Abstract
BackgroundSulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against Plasmodium falciparum infection. However, increasing SP resistance (SPR) of P. falciparum affects the therapeutic efficacy of SP, and pfdhfr (encoding dihydrofolate reductase) and pfdhps (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of pfdhfr and pfdhps in P. falciparum isolated from infected Chinese migrant workers returning from Africa.MethodsIn total, 159 blood samples from P. falciparum-infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in pfdhfr and pfdhps were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview.ResultsHigh frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in pfdhfr, respectively. A triple mutation (IRN) in pfdhfr was the most prevalent haplotype (86.83%). Six point mutations were detected in pfdhps DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The pfdhps K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in pfdhps. In total, 5 haplotypes of the pfdhfr gene and 13 haplotypes of the pfdhps gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the pfdhfr-pfdhps combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA).ConclusionA high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous in vitro molecular monitoring of Sulfadoxine-Pyrimethemine combined in vivo therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.
Highlights
Imported Plasmodium falciparum infections are of great concern in China during malaria elimination and post-elimination stages, because China achieved zero indigenous malaria cases in 2017 (Feng et al, 2018)
Sulfadoxine-pyrimethamine (SP) is a second-line antimalarial for uncomplicated P. falciparum malaria treatment, as recommended by the World Health Organization (WHO), which is used as an intermittent preventive treatment in pregnancy (IPTp) and as an intermittent preventive treatment in infants (IPTi) in malariaendemic regions (Gosling et al, 2010; Konate et al, 2011)
Studies have identified point mutations in codons N51I, C59R, and S108N, I164L of pfdhfr located on chromosome 4 and codons I431V, S436A, A437G, K540E, A581G, and A613S of pfdhps located on chromosome 8, all of which were associated with P. falciparum SP treatment failure (Triglia et al, 1997; Berglez et al, 2004; Pearce et al, 2009)
Summary
Imported Plasmodium falciparum infections are of great concern in China during malaria elimination and post-elimination stages, because China achieved zero indigenous malaria cases in 2017 (Feng et al, 2018). Appropriate treatment for P. falciparum according to the national plan is important; some studies have demonstrated mutations in molecular markers related to artemisinin combination therapy (ACT) resistance among isolates from Africa, suggesting that careful surveillance of African parasite populations is still warranted (Feng et al, 2015a; Feng et al, 2019, Yan et al, 2020). The present study identified the polymorphisms in pfdhfr and pfdhps in P. falciparum among returned migrant workers from Africa in 2017–2019 reported in eastern China. Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against Plasmodium falciparum infection. Increasing SP resistance (SPR) of P. falciparum affects the therapeutic efficacy of SP, and pfdhfr (encoding dihydrofolate reductase) and pfdhps (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. We analyzed single nucleotide polymorphisms (SNPs) of pfdhfr and pfdhps in P. falciparum isolated from infected Chinese migrant workers returning from Africa
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