Artemisinin combination therapy (ACT) is widely used to treat uncomplicated
Plasmodium falciparum malaria in endemic areas. Significantly reduced susceptibility to artemisinins, characterized by delayed parasite clearance in vivo and enhanced survival of early stage parasites in vitro, has been reported in Southeast Asia [
1,
2]. Most recently, these parasite phenotypes have been associated with mutations in the
pfk13 gene of
P. falciparum, encoding the kelch-domain protein K13 [
3]. Further studies reported direct evidence of resistance to artemisinin using genetic modification of different
pfk13 loci [
4]. This work has led to an operational definition of partial artemisinin resistance: ≥5 % of patients carrying K13 resistance-associated mutations, all of whom have been found to have either persistent parasitaemia by microscopy on day 3, or a parasite clearance half-life of ≥5 h after treatment with ACT or artesunate monotherapy [
5].
In Africa, ACT is the first-line anti-malarial treatment and remains efficacious and safe [
3,
6]. However, resistance to previous generations of anti-malarial drugs such as chloroquine, sulfadoxine-pyrimethamine (SP) emerged in the 1970s in Southeast Asia and eventually spread to the Indian sub-continent and then to Africa [
7]. It is, therefore, critical that continuous monitoring of the therapeutic response of ACT is carried out in endemic areas in order to detect early warning signs and effectively track and contain the development and spread of artemisinin resistance. Currently, delayed clearance of microscopically detectable parasites has not been observed in Africa. In addition, there are limited data about the in vitro susceptibility of ring stage of parasite development against artemisinins as well as the presence and prevalence of
pfk13 mutations [
8]. Recently, a cross-sectional survey was carried out to determine the prevalence of
pfk13 mutations in 14 sub-Saharan African countries. The study reported the absence of mutations that were associated with artemisinin resistance in Southeast Asia, with the exception of codon 543 [
9]. In previous study, the presence of residual sub-microscopic
P. falciparum parasites in western Kenyan children on day 3 after ACT treatment was reported and this was associated with subsequent recrudescence and transmission [
10]. In addition, the authors have shown in the same Kenyan patient that
P. falciparum parasites carrying certain genotypes at
pfmdr1, pfcrt, pfubp1, and
pfap2mu genes were found to survive more often after ACT treatment at sub-microscopic level [
11]. The aim of this study was to investigate whether these sub-microscopic residual parasites also harboured mutations at the propeller region of
pfk13 and whether the mutations, if any, affect treatment outcome.