Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.

<h4>Background</h4>The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that ass...

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Main Authors: Cho Naing, Maxine A Whittaker, Norah Htet Htet, Saint Nway Aye, Joon Wah Mak
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225882&type=printable
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author Cho Naing
Maxine A Whittaker
Norah Htet Htet
Saint Nway Aye
Joon Wah Mak
author_facet Cho Naing
Maxine A Whittaker
Norah Htet Htet
Saint Nway Aye
Joon Wah Mak
author_sort Cho Naing
collection DOAJ
description <h4>Background</h4>The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.<h4>Methods</h4>Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.<h4>Results</h4>Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.<h4>Discussion/ conclusions</h4>The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.
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spelling doaj-art-8f88ad0f98ce42089d42b3be3fae9d8a2025-08-20T02:46:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011412e022588210.1371/journal.pone.0225882Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.Cho NaingMaxine A WhittakerNorah Htet HtetSaint Nway AyeJoon Wah Mak<h4>Background</h4>The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.<h4>Methods</h4>Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.<h4>Results</h4>Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.<h4>Discussion/ conclusions</h4>The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225882&type=printable
spellingShingle Cho Naing
Maxine A Whittaker
Norah Htet Htet
Saint Nway Aye
Joon Wah Mak
Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
PLoS ONE
title Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
title_full Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
title_fullStr Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
title_full_unstemmed Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
title_short Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: A network meta-analysis.
title_sort efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in asian region a network meta analysis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225882&type=printable
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