Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso.

Zoungrana A, Coulibaly B, Sié A, Walter-Sack I, Mockenhaupt FP, Kouyaté B, Schirmer RH, Klose C, Mansmann U, Meissner P, Müller O

PloS one20 Feb 2008Cited by 67 (Europe PMC)

PMID18286187PMCIDPMC2238815DOI10.1371/journal.pone.0001630PepBankPUB-18286187

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Summary

BackgroundBesides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso.Methods and findingsOpen-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).ConclusionsMB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention.Trial registrationClinicalTrials.gov NCT00354380.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone12

In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Methylene blue.

01HumanNot a test of Methylene blue aloneRandomized controlled trialSafety outcome
In children with malaria, no drug-related serious adverse events occurred across groups, including methylene blue combination regimens.
In plain wordsIn children with malaria, no drug-related serious adverse events occurred across groups, including methylene blue combinations.
Peptide
Methylene blue
Outcome
Not applicableDrug-related serious adverse events
Study
n = 180
Outcome group
Adverse events · Whole body
Source sentences
Summary
No drug-related serious adverse events and no deaths occurred.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618701
02HumanNot a test of Methylene blue aloneRandomized controlled trialSafety outcome
In children with malaria, no deaths occurred across groups, including methylene blue combination regimens.
In plain wordsIn children with malaria, no deaths occurred across groups, including methylene blue combinations.
Peptide
Methylene blue
Outcome
Not applicableDeaths
Study
n = 180
Outcome group
Mortality · Whole body
Source sentences
Summary
No drug-related serious adverse events and no deaths occurred.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618702
03HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, no early treatment failures occurred across groups, including methylene blue combinations.
In plain wordsIn children with malaria, no early treatment failures occurred across groups, including methylene blue combinations.
Peptide
Methylene blue
Outcome
Not applicableEarly treatment failure
Study
n = 180
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
No early treatment failures were observed.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618705
04HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, parasite clearance time differed significantly among groups and was shortest with MB-AS.
In plain wordsIn children with malaria, parasites cleared fastest with methylene blue plus artesunate among the three treatment groups.
Peptide
Methylene blue
Outcome
DecreaseParasite clearance time
Study
n = 180
Comparator
MB-AQ and AS-AQ
Outcome group
Infection and antimicrobial activity · Infection
Source sentences
Summary
Parasite clearance time differed significantly among groups and was the shortest with MB-AS.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618706
05HumanNot a test of Methylene blue aloneRandomized controlled trialSafety outcome
In children with malaria, methylene blue combination regimens were associated with mild vomiting.
In plain wordsIn children with malaria, methylene blue combinations were linked to mild vomiting.
Peptide
Methylene blue
Outcome
Not applicableVomiting
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
MB-containing regimens were associated with mild vomiting and dysuria.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618703
06HumanNot a test of Methylene blue aloneRandomized controlled trialSafety outcome
In children with malaria, methylene blue combination regimens were associated with mild dysuria.
In plain wordsIn children with malaria, methylene blue combinations were linked to mild painful urination.
Peptide
Methylene blue
Outcome
Not applicableDysuria
Study
n: not reported in source
Outcome group
Adverse events · Kidney and urinary
Source sentences
Summary
MB-containing regimens were associated with mild vomiting and dysuria.
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618704
07HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, corrected response at day 14 was lower with MB-AS than MB-AQ.
In plain wordsIn children with malaria, corrected response at day 14 was lower with MB-AS than MB-AQ.
Peptide
Methylene blue
Outcome
DecreaseDay 14 clinical and parasitological response MB-AS versus MB-AQ
Study
n: not reported in source
Comparator
MB-AQ
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Adequate clinical and parasitological response, PCR-corrected
87%
MB-AS, day 14
Adequate clinical and parasitological response, PCR-corrected
100%
MB-AQ, day 14
Source sentences
Summary
By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618707
08HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, corrected response at day 14 was lower with MB-AS than AS-AQ.
In plain wordsIn children with malaria, corrected response at day 14 was lower with MB-AS than AS-AQ.
Peptide
Methylene blue
Outcome
DecreaseDay 14 clinical and parasitological response MB-AS versus AS-AQ
Study
n: not reported in source
Comparator
AS-AQ
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Adequate clinical and parasitological response, PCR-corrected
87%
MB-AS, day 14
Adequate clinical and parasitological response, PCR-corrected
100%
AS-AQ, day 14
Source sentences
Summary
By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618708
09HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, MB-AQ achieved the reported corrected clinical and parasitological response at day 14.
In plain wordsIn children with malaria, MB-AQ achieved the reported treatment response at day 14.
Peptide
Methylene blue
Outcome
Not applicableDay 14 clinical and parasitological response MB-AQ
Study
n: not reported in source
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Response
100%
MB-AQ
Source sentences
Summary
By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618709
10HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, corrected response at day 28 was lower with MB-AS than AS-AQ.
In plain wordsIn children with malaria, corrected response at day 28 was lower with MB-AS than AS-AQ.
Peptide
Methylene blue
Outcome
DecreaseDay 28 response MB-AS versus AS-AQ
Study
n: not reported in source
Comparator
AS-AQ
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Adequate clinical and parasitological response, PCR-corrected
62%
MB-AS, day 28
Adequate clinical and parasitological response, PCR-corrected
82%
AS-AQ, day 28
Source sentences
Summary
By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618710
11HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, corrected response at day 28 was higher with MB-AQ than AS-AQ.
In plain wordsIn children with malaria, corrected response at day 28 was higher with MB-AQ than AS-AQ.
Peptide
Methylene blue
Outcome
IncreaseDay 28 response MB-AQ versus AS-AQ
Study
n: not reported in source
Comparator
AS-AQ
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Adequate clinical and parasitological response, PCR-corrected
95%
MB-AQ, day 28
Adequate clinical and parasitological response, PCR-corrected
82%
AS-AQ, day 28
Source sentences
Summary
By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618711
12HumanNot a test of Methylene blue aloneRandomized controlled trialEfficacy outcome
In children with malaria, corrected response at day 28 was higher with MB-AQ than MB-AS.
In plain wordsIn children with malaria, corrected response at day 28 was higher with MB-AQ than MB-AS.
Peptide
Methylene blue
Outcome
IncreaseDay 28 response MB-AQ versus MB-AS
Study
n: not reported in source
Comparator
MB-AS
Outcome group
Infection and antimicrobial activity · Infection
Measurements
Adequate clinical and parasitological response, PCR-corrected
95%
MB-AQ, day 28
Adequate clinical and parasitological response, PCR-corrected
62%
MB-AS, day 28
Source sentences
Summary
By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).
2 context sentences(design, population, supporting numbers)
Summary · context
Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso.
Summary · context
Follow-up was for 28 days and analysis by intention-to-treat.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-1828618712

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT00354380

Safety and Efficacy of Methylene Blue Combined With Artesunate or Amodiaquine for Malaria Treatment in Children of Burkina Faso: a Pilot Study

Heidelberg UniversitySept 2006 to Nov 2006

Malaria

Trial page ClinicalTrials.govUpdated 24 Oct 2006

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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