High Frequency Mutations in and of in Response to Sulfadoxine-Pyrimethamine: A Cross-Sectional Survey in Returning Chinese Migrants From Africa.

Background: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against infection. However, increasing SP resistance (SPR) of affects the therapeutic efficacy of SP, and (encoding dihydrofolate reductase) and (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of and in isolated from infected Chinese migrant workers returning from Africa.

Methods: In total, 159 blood samples from -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 and were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview.

Results: High 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 , respectively. A triple mutation (IRN) in was the most prevalent haplotype (86.83%). Six point mutations were detected in DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in . In total, 5 haplotypes of the gene and 13 haplotypes of the gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA).

Conclusion: A high prevalence of point mutations in the and genes of isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous molecular monitoring of Sulfadoxine-Pyrimethemine combined therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.