Surveillance of Antimalarial Resistance Pfcrt, Pfmdr1, and Pfkelch13 Polymorphisms in African Plasmodium falciparum imported to Shandong Province, China

Antimalarial drug resistance is a major public health problem in China. From 2012 to 2015, more than 75% of malaria cases in Shandong Province were P. falciparum returned from Africa. However, molecular marker polymorphisms of drug resistance in imported P. falciparum cases have not been evaluated. In this study, we analyzed polymorphisms of the Pfcrt, Pfmdr1, and Pfkelch13 genes in 282 P. falciparum cases returned from Africa to Shandong between 2012 and 2015. Among the isolates, polymorphisms were detected in codons 74-76 of Pfcrt and 86, 184, 1246 of Pfmdr1, among which K76T (36.6%) and Y184F (60.7%) were the most prevalent, respectively. Six Pfcrt haplotypes and 11 Pfmdr1 haplotypes were identified and a comparison was made on the prevalence of haplotypes among East Africa, West Africa, Central Africa and South Africa. One synonymous and 9 nonsynonymous mutations in Pfkelch13 were detected in the isolates (4.6%), among which a candidate artemisinin (ART) resistance mutation P553L was observed. The study establishes fundamental data for detection of chloroquine resistance (CQR) and ART resistance with molecular markers of the imported P. falciparum in China, and it also enriches the genetic data of antimalarial resistance for the malaria endemic countries in Africa.