Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

Abstract

Abstract Background The artemisinin-based combination therapies (ACTs) was recommended as the first line drugs by the World Health Organization to treat uncomplicated Plasmodium falciparum. However, the emergence and spread of P. falciparum resistant to artemisinins and their partner drugs is a significant risk for the global effort to reduce disease burden facing the world. Method A retrospective study was conducted to explore the prevalence and spatial distribution of pfK13 and pfcrt polymorphisms among imported P. falciparum isolates in years 2015–2019 in Shandong Province in eastern China. Individual epidemiological information was collected from a web-based reporting system were reviewed and analysed. Results A total of 425 P. falciparum blood samples in 2015–2019 were included and we found that 7.3% (31/425) carried pfK13 mutations. Out of the isolates that carried K13 mutations, 54.8% (17/31) were nonsynonymous polymorphisms. The mutant allele A578S, Q613H, C469C, and S549S in pfK13 were the more frequently detected allele, the mutation rate was the same as 0.7% (3/425). Another allele pfK13C580Y, closely associated with artemisinin (ART) resistance, was found as 0.5% (2/425), which was found in Cambodia. About 45.2% (14/31) of the P. falciparum isolates had pfK13 mutations resembled those from Western Africa. For the pfcrt gene, T76T356 and T76 were more frequent in all 13 different haplotypes with 4.7% (20/425) and 4.2% (18/425) that identified in 77 isolates (18.1%, 77/425). The CVIET and CVIKT mutant at loci 72–76 have exhibited a prevalence of 3.5% and 0.7%, respectively. The CVIET were mainly distributed in Congo (5.2%, 4/77) and Mozambique (5.2%, 4/77). No mutations were found at loci 97, 101 and 145. For polymorphisms at locus 356, a total of 24 isolates were identified and mainly from Congo (29.2%, 7/24). Conclusion These findings indicate a low prevalence of pfK13 in the African isolates, while the mutations related to piperaquine (PPQ) resistance remain at a certain level. Therefore, continuous molecular surveillance of pfcrt mutations and in vitro susceptibility tests related to PPQ are necessary.