Study of efficacy and cost effectiveness of topical permethrin, benzyl benzoate and oral ivermectin in the treatment of scabies

Background: Scabies is an ectoparasitic infestation caused by the mite Sarcoptes scabiei var hominis that occurs due to direct skin to skin contact.It is a common public health problem that affects humans regardless of age, gender and social class.An ideal scabicide should be effective against both adult and egg of the mite, easily applicable, acceptable, nontoxic, and economical. It should be safe to use in all ages. Objectives: To compare the therapeutic efficacy and cost effectiveness of topical 5% permethrin, 25% benzyl benzoate and oral ivermectin (200mcg/kg/dose) in the treatment of scabies. Materials and Methods: A total of 90 patients with scabies attending the dermatology outpatient at the Department Of Dermatology, Venereology and Leprosy, Adichunchanagiri Hospital and Research Centre, B.G. Nagara, were randomly divided into three treatment groups A, B and C with 30 patients in each group. Group A patients received 5% permethrin cream which was made to remain in contact with the skin for at least 8 hours. This was repeated after 7 days. Group B patients received 25% benzyl benzoate lotion which was made to remain in contact with the skin for at least 8 hours. This was done for three consecutive nights. Group C patients received oral ivermectin in a single dose of 200mcg/kg body weight taken with meals and it was repeated after 10 days. All patients were followed up at the end of first, second and third week to assess clinical grading score and pruritus grading score by visual analogue scale. The cost effectiveness was calculated on basis of total expenditure on medicine at the end of the third week and cure rate of the three groups were compared on the basis of amount needed to treat one case successfully. Results: At the end of third week, complete clinical cure was seen in 28 (93.3%) patients in group A, 13 (43.3%) patients in group B and 22 (73.3%) of patients in group C. Permethrin was more efficacious than benzyl benzoate and ivermectin, which was found to be statistically significant (p value= 0.00003, 0.037 respectively). At the end of treatment, benzyl benzoate was more cost effective than permethrin (p value<0.00001) and ivermectin. This was found to be statistically significant. Conclusion: From this study it can be concluded that topical permethrin is the most efficacious in the treatment of scabies, compared to oral ivermectin and topical benzyl benzoate. However, topical benzyl benzoate was most cost effective than topical permethrin and oral ivermectin. © This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Introduction
Scabies is an ectoparasitic infestation caused by the mite Sarcoptes scabiei var hominis that occurs due to direct skin to skin contact. 1 It is a common public health problem disease is highest in developing countries where the disease is endemic.
Management of scabies includes use of topical antiscabietic drugs like permethrin 5% cream, benzyl benzoate 10-25% lotion, gamma benzene hexachloride 1% lotion, crotamiton 10% lotion, malathion 0.5% lotion applied all over the body for a specified contact period to patients and their close contacts and oral ivermectin in the dose of 200mcg/kg body weight. 1 An ideal scabicide should be effective against both adult and egg of the mite, easily applicable, acceptable, nontoxic, and economical. It should be safe to use in all ages. There are various treatment modalities for scabies but yet there is a lacuna for an ideal scabicide. 1 The economical and psycho-social impact of this commonly prevalent disease is significant especially among the population who have poor affordability for the most efficacious anti-scabietic drug, hence carried out the present study to compare the therapeutic efficacy and cost effectiveness of topical 5% permethrin, benzyl benzoate 25% and oral ivermectin in patients with scabies at a rural tertiary care hospital. 1. To compare the therapeutic efficacy of topical 5% permethrin, 25% benzyl benzoate and oral ivermectin (200mcg/kg/dose) in the treatment of scabies. 2. To compare the cost effectiveness of topical 5% permethrin, 25% benzyl benzoate and oral ivermectin in the treatment of scabies.

Source of data
The study was conducted at the Department Of Dermatology, Venereology and Leprosy, Adichunchanagiri Hospital and Research Centre, B.G. Nagara, Nagamangala Taluk, Mandya District, on an outpatient basis.

Study duration
18 Months.

Study subjects
New patients of scabies diagnosed by dermatologist of either gender aged between 5 and 60.

Study design
Quasi experimental study.

Sample size
Patientse in each group Total of 90 patients.

Procedure of the study
A total of 90 patients with scabies attending the dermatology outpatient department and satisfying the aforementioned inclusion and exclusion criteria were recruited in the study. A detailed dermatological examination of the lesions along with baseline itching and clinical grade scoring was done.

Diagnosis of scabies
For the diagnosis of scabies, the following criteria was taken into consideration: 5 1. History of intense nocturnal pruritus. 2. History of similar complaints in the close family members or contacts. 3. Patient presenting with typical lesions of scabies like burrows, vesicles, papules, nodules or pustules at classical sites on the body like interdigital folds of the hands, the flexor aspects of the wrists, elbows, the anterior and posterior axillary folds, the periumbilical areas, waist, shaft of penis, vulva, gluteal region and the lateral aspects of the feet. 6 4. Microscopic demonstration of the mite, egg, fecal pellets or larvae using 10% potassium hydroxide.

Clinical grading of scabies
At baseline, the severity of the lesions was clinically graded objectively on a scale of 0 to 3. 1 • Grade 0-free of lesions (no lesions) • Grade 1-10 or fewer lesions (mild) • Grade 2-11 to 49 lesions (moderate) • Grade 3-50 or more lesions (severe)

Grading of pruritus
The assessment of pruritus was done subjectively on a scale of 0 to 10 using visual analogue scale (VAS) at baseline. Itching was graded on a visual analogue scale of 0 to 3 on basis of severity.

Sampling
90 patients diagnosed with scabies was randomly divided into three treatment groups A, B and C according to computer generated random numbers and the following interventions were applied:

Group A
Patients received 5% permethrin cream 30g and they were advised to apply the cream to the whole body covering from below neck to toe and it was made to remain in contact with the skin for at least 8 hours. The participants were advised to take scrub bath with warm water before application and on subsequent morning. A second application of same treatment was advised after 7 days.

Group B
Patients received 25% benzyl benzoate lotion and they were advised to apply the lotion to the whole body covering from below neck to toe and it was made to remain contact with the skin for at least 8 hours. The participants were advised to take scrub bath with warm water before application and on subsequent morning. This was done for three consecutive nights.

Group C
Patients received oral ivermectin in a single dose of 200mcg/kg body weight taken with meals and it was repeated after 10 days.
Patients were advised not to use any other medication including anti pruritic agents during the study period.
Participants were advised about treatment of the family members and their close contacts at the same time during the first visit. They were also be advised regarding prevention of fomite transmission by washing all infested clothes and bedding and drying them in the sun.

Clinical assessment
All patients were followed up at the end of first, second and third week to assess the compliance and to evaluate the efficacy and safety of treatment.
At each of the three visits detailed examination of the entire body surface was performed and compared with baseline clinical grading score and itching grading score.

At each visit, improvement was graded as: 7
Mild: clinical grading score (grade 2 or 3) + itching grading score (grade 2 or 3). Moderate: clinical grading score (grade 1) + itching grading score (grade 1). Good: clinical grading score (grade 0) + itching grading score (grade 0). The participants who were not cured at the end of three weeks were switched over to treatment with standard 5% permethrin cream.
The patients were asked for any adverse events occurring during the period of study which was recorded in detail during each follow up visits.

Cost effectiveness assessment
The cost effectiveness was calculated on basis of total expenditure on medicine (in INR) at the end of the third week and cure rate (in %) and the three groups were compared on the basis of amount needed to treat one case successfully. 1 • Cost of permethrin 5% 30g-Rs. 54.75. • Cost of ivermectin 12mg-Rs. 23 and 6mg-Rs. 16. Graph 1: Improvement in pruritus grade at each follow up in the three groups of patients studied.
At the end of third week, assessment of improvement in clinical grade showed that significant number of patients in group A 18 (60%) had clinical grade 0 compared to 11 (36.7%) patients in group B and 12(40%) patients in group C respectively. Graph 2: Improvement in clinical grade at each follow up in the three groups of patients studied 1. At the end of third week, complete microscopic clearance was seen in all (100%) patients in group A, whereas 20 (66.7%) in group B and 24 (80%) in group C had complete microscopic clearance.

At the end of 3 weeks, the mean lesion count in group
A patients treated with permethrin cream was less than that of group B patients treated with benzyl benzoate (p=0.818, which was not statistically significant) and group C patients treated with oral ivermectin (p=0.448 which was not statistically significant). 3. At the end of treatment, group A was having better mean percentage reduction of lesions (11.2%) as compared to 7.7% patients in group B ( p=0.818) and 9.7% in group C (p=0.594). This was not found to be statistically significant.
Graph 3: Mean percentage of reduction in lesion count in the three groups of patients studied 1. In the present study at the end of 3 weeks, 36.7% in group A, 13.3% in group B and 23.3% in group C had good improvement. Hence, permethrin showed better improvement than benzyl benzoate (p=0.0268 which was significant) and ivermectin (p=0.3175, which was not found to be significant). 2. At the end of third week, complete clinical cure was seen in 28 (93.3%) patients in group A, 13 (43.3%) patients in group B and 22 (73.3%) patients in group C. Hence permethrin was more efficacious than benzyl benzoate (p=0.00003 which was highly significant) and ivermectin (p=0.037 which was significant). Ivermectin was more efficacious than benzyl benzoate (p=0.018 which was significant).
Graph 4: Comparison of complete clinical cure in the three groups of patients at the end of three weeks 1. At the end of treatment at 3 weeks, benzyl benzoate was more cost effective than permethrin (p value<0.00001) and ivermectin. (p value<0.00001) which was highly significant. 2. No adverse effects were observed in any of the treatment groups.
Graph 5: Cost in rupees to effectively cure cases in the three groups of patients studied

Introduction
Scabies is a common public health problem that affects humans regardless of age, gender and social class. The economical and psycho-social impact of this commonly prevalent disease is significant especially among the population who have poor affordability for the most efficacious anti-scabietic drug, hence we conducted the present study to compare the therapeutic efficacy and cost effectiveness of topical 5% permethrin, benzyl benzoate 25% and oral ivermectin in patients with scabies at rural tertiary care hospital.

Baseline parameters
1. In the present study, mean age was found to be 23.7111 ±2.276. In a study conducted by Abdel-Raheem TA et al, 3 mean age was found to be 25.33 ±12.84 years. 2. In our study, age range was found to be from 6 years to 57 years. In a study conducted by Abdel-Raheem et al, 3 age range was found to be between 7 years to 50 years. 3. In the present study, overall male preponderance was seen with male is to female ratio being 1.43:1. In another study conducted by Sharma et al, 5 overall male preponderance was seen with male is to female ratio being 1.5:1. In a study conducted by Abdel-Raheem et al, 3 overall female preponderance was seen with male to female ratio being 0.72:1.

Improvement in clinical grading at each follow up
1. Group A-In the present study, 30 patients were treated with permethrin 5% cream which was applied to the whole body covering from below neck to toe and it remained in contact with the skin for at least 8 hours.
At the end of first week, 26.7% (8)  Permethrin was more efficacious than benzyl benzoate and ivermectin, which was found to be statistically significant (p value= 0.00003, 0.037 respectively). 5. In a study done by Abdel-Raheem TA et al, 3 at the end of two weeks, complete clinical cure was seen in 88% of patients treated with permethrin, 80% of patients treated with benzyl benzoate and 84% of patients treated with oral ivermectin.

Cost effectiveness of three groups at the end of treatment
In the present study when cost effectiveness of the three groups was compared at the end of treatment, benzyl benzoate (Rs 46.20) was found to be more cost effective than permethrin (Rs 121.10) (p value<0.00001), and ivermectin (Rs 55.70). Bachewar NP et al 9 found that permethrin gave faster symptomatic relief but ivermectin was more cost effective. Similarly, Prabodh et al 1 found that ivermectin was more cost effective than permethrin. Abdel-Raheem TA et al 3 found that benzyl benzoate was more cost effective than ivermectin. Meenakshi M et al 7 found that ivermectin is more cost effective than permethrin and gamma benzene hexachloride. Chhaiya SB et al 10 found that ivermectin is more cost effective than permethrin.

Conclusion
From this study it can be concluded that topical permethrin is the most efficacious in the treatment of scabies, compared to oral ivermectin and topical benzyl benzoate. However, topical benzyl benzoate was more cost effective than topical permethrin and oral ivermectin.

Source of Funding
No financial support was received for the work within this manuscript.

Conflict of Interest
The authors declare that they have no conflict of interest.