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1

Supplemental Table I. Databases and search strategies

Database Step Query Items found

MEDLINE via PubMed

#1 scabi* 4555 #2 sulfur 76488 #3 sulphur 76488 #4 "benzyl benzoate" 493 #5 lindane 5422 #6 "benzene hexachloride" 695 #7 hexachlorocyclohexane 6123 #8 malathion 3482 #9 malation 11 #10 crotamiton 147 #11 permethrin 3273 #12 ivermectin 6985 #13 pyrethr* 9580 #14 aloe* 3046 #15 "Plants, Medicinal"[Mesh] 56204 #16 #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11

OR #12 OR #13 OR #14 OR #15 161400

#17 #1 AND #16 1080 #18 #1 AND #16 Filters: Humans 806

Scopus #1 ALL ( scabi* ) 18593 #2 ALL ( sulfur ) 838627 #3 ALL ( sulphur ) 838627 #4 ALL ( "benzyl benzoate" ) 2833 #5 ALL ( lindane ) 22366 #6 ALL ( "benzene hexachloride" ) 2196 #7 ALL ( hexachlorocyclohexane ) 12811 #8 ALL ( malathion ) 21789 #9 ALL ( malation ) 208 #10 ALL ( crotamiton ) 962 #11 ALL ( permethrin ) 18777 #12 ALL ( ivermectin ) 22790 #13 ALL ( pyrethr* ) 42890 #14 ALL ( aloe* ) 33768 #15 ALL ( plant* ) 4543180 #16 ALL ( herb* ) 1521822 #17 ALL ( sulfur OR sulphur OR "benzyl

benzoate" OR lindane OR "benzene hexachloride" OR hexachlorocyclohexane OR malathion OR malation OR crotamiton OR permethrin OR ivermectin OR pyrethr* OR aloe* OR plant* OR herb* )

6189842

#18 ( ALL ( scabi* ) ) AND ( ALL ( sulfur OR sulphur OR "benzyl benzoate" OR lindane OR "benzene hexachloride" OR hexachlorocyclohexane OR malathion OR malation OR crotamiton OR permethrin OR ivermectin OR pyrethr* OR aloe* OR plant* OR herb* ) )

8297

#19 ALL ( "clinical trial" ) 2151728 #20 ALL ( randomi* ) 2993656 #21 ( ( ALL ( scabi* ) ) AND ( ALL ( sulfur OR sulphur OR "benzyl

benzoate" OR lindane OR "benzene hexachloride" OR hexachlorocyclohexane OR malathion OR malation OR crotamiton OR permethrin OR ivermectin OR pyrethr* OR aloe* OR plant* OR herb* ) ) ) AND ( ( ALL ( "clinical trial" ) ) OR ( ALL ( randomi* ) ) )

1192

Cochrane Central

#1 scabies (in ‘all text’) 169 #2 #1 Limit: Trials 150

2

Register of Controlled Trials Online Computer Library Center

#1 scabies 12819 #2 #1 Limit: Thesis/dissertation 292

Thai-Journal Citation Index Centre

#1 scabies (in abstract, keywords; only from 2014 onwards) 0 #2 scabies (in title) 5

WHO-ICTRP

#1 scabies 216

3

Supplemental Table II. Studies excluded on full text

Citation Reason for exclusion

Alebiosu CO, Ogunledun A , Ogunleye DS. A report of clinical trial conducted on Toto ointment and soap products. J Natl Med Assoc 2003;95:95-105.

Non-RCT

Alrawashdeh B , Alazab K. Comparison between 25% benzyl benzoate, 5% permethrin and 10% crotamiton in the treatment of scabies in Gaza. Rawal Medical Journal 2013;38:125-6.

Non-RCT

Amer M, El-Bayoumi M , Rizk MK. Treatment of scabies: preliminary report. Int J Dermatol 1981;20:289-90.

Non-RCT

Bockarie MJ, Alexander ND, Kazura JW, Bockarie F, Griffin L , Alpers MP. Treatment with ivermectin reduces the high prevalence of scabies in a village in Papua New Guinea. Acta Trop 2000;75:127-30.

Non-RCT

Burkhart CN , Burkhart CG. Before using ivermectin therapy for scabies. Pediatr Dermatol 1999;16:478-9; discussion 80.

Narrative review

Elgart ML. Cost-benefit analysis of ivermectin, permethrin and benzyl benzoate in the management of infantile and childhood scabies. Expert Opin Pharmacother 2003;4:1521-4.

Narrative review

Goldust M , Rezaee E. Comparative trial of oral ivermectin versus sulfur 8% ointment for the treatment of scabies. J Cutan Med Surg 2013;17:299-300.

Comment/letter

Goldust M, Babae NS, Rezaee E , Raghifar R. Comparative trial of permethrin 5% versus lindane 1% for the treatment of scabies. Journal of Dermatological Treatment.

Duplicate study

Gulzar K, Mujtaba G , Hameed S. Comparison between effectiveness of topical 1% lindane cream and oral ivermectin in the management of scabies. Medical forum monthly.

Non-RCT

Haas N, Frank K, Jacobi U, Katzung W, Sterry W , Lademann J. [Inside-out application of ivermectin in scabies -- a hypothesis]. J Dtsch Dermatol Ges 2003;1:933-7.

Non-comparative

Hansen R, Remmers E , Menter M. A controlled comparative trial of permethrin 5 per cent cream and 1 per cent lindane lotion for the treatment of scabies. Clinical research

Duplicate study

Isaacs D , Britton P. Scabies control with ivermectin. Journal of Paediatrics and Child Health 2016;52:579.

Comment/letter

Kullavanijaya P, Pakunwanich W, Sudsuk N, Jongsatian S. [Treatment of scabies with sugar apple leaf extract in coconut oil]. Journal of the Department of Medical Services. 1992: 31-4.

Non-RCT

Mohebbipour A, Saleh P, Goldust M, Amirnia M, Zadeh YJ, Mohamad RM et al. Comparison of oral ivermectin vs. lindane lotion 1% for the treatment of scabies. Clin Exp Dermatol 2013;38:719-23.

Duplicate study

Mounsey KE, Bernigaud C, Chosidow O , McCarthy JS. Prospects for Moxidectin as a New Oral Treatment for Human Scabies. PLoS Neglected Tropical Diseases 2016;10.

Narrative review

NCT00262418. Comparison of the Efficacy and Safety of Ivermectin to Permethrin 2005.

Registered trial without author contact information

Oladimeji FA, Orafidiya LO, Ogunniyi TAB, Adewunmi TA , Onayemi O. A comparative study of the scabicidal activities of formulations of essential oil of Lippia multiflora Moldenke and benzyl benzoate emulsion BP. International Journal of Aromatherapy 2005;15:87-93.

Non-RCT

Oladimeji FA, Orafidiya OO, Ogunniyi TA , Adewunmi TA. Pediculocidal and scabicidal properties of Lippia multiflora essential oil. J Ethnopharmacol 2000;72:305-11.

Non-RCT

Riska O. [Treatment of scabies in Senegal]. Tidsskr Nor Laegeforen 2009;129:1490.

Comment/letter

Saeedi M, Hajheydari Z, Akbari J, Morteza-Semnani K , Emadian A. Preparation of malathion 0.5% lotion and studying its effect on healing scabies compared with permethrin cream 5%. Journal of Mazandaran University of Medical Sciences 2015;25:128-31.

RCT without outcomes of interest (exclusively compared efficacy using mean lesion

4

count; safety not assessed)

Sule HM , Thacher TD. Comparison of ivermectin and benzyl benzoate lotion for scabies in Nigerian patients. Am J Trop Med Hyg 2007;76:392-5.

Non-RCT

Wong LC, Amega B, Barker R, Connors C, Dulla ME, Ninnal A et al. Factors supporting sustainability of a community-based scabies control program. Australas J Dermatol 2002;43:274-7.

Non-comparative

RCT, randomized controlled trial.

5

Supplemental Table III. Characteristics of included trials

Country Treatments n Setting Age group(s)

% Male patients

% Severe cases

Use of microscopy in diagnosis and cure assessment

Abdel-Raheem (2016)19

Egypt OralIverm vs Permethrin vs BenzylB vs Sulfur

200 Hospital out-patient Both 42.0 NR Yes

Aggarwal (2014)66 India OralIverm vs Permethrin 100 Hospital out-patient Both 54.5 NR No

Ahmad (2016)21 Egypt TopIverm vs OralIverm 62 Hospital out-patient Both 41.9 56.5 Yes

Alipour (2015)22 Iran OralIverm vs Sulfur 420 Hospital out-patient Both NR NR Yes

Amer (1992)48 Egypt Permethrin vs Crotamiton vs Lindane 150 Hospital in-patient Both NR NR Yes

Amerio (2003)40 Italy SynPyrethr vs Permethrin 40 Hospital out-patient Adults 22.5 NR Yes

Ayaz (2011)58 Pakistan Herb (ScaNeem ointment) vs BenzylB 120 Hospital out-patient Both 81.7 NR Yes

Bachewar (2009)59 India OralIverm vs Permethrin vs BenzylB 80 Hospital out-patient Both 61.2 NR No

Biele (2006)37 Italy SynPyrethr vs BenzylB 240 Prison Adults 100.0 NR Yes

Bokhari (2000)62 Pakistan Permethrin vs Lindane 78 Hospital out-patient Both NR NR Yes

Brooks (2002)41 Vanautu OralIverm vs BenzylB 80 Hospital out-patient Children NR NR No

Castillo (2013)56 Philippines Herb (Tinospora cordifolia lotion) vs Permethrin

60 Youth reception centers

Both NR 1.7 No

Chhaiya (2012)32 India TopIverm vs OralIverm vs Permethrin 300 Hospital out-patient Both 55.6 16.2 Yes

Chouela (1999)45 Argentina OralIverm vs Lindane 42 Hospital out-patient Adults 35.8 NR Yes

Daneshpajooh (1999)63

Iran OralIverm vs Lindane 58 Hospital out-patient Both 63.8 NR Yes

Das (2006)70 India OralIverm vs Permethrin vs Lindane vs Paraffin

200 Hospital out-patient Both 70.0 NR Yes

Glaziou (1993)46 French Polynesia

OralIverm vs BenzylB 44 NR Both 52.3 NR No

Goldust (2014)28 Iran OralIverm vs Crotamiton 320 Hospital out-patient Both 62.5 57.8 Yes

Goldust (2014)23 Iran OralIverm vs Malathion 340 Hospital out-patient Both 61.8 57.4 Yes

Goldust (2014)24 Iran TopIverm vs Crotamiton 340 Hospital out-patient Both 55.9 52.9 Yes

6

Goldust (2013)25 Iran TopIverm vs Permethrin 380 Hospital out-patient Both 57.9 55.3 Yes

Goldust (2013)26 Iran OralIverm vs Lindane 440 Hospital out-patient Both 54.5 60.2 Yes

Goldust (2013)27 Iran Permethrin vs BenzylB (Tenutex®) 440 Hospital out-patient Both 65.9 54.5 Yes

Goldust (2012)33 Iran OralIverm vs Permethrin 242 Hospital out-patient Both 54.5 56.2 Yes

Gulati (1978)61 India BenzylB vs Sulfur 158 General community Both 47.5 NR No

Kanwar (2016)68 India OralIverm vs Permethrin vs Lindane 306 Hospital out-patient Both 58.5 NR No

Khan (2007)60 Pakistan OralIverm vs Permethrin 30 Hospital out-patient Both 63.3 NR No

Ly (2009)35 Senegal OralIverm vs BenzylB 181 Clinic Both 64.1 NR Yes

Macotela-Ruiz (1993)47

Mexico OralIverm vs Placebo 55 Hospital out-patient Both 32.7 NR No

Madan (2001)42 India OralIverm vs Lindane 150 Hospital out- and in-patient

Both 66.0 NR Yes

Manjhi (2014)65 India OralIverm vs Permethrin vs Lindane vs BenzylB

240 Hospital out-patient Both NR NR No

Meenakshi (2014)67

India OralIverm vs Permethrin vs Lindane 210 Hospital out-patient Both 67.1 21.2 No

Mila-Kierzenkowska (2017)53

Poland Permethrin vs Crotamiton vs Sulfur 54 NR Adults 40.7 NR No

Mohebbipour (2012)29

Iran OralIverm vs Lindane 248 Hospital out-patient Both 53.2 NR Yes

Mushtaq (2010)64 Pakistan OralIverm vs Permethrin 86 Hospital out-patient Both 48.8 43.0 Yes

Nnoruka (2001)43 Nigeria OralIverm vs BenzylB 59 Hospital out-patient Both NR NR Yes

Oyelami (2009)36 Nigeria Herb (crude Aloe vera gel) vs BenzylB 28 Prison and hospital out-patient

Both 73.3 NR Yes

Pourhasan (2013)30 Iran Permethrin vs Crotamiton 400 Hospital out-patient Both NR NR Yes

Rahman (2015)54 India Herb (Jarb wahikka paste) vs BenzylB 60 Hospital out-patient Adults 56.7 NR No

Ranjkesh (2013)31 Iran OralIverm vs Permethrin 60 Hospital out-patient Both 70.0 58.3 Yes

Razaee (2015)20 Iran Permethrin vs Lindane 120 Hospital out-patient Both 56.7 66.7 Yes

Razaee (2015)55 Iran TopIverm vs BenzylB (Tenutex®) 360 Clinic Both 55.6 58.3 Yes

Saqib (2012)57 Pakistan OralIverm vs Permethrin 120 Hospital out-patient Adults NR NR Yes

7

Schultz (1990)50 Mexico, USA

Permethrin vs Lindane 404 Clinic Both 63.6 51.0 Yes

Shaheen (2017)52 Pakistan OralIverm vs Permethrin 140 Hospital out-patient Adults 72.1 20.0 Yes

Sharma (2011)34 India OralIverm vs Permethrin 117 Hospital out-patient Both 60.0 69.2 Yes

Singalavanija (2003)39

Thailand Lindane vs Sulfur 68 Hospital out-patient Children 60.0 100.0 Yes

Taplin (1990)49 Panama Permethrin vs Crotamiton 94 General community Children 43.8 9.4 Yes

Taplin (1986)51 Panama Permethrin vs Lindane 46 General community Both 43.1 62.7 Yes

Usha (2000)44 India OralIverm vs Permethrin 85 Hospital out-patient Both 71.8 10.6 Yes

Wankhade (2016)69 India Perm+OralIverm vs OralIverm vs Permethrin

150 Hospital out-patient Both 58.0 18.0 Yes

Zargari (2006)38 Iran Permethrin vs Lindane 99 Hospital out-patient Both 55.6 NR Yes

BenzylB, benzyl benzoate; Herb, herbal medicine; NR, not reported; OralIverm, oral ivermectin; Paraffin, white soft paraffin; Perm+OralIverm, permethrin and oral ivermectin combination; SynPyrethr, synergized pyrethrins; TopIverm, topical ivermectin.

8

Supplemental Table IV. Additional characteristics of included studies

Multi-center

Mean (range) age, years

% Crusted scabies cases

Treatment of contacts

Prevention of fomite transmission

Abdel-Raheem (2016)19 No 25.3 (7-50) NR Yes Yes

Aggarwal (2014)66 0 NR (NR) NR Yes NR

Ahmad (2016)21 No 21.8 (5-75) 0 Yes Yes

Alipour (2015)22 No 42.2 (4-72) 0 Yes NR

Amer (1992)48 No NR (NR) NR NR NR

Amerio (2003)40 No 44.0 (NR) 0 NR NR

Ayaz (2011)58 No NR (NR) NR NR NR

Bachewar (2009)59 No NR (12-NR) 0 Yes NR

Biele (2006)37 Yes 30.5 (NR) 0 NR NR

Bokhari (2000)62 No 14.7 (NR) NR NR NR

Brooks (2002)41 No 4.9 (NR) NR NR Yes

Castillo (2013)56 Yes 14.6 (2-22) NR NR NR

Chhaiya (2012)32 No 22.6 (NR) 0 NR NR

Chouela (1999)45 No 40.8 (NR) NR Yes Yes

Daneshpajooh (1999)63 No 28.9 (7-77) 0 Yes NR

Das (2006)70 No NR (3-71) NR Yes NR

Glaziou (1993)46 No NR (5-56) NR Yes Yes

Goldust (2014)28 No 42.4 (4-72) 0 Yes NR

Goldust (2014)23 No 44.9 (4-72) 0 Yes NR

Goldust (2014)24 No 48.3 (4-72) 0 Yes NR

Goldust (2013)25 No 46.6 (4-72) 0 Yes NR

Goldust (2013)26 No 42.2 (4-72) 0 Yes NR

Goldust (2013)27 No 42.5 (4-72) 0 Yes NR

Goldust (2012)33 No 36.2 (2-84) 0 Yes NR

Gulati (1978)61 No 16.6 (NR) NR Yes NR

Kanwar (2016) No NR (6-60) NR NR NR

Khan (2007)60 No 36.9 (NR) NR NR NR

Ly (2009)35 No 16.5 (5-63) NR Yes Yes

Macotela-Ruiz (1993)47 No 24.3 (NR) NR NR NR

Madan (2001)42 No NR (NR) 1.5 Yes Yes

Manjhi (2014)65 No NR (NR) NR NR NR

Meenakshi (2014)67 No 26.7 (NR) NR Yes Yes

Mila-Kierzenkowska (2017)53 No NR (19-83) 0 Yes NR

Mohebbipour (2012)29 No 40.4 (4-72) 0 Yes NR

Mushtaq (2010)64 No NR (NR) NR NR NR

Nnoruka (2001)43 No 27.9 (5-63) NR Yes Yes

Oyelami (2009)36 Yes NR (0.5-60) NR NR NR

Pourhasan (2013)30 No 42.9 (4-72) 0 Yes NR

Rahman (2015)54 No 35.4 (NR) 0 Yes NR

Ranjkesh (2013)31 No 44.2 (4-72) 0 Yes NR

Razaee (2015)20 No 41.4 (NR) 0 NR NR

Razaee (2015)55 No 41.9 (4-72) 0 Yes NR

9

Saqib (2012)57 No 30.5 (18-60) NR Yes Yes

Schultz (1990)50 Yes 22.1 (0.167-75) NR Yes NR

Shaheen (2017)52 No 30.3 (14-53) 0 NR NR

Sharma (2011)34 No 22.8 (NR) 0 Yes Yes

Singalavanija (2003)39 No 3.2 (NR) NR Yes Yes

Taplin (1990)49 No 2.6 (NR) NR NR NR

Taplin (1986)51 No 9.1 (NR) NR Yes NR

Usha (2000)44 No 21.9 (NR) NR Yes Yes

Wankhade (2016)69 No 20.8 NR NR NR

Zargari (2006)38 No 30.2 (6-64) NR Yes Yes

NR, not reported.

10

Supplemental Table V. Dosages and regimens of treatments

Drug Concentration (%) or oral ivermectin dosage (mcg/kg)

Formulation Day(s) of drug application/ ingestion


Oral ivermectin 200 Tablet 1, 8

Permethrin 2.5 (children), 5 (adults)

Lotion 1, 2, 3, 4, 5

Benzyl benzoate 20 Cream 1, 2, 3, 4, 5

Sulfur 5 (children), 10 (adults)

Ointment 1, 2, 3, 4, 5

Aggarwal (2014)66 Oral ivermectin 200 Tablet 1

Permethrin 5 Cream 1

Ahmad (2016)21 Topical ivermectin 1 Solution 1

Oral ivermectin 100 Tablet 1

Alipour (2015)22 Oral ivermectin 200 Tablet 1

Sulfur 10 Ointment 1, 2, 3

Amer (1992)48 Permethrin 5 NR 1, 2

Crotamiton 10 NR 1, 2

Lindane 1 NR 1, 2

Amerio (2003)40 Synergized pyrethrins 0.165 Foam 1, 2, 15, 16

Permethrin 5 Cream 1, 2, 15, 16

Ayaz (2011)58 ScaNeem NR Ointment 1, 2, 3

Benzyl benzoate NR Lotion NR

Bachewar (2009)59 Oral ivermectin 200 Tablet 1


Benzyl benzoate 25 Lotion 1, 2

Biele (2006)37 Synergized pyrethrins 0.165 Foam 1, 2, 3

Benzyl benzoate 10 Lotion 1, 2, 3, 4, 5

Bokhari (2000)62 Permethrin 5 Cream NR

Lindane 1 Cream NR

Brooks (2002)41 Oral ivermectin 200 Tablet 1

Benzyl benzoate 10 NR 1

Castillo (2013)56 Tinospora cordifolia NR Lotion 1, 2, 3, 8, 9, 10

Permethrin 5 Lotion 1, 2, 3, 8, 9, 10

Chhaiya (2012)32 Topical ivermectin 1 Lotion 1



Chouela (1999)45 Oral ivermectin 150-200 Tablet 1

Lindane 1 Solution 1


Oral ivermectin 200 Tablet 1 ± 8

Lindane 1 Lotion 1, 8

Das (2006)70 Oral ivermectin 200 Tablet 1, 15

Permethrin 5 NR 1

Lindane 1 NR 1, 2

White soft paraffin - Ointment 1, 2

Glaziou (1993)46 Oral ivermectin 100 Tablet 1

11

Benzyl benzoate 10 NR NR

Goldust (2014)28 Oral ivermectin 200 Tablet 1

Crotamiton 10 Cream 1, 2, 3, 4, 5


Malathion 0.5 Lotion 1, 8

Goldust (2014)24 Topical ivermectin 1 Solution 1, 8


Goldust (2013)25 Topical ivermectin 1 Solution 1, 8

Permethrin 2.5 Cream 1, 8



Goldust (2013)27 Permethrin 2.5 Cream 1, 8

Benzyl benzoate (Tenutex®)

22.5 Emulsion 1


Permethrin 5 Cream 1, 8

Gulati (1978)61 Benzyl benzoate 25 Emulsion 1, 1, 2

Sulfur NR Ointment 1, 1, 2

Kanwar (2016)68 Oral ivermectin 200 Tablet 1

Permethrin 5 NR 1

Lindane 1 NR 1

Khan (2007)60 Oral ivermectin 200 Tablet 1, 8

Permethrin 5 NR 1, 8

Ly (2009)35 Oral ivermectin 150-200 Tablet 1

Benzyl benzoate 12.5 NR 1, 2

Benzyl benzoate 12.5 NR 1



Placebo - Tablet 1

Madan (2001)42 Oral ivermectin 200 Tablet 1

Lindane 1 Lotion 1

Manjhi (2014)65 Oral ivermectin 200 Tablet 1


Lindane 1 Lotion 1

Benzyl benzoate 25 Lotion 1

Meenakshi (2014)67 Oral ivermectin 200 Tablet 1, 8




Permethrin 5 Cream 1 ± 8

Crotamiton NR Lotion 1, 2, 8, 9

Sulfur 10 Ointment 1, 2, 8, 9



Lindane 1 Lotion NR

Mushtaq (2010)64 Oral ivermectin 200 Tablet 1


Nnoruka (2001)43 Oral ivermectin 200 Tablet 1

Benzyl benzoate 25 Emulsion 1

12

Oyelami (2009)36 Crude Aloe vera gel NR Gel 1, 2, 3, 8, 9, 10

Benzyl benzoate 12.5 (children), 25 (adults)

Lotion 1, 2, 3, 8, 9, 10

Pourhasan (2013)30 Permethrin 5 Cream 1, 8


Rahman (2015)54 Jarb wahikka NR Paste 1, 2, 3

Benzyl benzoate 25 NR 1, 2, 3

Ranjkesh (2013)31 Oral ivermectin 200 Tablet 1


Razaee (2015)20 Permethrin 5 Cream NR

Lindane 1 Lotion NR

Razaee (2015)55 Topical ivermectin 1 Solution 1, 8


22.5 Emulsion 1

Saqib (2012)57 Oral ivermectin 200 Tablet 1

Permethrin 5 Lotion 1

Schultz (1990)50 Permethrin 5 Cream 1

Lindane 1 Lotion 1

Shaheen (2017)52 Oral ivermectin NR Tablet 1


Sharma (2011)34 Oral ivermectin 200 Tablet 1, 15




Lindane 0.3 Gel 1, 8

Sulfur 10 Ointment 1, 2, 3, 4, 5, 6, 7

Taplin (1990)49 Permethrin 5 Cream 1

Crotamiton 10 Cream 1

Taplin (1986)51 Permethrin 5 Cream 1

Lindane 1 Lotion 1

Usha (2000)44 Oral ivermectin 200 Tablet 1


Wankhade (2016)69 Permethrin+oral ivermectin combination

5 (permethrin), 200 (ivermectin)

NR (permethrin), tablet (ivermectin)

1


Permethrin 5 NR 1

Zargari (2006)38 Permethrin 5 Cream 1, 8

Lindane 1 Cream 1, 8

NR, not reported.

13

Supplemental Table VI. Definition of severe case at baseline and outcomes

Definition of severe case at baseline

Term used for cure outcome

Definition of cure outcome Definition of persistent itching outcome


Severity NR Cure Negative parasitological examination, absence of new lesions

Presence of itch

Aggarwal (2014)66 > 50 lesions Efficacy Clearance of lesions, itching and absence of mites on microscopy

Outcome NR

Ahmad (2016)21 > 50 lesions Effective Marked to excellent improvement in pruritus, no lesions, absence of mites/products on microscopy

Presence of itch

Alipour (2015)22 Severity NR Cure Absence of new lesions and healing of all old lesions, regardless of postscabietic nodules

Outcome NR

Amer (1992)48 Severity NR Cure No new lesions and all original active lesions healed Outcome NR

Amerio (2003)40 Severity NR No lesion Cleared from lesions Presence of itch

Ayaz (2011)58 Severity NR Not described Improved on examination of skin (no further description) Not improved

Bachewar (2009)59 Severity NR Cure Did not have any new lesions Outcome NR

Biele (2006)37 Severity NR Clinical cure No or mild itching, no dermatological evidence of scabies, absence of positive signs of infestation in skin scrapings

Moderate to severe itch

Bokhari (2000)62 Severity NR Successfully treated

(No description) Outcome NR

Brooks (2002)41 Severity NR Not described No skin lesions Nocturnal itch

Castillo (2013)56 > 10 body sites affected

Clinical cure Complete disappearance of signs and symptoms Outcome NR

Chhaiya (2012)32 > 50 lesions Clinical cure Clinical cure of scabietic lesions (no further description) Presence of itch

Chouela (1999)45 Severity NR Clinical cure, heal

Absence of both pruritus and clinical lesions or reduction of signs and symptoms to a mild degree

Outcome NR


Severity NR Recovery Elimination of skin lesions, absence of any symptoms of scabies, negative microscopy

Itching and scratching

Das (2006)70 Severity NR Outcome NR (Efficacy reported as % improvement of lesions) Outcome NR

Glaziou (1993)46 Severity NR Recovery Complete disappearance of initial skin lesions and pruritus Outcome NR

Goldust (2014)28 > 100 lesions Cure Absence of new lesions, healing of all old lesions, regardless of postscabietic nodules

Outcome NR


Outcome NR

14


Outcome NR


Outcome NR


Outcome NR


Outcome NR

Goldust (2012)33 > 100 lesions Cure, effective Absence of new lesions and all old lesions healed Outcome NR

Gulati (1978)61 Severity NR No lesions Clearance of scabies lesions Outcome NR

Kanwar (2016)68 Severity NR Not described Severity of lesions (based on number of lesions) improved Severity of itching (based on visual analog scale) not improved

Khan (2007)60 Severity NR Efficacy, cure Relief of symptoms and disappearance of lesions Outcome NR

Ly (2009)35 Severity NR Effectiveness Complete disappearance of visible lesions and itching Outcome NR


Severity NR Clinical cure Absence of itching and no dermatologically active lesions Outcome NR

Madan (2001)42 Severity NR Complete improvement scale

No signs or symptoms of scabies Presence of itch

Manjhi (2014)65 Severity NR Not described Improvement seen with severity of lesions as parameter (no further description)

Not improved

Meenakshi (2014)67 > 50 lesions Clinical cure Reduction both in clinical grading score (up to grade 0 or 1) and itching grading score (up to grade 0, 1, or 2)

Outcome NR


Severity NR Cure Absence of new lesions, clinical improvement in skin lesions and improvement in pruritus

Outcome NR


Severity NR Cure Absence of new lesions, healing of all old lesions, regardless of postscabietic nodules

Outcome NR

Mushtaq (2010)64 > 50 lesions Efficacy, cure Disappearance of itching, clearance of skin lesions, absence of mites on microscopy

Nocturnal itch

Nnoruka (2001)43 Severity NR Recovery, heal Complete disappearance of initial skin lesions and pruritus Reported in 4-point scale, but with inconsistent n (data not included in meta-analyses)

Oyelami (2009)36 Severity NR Not described Skin lesions cleared Presence of itch

Pourhasan (2013)30 Severity NR Cure Absence of new lesions, healing of all old lesions, regardless of postscabietic nodules

Outcome NR

Rahman (2015)54 Severity NR No lesions No lesions on clinical grading Reported mean, SD of itch visual analog scale (data not included in meta-analyses)

15

Ranjkesh (2013)31 > 100 lesions Cure Absence of new lesions, healing of all old lesions, regardless of postscabietic nodules

Outcome NR

Razaee (2015)20 > 100 lesions Cure, effective Absence of new lesions, all old lesions healed Outcome NR

Razaee (2015)55 > 100 lesions Cure Absence of new lesions, healing of all old lesions, regardless of postscabietic nodules

Outcome NR

Saqib (2012)57 Severity NR Cure Absence of itching and skin lesions, negative microscopy Outcome NR

Schultz (1990)50 > 50 lesions Cure All original primary lesions were healed Presence of itch

Shaheen (2017)52 Severe itching Cure No history of itching and pruritus, evaluation of sites of lesion by physician

Outcome NR

Sharma (2011)34 > 50 lesions Clinical cure Reduction in both the number of lesions and grade of pruritus by more than or equal to 50%, and negative microscopy

At least 50% improvement in pruritus


> 100 lesions Parasitic cure No new lesions and healing of all old lesions, absence of parasites by skin scraping

Outcome NR

Taplin (1990)49 > 100 lesions Cure No new lesions, all original lesions healed Presence of itch

Taplin (1986)51 > 100 lesions Cure Absence of new lesions, all old lesions healed Outcome NR

Usha (2000)44 NR Improved Improvement in pruritus, clinical improvement in skin lesions with no new lesions, absence of mites or their products on microscopy

Outcome NR

Wankhade (2016)69 > 50 lesions Cure No new clinical lesions and improvement in pruritus Outcome NR

Zargari (2006)38 Severity NR Effective Signs of improvement of itching and no new lesions Outcome NR

NR, not reported.

16

Supplemental Table VII. Findings of re-infestation outcome

Term used for re-infestation

Time of assessment

Treatment Total patients

Patients re-infested

Re-infestation rate (%)

Quote

Ahmad (2016)21

Recurrence 4 weeks Topical ivermectin

32 0 0.0 With further follow up, lesions completely disappeared in all patients after 2 weeks of treatment with no recurrences at 4-weeks end point Oral ivermectin 30 0 0.0

Castillo (2013)56

Reinfestation 4 weeks Tinospora cordifolia

34 1 2.9 Another patient was considered reinfested because marked improvement (50%) was seen on seventh day but only a mild improvement at 14th day (17%) and 21st day (17%) was observed while on 28th day, no improvement was noted and there was reappearance of new papules in the wrist, legs and interdigits and persistent papules on genitals from 14-28th days were noted.

Permethrin 32 0 0.0

Glaziou (1993)46

Relapse 30 days Oral ivermectin 23 0 0.0 Among the patients healed before day 30 (whatever the group), no relapse was observed until day 30. Benzyl

benzoate 21 0 0.0

Gulati (1978)61 Recurrence 6 months Benzyl benzoate

89 7 7.9 On revisit six months after the entire family had been treated, it was found I that scabies had recurred in 21 (13.3 percent) of the 158 cases. The recurrence was only in 7 (7.9 percent) of the 89 patients treated with benzyl benzoate as compared to 14 (20.4 percent) of the 69 patients treated with sulphur ointment.

Sulfur 69 14 20.3


Reinfestation 1 month Permethrin 18 0 0.0 None of the patients experienced worsening of infestation during the study, but at two patients treated with sulfur ointment re-infestation occurred at one-month follow-up.

Crotamiton 18 0 0.0

Sulfur 18 2 11.1

Nnoruka (2001)43

Relapse 30 days Oral ivermectin 29 0 0.0 Amongst the patients healed before day 30 (whatever group), no relapse was observed. Benzyl

benzoate 29 0 0.0

Saqib (2012)57 Relapse, reinfested

2 weeks Oral ivermectin 60 4 6.7 A total of 8 patients in our study became reinfested with S. scabiei two weeks after treatment, n=4 in each group. Permethrin 60 4 6.7

Taplin (1986)51 Reinfestation 4 weeks Permethrin 27 1 3.7 Four weeks was considered the definitive point for evaluating the efficacy of treatments. At this time only two patients treated with permethrin had active lesions, and we were able to recover mites from both of them. One

Lindane 25 0 0.0

17

had previously been scored as completely cured at 2 weeks. We considered this patient to have become reinfested after successful treatment.

Usha (2000)44 Recurrence 8 weeks Oral ivermectin 50 0 0.0 All the patients were completely cured at the end of 8 weeks. There was no recurrence of scabies at the end of 2 months of follow-up in either group.

Permethrin 45 0 0.0

18

Supplemental Table VIII. Data for pooling

Treatment Total patients

Patients with cure at 1-2 weeks (week of assess-ment)

Patients with cure at 3-6 weeks (week of assess-ment)

Patients with persistent itching

Patients with adverse events


Oral ivermectin 55 42 (2) 13 7

Permethrin 54 44 (2) 10 4

Benzyl benzoate 53 40 (2) 19 13

Sulfur 54 26 (2) 30 50

Aggarwal (2014)66

Oral ivermectin 50 27 (2) 33 (4)

Permethrin 50 39 (2) 43 (4)

Ahmad (2016)21 Topical ivermectin 32 32 (2) 32 (4) 0

Oral ivermectin 30 30 (2) 30 (4) 0

Alipour (2015)22 Oral ivermectin 240 130 (2) 165 (4)

Sulfur 240 95 (2) 125 (4)

Amer (1992)48 Permethrin 50 49 (4) 0

Crotamiton 50 44 (4) 0

Lindane 50 37 (4) 0

Amerio (2003)40 Synergized pyrethrins 20 19 (2) 20 (4) 0 2

Permethrin 20 18 (2) 20 (4) 4 10

Ayaz (2011)58 ScaNeem 60 21 0

Benzyl benzoate 60 10 6

Bachewar (2009)59

Oral ivermectin 34 27 (2)

Permethrin 34 27 (2)

Benzyl benzoate 35 23 (2)

Biele (2006)37 Synergized pyrethrins 120 90 (2) 114 (4) 6 3

Benzyl benzoate 120 85 (2) 109 (4) 10 22

Bokhari (2000)62

Permethrin 40 35 (4) 2

Lindane 40 35 (4) 6

Brooks (2002)41 Oral ivermectin 55 24 (3) 22 15


Castillo (2013)56 Tinospora cordifolia 34 8 (2) 21 (4) 18

Permethrin 32 7 (2) 15 (4) 16

Chhaiya (2012)32

Topical ivermectin 105 101 (2) 101 (3) 9 4

Oral ivermectin 105 63 (2) 99 (3) 57 6

Permethrin 105 98 (2) 99 (3) 15 7

Chouela (1999)45


Lindane 27 13 (2) 23 (4) 9


Oral ivermectin 37 37 (2) 1 6

Lindane 21 18 (2) 5 4

Das (2006)70 Oral ivermectin 50 0

Permethrin 50 0

Lindane 50 0

19

White soft paraffin 50 0

Glaziou (1993)46


Benzyl benzoate 21 3 (2) 10 (4) 5

Goldust (2014)28

Oral ivermectin 174 100 (2) 140 (4) 38

Crotamiton 174 75 (2) 100 (4) 26

Goldust (2014)23

Oral ivermectin 189 108 (2) 145 (4) 49

Malathion 189 75 (2) 105 (4) 29

Goldust (2014)24

Topical ivermectin 200 110 (2) 140 (4) 60

Crotamiton 200 70 (2) 110 (4) 50

Goldust (2013)25

Topical ivermectin 210 120 (2) 160 (4) 50

Permethrin 210 125 (2) 170 (4) 40

Goldust (2013)26

Oral ivermectin 250 140 (2) 180 (4) 60

Lindane 250 100 (2) 140 (4) 50

Goldust (2013)27

Permethrin 240 140 (2) 190 (4) 40


240 100 (2) 130 (4) 60

Goldust (2012)33

Oral ivermectin 133 104 (2) 15


Gulati (1978)61 Benzyl benzoate 89 88 (2)

Sulfur 69 69 (2)

Kanwar (2016)68

Oral ivermectin 102 77 (6) 27


Lindane 102 59 (6) 44

Khan (2007)60 Oral ivermectin 15 15 (2) 4


Ly (2009)35 Oral ivermectin 150 16 (2) 28 (4) 90

Benzyl benzoate* 250 70 (2) 98 (4) 164



Placebo 26 4 (1)

Madan (2001)42 Oral ivermectin 100 30 (2) 57 (4) 37

Lindane 100 19 (2) 36 (4) 47

Manjhi (2014)65 Oral ivermectin 60 32 (1) 48 (6) 9

Permethrin 60 43 (1) 53 (6) 6

Lindane 60 28 (1) 43 (6) 15


Meenakshi (2014)67


Permethrin 70 52 (1) 58 (3) 8

Lindane 70 43 (1) 44 (3) 15



Crotamiton 18 12 (2)

Sulfur 18 7 (2)


Oral ivermectin 132 72 (2) 115 (4) 8

Lindane 140 55 (2) 89 (4) 16

Mushtaq (2010)64

Oral ivermectin 50 24 (2) 35 (4) 9 10

Permethrin 50 20 (2) 37 (4) 9 9

Oral ivermectin 29 19 (2) 27 (4) 2 0

20

Nnoruka (2001)43

Benzyl benzoate 29 10 (2) 14 (4) 16 7

Oyelami (2009)36

Crude Aloe vera gel 16 16 (2) 2 2


Pourhasan (2013)30

Permethrin 225 140 (2) 170 (4) 45

Crotamiton 225 90 (2) 130 (4) 55

Rahman (2015)54

Jarb wahikka 30 6 (2) 26 (3) 0


Ranjkesh (2013)31


Permethrin 34 28 (2) 30 (4) 4

Razaee (2015)20 Permethrin 66 48 (2) 9

Lindane 68 28 (2) 10

Razaee (2015)55 Topical ivermectin 205 120 (2) 150 (4) 65


205 85 (2) 120 (4) 45

Saqib (2012)57 Oral ivermectin 60 40 (2)


Schultz (1990)50 Permethrin 234 74 (2) 181 (4) 67 58

Lindane 233 79 (2) 177 (4) 85 45

Shaheen (2017)52



Sharma (2011)34 Oral ivermectin** 80 57 (2) 71 (4) 9 1

Permethrin 40 33 (2) 36 (4) 4 5


Lindane 50 30 (2) 27 (4) 20 6

Sulfur 50 27 (2) 30 (4) 17 10

Taplin (1990)49 Permethrin 48 14 (2) 42 (4) 6

Crotamiton 48 6 (2) 28 (4) 20

Taplin (1986)51 Permethrin 27 10 (2) 21 (4) 4

Lindane 25 3 (2) 15 (4) 2

Usha (2000)44 Oral ivermectin 40 28 (2) 38 (4)

Permethrin 45 44 (2) 45 (4)

Wankhade (2016)69

Permethrin+oral ivermectin combination

50 43 (1) 48 (4) 3


Permethrin 50 39 (1) 45 (4) 2

Zargari (2006)38 Permethrin 59 44 (2) 9

Lindane 58 23 (2) 12

* Data in both benzyl benzoate arms were merged into 1 arm in meta-analyses. ** Data in both oral ivermectin arms were merged into 1 arm in meta-analyses.

21

Supplemental Table IX. Cutaneous adverse events as reported in the studies

Treatment Irritation

Erythema

Dermatitis

Pustular eruption

Cellulitis

Increased itching

Ulcer Scales Rash Infection

Tingling

Skin dryness


Oral ivermectin

0 - - - - - - - - - - -

Permethrin 0 - - - - - - - - - - -

Benzyl benzoate

10 - - - - - - - - - - -

Sulfur 46 - - - - - - - - - - -

Aggarwal (2014)66

Oral ivermectin

Outcome NR

Permethrin Outcome NR

Ahmad (2016)21 Topical ivermectin

Outcome NR

Oral ivermectin

Outcome NR

Alipour (2015)22

Oral ivermectin

Outcome NR

Sulfur Outcome NR

Amer (1992)48 Permethrin 0 - - - - - - - - - - -

Crotamiton 0 - - - - - - - - - - -

Lindane 0 - - - - - - - - - - -

Amerio (2003)40

Synergized pyrethrins

- - - - - - - - - 2 - -

Permethrin - - - - - - - - - 10 - -

Ayaz (2011)58 ScaNeem 0 - - - - - 0 - - - - -

Benzyl benzoate

6 - - - - - 1 - - - - -

Bachewar (2009)59

Oral ivermectin

Outcome NR

22


Benzyl benzoate

Outcome NR

Biele (2006)37 Synergized pyrethrins

3 - - - - - - - - - - -

Benzyl benzoate

22 - - - - - - - - - - -

Bokhari (2000)62

Permethrin 2 1 - - - 2 - - 1 - - -

Lindane 4 2 - - - 3 - - 2 - - -

Brooks (2002)41 Oral ivermectin

0 - 0 3 - - - - - - - -

Benzyl benzoate

6 - 6 0 - - - - - - - -

Castillo (2013)56

Tinospora cordifolia

6 5 - - - 14 - - - - - -

Permethrin 5 5 - - - 14 - - - - - -

Chhaiya (2012)32

Topical ivermectin

0 - - - - 0 - - - - - -

Oral ivermectin

0 - - - - 1 - - - - - -

Permethrin 1 - - - - 0 - - - - - -

Chouela (1999)45

Oral ivermectin

Outcome NR

Lindane Outcome NR


Oral ivermectin

- - - - - 1 - - - - - 6

Lindane - - - - - 2 - - - - - 4

Das (2006)70 Oral ivermectin

0 - - - - - - - - - - -

Permethrin 0 - - - - - - - - - - -

Lindane 0 - - - - - - - - - - -

White soft paraffin

0 - - - - - - - - - - -

23

Glaziou (1993)46

Oral ivermectin

- - - - - 0 - - - - - -

Benzyl benzoate

- - - - - 5 - - - - - -

Goldust (2014)28

Oral ivermectin

24 - - - - - - - - - - -

Crotamiton 12 - - - - - - - - - - -

Goldust (2014)23

Oral ivermectin

30 - - - - - - - - - - -

Malathion 10 - - - - - - - - - - -

Goldust (2014)24

Topical ivermectin

30 - - - - - - - - - - -

Crotamiton 20 - - - - - - - - - - -

Goldust (2013)25

Topical ivermectin

30 - - - - - - - - - - -

Permethrin 20 - - - - - - - - - - -

Goldust (2013)26

Oral ivermectin

30 - - - - - - - - - - -

Lindane 20 - - - - - - - - - - -

Goldust (2013)27

Permethrin 20 - - - - - - - - - - -


40 - - - - - - - - - - -

Goldust (2012)33

Oral ivermectin

3 - - - - - - - - - - -

Permethrin 6 - - - - - - - - - - -

Gulati (1978)61 Benzyl benzoate

Outcome NR

Sulfur Outcome NR

Kanwar (2016)68

Oral ivermectin

Outcome NR


Lindane Outcome NR

24

Khan (2007)60 Oral ivermectin

0 - - - - - - - - 4 - -

Permethrin 13 - - - - - - - - 6 - -

Ly (2009)35 Oral ivermectin

0 - - - - - - - - - - -

Benzyl benzoate*

30 - - - - - - - - - - -


Oral ivermectin

Outcome NR

Placebo Outcome NR

Madan (2001)42 Oral ivermectin

Outcome NR

Lindane Outcome NR

Manjhi (2014)65 Oral ivermectin

Outcome NR


Lindane Outcome NR

Benzyl benzoate

Outcome NR

Meenakshi (2014)67

Oral ivermectin

0 - - - - - - - - - - -

Permethrin 0 - - - - - - - - - - -

Lindane 0 - - - - - - - - - - -



Crotamiton Outcome NR

Sulfur Outcome NR


Oral ivermectin

0 - - - - - - - - - - -

Lindane 0 - - - - - - - - - - -

25

Mushtaq (2010)64

Oral ivermectin

0 - - - - 4 - - - 3 - -

Permethrin 1 - - - - 0 - - - 0 - -

Nnoruka (2001)43

Oral ivermectin

0 - - - - - - - - - - -

Benzyl benzoate

7 - - - - - - - - - - -

Oyelami (2009)36

Crude Aloe vera gel

- - - - - - - - - 2 - -

Benzyl benzoate

- - - - - - - - - 1 - -

Pourhasan (2013)30

Permethrin 20 - - - - - - - - - - -

Crotamiton 30 - - - - - - - - - - -

Rahman (2015)54

Jarb wahikka

0 - - - - - - - - - - -

Benzyl benzoate

0 - - - - - - - - - - -

Ranjkesh (2013)31

Oral ivermectin

0 - - - - - - - - - - -

Permethrin 0 - - - - - - - - - - -

Razaee (2015)20 Permethrin 3 - - - - - - - - - - -

Lindane 2 - - - - - - - - - - -

Razaee (2015)55 Topical ivermectin

40 - - - - - - - - - - -


20 - - - - - - - - - - -

Saqib (2012)57 Oral ivermectin

Outcome NR


Schultz (1990)50 Permethrin 23 5 - - - 15 - - 2 - 4 -

Lindane 12 3 - - - 17 - - 2 - 5 -

Shaheen (2017)52

Oral ivermectin

Outcome NR

26


Sharma (2011)34

Oral ivermectin**

0 - - - - 0 - - - - - -

Permethrin 3 - - - - 2 - - - - - -


Lindane 6 5 - - - - - - - - - -

Sulfur 2 2 - - - - - - - - - -

Taplin (1990)49 Permethrin Outcome NR


Taplin (1986)51 Permethrin 0 - - - - - - - - - - -

Lindane 0 - - - - - - - - - - -

Usha (2000)44 Oral ivermectin

Outcome NR


Wankhade (2016)69


0 - - - - - - - - - - -

Oral ivermectin

0 - - - - - - - - - - -

Permethrin 0 - - - - - - - - - - -

Zargari (2006)38 Permethrin 2 - - - - - - - - - - -

Lindane 1 - - - - - - - - - - -

NR, not reported.


27

Supplemental Table X. Systemic adverse events as reported in the studies

Treatment Foul smell

Nausea/ vomiting

Abdominal pain

Diarrhea Blurred vision

Fever Headache Insomnia Hypo-tension

Minor adverse drug reactions


Oral ivermectin

- 2 - - - - - - - -

Permethrin - 0 - - - - - - - -

Benzyl benzoate

- 0 - - - - - - - -

Sulfur - 0 - - - - - - - -

Aggarwal (2014)66

Oral ivermectin

Outcome NR


Ahmad (2016)21 Topical ivermectin

Outcome NR

Oral ivermectin

Outcome NR

Alipour (2015)22

Oral ivermectin

Outcome NR

Sulfur Outcome NR

Amer (1992)48 Permethrin - - - - - - - - - -

Crotamiton - - - - - - - - - -

Lindane - - - - - - - - - -

Amerio (2003)40

Synergizedd pyrethrins

- - - - - - - - - -

Permethrin - - - - - - - - - -

Ayaz (2011)58 ScaNeem - - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Bachewar (2009)59

Oral ivermectin

Outcome NR

28


Benzyl benzoate

Outcome NR

Biele (2006)37 Synergizedd pyrethrins

- - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Bokhari (2000)62

Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

Brooks (2002)41 Oral ivermectin

- - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Castillo (2013)56

Tinospora cordifolia

- - - - - - - - - -

Permethrin - - - - - - - - - -

Chhaiya (2012)32

Topical ivermectin

- - - - - - 0 - - -

Oral ivermectin

- - - - - - 1 - - -

Permethrin - - - - - - 0 - - -

Chouela (1999)45

Oral ivermectin

- 1 1 - - - 1 - 1 -

Lindane - 0 0 - - - 6 - 0 -


Oral ivermectin

- - - - - 1 - - - -

Lindane - - - - - 0 - - - -

Das (2006)70 Oral ivermectin

- - - - - - - - - -

Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

White soft paraffin

- - - - - - - - - -

Glaziou (1993)46

Oral ivermectin

- - - - - - - - - -

29

Benzyl benzoate

- - - - - - - - - -

Goldust (2014)28

Oral ivermectin

- - - - - - - - - -

Crotamiton - - - - - - - - - -

Goldust (2014)23

Oral ivermectin

- - - - - - - - - -

Malathion - - - - - - - - - -

Goldust (2014)24

Topical ivermectin

- - - - - - - - - -

Crotamiton - - - - - - - - - -

Goldust (2013)25

Topical ivermectin

- - - - - - - - - -

Permethrin - - - - - - - - - -

Goldust (2013)26

Oral ivermectin

- - - - - - - - - -

Lindane - - - - - - - - - -

Goldust (2013)27

Permethrin - - - - - - - - - -


- - - - - - - - - -

Goldust (2012)33

Oral ivermectin

- - - - - - - - - -

Permethrin - - - - - - - - - -

Gulati (1978)61 Benzyl benzoate

Outcome NR

Sulfur Outcome NR

Kanwar (2016)68

Oral ivermectin

Outcome NR


Lindane Outcome NR

Khan (2007)60 Oral ivermectin

- - - - - - - - - -

30

Permethrin - - - - - - - - - -

Ly (2009)35 Oral ivermectin

- - 5 2 - - - - - -

Benzyl benzoate*

- - 0 0 - - - - - -


Oral ivermectin

Outcome NR

Placebo Outcome NR

Madan (2001)42 Oral ivermectin

Outcome NR

Lindane Outcome NR

Manjhi (2014)65 Oral ivermectin

Outcome NR


Lindane Outcome NR

Benzyl benzoate

Outcome NR

Meenakshi (2014)67

Oral ivermectin

- - - - - - - - - -

Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -




Sulfur Outcome NR


Oral ivermectin

- - - - - - - - - -

Lindane - - - - - - - - - -

Mushtaq (2010)64

Oral ivermectin

- - - - - - 1 - - -

31

Permethrin - - - - - - 0 - - -

Nnoruka (2001)43

Oral ivermectin

- - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Oyelami (2009)36

Crude Aloe vera gel

- - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Pourhasan (2013)30

Permethrin - - - - - - - - - -

Crotamiton - - - - - - - - - -

Rahman (2015)54

Jarb wahikka

- - - - - - - - - -

Benzyl benzoate

- - - - - - - - - -

Ranjkesh (2013)31

Oral ivermectin

- - - - - - - - - -

Permethrin - - - - - - - - - -

Razaee (2015)20 Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

Razaee (2015)55 Topical ivermectin

- - - - - - - - - -


- - - - - - - - - -

Saqib (2012)57 Oral ivermectin

Outcome NR


Schultz (1990)50 Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

Shaheen (2017)52

Oral ivermectin

Outcome NR


32

Sharma (2011)34

Oral ivermectin**

- - - - - - - - - -

Permethrin - - - - - - - - - -


Lindane 3 - - - - - - - - -

Sulfur 10 - - - - - - - - -

Taplin (1990)49 Permethrin Outcome NR


Taplin (1986)51 Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

Usha (2000)44 Oral ivermectin

Outcome NR


Wankhade (2016)69


- - - - - - - - - 3

Oral ivermectin

- - - - - - - - - 1

Permethrin - - - - - - - - - 2

Zargari (2006)38 Permethrin - - - - - - - - - -

Lindane - - - - - - - - - -

NR, not reported.


33

Supplemental Table XI. Results of risk of bias assessment

Random sequence generation

Allocation concealment

Blinding of participants and personnel

Blinding of outcome assessment

Incomplete outcome data Selective reporting

Cure Persistent itching

AEs Cure Persistent itching

AEs Cure Persistent itching

AEs


L U H H H U H H H H H H

Aggarwal (2014)66 H H H N N U N N H N N H

Ahmad (2016)21 L U H H H U H H L L U H

Alipour (2015)22 U U H N H L N H H N H L

Amer (1992)48 U U H N H U N H L N L L

Amerio (2003)40 L L H H H L H H L L L L

Ayaz (2011)58 U U H H H H H H H H H L

Bachewar (2009)59 L U H U U H U U H U U H

Biele (2006)37 L U H H H L H H L L L H

Bokhari (2000)62 U U H N H U N H H N H L

Brooks (2002)41 L L H H H L H H H H H L

Castillo (2013)56 L U H H H U H H H H H H

Daneshpajooh (1999)63 U U H H H U H H L L L L

Das (2006)70 U U H H H U H H U U U U

Chhaiya (2012)32 L U H H H H H H H H H L

Chouela (1999)45 L U L L L L L L H H H H

Glaziou (1993)46 U U H N H U N H L N L L

Goldust (2014)28 U U H N H L N H H N H L






Goldust (2012)33 U H H N H L N H H N H L

34

Gulati (1978)61 U U H N N U N N L N N H

Kanwar (2016)68 U U H H N U H N L L N H

Khan (2007)60 U U H N H H N H L N L L

Ly (2009)35 L U H N H H N H H N H L

Macotela-Ruiz (1993)47 U U U N N U N N U N N H

Madan (2001)42 U U H H N U H N H H N H

Manjhi (2014)65 U U H U N U U N U U N H

Meenakshi (2014)67 L U H N H H N H H N H L


U U H U H L U H L U L U

Mohebbipour (2012)29 U U H N H L N H H N H L

Mushtaq (2010)64 L U H U U U U U H H H L

Nnoruka (2001)43 L U H H H U H H L L L L

Oyelami (2009)36 U U H H H U H H H H H L

Pourhasan (2013)30 U U H N H L N H H N H L

Rahman (2015)54 L H H H H H H H L L L L

Ranjkesh (2013)31 U U H N H L N H H N H L

Razaee (2015)20 U U H N H L N H H N H L

Razaee (2015)55 U U H N H L N H H N H L

Saqib (2012)57 U U H U N U U N L U N H

Schultz (1990)50 U U H H H U H H H H H L

Shaheen (2017)52 L U H N N L N N L N N H

Sharma (2011)34 L L L L L U L L H H H H

Singalavanija (2003)39 L U H H H U H H H H H L

Taplin (1990)49 U U L L N L L N L H N H

Taplin (1986)51 U U H N H L N H H N H L

Usha (2000)44 U U H U N U U N L U N H

Wankhade (2016)69 U U H N H H N H L N L L

Zargari (2006)38 U L L N L U N L H N H L

Number (%) of studies

35

Low risk 17 (32.7)

4 (7.7)

4 (7.7)

3 (11.5)

3 (7.1)

21 (40.4)

3 (11.5)

3 (7.1)

17 (32.7)

7 (26.9)

10 (23.8)

33 (63.5)

High risk 1 (1.9)

3 (5.8)

47 (90.4)

17 (65.4)

37 (88.1)

8 (15.4)

17 (65.4)

37 (88.1)

32 (61.5)

13 (50.0)

29 (69.1)

17 (32.7)

Unclear risk 34 (65.4)

45 (86.5)

1 (1.9)

6 (23.1)

2 (4.8)

23 (44.2)

6 (23.1)

2 (4.8)

3 (5.8)

6 (23.1)

3 (7.1)

2 (3.9)

AEs, adverse events; H, high risk; L, low risk; N, outcome not assessed in study; U, unclear risk.

The majority of RCTs had unclear risk of bias in random sequence generation (65.4%) and allocation concealment (86.5%), due to their lack of description for the processes. For blinding of participants and personnel, the risk was high for most RCTs (90.4%) because they were investigator-blind or open-label, or did not use double dummy technique when drugs in different formulations were studied. For blinding of outcome assessment, fewer studies were at high risk in cure outcome (15.4%) than in persistent itching (65.4%) and AEs (88.1%) because cure was mainly assessed by blind investigators but itching and AEs by unblinded patients. Risk of bias for incomplete outcome data was high in 50.0-69.1% of the studies due to high dropout. For selective reporting, 32.7% of studies were at high risk because AEs were not reported.

36

Supplemental Table XII. Results of direct meta-analysis for cure at 1-2 weeks

Author (year) Treatment and number of patients

RR (95% CI) % Weight

I2 (%)

Oral ivermectin Permethrin

Cured Uncured Cured Uncured

Cure assessed at 2 weeks

Usha (2000)44 28 12 44 1 0.72 (0.58, 0.88) 7.14

Khan (2007)60 15 0 15 0 1.00 (0.88, 1.13) 8.59

Bachewar (2009)59 27 7 27 7 1.00 (0.79, 1.27) 6.52

Mushtaq (2010)64 24 26 20 30 1.20 (0.77, 1.87) 3.65

Sharma (2011)34 57 23 33 7 0.86 (0.71, 1.05) 7.29

Chhaiya (2012)32 63 42 98 7 0.64 (0.55, 0.76) 7.92

Goldust (2012)33 104 29 112 27 0.97 (0.86, 1.10) 8.64

Saqib (2012)57 40 20 40 20 1.00 (0.78, 1.29) 6.33

Ranjkesh (2013)31 22 12 28 6 0.79 (0.59, 1.05) 5.65

Aggarwal (2014)66 27 23 39 11 0.69 (0.52, 0.93) 5.62

Abdel-Raheem (2016)19 42 13 44 10 0.94 (0.77, 1.14) 7.38

Shaheen (2017)52 62 8 51 19 1.22 (1.03, 1.44) 7.89

Subtotal DL pooled RR 0.90 (0.80, 1.01) 82.62 75.3

Cure assessed at 1 week

Manjhi (2014)65 32 28 43 17 0.74 (0.56, 0.99) 5.78

Meenakshi (2014)67 32 38 52 18 0.62 (0.46, 0.82) 5.70

Wankhade (2016)69 29 21 39 11 0.74 (0.56, 0.98) 5.90


Overall DL pooled RR 0.86 (0.77, 0.96) 100 74.4

Author (year) Oral ivermectin Lindane RR (95% CI) % Weight

I2 (%)


Microscopy used in diagnosis and cure assessment

Chouela (1999)45 14 12 13 14 1.12 (0.66, 1.90) 7.44

Daneshpajooh (1999)63 37 0 18 3 1.17 (0.98, 1.41) 20.77

Madan (2001)42 30 70 19 81 1.58 (0.95, 2.61) 7.99

Mohebbipour (2012)29 72 60 55 85 1.39 (1.07, 1.80) 16.81

Goldust (2013)26 140 110 100 150 1.40 (1.16, 1.69) 20.66


Microscopy not used in diagnosis and cure assessment

Manjhi (2014)65 32 28 28 32 1.14 (0.80, 1.64) 12.27

Meenakshi (2014)67 32 38 43 27 0.74 (0.54, 1.02) 14.07



Author (year) Permethrin Lindane RR (95% CI) % Weight

I2 (%)

37


Male patients < 60% (median)

Taplin (1986)51 10 17 3 22 3.09 (0.96, 9.94) 4.02

Zargari (2006)38 44 15 23 35 1.88 (1.32, 2.67) 17.36

Razaee (2015)20 48 18 28 40 1.77 (1.28, 2.43) 18.36


Male patients ≥ 60%

Schultz (1990)50 74 160 79 154 0.93 (0.72, 1.21) 20.37

Meenakshi (2014)67 52 18 43 27 1.21 (0.96, 1.52) 21.31


% Sex not reported

Manjhi (2014)65 43 17 28 32 1.54 (1.12, 2.10) 18.58

Subtotal DL pooled RR 1.54 (1.12, 2.10) 18.58 -


Author (year) Oral ivermectin Benzyl benzoate RR (95% CI) % Weight

I2 (%)


Glaziou (1993)46 8 15 3 18 2.44 (0.74, 7.99) 6.41

Nnoruka (2001)43 19 10 10 19 1.90 (1.08, 3.35) 14.86

Ly (2009)35 16 134 70 180 0.38 (0.23, 0.63) 16.18

Bachewar (2009)59 27 7 23 12 1.21 (0.90, 1.62) 20.75

Manjhi (2014)65 32 28 29 31 1.10 (0.78, 1.57) 19.50

Abdel-Raheem (2016)19 42 13 40 13 1.01 (0.82, 1.25) 22.31

DL pooled RR 1.06 (0.75, 1.50) 100 78.0

Author (year) Permethrin Benzyl benzoate RR (95% CI) % Weight

I2 (%)


Multiple (> 1) applications of benzyl benzoate

Bachewar (2009)59 27 7 23 12 1.21 (0.90, 1.62) 18.51

Abdel-Raheem (2016)19 44 10 40 13 1.08 (0.89, 1.32) 30.64


Single application of benzyl benzoate

Goldust (2013)27 140 100 100 140 1.40 (1.17, 1.68) 33.39

Manjhi (2014)65 43 17 29 31 1.48 (1.09, 2.01) 17.45



Author (year) Permethrin Crotamiton % Weight

I2 (%)


Taplin (1990)49 14 34 6 42 2.33 (0.98, 5.56) 3.47

Pourhasan (2013)30 140 85 90 135 1.56 (1.29, 1.88) 72.84

38


18 0 12 6 1.48 (1.06, 2.06) 23.69

IV pooled RR 1.56 (1.33, 1.83) 100 0.0.

CI, confidence interval; DL, DerSimonian and Laird (random effects); IV, inverse variance (fixed effect); RR, risk ratio.

39

Supplemental Table XIII. Results of direct meta-analysis for cure at 3-6 weeks

Author (year) Treatment and number of patients RR (95% CI) % Weight

I2 (%)



Usha (2000)44 38 2 45 0 0.95 (0.87, 1.03) 22.10

Mushtaq (2010)64 35 15 37 13 0.95 (0.74, 1.21) 2.58

Sharma (2011)34 71 9 36 4 0.99 (0.87, 1.12) 9.24

Chhaiya (2012)32 99 6 99 6 1.00 (0.94, 1.07) 34.90

Ranjkesh (2013)31 28 6 30 4 0.93 (0.77, 1.14) 3.94

Manjhi (2014)65 48 12 53 7 0.91 (0.78, 1.06) 6.33

Aggarwal (2014)66 33 17 43 7 0.77 (0.61, 0.96) 2.97

Meenakshi (2014)67 57 13 58 12 0.98 (0.84, 1.15) 6.48

Kanwar (2016)68 77 25 77 25 1.00 (0.86, 1.17) 6.33

Wankhade (2016)69 39 11 45 5 0.87 (0.73, 1.03) 5.12

IV pooled RR 0.96 (0.92, 1.00); P=0.049

100 0.0


I2 (%)


Chouela (1999)45 18 8 23 4 0.81 (0.60, 1.10) 9.20

Madan (2001)42 57 43 36 64 1.58 (1.16, 2.16) 8.76

Mohebbipour (2012)29 115 17 89 51 1.37 (1.19, 1.58) 19.20

Goldust (2013)26 180 70 140 110 1.29 (1.12, 1.47) 19.80

Manjhi (2014)65 48 12 43 17 1.12 (0.91, 1.37) 14.45

Meenakshi (2014)67 57 13 44 26 1.30 (1.05, 1.60) 13.86

Kanwar (2016)68 77 25 59 43 1.31 (1.07, 1.59) 14.73

DL pooled RR 1.25 (1.12, 1.40) 100 54.5


I2 (%)


Studies with 3 or 4 treatment arms

Amer (1992)48 49 1 37 13 1.32 (1.12, 1.57) 15.69

Manjhi (2014)65 53 7 43 17 1.23 (1.03, 1.48) 14.66

Meenakshi (2014)67 58 12 44 26 1.32 (1.07, 1.63) 13.01

Kanwar (2016)68 77 25 59 43 1.31 (1.07, 1.59) 13.64


Studies with 2 treatment arms

Taplin (1986)51 21 6 15 10 1.30 (0.89, 1.89) 6.16

Schultz (1990)50 181 53 177 56 1.02 (0.92, 1.13) 20.92

Bokhari (2000)62 35 5 35 5 1.00 (0.85, 1.18) 15.93



40

Author (year) Permethrin Benzyl benzoate RR (95% CI) % Weight

I2 (%)


Glaziou (1993)46 16 7 10 11 1.46 (0.87, 2.47) 18.05

Nnoruka (2001)43 27 2 14 15 1.93 (1.31, 2.85) 20.18

Brooks (2002)41 24 31 19 36 1.26 (0.79, 2.03) 18.90

Ly (2009)35 28 122 98 152 0.48 (0.33, 0.69) 20.51

Manjhi (2014)65 48 12 39 21 1.23 (0.98, 1.54) 22.36

DL pooled RR 1.15 (0.73, 1.82) 100 78.0

Author (year) Permethrin Crotamiton RR (95% CI) % Weight

I2 (%)


Study with 3 or 4 treatment arms

Amer (1992)48 49 1 44 6 1.11 (1.00, 1.24) 41.35

Subtotal DL pooled RR 1.11 (1.00, 1.24) 41.35 -

Studies with 2 treatment arms

Taplin (1990)49 42 6 28 20 1.50 (1.15, 1.95) 21.10

Pourhasan (2013)30 170 55 130 95 1.31 (1.14, 1.50) 37.55




41

Supplemental Table XIV. Results of direct meta-analysis for persistent itching outcome


I2 (%)


With itching

Without itching

With itching

Without itching

Mushtaq (2010)64 9 41 9 41 1.00 (0.43, 2.31) 15.43

Sharma (2011)34 9 71 4 36 1.13 (0.37, 3.43) 11.71

Chhaiya (2012)32 57 48 15 90 3.80 (2.30, 6.27) 20.94

Manjhi (2014)65 9 51 6 54 1.50 (0.57, 3.95) 13.54


13 42 10 44 1.28 (0.61, 2.66) 17.04

Kanwar (2016)68 27 75 24 78 1.13 (0.70, 1.81) 21.34

DL pooled RR 1.51 (0.91, 2.53) 100 67.7

Author (year) Oral ivermectin Benzyl benzoate RR (95% CI) % Weight

I2 (%)

With itching

Without itching

With itching

Without itching

Nnoruka (2001)43 2 27 16 13 0.13 (0.03, 0.50) 9.41

Brooks (2002)41 22 33 32 23 0.69 (0.46, 1.02) 38.41

Manjhi (2014)65 9 51 19 41 0.47 (0.23, 0.96) 23.82


13 42 19 34 0.66 (0.36, 1.20) 28.35

DL pooled RR 0.53 (0.33, 0.84) 100 49.7


I2 (%)

With itching

Without itching

With itching

Without itching


1 36 5 16 0.11 (0.01, 0.91) 1.31

Madan (2001)42 37 63 47 53 0.79 (0.57, 1.10) 51.92

Manjhi (2014)65 9 51 15 45 0.60 (0.29, 1.26) 10.17

Kanwar (2016)68 27 75 44 58 0.61 (0.41, 0.91) 36.60

IV pooled RR 0.68 (0.54, 0.86) 100 24.5


I2 (%)

With itching

Without itching

With itching

Without itching

Microscopy used in diagnosis and cure assessment

Schultz (1990)50 67 167 85 148 0.79 (0.60, 1.02) 51.61

Subtotal DL pooled RR

0.79 (0.60, 1.02) 51.61 -

Microscopy not used in diagnosis and cure assessment

Manjhi (2014)65 6 54 15 45 0.40 (0.17, 0.96) 12.73

42

Kanwar (2016)68 24 78 44 58 0.55 (0.36, 0.83) 35.65


0.52 (0.35, 0.75) 48.39 0.0

Overall DL pooled RR

0.63 (0.45, 0.89) 100 44.9


43

Supplemental Table XV. Results of direct meta-analysis for adverse events outcome


I2 (%)


With AEs

Without AEs

With AEs

Without AEs

AEs assessed at 1 or 2 weeks

Khan (2007)60 4 11 13 2 0.31 (0.13, 0.73) 9.92

Goldust (2012)33 15 118 24 115 0.65 (0.36, 1.19) 15.24


7 48 4 50 1.72 (0.53, 5.53) 6.32


0.65 (0.29, 1.47) 31.48 63.5

AEs assessed after 2 weeks

Das (2006)70 0 50 0 50 1.00 (0.96, 1.04) 30.52

Mushtaq (2010)64 10 40 9 41 1.11 (0.49, 2.50) 10.76

Sharma (2011)34 1 79 5 35 0.10 (0.01, 0.83) 2.26

Chhaiya (2012)32 6 99 7 98 0.86 (0.30, 2.47) 7.41

Ranjkesh (2013)31 4 30 4 30 1.00 (0.27, 3.68) 5.32

Meenakshi (2014)67

12 58 8 62 1.50 (0.65, 3.44) 10.42

Wankhade (2016)69

1 49 2 48 0.50 (0.05, 5.34) 1.83


1.00 (0.96, 1.04) 68.52 0.0

Overall DL pooled RR

0.84 (0.61, 1.17) 100 43.2


I2 (%)

With AEs

Without AEs

With AEs

Without AEs

Taplin (1986)51 4 23 2 23 1.85 (0.37, 9.25) 0.03

Schultz (1990)50 58 176 45 188 1.28 (0.91, 1.81) 0.62

Amer (1992)48 0 50 0 50 1.00 (0.96, 1.04) 49.49

Bokhari (2000)62 2 38 6 34 0.33 (0.07, 1.55) 0.03

Zargari (2006)38 9 50 12 46 0.74 (0.34, 1.62) 0.12

Das (2006)70 0 50 0 50 1.00 (0.96, 1.04) 49.49

Meenakshi (2014)67

8 62 15 55 0.53 (0.24, 1.18) 0.12

Razaee (2015)20 9 57 10 58 0.93 (0.40, 2.14) 0.11

IV pooled RR 1.00 (0.97, 1.03) 100 7.5


I2 (%)

With AEs

Without AEs

With AEs

Without AEs

Chouela (1999)45 9 17 9 18 1.04 (0.49, 2.20) 0.26


6 31 4 17 0.85 (0.27, 2.68) 0.11

Das (2006)70 0 50 0 50 1.00 (0.96, 1.04) 97.77

44


8 124 16 124 0.53 (0.24, 1.20) 0.22

Goldust (2013)26 60 190 50 200 1.20 (0.86, 1.67) 1.32

Meenakshi (2014)67

12 58 15 55 0.80 (0.40, 1.58) 0.31

IV pooled RR 1.00 (0.96, 1.04) 100 0.0


I2 (%)

With AEs

Without AEs

With AEs

Without AEs

Glaziou (1993)46 0 23 5 16 0.08 (0.01, 1.42) 2.87

Nnoruka (2001)43 0 29 7 22 0.07 (0.00, 1.12) 2.91

Brooks (2002)41 15 40 24 31 0.63 (0.37, 1.06) 30.35

Ly (2009)35 90 60 164 86 0.92 (0.78, 1.07) 43.95


7 48 13 40 0.52 (0.22, 1.20) 19.92

DL pooled RR 0.63 (0.38, 1.03) 100 56.3

Author (year) Herbal medicine Benzyl benzoate

% Weight

I2 (%)

With AEs

Without AEs

With AEs

Without AEs

Oyelami (2009)36 2 14 3 11 0.58 (0.11, 3.01) 23.90

Ayaz (2011)58 0 60 6 54 0.08 (0.00, 1.34) 10.42

Rahman (2015)54 0 30 0 30 1.00 (0.94, 1.07) 65.68

DL pooled RR 0.67 (0.25, 1.84) 100 43.1

AEs, adverse events; CI, confidence interval; DL, DerSimonian and Laird (random effects); IV, inverse variance (fixed effect); RR, risk ratio.

45

Supplemental Table XVI. Results of network meta-analysis of cure at 1-2 weeks and persistent itching outcomes

Persistent itching

Cu

re a

t 1-

2 w

eek

s

TopIverm 0.37 (0.07, 1.85)

0.14 (0.04, 0.44)

- 0.35 (0.13, 0.94)

- 0.26 (0.10, 0.71)

- 0.17 (0.06, 0.49)

0.12 (0.03, 0.50)

0.10 (0.02, 0.49)

0.15 (0.05, 0.44)

1.10 (0.80, 1.51)

SynPyrethr 0.37 (0.09, 1.46)

- 0.93 (0.26, 3.38)

- 0.71 (0.20, 2.52)

- 0.46 (0.12, 1.73)

0.32 (0.07, 1.43)

0.28 (0.05, 1.61)

0.40 (0.12, 1.34)

1.62 (1.26, 2.09)

1.48 (1.06, 2.06)

Sulfur - 2.54 (1.27, 5.09)

- 1.93 (0.98, 3.80)

- 1.27 (0.65, 2.48)

0.87 (0.27, 2.82)

0.76 (0.19, 3.00)

1.10 (0.53, 2.26)

6.10 (2.25, 16.50)

5.55 (2.00, 15.41)

3.76 (1.38, 10.22)

Placebo - - - - - - - -

1.02 (0.86, 1.21)

0.93 (0.71, 1.23)

0.63 (0.51, 0.78)

0.17 (0.06, 0.45)

Permethrin - 0.76 (0.49, 1.17)

- 0.50 (0.31, 0.80)

0.34 (0.12, 1.02)

0.30 (0.09, 0.98)

0.43 (0.24, 0.76)

0.87 (0.60, 1.27)

0.79 (0.51, 1.23)

0.54 (0.36, 0.80)

0.14 (0.05, 0.40)

0.85 (0.61, 1.20)

Perm+ OralIverm

- - - - - -

1.18 (1.00, 1.41)

1.08 (0.81, 1.43)

0.73 (0.59, 0.89)

0.19 (0.07, 0.52)

1.16 (1.05, 1.27)

1.36 (0.96, 1.91)

OralIverm - 0.66 (0.41, 1.05)

0.45 (0.16, 1.29)

0.39 (0.11, 1.39)

0.57 (0.34, 0.95)

1.70 (1.10, 2.63)

1.55 (0.95, 2.53)

1.05 (0.67, 1.64)

0.28 (0.10, 0.81)

1.66 (1.10, 2.51)

1.95 (1.15, 3.31)

1.44 (0.97, 2.15)

Malathion - - - -

1.45 (1.18, 1.80)

1.32 (0.97, 1.80)

0.89 (0.71, 1.12)

0.24 (0.09, 0.64)

1.42 (1.23, 1.64)

1.66 (1.15, 2.40)

1.23 (1.07, 1.41)

0.85 (0.56, 1.30)

Lindane 0.69 (0.23, 2.08)

0.60 (0.17, 2.15)

0.86 (0.48, 1.56)

1.21 (0.81, 1.80)

1.10 (0.70, 1.71)

0.74 (0.49, 1.12)

0.20 (0.07, 0.57)

1.18 (0.81, 1.72)

1.38 (0.83, 2.29)

1.02 (0.70, 1.49)

0.71 (0.41, 1.23)

0.83 (0.56, 1.23)

Herb 0.87 (0.18, 4.36)

1.26 (0.50, 3.18)

1.58 (1.25, 2.00)

1.44 (1.02, 2.02)

0.97 (0.73, 1.29)

0.26 (0.09, 0.71)

1.54 (1.25, 1.90)

1.81 (1.22, 2.69)

1.34 (1.08, 1.65)

0.93 (0.59, 1.46)

1.09 (0.85, 1.39)

1.31 (0.86, 2.00)

Crotamiton 1.44 (0.39, 5.35)

1.31 (1.07, 1.60)

1.19 (0.90, 1.57)

0.81 (0.65, 1.00)

0.21 (0.08, 0.58)

1.28 (1.10, 1.49)

1.50 (1.04, 2.17)

1.11 (0.95, 1.29)

0.77 (0.50, 1.18)

0.90 (0.74, 1.09)

1.09 (0.76, 1.55)

0.83 (0.65, 1.06)

BenzylB

BenzylB, benzyl benzoate; Herb, herbal medicine; OralIverm, oral ivermectin; Perm+OralIverm, permethrin and oral ivermectin combination; SynPyrethr, synergized pyrethrins; TopIverm, topical ivermectin.

Results are risk ratios (95% confidence intervals) from network meta-analysis between each pair of treatments. Comparisons are read from left to right. Bold font indicates statistical significance.

46

Supplemental Fig 1. Network map of direct comparisons for each outcome: cure at 1-2 weeks (A), cure at 3-6 weeks (B), persistent itching (C), and adverse events (D). Sizes of nodes and edges correspond to numbers of trials and included patients, respectively. BenzylB, benzyl benzoate; Herb, herbal medicine; OralIverm, oral ivermectin; Paraffin, white soft paraffin; Perm+OralIverm, permethrin+oral ivermectin combination; SynPyrethr, synergized pyrethrins; TopIverm, topical ivermectin.

47

Supplemental Fig 2. Comparison-adjusted funnel plot of studies included in network meta-analysis for cure at 1-2 weeks

48

Supplemental Fig 3. Comparison-adjusted funnel plot of studies included in network meta-analysis for cure at 3-6 weeks

49

Supplemental Fig 4. Comparison-adjusted funnel plot of studies included in network meta-analysis for persistent itching outcome

50

Supplemental Fig 5. Comparison-adjusted funnel plot of studies included in network meta-analysis for adverse events outcome

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