adverse events were reported for all three treatments and were largely Discussion
described as itching, stinging or burning. The sensations Head lice are a community concern that is not dissipated when the treatments were washed out after being sufficiently addressed by current treatments, the prescribed application periods. Overall the three be they traditional, herbal or combing. The World treatments were well tolerated by the subjects.
Health Organisation has recognised that without new compounds it will be difficult to maintain effective Treatment failure versus
control of head lice,29 and with head lice infestations reinfestation
causing increasing parental frustration, and fear and While MOOV Head Lice Solution is significantly anxiety in children,2,7 effective treatments are needed.
better than the comparator products, it did not MOOV Head Lice Solution is an herbal-based head achieve a 100% cure rate. As preliminary clinical data lice treatment that has been clinical y proven to be more submitted to the TGA demonstrated that MOOV effective than both malathion and piperonyl butoxide/ Head Lice Solution killed all live lice on the scalp in one application, and the three treatment protocol ensures that eggs and all hatching lice are killed, the 17.5% This present study addressed all the concerns raised failure rate can be attributed to reinfestation. The final in the Cochrane Review11 and the TGA Review20 and efficacy checkpoint was seven days after the last product included strict definitions of head lice infestation, application, giving seven days for reinfestation to occur. i.e. live head lice had to be found, eggs alone were As it was not possible to treat all the children in a given not enough. Further to this, subjects that had been class or school due to lack of parental consent, it is likely treated with a head lice product in the previous four that children cured after the last application may have weeks were excluded to avoid complications from any become reinfested before the final efficacy endpoint, residual product, combing procedures were defined and thus be counted as treatment failure. Unlike many and standardised, trained operators performed the other childhood diseases, having head lice once does not prevent repeat infestation. A highly efficacious treatment children, this represents a significant improvement in the in combination with constant vigilance is the best lifestyle impact of a head lice infestation.
Reinfestation is an ongoing concern for diligent Resistance
parents. Although currently no product can prevent reinfestation, the availability of an effective head lice The relatively low cure rates for Banlice and KP24 product will always make the treatment of a head lice may be explained by resistance within the louse population, or by the stringent definition of a cure as measured one week after the last treatment application. Conclusion
It has clearly been demonstrated that head lice around the globe is becoming increasingly resistant to traditional MOOV Head Lice Solution has been shown in a head lice treatments such as malathion and permethrin.
randomised, double-blind clinical trial in a relevant population to be twice as effective in curing head lice 19 The residual nature of these materials results in low levels remaining in the hair for many days after product infestations as two popular treatments, piperonyl application. These persistent low levels, allow for the butoxide with pyrethrins, and malathion.
selection and dominance of resistant lice. Although MOOV Head Lice Solution is the first herbal-based once very effective, due to their residual nature, these head lice treatment registered by the Australian TGA. In treatments have now become ineffective.
addition it does not need to be combined with combing MOOV Head Lice Solution has a volatile active to effect a cure; this represents a significant time saving combination that will enable the high cure rates observed for parents and an improvement in the lifestyle impact a in this trial to be maintained into the future. Once the product is washed from the hair, any residual eucalyptus MOOV Head Lice Solution is an effective head lice oil will rapidly volatilise from the hair. This should treatment using natural active ingredients that provides prevent the emergence of resistance, thus helping to a quick treatment protocol that is twice as effective as maintain the efficacy of MOOV Head Lice Solution. traditional treatments and does not require supportive Wet combing
The best technique for detecting a head lice infestation Kerryn Greive and Jane Oppenheim are employed full time by Ego is the wet-combing technique.27,28 The conditioner that is Pharmaceuticals, the sponsor of the clinical trial and manufacturer combed from the hair provides a contrast to the black- of MOOV Head Lice Solution. James Rowe, Phillip Altman and grey lice that are combed from the hair. An infestation John Staton are consultants employed by Ego Pharmaceuticals. is confirmed by finding live lice.7 Nits on their own do not represent an active infestation and should not be treated as one.7 Once a head lice infestation is confirmed by finding live lice, treatment should begin immediately to prevent the infestation getting worse or transmitting to others. Prophylactic or ‘just in case’ treatment should It is common for head lice products to recommend 1. Burgess IF. Human head lice and their management. Adv Parasitol 1995; that product application be followed with the wet 2. Chosidow O. Scabies and pediculosis. Lancet 2000;355:819-26.
combing procedure. If a head lice product is effective, 3. Roberts RJ, Burgess IF. New head-lice treatments: hope or hype? Lancet the use of wet combing is unnecessary and significantly 4. Speare R, Buettner PG. Head lice in pupils of a primary school in Australia and increases the time burden of treatment. If a head lice implications for control. Int J Dermatol 1999;38:285-90.
product needs wet combing as a supportive procedure the 5. Speare R, Thomas G, Cahill C. Head lice are not found on floors in primary school classrooms. Aust N Z J Public Health 2002;26(3):201-11.
product efficacy must be questioned and an alternative 6. Jorm LR, Capon AG. Communicable disease outbreaks in long day care product should be sought. With wet combing shown to centres in western Sydney: occurrences and risk factors. J Pediatr Child Health 1994;30:151-4.
be ineffective as a treatment or a supportive practice, it 7. Nash B. Clinical review: treating head lice. Brit Med J 2003;326:1256-9.
is redundant in the treatment of head lice.
8. Burkhart CH, Burkhart CG. Head lice: scientific assessment of the nit sheath with clinical ramifications and therapeutic options. J Am Acad Dermatol trial was conducted without wet combing and clearly 9. Mumcuoglu KY, Klaus S, Kafka D, Teiler M, Miller J. Clinical observations demonstrated that MOOV Head Lice Solution is highly related to head lice infestation. J Am Acad Dermatol 1991;25:248-51.
effective and does not need wet combing as a supportive 10. Victorian Government Health Information. Headlice: scratching for answers? Melbourne: Dept of Human Services; Jun 2006.
procedure. This significantly reduces the time burden 11. Dodd CS. Interventions for treating headlice. (Cochrane Review). associated with treating head lice to a total of three In: The Cochrane Library Issue, 2, 2003. Oxford: Updates Software.
12. Mumcuoglu KY. Prevention and treatment of head lice in children [Review]. 10 minute applications. For a family with several 13. Hunter JA, Barker SC. Susceptibility of head lice (pediculus humanus capitus) 21. Personal Communication, Assoc. Prof. Stephen Barker. Uniquest.
to pediculcides in Australia. Parasitol Res 2003;90(6):476-8.
22. Department of Health. Government of Western Australia. Head Lice Fact 14. Meinking TL, Clineschmidt CM, Chen C, et al. An observer-blinded study of Sheet. 2005. At: www.population.health.wa.gov.au/Communicable/headlice_ 1% permethrin crème rinse with and without adjunctive combing in patients with head lice. J Pediatr 2002;141:655-70.
23. ACT Health. Fact Sheet. Head Lice. [Accessed 14 Nov 2006]. At: www.health.
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study of the bug buster kit and over the counter pediculicide treatments 27. Counahan ML, Andrew RM, Speare R. Reliability of parental reports of head against head lice in the United Kingdom. Brit Med J 2005; 331(7513):362-3.
lice in their children. Med J Aust 2005;182(3):137-8.
19. Downs AMR, Stafford KA, Harvey I, Coles GC. Evidence for double resistance 28. Mottram P. Research report on the effectiveness of hair conditioner as a non- to permethrin and malathion in head lice. Brit J Dermatol 1999;141:508-11.
chemical agent to control head lice. Brisbane: Queensland Health; 2000.
20. James S. A review of the regulation of head lice treatments in Australia. 29. Gratz NG. Human lice. Their prevalence, control and resistance to insecticides. Prepared for the Medicines Evaluation Committee, Therapeutic Goods h e r b a l m e d i c i n e – h o w b l a c k i s y o u r c o h o s h ? My readings over the years have suggested Natural y, at the first sign of liver problems, remedial that hepatotoxicity remains one of the principal action should be taken by ceasing the use of the herb manifestations of herbal toxicity, when it occurs. The or herbal medicine in question. Determination of liver liver is the major site of biotransformation of foreign enzyme values, risk factors (such as alcohol and age), and molecules, those exotic to our normal biochemical co-administration of other drugs may then be warranted. system. Many organic phytochemicals have an inherent The symptoms of liver damage may include a yellowish ability to bind to or interfere with the chemical jaundiced skin tone, nausea, vomiting, fatigue, anorexia, components of metabolic pathways, and of course, that is why they may be physiologically active. In consequence, natural compounds may exert a lethal effect on cells, In conclusion, I do tend to be ambivalent about cellular components or biochemical processes.
relative risk in all things. The final decision is the patient’s after due consideration of all the available A number of herbs have a reputation for inducing evidence presented to them. However, one may well ask some degree of hepatotoxicity, and let’s face it, even whether good, unbiased information has been presented that popular social drug alcohol, when consumed to to them in the first place. In health, opinions are often as excess for an extended period of time, may also initiate many as the molecules involved. Now, where did I put cirrhosis of the liver. Liver damage caused by herbs such my car keys? Am I prepared to take the risk of driving? as coltsfoot, borage and comfrey can be firmly linked to Of course I am, we all are, aren’t we? the presence of covalently-binding pyrrolidizine alkaloids that cause human hepatic veno-occlusive disease. The Dr Bob Longmore is a consultant on herbal matters. He lectures question of whether the herb kava is truly hepatotoxic in pharmacognosy and holds the honorary position of Adjunct may be linked to the method of preparation of extracts Associate Professor at Curtin University of Technology, WA. email: [email protected] using organic solvents such as acetone or methanol.7 Chaparral, Larrea tridenta, is definitely hepatotoxic due to nordihydroguaiaretic acid8 and should certainly to be 1. Castleman M. The New Healing Herbs. Rodale 2001;87-90.
2. Barnes J, Anderson LA, Phillipson JD. Herbal Medicines, 2nd edition. London The constituents of black cohosh responsible for 2002. The Pharmaceutical Press;141-6, and references contained therein.
potential hepatotoxicity have not been formally identified 3. Black cohosh and liver toxicity – an update. Aust Adv Drug React Bull, Jun as such but my bet is on the quinolizidine alkaloid 4. ADRAC. Hepatotoxicty with black cohosh. Idem. 2006;25:6.
N-methylcytisine, a known teratogen, and related 5. Black cohosh (Cimicifuga racemosa). New labelling requirements and consumer information for medicines containing black cohosh. Update 29 May candidates present in black cohosh.1 Perhaps the question 2007. At www.tga.gov.au/cm/0705blkcohosh.htm of this potential is related to variation in naturally 6. Law R. Safety of dietary supplements; At: www.laleva.cc/petizione/english/ occurring concentrations of these alkaloids together with 7. Balick MJ, Lee R. Traditional use of sakua (kava) in Pohnpei: lessons for variation induced by extraction methods? The question integrative medicine. Alternative Therapies.2002;8(4):96-8; available in summary at HerbClip, http://content.herbalgram.org/naturemade/herbclip/ remains open at the moment, but begs a modicum of caution to be exercised in the use of black cohosh.
8. Natural products – plants (sources of mild or lethal toxicity). At http://faculty.

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