Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso

• Verfasst von: Müller, Margarida Melo Mendes Jorge [VerfasserIn]
• Verfasst von: Ouermi, Lucienne [VerfasserIn]
• Verfasst von: Meissner, Peter [VerfasserIn]
• Verfasst von: Compaoré, Guillaume [VerfasserIn]
• Verfasst von: Coulibaly, Boubacar [VerfasserIn]
• Verfasst von: Nebie, Eric [VerfasserIn]
• Verfasst von: Krisam, Johannes [VerfasserIn]
• Verfasst von: Klose, Christina [VerfasserIn]
• Verfasst von: Kieser, Meinhard [VerfasserIn]
• Verfasst von: Jahn, Albrecht [VerfasserIn]
• Verfasst von: Lu, Guangyu [VerfasserIn]
• Verfasst von: D'Alessandro, Umberto [VerfasserIn]
• Verfasst von: Sié, Ali [VerfasserIn]
• Verfasst von: Mockenhaupt, Frank Peter [VerfasserIn]
• Verfasst von: Müller, Olaf [VerfasserIn]
• Titel: Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso
• Titelzusatz: a randomized controlled trial
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: October 10, 2019
• Umfang: 16 S.
• Fussnoten: Gesehen am 09.12.2019
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2019
• Band/Heft Quelle: 14(2019,10) Artikel-Nummer e0222993, 16 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0222993
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antimalarials
• Sach-SW: Artemisinin
• Sach-SW: Gametocytes
• Sach-SW: Malaria
• Sach-SW: Malarial parasites
• Sach-SW: Methylene blue
• Sach-SW: Plasmodium
• Sach-SW: Vomiting
• K10plus-PPN: 1684882699
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.