Limits...
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 ONE (2008)

Bottom Line: No drug-related serious adverse events and no deaths occurred.MB-containing regimens were associated with mild vomiting and dysuria.Parasite clearance time differed significantly among groups and was the shortest with MB-AS.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.

ABSTRACT

Background: Besides 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 findings: Open-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).

Conclusions: MB-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 registration: ClinicalTrials.gov NCT00354380.

Show MeSH

Related in: MedlinePlus

Flow chart of study patients.Explanations: (1) Of 244 children assessed for eligibility, 64 were excluded because of not meeting inclusion criteria; (2) In group MB-AS, one child was lost to follow-up because of family out-migration after day 7; (3) all children followed up until the end of the study were included into the analysis
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2238815&req=5

pone-0001630-g001: Flow chart of study patients.Explanations: (1) Of 244 children assessed for eligibility, 64 were excluded because of not meeting inclusion criteria; (2) In group MB-AS, one child was lost to follow-up because of family out-migration after day 7; (3) all children followed up until the end of the study were included into the analysis

Mentions: Of 1 200 children seen at the fever measurement points, 244 children were referred to hospital for assessment, and of those 180 (61 MB-AS, 58 MB-AQ, 61 AS-AQ) were included into the study (Figure 1). These children form the a priori defined full analysis set (FAS) for the intention-to-treat analysis. There was one loss to follow-up due to out-migration from the study area (MB-AS group, after day 7). At enrolment, the demographic and clinical characteristics of the participants in the three study groups were similar, except a small but significant difference in weight (Table 1).


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 ONE (2008)

Flow chart of study patients.Explanations: (1) Of 244 children assessed for eligibility, 64 were excluded because of not meeting inclusion criteria; (2) In group MB-AS, one child was lost to follow-up because of family out-migration after day 7; (3) all children followed up until the end of the study were included into the analysis
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2238815&req=5

pone-0001630-g001: Flow chart of study patients.Explanations: (1) Of 244 children assessed for eligibility, 64 were excluded because of not meeting inclusion criteria; (2) In group MB-AS, one child was lost to follow-up because of family out-migration after day 7; (3) all children followed up until the end of the study were included into the analysis
Mentions: Of 1 200 children seen at the fever measurement points, 244 children were referred to hospital for assessment, and of those 180 (61 MB-AS, 58 MB-AQ, 61 AS-AQ) were included into the study (Figure 1). These children form the a priori defined full analysis set (FAS) for the intention-to-treat analysis. There was one loss to follow-up due to out-migration from the study area (MB-AS group, after day 7). At enrolment, the demographic and clinical characteristics of the participants in the three study groups were similar, except a small but significant difference in weight (Table 1).

Bottom Line: No drug-related serious adverse events and no deaths occurred.MB-containing regimens were associated with mild vomiting and dysuria.Parasite clearance time differed significantly among groups and was the shortest with MB-AS.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche en Santé de Nouna, Nouna, Burkina Faso.

ABSTRACT

Background: Besides 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 findings: Open-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).

Conclusions: MB-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 registration: ClinicalTrials.gov NCT00354380.

Show MeSH
Related in: MedlinePlus