Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Speich B, Ame SM, Ali SM, et al. Oxantel pamoate albendazole for Trichuris trichiura infection. N Engl J Med 2014;370: DOI: /NEJMoa

2 Supplementary Appendix Table of contents Authors and institutional affiliations... 2 Table S1. Egg-reduction rates based on arithmetic means Table S2. Cure rates and egg-reduction rates, stratified by school Table S3. Cure rates based on different imputation approaches Table S4. Number of specific adverse events

3 Oxantel Pamoate-Albendazole against Trichuris trichiura Infection Benjamin Speich, M.Sc., Shaali M. Ame, M.Sc., Said M. Ali, M.Sc., Rainer Alles, Ph.D., Jörg Huwyler, Ph.D., Jan Hattendorf, Ph.D., Jürg Utzinger, Ph.D., Marco Albonico, M.D., Ph.D., and Jennifer Keiser, Ph.D. From the Departments of Medical Parasitology and Infection Biology (B.S., J.K.) and Epidemiology and Public Health (J. Hattendorf, J.U.), Swiss Tropical and Public Health Institute, and the Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel (R.A., J. Huwyler) all in Basel, Switzerland; the Laboratory Division, Public Health Laboratory Ivo de Carneri, Chake Chake, Tanzania (S.M. Ame, S.M. Ali); and the Ivo de Carneri Foundation, Milan (M.A.). Address reprint requests to Dr. Keiser at the Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland, or at 2

4 Table S1. Egg reduction rates of oxantel pamoate plus albendazole; oxantel pamoate; albendazole; and mebendazole; against Trichuris trichiura based on arithmetic means. Oxantel Pamoate- Albendazole (N=114) Oxantel Pamoate (N=116) Albendazole (N=116) Mebendazole (N=112) Trichuris trichiura Arithmetic mean EPG Before After Egg-reduction rate-% Hookworm Arithmetic mean EPG Before After Egg-reduction rate-% Ascaris lumbricoides Arithmetic mean EPG Before , After , Egg-reduction rate-% EPG: Eggs per 1g of stool 3

5 Table S2. Cure rates and egg-reduction rates of oxantel pamoate plus albendazole; oxantel pamoate; albendazole; and mebendazole against Trichuris trichiura, stratified by school. Oxantel Pamoate- Albendazole Oxantel Pamoate Albendazole Mebendazole Mchangamdogo school No. of children positive for T. trichiura infection before No. of children cured after Cure rate-% Geometric mean EPG Before After Egg-reduction rate-% Shungi school No. of children positive for T. trichiura infection before No. of children cured after Cure rate-% Geometric mean EPG Before After Egg-reduction rate-% EPG: Eggs per 1g of stool 4

6 Table S3. Cure rates of oxantel pamoate plus albendazole; oxantel pamoate; albendazole; and mebendazole against Trichuris trichiura based on different imputation approaches. Worst case (all dropouts remain infected) Cure rate-% (95% CI) Best case (all dropouts are cured) Cure rate-% (95% CI) Multiple imputations (R 3.0.0)* Cure rate-% ( 95% CI) Oxantel pamoate- Albendazole Oxantel Pamoate Albendazole Mebendazole 29.9 (21.5 to 38.3) 34.2 (25.5 to 42.9) 25.2 (17.3 to 33.1) 29.4 (21.1 to 37.7) 2.5 (0.0 to 5.4) 5.9 (1.6 to 10.3) 11.0 (5.3 to 16.7) 17.8 (10.8 to 24.8) 30.8 (22.9 to 39.9) 26.2 (18.9 to 35.1) 2.5 (0.8 to 7.6) *Imputation method: bootstrap, 5 chains; only children infected with T. trichiura at baseline are included (6.6 to 18.3) 5

7 Table S4. Number of specific adverse events, stratified by arm, as assessed at different time points. Adverse event Before 3 hr after first 24 hr after first 3 hr after second 24 hr aftersecond Children reporting at least once adverse events (%) b Treatment arm Treatment arm Treatment arm Treatment arm Treatment arm Overall Overall Overall Overall Overall Abdominal cramps (15.1) Headache (12.4) Nausea (6.7) Vertigo (4.4) Fatigue (4.2) Allergic reaction (4.2) Fever a a (2.3) Vomiting (2.1) Diarrhea a a (0.6) Any adverse events: Total (30.9) a 1 participant reported moderate fever and moderate diarrhea b Total number of adverse events does not include adverse events observed before Adverse events were assessed at five time points (before, 3 hours and 24 hours after first, and 3 hours and 24 hours after second ). Oxantel pamoate was given on the first day of, while albendazole and mebendazole was given on the second day of. Treatment arms are the following: 1, Oxantel pamoate plus albendazole, administered sequentially over two consecutive days; 2, oxantel pamoate; 3, albendazole; and 4, mebendazole 6