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Background  Resistance to anti-malarial drugs hinders malaria elimination. Monitoring the molecular markers of drug resistance helps improve malaria treatment policies. This study aimed to assess the distribution of molecular markers of imported  Plasmodium falciparum  infections.    Methods  In total, 485  P. falciparum  cases imported from Africa, Southeast Asia, and Oceania into Zhejiang province, China, from 2016 to 2018 were investigated. Most were imported from Africa, and only a few cases originated in Asia and Oceania. Blood samples were collected from each patient.  Plasmodium falciparum  chloroquine resistance transporter ( Pfcrt ) at residues 72–76 and Kelch13-propeller ( k13 ) were determined by nested PCR and DNA sequence.    Results  Wild-type  Pfcrt  at residues 72–76 was predominant (72.61%), but mutant and mixed alleles were also detected, of which CVIET (22.72%) was the most common. Mutant  Pfcrt  haplotypes were more frequent in patients from West Africa (26.92%), North Africa (25%), and Central Africa (21.93%). The number of cases of  P. falciparum  infections was small in Southeast Asia and Oceania, and these cases involved  Pfcrt  mutant type. For the  k13  propeller gene, 26 samples presented 19 different point mutations, including eight nonsynonymous mutations (P441S, D464E, K503E, R561H, A578S, R622I, V650F, N694K). In addition, R561H, one of the validated SNPs in  k13 , was detected in one patient from Myanmar and one patient from Rwanda. A578S, although common in Africa, was found in only one patient from Cameroon. R622I was detected in one sample from Mozambique and one sample from Somalia. The genetic diversity of  k13  was low in most regions of Africa and purifying selection was suggested by Tajima’s D test.    Conclusions  The frequency and spatial distributions of  Pfcrt  and  k13  mutations associated with drug resistance were determined. Wild-type  Pfcrt  was dominant in Africa. Among  k13  mutations correlated with delayed parasite clearance, only the R561H mutation was found in one case from Rwanda in Africa. Both  Pfcrt  and  k13  mutations were detected in patients from Southeast Asia and Oceania. These findings provide insights into the molecular epidemiological profile of drug resistance markers in the study region.

malaria journal

Molecular surveillance of Pfcrt and k13 propeller polymorphisms of imported Plasmodium falciparum cases to Zhejiang Province, China between 2016 and 2018