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.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Zhang Y,Yan H,Wei G,Han S,Huang Y,Zhang Q,Pan Wdoi
10.1128/AAC.00972-13subject
Has Abstractpub_date
2014-01-01 00:00:00pages
237-46issue
1eissn
0066-4804issn
1098-6596pii
AAC.00972-13journal_volume
58pub_type
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