Effectiveness of Topical 0.5% Ivermectin Shampoo in the Treatment of Pediculosis Capitis among School-going Female Children.

Background: Pediculosis is a common ectoparasitic infestation in children. There are different treatment modalities that have been used in the treatment of pediculosis capitis from time immemorial, each with their own shortcomings. Increasing emergence of resistance to permethrin has led to the lookout for newer alternatives. Aims and
Objectives: The role of topical ivermectin in the management of pediculosis in people with culturally different hair grooming practices is analyzed in this study. Materials and
Methods: This observational open-label clinical study was conducted in September-November 2019 in the schools that were under the rural health center at South India among school-going female children aged between 13 and 16 years of age and diagnosed with pediculosis.
Results: This study demonstrated that a single application of ivermectin shampoo was able to kill head lice in 86.2% of the participants. In participants with persistent infection (13.8%), a repeat application killed the entire louse and 100% efficacy was demonstrated. Topical ivermectin is devoid of systemic side effects of oral ivermectin. Topical ivermectin has found to be more effective than contemporary recommended agents such as malathion and permethrin. Copyright:

INTRODUCTION

Pediculosis is a common ectoparasitic infestation in children. Head lice (Pediculus humanus capitis) infestation causes many physical symptoms such as pruritus, excoriation, cervical lymphadenopathy, and conjunctivitis.[1] It also causes various negative social impacts such as anxiety in parents and stigmatization of infested children.[2] Different treatment modalities have been used in the treatment of pediculosis capitis. They include both physician prescribed and over the counter drugs. Indiscriminate and irrational use of pediculicides had led to the emergence of resistance for many pediculicidals.[3] Increasing emergence of resistance to permethrin has led to look out for newer alternatives.[4] Topical ivermectin has been found to be effective in the treatment of pediculosis.[5] Ivermectin is used extensively as oral treatment for louse infestation. Topical ivermectin formulation could avoid the need for administration of systemic medication.[5] Topical ivermectin avoids the side effects that develop due to oral treatment.[6] The role of topical ivermectin in the management of pediculosis in people with culturally different hair grooming practices are analyzed in this study.

METHODOLOGY

Study design

This observational, open-label clinical study was conducted in September–November 2019 in the schools that were under the rural health center at Thiruvenainallur, Villupuram district, Tamil Nadu, South India. The rural health center is under the control of Sri Manakula Vinayagar Medical College and Hospital, Pondicherry. Rural populations are the most understudied and the diseases like pediculosis which are prevalent in this population provide an opportunity to study this population.

The study was approved by the Institute Ethics Committee and was performed according to the World Medical Association declaration of Helsinki ethical principles for medical research involving human subjects and the Indian Council for Medical Research guidelines for biomedical research in human participants. Further, the required permission was obtained from the concerned school health authorities.

Inclusion criteria

School-going female children aged between 13 and 16 years of age and diagnosed with pediculosis. Females are more likely to contract head lice, possibly due to their typically longer hair and more frequent head-to-head contact with other people.

Hence, only female children were included in the study.

Exclusion criteria

Participants who have used any head lice treatment within 4 weeks of enrolment were not included in the study. Children with scalp disorders, history of seizures, psychiatric disorders, and known hypersensitivity to any pediculocidal drugs were excluded from the study.

Study protocol

All the children diagnosed to have pediculosis and with the assent of the parent were included in the study based on the recommendation of International Guidelines for clinical trials with pediculicides.[7] It recommends that at least five live lice and five apparently live eggs should be visualized.

This was done using a hand lens and combing the hair with combs with gap of 2 mm and having blunt tips with parallel-sided teeth. The children were given verbal instructions about the usage of ivermectin 0.5% shampoo and a bottle of 100 ml ivermectin shampoo was given to them. They were also provided with a written instruction in the local dialect. The treatment was given on day 1, day 7, and day 14. The children were provided with a plastic comb and very strictly instructed to use only the comb to avoid fomite transmission. The efficacy of the treatment was judged by the disappearance of the lice and nits using dry comb after one, two, or three applications. Additional assessment such as

Intensity of pruritus

Clinical scoring of dryness, redness, irritation, and flakiness was studied using the Visual Analog Scale

Clinical scoring of irritation, discomfort, and itching during the treatment to assess side effects of topical medication.

The grading in the Visual Analog Scale was mild, moderate, and severe.

Evaluation criteria

Main efficacy criterion

The children during the visit on day 1 were subjected to dry combing four to five times by social worker and observed by the primary investigator. The absence of any lice was taken as “louse free.” In case of the detection of live louse, the child was enquired about the proper usage. In case of live lice in spite of the proper treatment, a repeat treatment with ivermectin shampoo was advised.

The efficacy of treatment was expected as louse-free rate. The failure of treatment was declared on the detection of louse after two treatments.

Secondary efficacy

The children were evaluated following the same procedure as on the first visit on their subsequent visits on day 7 and 14. The detection of lice on any of the visits was considered as treatment failure.

Criteria for evaluation of symptoms

Pediculosis can be associated with dryness, redness, irritation, and flakiness. During each visit, patients were evaluated on these parameters and if present were scored on a Visual Analog Score.

Criteria for evaluation of safety (local tolerance)

The investigator interviewed the participant during each visit for any adverse effects following the application of ivermectin shampoo. They were enquired for irritation, discomfort, and itching during and after application.

RESULTS

A total of 196 children were included in the study after they were diagnosed with pediculosis capitis based on International guidelines for clinical trials with pediculicides.

The mean (±standard deviation) age of the children included in the study was 12.78 ± 1.373, and all were female children. About 109 (55.6%) children reported to have long hair and 73.5% had straight hair. It is also to be noted that all our patients had hair up to their shoulder. All of them plaited their hair. Long hair makes combing and maintenance of hair a perennial problem.

About 186 children (94.9%) reported previous infestation with head lice. Around 79.6% of the children gave a history of sharing comb, towel with family members, and 79.1% with a positive history of a family member with head lice infestation.

The baseline examination (day 0) of the head lice infestation before the treatment showed that 131 (66.8%) children had a Score of 1 (<10 lice), 51 (26%) had Score 2 (10–20 lice), 12 (6.1%) had Score 3 (≥20 lice), and 2 (1.1%) had Score 0 (no lice). The scoring of head lice infestation done after the application of 0.5% topical Ivermectin shampoo on day 7 showed that 86.2% of the children had Score 0 followed by 13.8% with Score 1 and none with Score 2 or 3. The proportions of children with Score 0 on the repeat examination done on day 14 and day 22 was 100% and 99%, respectively. Two children showed lice infestation (Score 1) on day 22 [Table 1].

Table 1

Cure rate of the study population before and after the application of 0.5% topical ivermectin shampoo

Score	Before treatment Day 0	After treatment
		Day 7	Day 14	Day 22
0=None	2 (1.1)	169 (86.2)	196 (100)	194 (99)
1=<10	131 (66.8)	27 (13.8)	0	2 (1)
2=10-20	51 (26)	0	0	0
3=>20	12 (6.1)	0	0	0

The self-reported symptoms associated with head lice infestation before treatment (day 0) showed that 45.4% of children had severe pruritus which decreased after the treatment to 1.5% on days 7 and 14. The number of children with absence of scalp dryness increased from 67.3% before treatment to 94.4% on day 22 after treatment. Redness was reported as a symptom by 1% of the children before treatment and none had redness after treatment on day 22.

The side effects reported by the children after treatment with 0.5% Ivermectin shampoo is shown in Table 2. On day 7, 3 (1.5%) reported light irritation, 2 (1%) had light discomfort, and none developed itching. Majority of the children, 98.5% had no irritation and 99% had no discomfort. On day 14, the proportion of children with light and severe irritation was 2.6% and 0.5%, respectively, whereas 4.6% of them developed severe discomfort and 1.5% had light discomfort and 2% had light itching. Similarly, the side effects reported on day 22 after treatment was 0.5% had light irritation, 1% had severe discomfort, 3.6% had severe discomfort, and 0.5% had light itching.

Table 2

Symptoms associated with head lice infestation before and after treatment with 0.5% topical ivermectin shampoo

Score	Before treatment Day 0	After treatment
		Day 7	Day 14	Day 22
1. Pruritis
0=Absent	6 (3.1)	143 (73)	167 (85.2)	190 (96.9)
1=Light	53 (27.0)	38 (19.4)	20 (10.2)	6 (3.1)
2=Moderate	48 (24.5)	12 (6.1)	6 (3.1)	0
3=Severe	89 (45.4)	3 (1.5)	3 (1.5)	0
2. Scalp dryness
0=Absent	132 (67.3)	179 (91.4)	170 (86.7)	185 (94.4)
1=Light	36 (18.4)	12 (6.1)	13 (6.6)	7 (3.6)
2=Moderate	15 (7.7)	3 (1.5)	6 (3.1)	4 (2.0)
3=Severe	13 (6.6)	2 (1.0)	7 (3.6)	0
3. Redness
0=Absent	194 (99)	195 (99.5)	194 (99)	196 (100)
1=Light	1 (0.5)	1 (0.5)	0	0
2=Moderate	0	0	1 (0.5)	0
3=Severe	1 (0.5)	0	1 (0.5)	0

DISCUSSION

Pediculosis is classified as one of the six epidermal parasitic skin disease categorized under neglected tropical diseases.[8] In developing countries plagued by many killer diseases, pediculosis is often dismissed as being too minor a problem. However, pediculosis capitis remains a public health issue with both social and medical implications.

The treatment with oral or topical medications is typically required for head lice eradication. Resistance to traditional topical therapies for head lice infestation is increasing, creating a need for consideration of additional treatment options. Resistance to 1% permethrin has been reported, but its prevalence is unknown. In this era of widespread resistance to pediculicidal agents such as permethrin, the efficacy of ivermectin as a topical agent gains importance.[7]

Topical ivermectin 0.5% lotion has been approved by the Food and Drug Administration. Topical ivermectin is absorbed transcutaneously by head lice and is actively transported across the cell membranes by P-glycoprotein. Ivermectin binds selectively, irreversibly, and with a high affinity to glutamate-gated chloride ion channel receptors which causes hyperpolarization, paralysis, and death.[9]

This study was conducted in a high endemic area for pediculosis capitis. This study demonstrated that a single application of ivermectin shampoo was able to kill head lice in 86.2% of the participants. In participants with persistent infection (13.8%), a repeat application killed the entire louse and 100% efficacy was demonstrated. As proposed by the international guidelines for clinical trials with pediculocides, a louse-free rate of 90% ±3% was almost achieved with a single dose.[7] The persistent infection could have been possibly due to improper application or failure to comply with the instructions. The cure rate was 100% on the day 7th of treatment, but two children had lice on examination on the 14th day. This could be due to inadequate exposure of ivermectin to louse eggs and reinfestation from the house hold contacts.

The efficacy of ivermectin shampoo 2 weeks after single treatment is intriguing. This is probably due to ovicidal action of ivermectin.[8] In this context, it is interesting to note that the girls and women wash their hair once weekly and not daily in the local community. They usually wash their hair only on Fridays which is considered to be auspicious. This habit of weekly washing of hair probably results in prolonged local action of topical ivermectin.

Pruritus is the hallmark of pediculosis which completely subsided after the single application in 73% of patients by day 1. In 96.9% of patients, the pruritus completely subsided and rest 3.1% had only mild pruritus. Pruritus in pediculosis is due to sensitization to salivary antigens and reduction in pruritus is an indication of eradication of infestation.

On the application of ivermectin, 1.5% children had irritation which increased to 3.1% on day 7. However, it subsided by day 14. These children did not have overt signs of irritant reaction.

Oral ivermectin is effective but with its own side effects.[10] Topical ivermectin is a safe alternative to oral agent. Meinking et al. in their study found that a single application of this formulation of ivermectin lotion was effective in eliminating head lice in most subjects within 6 h of treatment and in maintaining elimination for 14 days postapplication. In this dose selection study, the formulation containing 0.5% ivermectin provided the greatest reduction in head lice infestation.[11] In a study by Chosidow et al., ivermectin shampoo was effective than Malathion after a single application.[12]

Topical ivermectin 0.5% lotion has the advantage of requiring only a single treatment, which should improve adherence.[10]

It is also important to note that most treatment failure can be attributed to causes other than resistance.[13] These causes include poor compliance, improper use of the antilice product, lack of nit removal, new exposure to lice, and use of an out-of-date preparation.[14]

Topical ivermectin has a well-established safety profile and shows high efficacy within 24 h, with most treated patients remaining louse-free without the need for nit combing.[15]

This study was a community school-based study and controls were not used. Further, large scale studies are required to study the efficacy of ivermectin shampoo.

CONCLUSION

Topical ivermectin has found to be more effective than contemporary recommended agents such as malathion and permethrin. Widespread permethrin resistance has resulted in look out for alternatives that are less toxic and more effective. In this context, topical ivermectin provides a safe alternative with a good efficacy and very low toxicity profile.

Financial support and sponsorship

This study was financially supported by supply of drugs from Kaizen Pharma.

Conflicts of interest

There are no conflicts of interest.