The emergence and spread of multidrug resistance pose a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported since 2017, and China is approaching malaria elimination by 2020. Therefore, it is urgent to monitor antimalarial drug resistance and track the emergence and spread of the imported drug resistant malaria cases in China.
Dried blood samples were obtained from P. falciparum infected cases who returned from Africa to China between 2012–2015 prior to antimalarial drug treatment. The known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of the K13 gene were evaluated by nested PCR and sequencing. The GraphPad prism was used to plot the prevalence of each mutation. The chi-squared test and two-sided P value of < 0.05 were used to evaluate differences with statistical significance.
A total of 731 P. falciparum isolates were successfully genotyped at the pfcrt locus. The wild type haplotype of C72V73M74N75K76 was the most prevalent genotype with the prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype C72V73I74E75T76. Total 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were only observed in codons 86, 184, and 1246. Twelve haplotypes were identified and the prevalence of the wild type variant pfmdr1 N86Y184D1246 was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but D1246Y was rare. The double mutant genotype Y86F184D1246 was common in Africa. A total of 1381 P. falciparum isolates from 33 African countries were sequenced of K13-propeller domain and 1357 were successfully sequenced. The prevalence of K13 mutations was 3.6% and 26 different mutant alleles including 22 nonsynonymous and four synonymous variants (C469C, R471R, G496G, and A627A) were observed. The A578S was the most common haplotype of K13. Three mutation associated with artimisinin resistance (M476I, R539T, and P553L) were observed in three isolates.
The prevalence of mutant pfcrt and pfmdr1 was low or moderate in P. falciparum isolates imported from Africa to China between 2012–2015. K13-propeller mutations were highly diverse but most mutations were only found in a few isolates. This study provides evidence for the antimalarial drug resistance level of the imported malaria cases from Africa and the efficacy of antimalarial drug policy in China to treat these imported cases.