Gametocyte clearance kinetics determined by quantitative magnetic fractionation in Melanesian children with uncomplicated malaria treated with artemisinin combination therapy

Karl, Stephan, Laman, Moses, Moore, Brioni R., Benjamin, John, Koleala, Tamarah, Ibam, Clemencia, Kasian, Bernadine, Siba, Peter M., Waltmann, Andreea, Mueller, Ivo, Woodward, Robert C., St Pierre, Timothy G., and Davis, Timothy M.E. (2015) Gametocyte clearance kinetics determined by quantitative magnetic fractionation in Melanesian children with uncomplicated malaria treated with artemisinin combination therapy. Antimicrobial Agents and Chemotherapy, 59 (8). pp. 4489-4496.

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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 Plasmodium falciparum and/or Plasmodium 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 P. falciparum gametocyte density with both treatments, but it was more pronounced in the artemisinin-naphthoquine group. Model-derived estimates of the median pretreatment sequestered gametocyte population were 21/μl for artemether-lumefantrine and 61/μl for artemisinin-naphthoquine (P < 0.001). The median time for P. falciparum gametocyte density to fall to <2.5/μl (below which transmission becomes unlikely) was 16 days in the artemether-lumefantrine group and 20 days in artemisinin-naphthoquine group (P < 0.001). Gametocyte prevalence modeling suggested that artemisinin-naphthoquine-treated children became gametocytemic faster (median, 2.2 days) than artemether-lumefantrine-treated children (median, 5.3 days; P < 0.001) and had a longer median P. falciparum gametocyte carriage time per individual (20 versus 13 days; P < 0.001). Clearance of P. vivax gametocytes was rapid (within 3 days) in both groups; however, consistent with the reappearance 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% of children in the artemisinin-naphthoquine group. These data suggest that artemisinin is less active than artemether against sequestered gametocytes. Greater initial gametocyte release after artemisinin-naphthoquine increases the period of potential P. falciparum transmission by 4 days relative to artemether-lumefantrine, but the longer elimination half-life of naphthoquine than of lumefantrine suppresses P. vivax recurrence and consequent gametocytemia.

Item ID: 42040
Item Type: Article (Research - C1)
ISSN: 1098-6596
Funders: National Health and Medical Research Council of Australia (NHMRC)., Early Career, Esso-highlands PNG Institute of Medical Research, Australian Research Council (ARC)
Projects and Grants: NHMRC 634343, NHMRC 1052760, Early Career Fellowship 1036951, ARC 120103560, NHMRC 1043345, NHMRC 572561
Date Deposited: 08 Dec 2015 18:32
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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