title: Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children.
abstract: Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010-2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1-10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002-2004. Of 100 children enrolled in the 2010-2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002-2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0) and did not significantly decline until day 21 of follow-up (23% vs. 6%, p = 0.003). The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/μL vs. 16 gametocytes/μL, p = 0.6). Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002-2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting.
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimde
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Amelia W
authors.initials: AW
authors.lastname: Maiga
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Dinkorma
authors.initials: D
authors.lastname: Ouologuem
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Bakary
authors.initials: B
authors.lastname: Fofana
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Demba
authors.initials: D
authors.lastname: Dembele
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Sekou
authors.initials: S
authors.lastname: Toure
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Kassim
authors.initials: K
authors.lastname: Sanogo
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Souleymane
authors.initials: S
authors.lastname: Dama
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Bakary
authors.initials: B
authors.lastname: Sidibe
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, P.O. Box 1805, Mali.
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D002353:Carrier State / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D005854:Germ Cells / Q000187:drug effects*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008302:Mali / Q000453:epidemiology; D018512:Parasitemia / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011446:Prospective Studies; D016037:Single-Blind Method
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate
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