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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


Autoři: Margarida Mendes Jorge aff001;  Lucienne Ouermi aff002;  Peter Meissner aff003;  Guillaume Compaoré aff002;  Boubacar Coulibaly aff002;  Eric Nebie aff002;  Johannes Krisam aff004;  Christina Klose aff004;  Meinhard Kieser aff004;  Albrecht Jahn aff001;  Guangyu Lu aff005;  Umberto D`Alessandro aff006;  Ali Sié aff002;  Frank Peter Mockenhaupt aff007;  Olaf Müller aff001
Působiště autorů: Heidelberg Institute of Global Health, University Hospital, Heidelberg, Baden-Württemberg, Germany aff001;  Centre de Recherche en Santé de Nouna, Nouna, Kossi, Burkina Faso aff002;  Department of Paediatrics, University Hospital, Ulm, Germany aff003;  Institut of Medical Biometry and Informatics, University Hospital, Heidelberg, Baden-Württemberg, Germany aff004;  Medical College, Yangzhou University, Yangzhou, Jiangsu, China aff005;  MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, London, United Kingdom aff006;  Institute of Tropical Medicine and International Health, Charité-Universitätsmedizin Berlin, Berlin, Germany aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222993

Souhrn

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.

Klíčová slova:

Antimalarials – Gametocytes – Malaria – Malarial parasites – Plasmodium – Methylene blue – Vomiting – Artemisinin


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