Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Moser W, Coulibaly JT, Ali SM, et al. Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d Ivoire: a randomised, controlled, single-blinded, non-inferiority trial. Lancet Infect Dis 2017; published online August 29. http://dx.doi.org/10.1016/s1473-3099(17)30487-5.
Appendix Table of contents Table S1... 3 Table S2... 4 Table S3... 7 Table S4... 10 Table S5... 11 Table S6... 12 Table S7... 13 Figure S1... 14 1
Efficacy and safety of tribendimidine, tribendimidine-ivermectin, tribendimidine-oxantel pamoate and albendazole-oxantel pamoate against hookworm and concomitant soiltransmitted helminth infections in Tanzania and Côte d Ivoire: a randomised, controlled, single blinded, non-inferiority trial Wendelin Moser, Jean T Coulibaly, Said M. Ali, Shaali M. Ame, Amour K. Amour, Richard B. Yapi, Marco Albonico, Maxim Puchkov, Jörg Huwyler, Jan Hattendorf, Jennifer Keiser Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland (W Moser MSc, J T Coulibaly PhD, Prof J Keiser); Laboratory Division, Public Health Laboratory-Ivo de Carneri, Chake Chake, Tanzania (S M Ali MSc, S M Ame MSc, A K Amour); Centre Suisse de Recherches Scientifiques, Abidjan, Côte d Ivoire (R B Yapi PhD, J T Coulibaly PhD); Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, and University of Basel, Basel, Switzerland (M Puchkov PhD, Prof J Huwyler PhD); Centre for Tropical Diseases, Sacro Cuore Hospital, Negrar Verona, and University of Turin, Turin, Italy (Prof M Albonico PhD); Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland (J Hattendorf PhD) Correspondence to: Prof Jennifer Keiser, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland jennifer.keiser@unibas.ch 2
Table S1 Detailed inclusion and exclusion criteria for participants (age 15-18) in Tanzania and Côte d Ivoire. Inclusion criteria Written informed consent signed by parents and/or legal guardian; and assent by children. Able and willing to be examined by a study physician at the beginning of the study. Able and willing to provide two stool samples at the beginning (baseline) and approximately three weeks after treatment (follow-up). Exclusion criteria No written informed consent by parents and/or legal guardian and assent for children. Presence of major systemic illnesses (e.g. diabetes, anemia) as assessed by a medical doctor, upon initial clinical assessment. History of acute or severe chronic disease. Positive for hookworm eggs in the stool. Recent use of anthelminthic drug (within past 4 weeks). Absence of major systemic illnesses (e.g. Attending other clinical trials during the study. diabetes, anemia) as assessed by a medical doctor, upon initial clinical assessment. No known or reported history of chronical illness as cancer, diabetes, chronic heart, liver or renal disease. No recent anthelminthic treatment (within past 4 weeks). No known allergy to study medications (e.g. albendazole, mebendazole). Negative diagnostic result for hookworm eggs in the stool. 3
Table S2 Baseline characteristics for the participants of the four treatment arms tribendimidine; tribendimidineivermectin; tribendimidine-oxantel pamoate and albendazole-oxantel pamoate for Tanzania (TZ), Côte d Ivoire ( and the total. Tribendimidine Tribendimidine- Tribendimidine- Albendazole- Ivermectin Oxantel pamoate Oxantel pamoate TZ No 101 102 102 103 CI 58 57 55 58 Tot 159 159 157 161 TZ Age years Ŧ 15 6(0 7) 15 6(0 8) 15 7(0 9) 15 6(0 9) CI 16 1(1 1) 16 3(1 1) 16 4(1 1) 16 2(1 1) Tot 15 8(0 9) 15 9(1 0) 15 9(1 0) 15 8(1 0) TZ Sex no boys 31 28 39 33 CI 43 37 45 42 Tot 74 65 84 75 Schools/Health districts TZ Wingwi 64 67 66 65 Mizingani 7 4 5 6 Wesha 16 17 18 17 Tumbe 14 14 13 15 CI Azaguié 19 18 17 10 Rubino 39 39 38 48 TZ Weight kg Ŧ 47 2(6 9) 47 8(8 5) 46 8(7 9) 46 5(7 9 CI 49 0(9 0) 50 9(8 8) 50 7(8 8) 52 2(7 9 Tot 47 9(7 8) 48 9(8 7) 48 2(8 3) 48 5(8 4 TZ Height cm Ŧ 156 6(8 2) 155 5(9 7) 156 0(14 7) 156 3(10 5) CI 159 5(9 1) 161 5(8 6) 162 5(10 2) 162 2(7 2) Tot 157 7(8 7) 157 6(9 8) 158 3(13 6) 158 5(9 8) Tanzania Côte d Ivoire Hookworm Tribendimidine Tribendimidine- Tribendimidine- Albendazole- Ivermectin Oxantel pamoate Oxantel pamoate Participants infected 101 102 102 103 Geometric mean no of eggs/g 191 8 168 5 173 4 183 8 Arithmetic mean no of eggs/g 386 7 377 9 378 5 456 3 Infection intensity no (%) + light 99 (98 0) 99 (97 0) 99 (97 0) 99 (96 0) moderate 2 (2 0) 2 (2 0) 3 (3 0) 2 (2 0) Heavy - 1 (1 0) - 2 (2 0) Participants infected no (%) 58 57 55 58 Geometric mean no of eggs/g 160 1 154 7 223 4 204 4 Arithmetic mean no of eggs/g 425 9 465 9 442 8 570 2 Infection intensity no (%) + light 54 (93 1) 54 (94 7) 54 (98 2) 55 (94 8) moderate 4 (6 9) 2 (3 5) 1 (1 8) 1 (1 7) Heavy - 1 (1 8) - 2 (3 5) 4
Total Participants infected no (%) 159 159 157 161 Geometric mean no of eggs/g 179 6 163 4 189 5 190 9 Arithmetic mean no of eggs/g 401 0 409 4 401 0 497 4 Infection intensity no (%) + light 153 (96 2) 153 (96 2) 153 (97 5) 154 (95 7) moderate 6 (3 8) 4 (2 5) 4 (2 6) 3 (1 9) Heavy - 2 (1 3) - 4 (2 5) Tanzania Côte d Ivoire Total Trichuris trichiura Tribendimidine Tribendimidine- Tribendimidine- Albendazole- Ivermectin Oxantel pamoate Oxantel pamoate Participants infected no (%) 99 (98 0) 102 (100 0) 98 (96 1) 103 (100 0) Geometric mean no of eggs/g 779 7 702 6 760 5 751 0 Arithmetic mean no of eggs/g 1813 5 1537 2 1661 3 1822 7 Infection intensity no (%) light 54 (54 6) 60 (58 8) 58 (59 2) 53 (51 5) moderate 43 (43 4) 41 (40 2) 38 (38 8) 50 (48 5) Heavy 2 (2 0) 1 (1 0) 2 (2 0) - Participants infected no (%) 3 (5 2) 4 (7 0) 3 (5 5) - Geometric mean no of eggs/g 106 8 75 5 33 9 - Arithmetic mean no of eggs/g 434 0 261 0 42 0 - Infection intensity no (%) light 2 (66 7) 4 (100 0) 3 (100 0) - moderate 1 (33 3) - - - Heavy - - - - Participants infected no (%) 102 (64 2) 106 (66 7) 101 (64 3) 103 (64 0) Geometric mean no of eggs/g 735 6 646 1 693 9 751 0 Arithmetic mean no of eggs/g 1772 9 1489 1 1613 2 1822 7 Infection intensity no (%) light 56 (54 9) 64 (60 4) 61 (60 4) 53 (51 5) moderate 44 (43 1) 41 (38 7) 38 (37 6) 50 (48 5) Heavy 2 (2 0) 1 (1 0) 2 (2 0) - 5
Ascaris lumbricoides Tribendimidine Tribendimidine- Tribendimidine- Albendazole- Ivermectin Oxantel pamoate Oxantel pamoate Participants infected no (%) 71 (70 3) 74 (72 6) 73 (71 6) 78 (75 7) Geometric mean no of eggs/g 2765 2 4428 4 2654 1 5059 8 Arithmetic mean no of eggs/g 11056 7 13770 2 11050 5 15229 3 Infection intensity no (%) light 35 (49 3) 30 (40 5) 34 (46 6) 34 (43 6) moderate 33 (46 5) 38 (51 4) 37 (50 7) 40 (51 3) Heavy 3 (4 2) 6 (8 1) 2 (2 7) 4 (5 1) Participants infected no (%) 3 (5 2) 3 (5 3) 2 (3 6) 1 (1 7) Geometric mean no of eggs/g 4885 7 1596 2 145 7 852 0 Arithmetic mean no of eggs/g 5040 0 2876 0 183 0 852 0 Infection intensity no (%) light 2 (66 7) 2 (66 7) 2 (100 0) 1 (100 0) moderate 1 (33 3) 1 (33 3) - - Heavy - - - - Participants infected no (%) 74 (46 5) 77 (48 4) 75 (47 8) 79 (49 1) Geometric mean no of eggs/g 2829 8 4255 8 2456 8 4947 0 Arithmetic mean no of eggs/g 10812 7 13345 8 10760 7 15047 3 Infection intensity no (%) light 37 (50 0) 32 (41 6) 36 (48 0) 35 (44 3) moderate 34 (46 0) 39 (50 7) 37 (49 3) 40 (50 6) Heavy 3 (4 1) 6 (7 8) 2 (2 7) 4 (5 1) Ŧ Values denote means (standard deviation) + Infection intensities for hookworm were categorized as light (1 to 1999 eggs per gram ), moderate (2000 to 3999 eggs per gram ), or heavy ( 4000 eggs per gram ). Infection intensities for T trichiura were categorized as light (1 to 999 eggs per gram ), moderate (1000 to 9999 eggs per gram ), or heavy ( 10,000 eggs per gram ). Infection intensities for A lumbricoides were categorized as light (1 to 4999 eggs per gram ), moderate (5000 to 49,999 eggs per gram ), or heavy ( 50,000 eggs per gram ). Tanzania Côte d Ivoire Total 6
Table S3 Cure rates and egg-reduction rates (geometric and arithmetic) for the four treatment arms tribendimidine, tribendimidine-ivermectin, tribendimidine-oxantel pamoate and albendazole-oxantel pamoate for Tanzania (TZ), Côte d Ivoire ( and the total. Tanzania Côte d Ivoire Total Hookworm Tribendimidine Tribendimidine - ivermectin Tribendimidine - Oxantel pamoate Albendazole - Oxantel pamoate Before treatment 96 100 95 99 After treatment 40 19 45 46 Cure rate - %(95% * 58 3 (47 8-68 3) 81 0 (71 9-88 2) 52 6 (42 1-63 0) 53 5 (43 2-63 6) Geometric mean no of eggs/g Before treatment 202 4 169 6 180 3 179 7 After treatment 4 7 1 0 6 1 5 0 Egg-reduction rate - % (95% 97 7 (96 1-98 7) 99 4 (99 0-99 7) 96 6 (94 6-97 9) 97 2 (95 4-98 4) * Arithmetic mean no of eggs/g Before treatment 399 1 377 3 385 5 458 8 After treatment 83 6 9 3 57 3 42 5 Egg-reduction rate - % (95% 79 0 (60 6-91 9) 97 5 (96 0-98 7) 85 1 (78 0-90 2) 90 7 (85 3-94 5) * Before treatment 55 54 53 49 After treatment 30 5 26 31 Cure rate - %(95% 45 5 (32 0-59 5) 90 7 (79 7-96 9) 50 9 (36 8-64 9) 36 7 (23 4-51 7) Geometric mean no of eggs/g Before treatment 153 7 158 7 215 3 228 6 After treatment 9 6 0 6 8 2 18 3 Egg-reduction rate - % (95% 93 8 (87 9-96 9) 99 6 (90 0-99 9) 96 2 (92 8-98 2) 92 0 (84 0-96 2) Arithmetic mean no of eggs/g Before treatment 420 8 485 2 423 8 628 5 After treatment 105 8 27 1 103 2 112 5 Egg-reduction rate - % (95% 74 9 (61 1-85 1) 94 4 (87 5-99 4) 75 6 (62 4-86 8) 82 1 (69 4-88 6) Before treatment 151 154 148 148 After treatment 70 24 71 77 Cure rate - %(95% 53 6 (45 4-61 8) 84 4 (77 7-89 8) 52 0 (43 7-60 3) 48 0 (39 7-56 3) Geometric mean no of eggs/g Before treatment 183 1 165 7 192 1 194 6 After treatment 6 1 0 8 6 8 7 8 Egg-reduction rate - % (95% 96 7 (94 9-97 8) 99 5 (99 2-99 7) 96 5 (94 9-97 6) 96 0 (93 9-97 4) Arithmetic mean no of eggs/g Before treatment 407 0 415 2 399 2 515 0 After treatment 91 7 15 5 73 8 65 7 Egg-reduction rate - % (95% 77 5 (65 4-86 8) 96 3 (93 8-98 3) 81 5 (74 5-87 1) 87 2 (82 1-90 8) 7
Tanzania Côte d Ivoire Total Trichuris trichiura Tribendimidine Tribendimidine - Tribendimidine - Oxantel pamoate Albendazole - Oxantel pamoate ivermectin Before treatment 94 100 92 99 After treatment 88 68 32 17 Cure rate - %(95% 6 4 (2 4-13 4) 32 0 (23 0-42 1) 65 2 (54 6-74 9) 82 8 (73 9-89 7) Geometric mean no of eggs/g Before treatment 821 4 700 1 789 1 753 9 After treatment 405 5 25 1 4 0 1 3 Egg-reduction rate - % (95% 50 6 (29 4-66 9) 96 4 (94 1-97 8) 99 5 (99 1-99 7) 99 8 (99 7-99 9) Arithmetic mean no of eggs/g Before treatment 1883 1 1545 8 1725 5 1843 7 After treatment 1600 1 176 4 102 0 55 0 Egg-reduction rate - % (95% 15 0 (-9 3-31 4) 88 6 (82 5-92 6) 94 1 (90 3-97 0) 97 0 (94 1-99 0) Before treatment 3 4 3 - After treatment 1 1 0 - Cure rate - %(95% 66 7 (9 4-99 2) 75 0 (19 4-99 4) 100 0 - Geometric mean no of eggs/g Before treatment 106 8 75 5 33 9 - After treatment 9 5 2 3 0 0 - Egg-reduction rate - % (95% 99 1 (47 8-100 0) 96 9 (86 6-100 0) 100 0 - Arithmetic mean no of eggs/g Before treatment 434 0 261 0 42 0 - After treatment 382 0 30 0 0 0 - Egg-reduction rate - % (95% 12 0 (-0 3-100 0) 88 5 (85 5-100 0) 100 0 - Before treatment 97 104 95 99 After treatment 89 69 32 17 Cure rate - %(95% 8 2 (3 6-15 6) 33 7 (24 7-43 6) 66 3 (55 9-75 7) 82 8 (73 9-89 7) Geometric mean no of eggs/g Before treatment 771 3 642 8 715 0 753 9 After treatment 362 0 23 1 3 8 1 3 Egg-reduction rate - % (95% 53 1 (32 0-68 3) 96 4 (94 3-97 8) 99 5 (99 1-99 7) 99 8 (99 7-99 9) Arithmetic mean no of eggs/g Before treatment 1838 3 1496 4 1672 4 1843 7 After treatment 1562 4 170 8 98 8 55 0 Egg-reduction rate - % (95% 15 0 (-7 7-31 8) 88 6 (82 5-92 4) 94 1 (90 2-97 0) 97 0 (94 1-99 0) 8
Tanzania Côte d Ivoire Total Ascaris lumbricoides Tribendimidine Tribendimidine - Tribendimidine - Oxantel pamoate Albendazole - Oxantel pamoate ivermectin Before treatment 69 73 68 77 After treatment 1 1 3 5 Cure rate - %(95% 98 6 (92 2-100 0) 98 6 (92 6-100 0) 95 6 (87 6-99 1) 93 5 (85 5-97 9) Geometric mean no of eggs/g Before treatment 2750 5 4320 2 2900 6 4936 1 After treatment 0 03 0 04 0 4 0 6 Egg-reduction rate - % (95% >99 99 (>99 99-100 0) >99 99 (>99 99-100 0) >99 99 (99 95-100 0) >99 99 (99 96-100 0) Arithmetic mean no of eggs/g Before treatment 11245 5 13589 8 11295 8 14985 3 After treatment 0 1 0 2 236 8 189 7 Egg-reduction rate - % (95% >99 99 (>99 99-100 0) >99 99 (>99 99-97 9 (93 7-100 0) 98 7 (96 9-99 8) 100 0) Before treatment 3 3 2 1 After treatment 0 0 1 0 Cure rate - %(95% 100 0 100 0 50 0 100 0 Geometric mean no of eggs/g Before treatment 4885 7 1596 2 145 7 852 After treatment 0 0 0 0 15 3 0 0 Egg-reduction rate - % (95% 100 0 100 0 89 5 100 0 Arithmetic mean no of eggs/g Before treatment 5040 2876 183 852 After treatment 0 0 132 0 Egg-reduction rate - % (95% 100 0 100 0 27 9 100 0 Before treatment 72 76 70 78 After treatment 1 1 4 5 Cure rate - %(95% 98 6 (92 5-100 0) 98 7 (92 9-100 0) 94 3 (86 0-98 4) 93 6 (85 7-97 9) Geometric mean no of eggs/g Before treatment 2817 2 4153 7 2663 4 4826 2 After treatment 0 03 0 03 0 5 0 6 Egg-reduction rate - % (95% >99 99 (>99 99- >99 99 (>99 99-99 98 (99 93-99 99 (99 96-100 0) 100 0) 100 0) 100 0) Arithmetic mean no of eggs/g Before treatment 10986 9 13166 9 10978 3 14804 1 After treatment 0 1 0 2 233 8 187 2 Egg-reduction rate - % (95% >99 99 (>99 99- >99 99 (>99 99-97 9 (93 8-100 0) 98 7 (96 9-99 8) 100 0) 100 0) *CI denotes the confidence interval 9
Table S4 Cure rates and egg-reduction rate of the four treatment arms with all missing data interpreted once as treatment success (cured, follow-up egg count=0) and once as treatment failure (not cured, follow-up egg counts equal to baseline). All missing data analysed as treatment success Variable Tribendimidine Tribendimidine - ivermectin *CI denotes the confidence interval Hookworm Tribendimidine - Oxantel pamoate Albendazole - Oxantel pamoate Before treatment 159 159 157 161 Missing participants 8 5 9 13 analysed as treatment success After treatment 70 24 71 77 Cure rate - %(95% * 56 0 (47 9-63 8) 84 9 (78 4-90 1) 54 8 (46 6-62 7) 52 2 (44 2-60 1) Geometric mean no of eggs/g Before treatment 179 7 163 4 189 5 190 9 After treatment 5 5 0 8 5 9 6 4 Egg-reduction rate - % (95% 96 9 (95 5-98 1) 99 5 (99 2-99 7) 96 9 (95 2-98 0) 96 6 (94 9-97 9) * All missing data analysed as treatment failure Variable Tribendimidine Tribendimidine - ivermectin Hookworm Tribendimidine - Oxantel pamoate Albendazole - Oxantel pamoate Before treatment 159 159 157 161 Missing participants 8 5 9 13 analysed as treatment failure After treatment 78 29 80 90 Cure rate - %(95% * 50 9 (42 9-58 9) 81 8 (74 9-87 4) 49 0 (41 0-57 1) 44 1 (36 3-52 1) Geometric mean no of eggs/g Before treatment 179 6 163 4 189 5 190 9 After treatment 7 2 1 1 8 2 10 1 Egg-reduction rate - % (95% 96 0 (94 0-97 3) 99 3 (98 9-99 6) 95 7 (93 6-97 1) 94 7 (91 9-96 6) * 10
Table S5 Clinical symptoms and adverse events of the treatments arms tribendimidine, tribendimidineivermectin, tribendimidine-oxantel pamoate and albendazole-oxantel pamoate assessed at three time points (pre-treatment, 3 and 24 hours post treatment) in Tanzania. Treatment group Symptoms Headache Vertigo Abdominal cramps Fatigue Allergic reaction Nausea Vomiting Diarrhoea Fever Total number of symptoms Number of participants with any symptoms (%) Pre-treatment Tribendimidine (n=101) 3 2 2 1 0 3 0 0 0 11 8(7 9) Tribendimidineivermectin (n=102) 4 2 3 0 1 0 0 0 0 10 10(9 8) Tribendimidine-oxantel 4 1 4 2 1 1 1 1 0 15 7(6 9) pamoate (n=102) Albendazole-oxantel pamoate (n=103) 4 0 1 1 0 1 0 0 0 7 7(6 8) Total (n=408) 15 5 10 4 2 5 1 1 0 43 32(7 8) 3 hours post-treatment Tribendimidine (n=101) 7 2 1 2 0 1 0 0 1 14 8(7 9) Tribendimidineivermectin 5 5 3 5 1 0 0 0 0 19 13(12 8) (n=102) Tribendimidine-oxantel 6 4 3 1 0 2 0 0 0 16 14(13 7) pamoate (n=102) Albendazole-oxantel 1 3 7 2 0 0 0 0 0 13 12(11 7) pamoate (n=103) Total (n=408) 19 14 14 10 1 3 0 0 1 62 47(11 5) 24 hours post-treatment Tribendimidine (n=96) 8 10 6 4 0 5 2 1 2 1 38 1 23(24 0) Tribendimidineivermectin 9 14 3 5 0 2 1 2 1 37 26(26 0) (n=100) Tribendimidine-oxantel 13 18 3 4 0 1 1 1 2 43 27(27 3) pamoate (n=99) Albendazole-oxantel 4 4 4 2 0 1 1 1 0 17 14(14 4) pamoate (n=97) 1 1 2 Total (n=392) 34 46 16 15 0 9 5 6 4 135 90(23 0) 2 1 3 moderate adverse event 11
Table S6 Clinical symptoms and adverse events of the treatments arms tribendimidine, tribendimidineivermectin, tribendimidine-oxantel pamoate and albendazole-oxantel pamoate assessed at three time points (pre-treatment, 3 and 24 hours post treatment) in Côte d Ivoire. Treatment group Symptoms moderate adverse event Headache Vertigo Abdominal cramps Fatigue Allergic reaction Nausea Vomiting Diarrhoea Fever Total number of symptoms Number of participants with any symptoms (%) Pre-treatment Tribendimidine (n=58) 11 5 17 2 1 0 0 5 3 44 29(50 0) Tribendimidineivermectin 9 1 12 6 2 0 0 3 4 37 21(36 8) (n=57) Tribendimidine-oxantel 13 3 8 9 2 0 0 2 4 41 30(54 6) pamoate (n=55) Albendazole-oxantel pamoate (n=58) 12 2 8 2 1 0 0 1 5 31 19(32 8) Total (n=228) 45 11 45 19 6 0 0 11 16 153 99(43 4) 3 hours post-treatment Tribendimidine (n=58) 8 10 2 1 0 0 1 0 0 22 15(25 9) Tribendimidineivermectin (n=57) Tribendimidine-oxantel 8 pamoate (n=55) 1 Albendazole- oxantel pamoate (n=58) Total (n=228) 30 1 8 3 3 4 0 0 0 0 0 18 14(24 6) 5 2 0 2 1 1 0 0 0 17 3 17(30 9) 6 3 1 1 1 1 0 0 0 13 8(13 8) 21 2 6 8 2 2 1 0 0 70 3 54(23 7) 24 hours post-treatment Tribendimidine (n=57) 2 1 0 2 0 0 0 4 0 9 7(12 3) Tribendimidineivermectin 3 2 0 2 0 1 1 3 0 12 8(15 4) (n=52) Tribendimidine-oxantel pamoate (n=51) 2 1 0 1 1 1 0 3 0 9 6(11 8) Albendazole-oxantel pamoate (n=53) 0 0 0 0 0 0 0 0 0 0 0 (0 0) Total (n=213) 7 4 0 5 1 2 1 10 0 30 21(9 9) 12
Table S7 Clinical symptoms and adverse events of the treatments arms tribendimidine, tribendimidineivermectin, tribendimidine-oxantel pamoate and albendazole-oxantel pamoate assessed at three time points (pre-treatment, 3 and 24 hours post treatment) in Tanzania and Côte d Ivoire. Treatment group Symptoms moderate adverse event Headache Vertigo Abdominal cramps Fatigue Allergic reaction Nausea Vomiting Diarrhoea Fever Total number of symptoms Number of participants with any symptoms Pre-treatment Tribendimidine (n=159) 14 7 19 3 1 3 0 5 3 55 37(23 3) Tribendimidine-ivermectin 13 3 15 6 3 0 0 3 4 47 31(19 5) (n=159) Tribendimidine-oxantel 17 4 12 11 3 1 1 3 4 56 37(23 6) pamoate (n=157) Albendazole-oxantel pamoate (n=161) 16 2 9 3 1 1 0 1 5 38 26(16 2) Total (n=636) 60 16 55 23 8 5 1 12 16 196 131(20 6) 3 hours post-treatment Tribendimidine (n=159) 15 12 3 3 0 1 1 0 1 36 23(14 5) Tribendimidine-ivermectin 13 8 6 9 1 0 0 0 0 37 27(17 0) (n=159) Tribendimidine-oxantel 14 9 3 3 1 3 0 0 0 33 31(19 8) pamoate (n=157) 1 2 3 Albendazole-oxantel 7 6 8 3 1 1 0 0 0 26 20(12 4) pamoate (n=161) Total (n=636) 49 1 35 2 20 18 3 5 1 0 1 132 3 101(15 9) 24 hours post-treatment Tribendimidine 10 11 6 6 0 5 2 6 1 47 30(19 6) (n=153) 1 1 Tribendimidine-ivermectin 12 16 3 7 0 3 2 5 1 49 34(22 4) (n=152) Tribendimidine-oxantel 15 19 3 5 1 2 1 4 2 52 33(22 0) pamoate (n=150) Albendazole-oxantel 4 4 4 2 0 1 1 1 0 17 14(9 3) pamoate (n=150) 1 1 2 Total (n=605) 41 50 16 20 1 11 6 2 16 1 4 165 3 111(18 3) 13
Figure S1 Predicted probability of being cured (A) and proportion of egg reduction (B) by baseline infection intensity stratified by treatment arm. Cure rate prediction were based on logistic regression estimates and the egg reduction via lowest scatterplot smoothing algorithm truncated at 1. Circles represent predicted values of participants cured after treatment, stars indicate participants remained infected after treatment. A B 14