Identification of Mutations in Antimalarial Resistance Gene <i>Kelch13</i> from <i>Plasmodium falciparum</i> Isolates in Kano, Nigeria

Abstract

Malaria control relies on first-line treatments that use artemisinin-combination therapies (ACT). Unfortunately, mutations in the plasmodium falciparum kelch13 gene result in delayed parasite clearance. Research on what is causing ACT failure is non-existent in northwestern Nigeria. Thus, the presence of mutations in kelch13 in P. falciparum isolates from Kano, Nigeria was investigated in this study. Microscopic examination of 154 blood samples obtained from patients revealed a high prevalence of P. falciparum infection (114 positive individuals, slide positivity rate = 74.03%). The 114 patients were administered Cartef® (ACT) and out of the 50 patients that returned for the 14-day follow up, 11 were positive for P. falciparum (slide positivity rate = 22%). On day 0, 80 samples out of 114 and 11 samples on day 14 (91 out of 125 microscopy-positive samples) were positive with Plasmodium according to the PCR of cytochrome oxidase I, which corresponds to 72.8%. A fragment of the kelch13 gene encompassing the propeller domains was sequenced in 49 samples, alongside samples of the susceptible strain pf_3D7. Low polymorphism was observed, suggesting a lack of selection on this gene, and only six mutations (Glu433Gly, Phe434Ile, Phe434Ser, Ile684Asn, Ile684Thr and Glu688Lys) were found. The epidemiologic impact of these mutations and their potential role in ACT resistance needs to be investigated further.

Keywords

• artemisinin combination therapy
• resistance
• SNP
• mutation
• <i>kelch13</i>
• <i>P. falciparum</i>