Gametocyte clearance in children, from western Kenya, with uncomplicated Plasmodium falciparum malaria after artemether-lumefantrine or dihydroartemisinin-piperaquine treatment

Abstract

Background: The efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya.

Methods: Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined.

Results: At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301).

Conclusion: The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.

Keywords: Artemether–lumefantrine; Dihydroartemisinin/piperaquine; Plasmodium falciparum gametocyte.

Fig. 1

Enrolment flow chart. Representation of patients screening, inclusion and follow-up of the study. a Dihydroartemisinin–piperaquine. b Artemether–lumefantrine

Fig. 2

Gametocyte prevalence after AL or DP treatment by Pfs25 qRT-PCR. The error bars indicate the upper limit of the 95% confidence interval for prevalence. DP dihydroartemisinin–piperaquine, AL artemether–lumefantrine

Fig. 3

Gametocyte density by Pfs25 qRT-PCR at enrolment and on days 7, 14, 21, 28, 42 after AL or DP treatment. Samples were considered negative if gametocyte levels were < 0.02/µl. Density is presented as median (IQR) for positive individuals only. DP dihydroartemisinin–piperaquine, AL artemether–lumefantrine

Fig. 4

Kaplan-Meier plot of time to the negativity of individuals who were gametocyte positive before either AL or DP treatment. The proportion of gametocyte positive children are shown on the Y-axis and time to complete gametocyte clearance in individuals who were gametocyte positive at enrolment on the X-axis. Time to disappearance was estimated for patients who were positive for gametocyte before treatment only. Artemether–lumefantrine (dashed line n = 43) or dihydroartemisinin–piperaquine (solid line n = 39) in weeks on the X-axis. p = 0.5731. Difference between arms was tested using the log-rank test