Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017

Abstract

Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy monitoring through a standardized therapeutic efficacy study (TES) protocol. From June 2016 to March 2017, children with uncomplicated P. falciparum mono-infection in Siaya County, Kenya were enrolled into a standardized TES and randomized (1:1 ratio) to a 3-day course of artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP). Efficacy outcomes were measured at 28 and 42 days. A total of 340 children were enrolled. All but one child cleared parasites by day 3. PCR-corrected adequate clinical and parasitological response (ACPR) was 88.5% (95% CI: 80.9 to 93.3%) at day 28 for AL and 93.0% (95% CI: 86.9 to 96.4%) at day 42 for DP. There were 9.6 times (95% CI: 3.4 to 27.2) more reinfections in the AL arm compared to the DP arm at day 28, and 3.1 times (95% CI: 1.9 to 4.9) more reinfections at day 42. Both AL and DP were efficacious (per WHO 90% cutoff in the confidence interval) and well tolerated for the treatment of uncomplicated malaria in western Kenya, but AL efficacy appears to be waning. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.

Trial registration: ClinicalTrials.gov NCT05060198.

Keywords: Kenya; artemether-lumefantrine; dihydroartemisinin-piperaquine; in vivo; malaria; recrudescence; therapeutic efficacy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIG 1

Trial enrollment by arm.

FIG 2

Changes in reinfection, recrudescence, and hemoglobin over time: cumulative reinfection and recrudescence in artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) arms, excluding late treatment failures with missing or inconclusive PCR results.

FIG 3

Intention-to-treat analysis: Kaplan-Meier curves for PCR-uncorrected and PCR-corrected ACPR survival function for time until failure at day 28 and 42, by drug.

FIG 4

Mean change in hemoglobin over time, by outcome. “Failure” included late clinical failure (LCF) and late parasitological failure (LPF); “no failure” included ACPR and loss to follow-up. P values at each time point: P = 0.31 for day 0; P = 0.81 for day 7; P = 0.31 for day 14; P = 0.09 for day 28; and P = 0.06 for day 42.