A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common...

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Main Authors: Olliaro, P. L., Vaillant, M. T., Belizario, V. J., Lwambo, N. J., Ouldabdallahi, M., Pieri, O. S., Amarillo, M. L., Kaatano, G. M., Diaw, M., Domingues, A. C., Favre, T. C., Lapujade, O., Alves, F., Chitsulo, L.
Format: Journal Article
Language:EN
Published: 2012
Subjects:
Abdominal Pain
Adolescent
Anthelmintics
Brazil
Child
Female
Humans
Incidence
Male
Mauritania
Parasite Egg Count
Philippines
Praziquantel
Recurrence
Schistosomiasis mansoni
Tanzania
Treatment Outcome
Young Adult
Online Access:http://hdl.handle.net/10986/5121
id okr-10986-5121
recordtype oai_dc
spelling okr-10986-51212021-04-23T14:02:21Z A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil Olliaro, P. L. Vaillant, M. T. Belizario, V. J. Lwambo, N. J. Ouldabdallahi, M. Pieri, O. S. Amarillo, M. L. Kaatano, G. M. Diaw, M. Domingues, A. C. Favre, T. C. Lapujade, O. Alves, F. Chitsulo, L. Abdominal Pain Adolescent Anthelmintics Brazil Child Female Humans Incidence Male Mauritania Parasite Egg Count Philippines Praziquantel Recurrence Schistosomiasis mansoni Tanzania Treatment Outcome Young Adult BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95% CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). CONCLUSION: A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries. 2012-03-30T07:31:24Z 2012-03-30T07:31:24Z 2011 Journal Article PLoS Negl Trop Dis 1935-2735 (Electronic) 1935-2727 (Linking) http://hdl.handle.net/10986/5121 EN http://creativecommons.org/licenses/by-nc-nd/3.0/igo World Bank Journal Article Philippines Mauritania Tanzania Brazil
repository_type Digital Repository
institution_category Foreign Institution
institution Digital Repositories
building World Bank Open Knowledge Repository
collection World Bank
language EN
topic Abdominal Pain
Adolescent
Anthelmintics
Brazil
Child
Female
Humans
Incidence
Male
Mauritania
Parasite Egg Count
Philippines
Praziquantel
Recurrence
Schistosomiasis mansoni
Tanzania
Treatment Outcome
Young Adult
spellingShingle Abdominal Pain
Adolescent
Anthelmintics
Brazil
Child
Female
Humans
Incidence
Male
Mauritania
Parasite Egg Count
Philippines
Praziquantel
Recurrence
Schistosomiasis mansoni
Tanzania
Treatment Outcome
Young Adult
Olliaro, P. L.
Vaillant, M. T.
Belizario, V. J.
Lwambo, N. J.
Ouldabdallahi, M.
Pieri, O. S.
Amarillo, M. L.
Kaatano, G. M.
Diaw, M.
Domingues, A. C.
Favre, T. C.
Lapujade, O.
Alves, F.
Chitsulo, L.
A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
geographic_facet Philippines
Mauritania
Tanzania
Brazil
relation http://creativecommons.org/licenses/by-nc-nd/3.0/igo
description BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95% CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). CONCLUSION: A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.
format Journal Article
author Olliaro, P. L.
Vaillant, M. T.
Belizario, V. J.
Lwambo, N. J.
Ouldabdallahi, M.
Pieri, O. S.
Amarillo, M. L.
Kaatano, G. M.
Diaw, M.
Domingues, A. C.
Favre, T. C.
Lapujade, O.
Alves, F.
Chitsulo, L.
author_facet Olliaro, P. L.
Vaillant, M. T.
Belizario, V. J.
Lwambo, N. J.
Ouldabdallahi, M.
Pieri, O. S.
Amarillo, M. L.
Kaatano, G. M.
Diaw, M.
Domingues, A. C.
Favre, T. C.
Lapujade, O.
Alves, F.
Chitsulo, L.
author_sort Olliaro, P. L.
title A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
title_short A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
title_full A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
title_fullStr A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
title_full_unstemmed A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
title_sort multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the philippines, mauritania, tanzania and brazil
publishDate 2012
url http://hdl.handle.net/10986/5121
_version_ 1764394024328757248

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