Gametocyte clearance kinetics determined by quantitative magnetic fractionation in Melanesian children with uncomplicated malaria treated with artemisinin combination therapy
- Author(s)
- Karl, S; Laman, M; Moore, BR; Benjamin, J; Koleala, T; Ibam, C; Kaisan, B; Siba, PM; Waltmann, A; Mueller, I; Woodward, RC; St Pierre, TG; Davis, TM;
- Journal Title
- Antimicrobial Agents and Chemotherapy
- Publication Type
- Journal Article in press
- Abstract
- Quantitative magnetic fractionation and a published mathematical model were used to characterize between-treatment differences in gametocyte density and prevalence in 70 Papua New Guinean children with uncomplicated falciparum and/or vivax malaria randomized to one of two artemisinin combination therapies (artemether-lumefantrine or artemisinin-naphthoquine) in an intervention trial. There was an initial rise in peripheral Plasmodium falciparum gametocyte density with both treatments, but it was more pronounced in the artemisinin-naphthoquine group. Model-derived estimates of the median pre-treatment sequestered gametocyte population were 21/muL for artemether-lumefantrine and 61/muL for artemisinin-naphthoquine (P<0.001). The median time for P. falciparum gametocyte density to fall to <2.5/muL (below which transmission becomes unlikely), was 16 days in the artemether-lumefantrine group and 20 days in artemisinin-naphthoquine-treated patients (P<0.001). Gametocyte prevalence modelling suggested that artemisinin-naphthoquine-treated children became gametocytemic faster (median 2.2 days) than artemether-lumefantrine-treated children (5.3 days; P<0.001) and had a longer median P. falciparum gametocyte carriage time per individual (20 vs 13 days; P<0.001). Clearance of P. vivax gametocytes was rapid (within three days) in both groups but, consistent with reappearances of asexual forms in the main trial, nearly 40% of children in the artemether-lumefantrine group developed P. vivax gametocytemia between Days 28 and 42 compared with 3% in artemisinin-naphthoquine-treated children. These data suggest that artemisinin is less active against sequestered gametocytes than artemether. Greater initial gametocyte release after artemisinin-naphthoquine increases the period of potential P. falciparum transmission by four days relative to artemether-lumefantrine but the longer elimination half-life of naphthoquine vs lumefantrine suppresses P. vivax recurrence and consequent gametocytemia.
- Publisher
- ACS
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 25987625
- Publisher's Version
- https://doi.org/10.1128/AAC.00136-15
- NHMRC Grants
- NHMRC/634343, NHMRC/1052760, NHMRC/1036951, NHMRC/1043345, NHMRC/572561,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-05-22 11:19:36
Last Modified: 2019-04-01 09:00:03