Gametocyte Dynamics After Antimalarial Treatment

This study aimed to determine the mean circulation time of gametocytes and the impact of ACT and PQ on existing gametocyte carriage. Therefore, individuals were selected who i) had gametocytes by Pfs25 QT-NASBA at any time between day 0 and day 28 after enrolment, ii) were successfully cured of their asexual parasites (defined as no asexual parasites after day 3 and a day 3 asexual density≤10% of the day 0 density) and had no detectable re-infection. SP-treated children experienced a very high treatment failure rate by microscopy (56%). Additional low level SP-treatment failures may have been missed by day 28 [33 (link)] and the slow parasite clearance time probably extended the generation of gametocytes from asexual stages after the initiation of SP treatment [34 (link)]. The SP monotherapy arm was therefore completely excluded from the current analyses. Instead, models were fitted on data from i) SP+AQ treated individuals (non-ACT arm) since this drug combination had a high efficacy and rapid asexual parasite clearance time [16 (link),35 (link)] but no activity against mature gametocytes[5 (link)]; ii) SP+AS and AL treated individuals that were combined as the ACT-arm since both drug combinations had an indistinguishable impact on gametocyte carriage [16 (link)]; iii) SP+AS+PQ (ACT-PQ) treated children. Frequent re-infections rendered the data from the trial in Tanzania less reliable after day 28 [15 ] and, therefore, only data up to this time-point were considered. Two phases in gametocyte carriage after treatment were considered. The first phase comprises day 0-3 when short acting artemisinins [36 (link)] and PQ [37 (link),38 (link)] may have a direct effect on gametocyte densities and gametocyte densities may be influenced by an efflux of sequestered gametocytes as a result of the drug treatment induced 'stress' [7 (link)]. The initial reduction in gametocyte carriage in this period was quantified by expressing the gametocyte density on day 3 as a proportion of the enrolment density for the three treatment arms. The second phase was defined as day 3 till day 28 (end of follow-up) and was used to estimate the mean circulation time of gametocytes after asexual parasites have been cleared and gametocytocidal drug levels have waned.

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Bousema T., Okell L., Shekalaghe S., Griffin J.T., Omar S., Sawa P., Sutherland C., Sauerwein R., Ghani A.C, & Drakeley C. (2010). Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malaria Journal, 9, 136.

Publication 2010

Arms Artemisinins Children Circulation time Drug Drug combinations Microscopy Nasba Parasites Re infection

Corresponding Organization : Radboud University Medical Center

Other organizations : Imperial College London, Kilimanjaro Christian Medical Centre, Kenya Medical Research Institute, International Centre of Insect Physiology and Ecology

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Variable analysis

independent variables

Treatment arms: SP+AQ (non-ACT), SP+AS and AL (ACT), SP+AS+PQ (ACT-PQ)

dependent variables

Mean circulation time of gametocytes
Impact of ACT and PQ on existing gametocyte carriage

control variables

Individuals who i) had gametocytes by Pfs25 QT-NASBA at any time between day 0 and day 28 after enrolment, ii) were successfully cured of their asexual parasites (defined as no asexual parasites after day 3 and a day 3 asexual density≤10% of the day 0 density) and had no detectable re-infection

positive controls

None specified

negative controls

The SP monotherapy arm was excluded from the analyses due to high treatment failure rate and slow parasite clearance time

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