Oral Ivermectin for Treatment of Pediculosis Capitis

ORIGINAL STUDIES Oral Ivermectin for Treatment of Pediculosis Capitis Mahreen Ameen, MPH, MRCP, MD,* Roberto Arenas, MD,† Janeth Villanueva-Reyes, MD,† Julieta Ruiz-Esmenjaud, MD,† Daniel Millar, MD,‡ Francisca Domínguez-Dueñas, MD,§ Alexandra Haddad-Angulo, MD,† and Mauricio Rodríguez-Álvarez, MD¶ Downloaded from http://journals.lww.com/pidj by BhDMf5ePHKbH4TTImqenVBaqevB2sTM0hbiKYi4gaMln8PmjXDom9op/n3U+FK2u on 12/29/2019 Background: Pediculosis capitis is a highly transmissible infestation prevalent worldwide. It is an important public health problem mainly affecting children. The emergence of drug resistance and high rates of treatment failure with several topical agents makes ivermectin, an antiparasitic drug, an attractive therapeutic option for lice control. Objective: To evaluate the efficacy and safety of oral ivermectin in the treatment of a pediatric population with pediculosis capitis. Methods: Children with pediculosis capitis from the ages of 6 to 15 years were recruited from an indigenous community in Mexico, and were treated with a single dose of oral ivermectin at 200 ␮g/kg. They were treated with a second dose of ivermectin 1 week later if there was evidence of persistent infestation. Results: Forty-four children (mean age, 9.8 years) with active infestation were treated. A single approximately 200-␮g/kg dose of ivermectin eradicated adult lice in all children. Forty-one percent (n ⫽ 18) required a second dose because of the presence of viable nits. At the third visit, 2 weeks after commencement of treatment there was no evidence of viable nits, and there was complete resolution of excoriations in all children and minimal or no symptoms of pruritus were reported in 93% (n ⫽ 41). There were no significant adverse effects due to ivermectin administration. Conclusions: Ivermectin demonstrates high efficacy and tolerability in the treatment of pediculosis capitis in children. A significant number of children required a second dose to ensure complete eradication. Key Words: ivermectin, nit, parasite, pediculosis capitis (Pediatr Infect Dis J 2010;29: 991–993) T he treatment of pediculosis capitis has conventionally consisted of the application of topical insecticides, sometimes combined with the mechanical removal of nits by wet combing. Lindane, permethrin, pyrethrin, and malathion have been commonly used. They exhibit variable efficacy and risks of toxicity, and significant problems with resistance and cross-resistance have emerged, which has contributed to the increased incidence of pediculosis capitis in both developed and nondeveloped countries.1,2 New non-neurotoxic topical agents are now available such as 50% isopropyl myristate, which acts by desiccating the louse exoskeleton3 and 5% benzyl alcohol lotion that asphyxiates louse Accepted for publication April 27, 2010. From the *Department of Dermatology, Royal Free Hampstead NHS Trust, London, United Kingdom; †Department of Dermatology, Hospital General Dr. Manuel Gea González, Mexico City, Mexico; ‡Department of Dermatology, University of California, San Francisco, CA; and §Research and Development of Viral Vaccines, ¶Laboratorio de Biológicos y Reactivos de México, SA de CV (Birmex), Mexico. Address for correspondence: Mahreen Ameen, MPH, MRCP, MD, Royal Free Hampstead NHS Trust, Belsize Park, London NW3 2QG, United Kingdom. E-mail: mahreenameen@hotmail.com. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.pidj.com). Copyright © 2010 by Lippincott Williams & Wilkins ISSN: 0891-3668/10/2911-0991 DOI: 10.1097/INF.0b013e3181e63f5f spiracles.4 Their mechanical mechanisms of action make development of resistance unlikely. Topical therapies are associated with noncompliance, treatment failure in cases of severe infestation, and treatment intolerance when skin is severely excoriated. This has led to ivermectin being tested topically and systemically for the treatment of pediculosis capitis5,6 and body lice.7 Ivermectin (22, 23-dihydroavermectin) is a semisynthetic analog of avermectin B1, which was isolated from Streptomyces avermitilis. It is a potent anthelmintic that has been an effective and safe treatment against intestinal helminths as well as onchocerciasis, bancroftian filariasis, loiasis, and also other cutaneous ectoparasitic infestations such as severe cases of scabies, cutaneous larva migrans, myiasis, and gnathostomiasis (reviewed in Omura, 2008).8 It acts by selectively binding to glutamate-gated chloride ion channels that are found in invertebrate nerve and muscle cells, resulting in free movement of chloride, which causes paralysis and death of the parasites. Permethrin and DDT resistance have been linked to mutations in voltage-gated sodium channel genes raising concerns that a similar mechanism of nerve resistance to ivermectin may arise.9 There have been concerns of potential neurotoxicity, but given at normal doses, ivermectin does not cross the healthy blood– brain barrier of humans.10,11 The objective of this study was to asses the safety and efficacy of ivermectin in a cohort of children with pediculosis capitis. Ivermectin was chosen to treat this pediatric population because they had limited access to running water, making the use of topical pediculicides extremely difficult. MATERIALS AND METHODS This was an open, prospective study of schoolchildren recruited from 2 rural populations in a Mazahua indigenous zone in the State of Mexico. Ethical approval was granted by the Gea Gonzalez General Hospital’s Medical Ethics Committee, and informed consent was obtained from the parents of all children entering the study. We recruited children with a body weight greater than 15 kg between the ages of 6 to 15 years. Criteria for inclusion included no prior treatment for pediculosis capitis within the previous month, and no concurrent use of any medication that might interact with ivermectin. At the initial visit, a full medical history was obtained and pediculosis capitis was diagnosed by scalp examination for live adult parasites of Pediculus humanus, nymphs, or viable nits. Viable nits are opalescent white, and are usually located within half a centimeter from the scalp. Nonviable nits are empty nit cases that are almost clear and are located more than one centimeter from the scalp. The quantity of adult parasites and nits was assessed before the commencement of treatment and at each successive visit, and was graded as few (⬍5), moderate (5–10), or abundant (⬎10). The intensity of pruritus and the extent of excoriations were also graded (mild, moderate, and severe). Children with a confirmed diagnosis of pediculosis capitis were treated with ivermectin (Stromectol MSD), 3-mg tablets in a dosage of approximately 200 ␮g/kg body weight (Table, Supplemental Digital Content 1, http://links.lww.com/INF/A508). The Pediatric Infectious Disease Journal • Volume 29, Number 11, November 2010 www.pidj.com | 991 The Pediatric Infectious Disease Journal • Volume 29, Number 11, November 2010 Ameen et al Follow-up was conducted 1 and 2 weeks after the commencement of treatment. A history of any adverse effects from ivermectin therapy was sought. A further dose of ivermectin was given to children who still had active infestation at week 2. The criteria for active infestation were the presence of lice or viable nits and pruritus. Demographic data and clinical evolution, as well as possible adverse effects of ivermectin were registered at each visit in individual files. Data were analyzed in XLSTAT 2008.6.01 Excel 11 software. RESULTS Forty-six children met the criteria for inclusion into the study, but 2 were subsequently excluded because of noncompliance as they failed to return for follow-up visits. The majority of the patients were female (67%, n ⫽ 28), with a general mean age of 9.8 years (CI 95%: 9.1–10.5) and a mean weight of 26.4 kg (CI 95%: 24 –28.8) (Table, Supplemental Digital Content 2, http://links.lww.com/INF/A509). Only 40 (32%) were able to report accurately the period of evolution of their pediculosis capitis, which on average was 6 months in duration (range, 1–12 months). All the female participants had long hair, while all the boys had short hair. We found no differences in pediculosis attributable to gender, weight or height. At the initial visit, all the affected children complained of pruritus (Table 1), and on examination 41% (n ⫽ 18) had excoriations localized to their scalp and posterior neck region. All 44 children had viable nits, the majority (93%, n ⫽ 41) with a moderate to abundant amount (Table 2), and 14 children (31.8%) had live adult lice. At the second visit, 1 week after treatment with a single dose of ivermectin, adult lice had been eradicated in all the children. Nits were still present in 40 (90.1%) children, although there was a reduction in nit density and most of these nits were nonviable. A second dose of ivermectin was given to 18 (41%) children who had moderate-to-abundant nits, some of which were viable. At the third and final visit, nits were present in 30 (68.2%) children, but most of these children (27/30) had only a few nits. On close inspection, these were nonviable nits. At both the second and third visits, 12 (27.3%) children complained of persistent pruritus, but the intensity of pruritus had decreased (Table 1). Excoriations had improved considerably by the second visit, when they were present in only 2 (4.5%) children, and had resolved in all the children by the third visit. To obtain reliable information about adverse drug effects and as most of the parents did not speak Spanish but spoke Mazahua, we asked specific closed questions such as “did your child get headaches” and “did your child complain of any problems after taking the medicine?” Treatment was very well-tolerated with no reports of adverse effects in any children. A single child reported the expulsion of helminths in the feces after the second dose of medication. DISCUSSION Pediculosis capitis is the most prevalent ectoparasitic infestation affecting humans in the United States and Europe.12 Its social, economic, and educational effect is considerable.13 Treat- TABLE 1. Intensity of Pruritus Children With Pruritus (%) Visit First Second Third 992 Negative Light Moderate Severe Total 0 32 (72.7) 32 (72.7) 2 (4.5) 9 (20.5) 9 (20.5) 17 (38.6) 2 (4.5) 2 (4.5) 25 (56.8) 1 (2.3) 1 (2.3) 44 44 44 | www.pidj.com TABLE 2. Presence of Excoriations No. Excoriations (%) Visit First Second Third Negative ⬍5 5–10 ⬎10 Total 26 (59.1) 42 (95.5) 44 (100) 14 (31.8) 2 (4.5) 0 4 (9.1) 0 0 0 0 0 44 44 44 ment with topical pesticides is time-consuming, unpleasant and has also been associated with adverse effects. Lindane, an organochloride with similar properties to DDT, is absorbed into adipose and neural tissue and is known to cause neurotoxicity and anemia.14 It is now rarely used with the availability of more tolerable treatments. Pyrethrin, permethrin, and malathion have low or negligible risks of percutaneous absorption, but they can be associated with irritation, rash, and allergic reactions. Malathion must be used with caution as it has an inflammable base.2,15 In addition, these agents have reduced efficacy and are associated with high rates of treatment failure attributed to the development of resistance. Insecticidal activity of the pyrethroids, for example, has dropped markedly from 100% in the 1980s in the United States to only 28% in 2000.5 Double resistance to malathion and pyrethrin has also been observed in parts of the United Kingdom, and the pattern of resistance in any region appears to follow the pattern of pediculicide used.16 Resistance may have developed as a result of changes to the formulation, improper use, slow pediculicidal action, and the effects of residual pediculicide.17 Mechanisms of resistance have been attributed to involvement of the cytochrome monooxygenase P450 system,18 glutathione-S-transferase-based resistance,19 and mutations of the voltage-gated sodium channel gene.20 Crossresistance among the pediculicides is also of concern, and may be due to nerve sheath resistance.15 Given that some of the causes of pediculicide resistance relate to their topical formulation, effective systemic agents associated with low risks of toxicity represent an attractive therapeutic alternative. Furthermore, in patients with severe skin excoriations, topical treatments can be painful, and systemic therapy is often preferable if there is severe secondary bacterial infection.9 Albendazole, a commonly used and well-tolerated agent used to treat a variety of helminth infestations, has been tested in a pediatric population with pediculosis capitis. A single dose (400 mg) produced only a 60% success rate compared with 80% for topical 1% permethrin.21 Levamisole, another antihelmintic, eradicated pediculosis capitis in 70% of cases, but this requires a 10-day course of treatment.22 Trimethoprim/sulfamethoxazole, which is believed to interfere with louse vitamin B synthesis, demonstrated an 83% success rate when given for two 3-day courses of treatment separated by a 1-week interval.23 A later large study using trimethoprim/sulfamethoxazole demonstrated no benefit.24 Ivermectin is an attractive option for the systemic treatment of pediculosis capitis as single-dose therapy has already demonstrated potent insecticidal effects in the treatment of scabies in children,25 and those younger than the age of 5 years.26 Its safety has been demonstrated for more than a decade in its use in the control of onchocerciasis.27 It is effective in the treatment of body lice.8 There have been very few clinical studies of its use in the management of pediculosis capitis. An early study demonstrated clinical and parasitologic cure after a single application of 0.8% topical solution in a cohort of 25 patients with pediculosis capitis,7 and the efficacy of topical ivermectin has recently been confirmed in an in vitro study.28 However, topical ivermectin therapy offers no additional benefits over existing topical pediculicides. There is © 2010 Lippincott Williams & Wilkins The Pediatric Infectious Disease Journal • Volume 29, Number 11, November 2010 only 1 study of systemic ivermectin in the English literature. Glaziou et al5 in an open study in French Polynesia treated a cohort of 26 patients (age range, 5–17 years) with a single dose of oral ivermectin (200 ␮g/kg). They reported clinical cure in 27% and a partial response in 77% of the remaining patients. Our study demonstrates that a single dose of ivermectin is sufficient to kill all adult parasites, but a second dose was required in 41% of children because of the presence of viable nits. One week after the second dose there was marked reduction in nit density and they were nonviable suggesting cure. It was not practical to conduct a further follow-up visit to this remote community to ensure that they remained lice-free. Our dosing schedule followed the accepted dosage and schedule used for the treatment of scabies.29 However, it has been suggested that on the basis of the head lice life cycle, a third treatment with ivermectin may be necessary to ensure complete clearance of all lice, including newly hatched nymphs.30 In addition, the use of a nit comb may ensure complete egg removal thereby improving the clearance of viable nits and removing their potential to hatch.15 This study demonstrates good efficacy and tolerability of ivermectin in the treatment of pediculosis capitis in children. To date, resistance to ivermectin has not been reported in head lice,9 making it a very useful option in the management of cases resistant to standard pediculicides. REFERENCES 1. 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