In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

Karamoko Niaré Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Antoine Dara Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Issaka Sagara Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Mahamadou S. Sissoko Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Cheick Oumar Guindo Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Nana H. Cissé Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Cheick Oumar Coulibaly Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Pascal Ringwald Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Françoise Benoit-Vical Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Antoine Berry Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Abdoulaye A. Djimdé Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Ogobara K. Doumbo Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali; World Health Organization Office, Bamako, Mali; Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland; Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique, Toulouse, France; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France; Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, Maryland

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Although artemisinin resistance has yet to be reported in Africa, surveillance of the efficacy of artemisinin-based combination therapies (ACTs) is warranted. Here, the efficacy of artesunate + sulfadoxine–pyrimethamine (AS + SP) and artemether–lumefantrine (AL) was evaluated in Mali. Randomized open-label comparative in vivo assay of AS + SP versus AL were carried out using the 28-day follow-up World Health Organization protocol. Patients with uncomplicated falciparum malaria and at least 6 months of age were recruited between October 2010 and January 2014. A subset of these patients was selected to measure Plasmodium falciparum clearance time. Polymerase chain reaction-corrected adequate clinical and parasitological responses were 100% for AS + SP and 98.2% for AL with no significant difference (P = 0.06). The reinfection rates were comparable (P = 0.63) with 8.0% for AS + SP and 12.6% for AL. Individuals under 8 years were more susceptible to treatment failure (relative risk = 1.9; 95% confidence interval = 1.2, 3.3). Median parasite clearance half-life was 1.7 hours (interquartile range [IQR] = 1.3–2.2) for AS + SP and 1.9 hours (IQR = 1.5–2.5) for AL with no statistically significant difference (P = 0.24). Efficacy of AS + SP and AL was high. This study provides baseline information on parasite clearance half-lives after ACT treatment, particularly AS + SP, in Mali.

Author Notes

* Address correspondence to Karamoko Niaré or Ogobara K. Doumbo, Département d'Epidémiologie des Affections Parasitaires (DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), P.O. Box 1805, Point G, Bamako, Mali. E-mails: karaniare@icermali.org or okd@icermali.org

Financial support: This study was primarily funded by Bill & Melinda Foundation through WHO to MRTC for in vivo assessment of two ACT efficacies in 2010 in Mali. French Mérieux Foundation provided additional fund through the grant 01/2007 Christophe Mérieux Award.

Authors' addresses: Karamoko Niaré, Issaka Sagara, Mahamadou S. Sissoko, Cheick Oumar Guindo, Nana H. Cissé, Abdoulaye A. Djimdé, and Ogobara K. Doumbo, Département d'Epidémiologie des Affections Parasitaire(DEAP), Malaria Research and Training Center (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali, E-mails: karaniare@icermali.org, isagara@icermali.org, mssissoko@icermali.org, guindo.cheickoumar@yahoo.fr, nanahouma@yahoo.fr, adjimde@icermali.org, and okd@icermali.org. Antoine Dara, Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mail: adara@medicine.umaryland.edu. Cheick Oumar Coulibaly, World Health Organization Office, Bamako, Mali, E-mail: coulibalyc@who.int. Pascal Ringwald, Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland, E-mail: ringwaldp@who.int. Françoise Benoit-Vical, Laboratoire de Chimie de Coordination (LCC), Centre National de la Recherche Scientifique (CNRS), Toulouse, France, E-mail: francoise.vical@inserm.fr. Antoine Berry, Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire (CHU) Toulouse, Toulouse, France, and Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, Toulouse, France, E-mail: antoine.berry@yahoo.fr.

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