Molecular Surveillance of Antimalarial Resistance Pfcrt, Pfmdr1 and Pfk13 Polymorphisms in African Plasmodium Falciparum Imported Parasites to Wuhan, China

Abstract Background: The development of drug resistance in Plasmodium falciparum becomes a severe problem for malaria control globally. Before finding a practical solution, monitoring the susceptibility of P. falciparum resistance-related genes is crucial. It will offer valuable information on the drug resistance in malaria-endemic areas and guides the rational clinical use of antimalarial drugs.Methods：Filter paper blood was taken from patients with positive P. falciparum during 2017-2019 in Wuhan, China. The target fragments from pfcrt, pfmdr1, and k13 propeller (pfk13) genes of P. falciparum were amplified and sequenced. Subsequently, the polymorphisms of pfcrt, pfmdr1, and pfk13 and the haplotypes of Pfcrt and Pfmdr1 were analyzed.Results: Totally, 106 samples were collected. Subsequently, 98.11% (104/106), 100% (106/106), and 86.79% (92/106) of these samples were successfully amplified and sequenced for the pfcrt, pfmdr1, and pfk13 genes, respectively. The prevalence of Pfcrt K76T, Pfmdr1 N86Y, and Pfmdr1 Y184F mutation were 9.62%, 4.72%, and 47.17%, respectively. At codons 72-76 of pfcrt gene locus were showed three haplotypes, including CVMNK (wild-type), CVIET (mutation type), CV M/I N/E K/T (mixed type), with 87.50%, 9.62%, and 2.88% prevalence, respectively. For the pfmdr1 gene, including NY (wild type), NF and YF (mutant type), N Y/F, Y Y/F, and N/Y Y/F (mixed type), accounted for 34.91%, 43.40%, 3.77%, 15.09%, 0.94%, and 1.89%, respectively. A total of eleven Pfcrt/Pfmdr1 combined haplotypes, including six types of combined haplotypes, and five combined haplotypes with mixed-type, For pfk13, no mutation was detected. Conclusions: The wild-type SNPs and haplotypes for the pfcrt, and pfmdr1 genes become predominant in the current study. It indicates these isolates entirely or partly recovery their susceptibility to antimalarial drugs, including chloroquine, amodiaquine, and mefloquine. Moreover, it demonstrates these drugs can continue to be effective drugs for P. falciparum malaria cases treatment in Africa. Although no mutation is detected in pfk13, continuous molecular surveillance is still urgently necessary.