title: Distinctive origin and spread route of pyrimethamine-resistant Plasmodium falciparum in southern China.
abstract: Southeast Asia (the Thailand-Cambodia border) has been considered the primal epicenter for most antimalarial drug resistance; however, numerous molecular epidemiological studies have successively reported multiple independent origins of sulfadoxine-pyrimethamine (SP) resistance-associated Plasmodium falciparum dhfr (pfdhfr) and pfdhps alleles in other areas. To better understand the origin and evolutionary pathway of the SP resistance in Southeast Asia, a total of 374 P. falciparum field isolates from the Yunnan-Burma border and Hainan Island in southern China have been collected for comprehensive investigations on the mutation patterns of the pfdhfr/pfdhps genes as well as their microsatellite haplotypes. By comparative analysis of single-nucleotide polymorphism (SNP) genotyping and flanking microsatellite haplotypes, we reveal a unique origin of pyrimethamine-resistant mutations in Pfdhfr gene in Hainan Island and an oriented spread route of the pyrimethamine resistance from the Thailand-Cambodia border into the Hainan area, which reflects the geographical traits and SP administration histories in the two geographically independent areas. Moreover, genetic linkages between the high-level SP resistance-conferring pfdhfr/pfdhps alleles have been established in the isolates from the Yunnan-Burma border, raising the concern of a genetic basis in adopting combination chemotherapies against falciparum malaria.
authors.affiliation: Institute of Infectious Disease and Vaccine Development, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Yan
authors.forename: Guiying
authors.initials: G
authors.lastname: Wei
authors.forename: Shitong
authors.initials: S
authors.lastname: Han
authors.forename: Yufu
authors.initials: Y
authors.lastname: Huang
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Pan
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D002681:China; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000635:transmission*; D018895:Microsatellite Repeats / Q000235:genetics; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D000962:Antimalarials