Boubacar Coulibaly1, Michael Pritsch2, Mamadou Bountogo1, Peter E Meissner3, Eric Nebié1, Christina Klose4, Meinhard Kieser4, Nicole Berens-Riha5, Andreas Wieser2, Sodiomon B Sirima6, Jörg Breitkreutz7, R Heiner Schirmer8, Ali Sié1, Frank P Mockenhaupt9, Chris Drakeley10, Teun Bousema11, Olaf Müller12. 1. Centre de Recherche en Santé de Nouna, Nouna. 2. Division of Infectious Diseases and Tropical Medicine, Medical Center Department of Bacteriology, Max von Pettenkofer-Institute, Ludwig Maximilian University of Munich German Center for Infection Research, Partner Site Munich. 3. Department of Pediatrics and Adolescent Medicine, Medical School, Ulm University. 4. Institute of Medical Biometry and Informatics. 5. Division of Infectious Diseases and Tropical Medicine, Medical Center. 6. Centre de Recherche et de la Formation au Paludisme, Ouagadougou, Burkina Faso. 7. Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Düsseldorf. 8. Biochemistry Centre, Ruprecht-Karls-University, Heidelberg. 9. Institute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin, Germany. 10. Department of Immunology & Infection, London School of Tropical Medicine and Hygiene, United Kingdom. 11. Department of Immunology & Infection, London School of Tropical Medicine and Hygiene, United Kingdom Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands. 12. Institute of Public Health, Medical School.
Abstract
BACKGROUND:Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties. METHODS: Three days of treatment with artesunate (AS)-amodiaquine (AQ) combined with MB was compared with AS-AQ treatment in a randomized controlled phase IIb study; the study included 221 children aged 6-59 months with uncomplicated falciparum malaria in Burkina Faso. The primary end point was gametocyte prevalence during follow-up, as determined by microscopy and real-time quantitative nucleic acid sequence-based amplification (QT-NASBA). RESULTS: The gametocyte prevalence of Plasmodium falciparum at baseline was 3.6% (microscopy) and 97% (QT-NASBA). It was significantly lower in the AS-AQ-MB than in the AS-AQ group on day 7 of follow-up (microscopy, 1.2% vs 8.9% [P < .05]; QT-NASBA, 36.7% vs 63.3% [P < .001]). Hemoglobin values were significantly lower in the AS-AQ-MB group than in the AS-AQ group at days 2 and 7 of follow-up. Vomiting of the study medication occurred significantly more frequently in the AS-AQ-MB group. CONCLUSIONS: The combination of MB with an artemisinin-based combination therapy has been confirmed to be effective against the gametocytes of P. falciparum. MB-based combinations need to be compared with primaquine-based combinations, preferably using MB in an improved pediatric formulation. Clinical Trials Registration: NCT01407887.
RCT Entities:
BACKGROUND:Methylene blue (MB) has been shown to be safe and effective against falciparum malaria in Africa and to have pronounced gametocytocidal properties. METHODS: Three days of treatment with artesunate (AS)-amodiaquine (AQ) combined with MB was compared with AS-AQ treatment in a randomized controlled phase IIb study; the study included 221 children aged 6-59 months with uncomplicated falciparum malaria in Burkina Faso. The primary end point was gametocyte prevalence during follow-up, as determined by microscopy and real-time quantitative nucleic acid sequence-based amplification (QT-NASBA). RESULTS: The gametocyte prevalence of Plasmodium falciparum at baseline was 3.6% (microscopy) and 97% (QT-NASBA). It was significantly lower in the AS-AQ-MB than in the AS-AQ group on day 7 of follow-up (microscopy, 1.2% vs 8.9% [P < .05]; QT-NASBA, 36.7% vs 63.3% [P < .001]). Hemoglobin values were significantly lower in the AS-AQ-MB group than in the AS-AQ group at days 2 and 7 of follow-up. Vomiting of the study medication occurred significantly more frequently in the AS-AQ-MB group. CONCLUSIONS: The combination of MB with an artemisinin-based combination therapy has been confirmed to be effective against the gametocytes of P. falciparum. MB-based combinations need to be compared with primaquine-based combinations, preferably using MB in an improved pediatric formulation. Clinical Trials Registration: NCT01407887.
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