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Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren

BACKGROUND: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimeth...

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Autores principales: Nankabirwa, Joaniter, Cundill, Bonnie, Clarke, Sian, Kabatereine, Narcis, Rosenthal, Philip J., Dorsey, Grant, Brooker, Simon, Staedke, Sarah G.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957410/
https://www.ncbi.nlm.nih.gov/pubmed/20976051
http://dx.doi.org/10.1371/journal.pone.0013438
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author Nankabirwa, Joaniter
Cundill, Bonnie
Clarke, Sian
Kabatereine, Narcis
Rosenthal, Philip J.
Dorsey, Grant
Brooker, Simon
Staedke, Sarah G.
author_facet Nankabirwa, Joaniter
Cundill, Bonnie
Clarke, Sian
Kabatereine, Narcis
Rosenthal, Philip J.
Dorsey, Grant
Brooker, Simon
Staedke, Sarah G.
author_sort Nankabirwa, Joaniter
collection PubMed
description BACKGROUND: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT. METHODS: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens. RESULTS: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003). CONCLUSIONS: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00852371
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spelling pubmed-29574102010-10-25 Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren Nankabirwa, Joaniter Cundill, Bonnie Clarke, Sian Kabatereine, Narcis Rosenthal, Philip J. Dorsey, Grant Brooker, Simon Staedke, Sarah G. PLoS One Research Article BACKGROUND: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT. METHODS: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens. RESULTS: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003). CONCLUSIONS: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00852371 Public Library of Science 2010-10-19 /pmc/articles/PMC2957410/ /pubmed/20976051 http://dx.doi.org/10.1371/journal.pone.0013438 Text en Nankabirwa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nankabirwa, Joaniter
Cundill, Bonnie
Clarke, Sian
Kabatereine, Narcis
Rosenthal, Philip J.
Dorsey, Grant
Brooker, Simon
Staedke, Sarah G.
Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title_full Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title_fullStr Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title_full_unstemmed Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title_short Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren
title_sort efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in ugandan schoolchildren
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957410/
https://www.ncbi.nlm.nih.gov/pubmed/20976051
http://dx.doi.org/10.1371/journal.pone.0013438
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