Abstract
Introduction: Plasmodium falciparum has developed resistance to artemisinin drugs in Southeast Asia, and its reduced sensitivity has been reported in other regions. This study aims to determine parasite susceptibility to the bioactive form of artemisinin derivatives- dihydroartemisinin (DHA)-, and to detect the K13 polymorphism in isolates from an endemic area of Nigeria.
 Methods: Ex-vivo response in 55 parasites isolates obtained from malaria-positive patients were exposed to pulse DHA concentration and cultured for 66 hours ex-vivo. Parasite ring stage survival (RSAex-vivo) relative to unexposed matched control was determined by microscopy, and parasite growth was compared using Mann-Whitney U-test at a significance level of P<0.05. The Kelch propeller gene was amplified using specific primers, then sequenced and analyzed for single nucleotide polymorphisms (SNPs), which were compared to reference PF3D7_1343700.
 Results: Overall, 151 of 375 (40.2%) individuals were positive during the study period. In 55 selected isolates, there was increased growth in unexposed wells but growth was inhibited in DHA-exposed wells, with growth rate between 14.9 – 96.7%. The mean RSAex-vivo value was 0.18 ± 0.09%, 95% CI (0.15-0.20). There was no significant mutation of the K13 gene in the parasite isolates evaluated.
 Conclusions: Plasmodium falciparum isolates from this endemic area show high sensitivity to dihydroartemisinin ex-vivo, with no mutations conferring artemisinin resistance. Continuous monitoring of parasite susceptibility to artemisinin combination drugs should be intensified to reduce chances of artemisinin resistance in endemic areas.
Highlights
Plasmodium falciparum has developed resistance to artemisinin drugs in Southeast Asia, and its reduced sensitivity has been reported in other regions
The sub-population included for the current study were children and adults with P. falciparum mono-infection and parasitemia between 1-5% as detectable by microscopy
Informed consent was sought from the par-ticipants and ethical approval was sought from local authorities and the Covenant Health Research Ethics Committee, Nigeria
Summary
Plasmodium falciparum has developed resistance to artemisinin drugs in Southeast Asia, and its reduced sensitivity has been reported in other regions. This study aims to determine parasite susceptibility to the bioactive form of artemisinin derivatives- dihydroartemisinin (DHA)-, and to detect the K13 polymorphism in isolates from an endemic area of Nigeria. Conclusions: Plasmodium falciparum isolates from this endemic area show high sensitivity to dihydroartemisinin ex-vivo, with no mutations conferring artemisinin resistance. DOI :10.15419/bmrat.v5i9.474 main in quiescent or dormant state, and exhibit phenotypic delayed clearance from peripheral blood [13,14,15] These parasites have ring stage survival value >1, delayed parasite clearance in-vivo, and polymorphisms Copyright. Of the Kelch propeller (K13) gene that confers resistance to artemisinin drugs [6,7,8,14,15,16]. These form the basis for detection and confirmation of parasite resistance to artemisinin drugs globally 17
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