Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial.
Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-5...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0222993 |
id |
doaj-3a11687625dc470792b3bf9bcf972284 |
---|---|
record_format |
Article |
spelling |
doaj-3a11687625dc470792b3bf9bcf9722842021-03-03T21:10:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022299310.1371/journal.pone.0222993Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial.Margarida Mendes JorgeLucienne OuermiPeter MeissnerGuillaume CompaoréBoubacar CoulibalyEric NebieJohannes KrisamChristina KloseMeinhard KieserAlbrecht JahnGuangyu LuUmberto D AlessandroAli SiéFrank Peter MockenhauptOlaf MüllerArtemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832-0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov NCT02851108.https://doi.org/10.1371/journal.pone.0222993 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Margarida Mendes Jorge Lucienne Ouermi Peter Meissner Guillaume Compaoré Boubacar Coulibaly Eric Nebie Johannes Krisam Christina Klose Meinhard Kieser Albrecht Jahn Guangyu Lu Umberto D Alessandro Ali Sié Frank Peter Mockenhaupt Olaf Müller |
spellingShingle |
Margarida Mendes Jorge Lucienne Ouermi Peter Meissner Guillaume Compaoré Boubacar Coulibaly Eric Nebie Johannes Krisam Christina Klose Meinhard Kieser Albrecht Jahn Guangyu Lu Umberto D Alessandro Ali Sié Frank Peter Mockenhaupt Olaf Müller Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. PLoS ONE |
author_facet |
Margarida Mendes Jorge Lucienne Ouermi Peter Meissner Guillaume Compaoré Boubacar Coulibaly Eric Nebie Johannes Krisam Christina Klose Meinhard Kieser Albrecht Jahn Guangyu Lu Umberto D Alessandro Ali Sié Frank Peter Mockenhaupt Olaf Müller |
author_sort |
Margarida Mendes Jorge |
title |
Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. |
title_short |
Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. |
title_full |
Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. |
title_fullStr |
Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. |
title_full_unstemmed |
Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. |
title_sort |
safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in burkina faso: a randomized controlled trial. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832-0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov NCT02851108. |
url |
https://doi.org/10.1371/journal.pone.0222993 |
work_keys_str_mv |
AT margaridamendesjorge safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT lucienneouermi safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT petermeissner safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT guillaumecompaore safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT boubacarcoulibaly safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT ericnebie safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT johanneskrisam safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT christinaklose safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT meinhardkieser safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT albrechtjahn safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT guangyulu safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT umbertodalessandro safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT alisie safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT frankpetermockenhaupt safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial AT olafmuller safetyandefficacyofartesunateamodiaquinecombinedwitheithermethyleneblueorprimaquineinchildrenwithfalciparummalariainburkinafasoarandomizedcontrolledtrial |
_version_ |
1714818408949743616 |