Local differentiation in Plasmodium falciparum drug resistance genes in Sudan

被引:30
|
作者
Abdel-Muhsin, AA
Mackinnon, MJ
Awadalla, P
Ali, E
Suleiman, S
Ahmed, S
Walliker, D
Babiker, HA [1 ]
机构
[1] Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland
[2] Univ Calif Davis, Sect Evolut & Ecol, Davis, CA 95616 USA
[3] Univ Khartoum, Fac Med, Dept Biochem, Khartoum, Sudan
[4] Natl Inst Res, Res Inst Trop Med, Khartoum, Sudan
关键词
malaria; Plasmodium falciparum; antimalarials; selection; drug resistance genes;
D O I
10.1017/S0031182003003020
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Studies of population genetic structure of parasites can be used to infer which parasite genes are under selection. Here, the population structure of 4 genes associated with drug resistance of Plasmodium falciparum (the chloroquine resistance transporter, pfcrt, dihydrofolate reductase, dhfr, dihydropteroate synthase, dhps, and multi-drug resistance, pfmdr-1) were examined in parasite populations in 3 villages in eastern Sudan and in an urban area of Khartoum, the capital. In order to differentiate the effects of drug selection from neutral influences on population structure, parasites were also genotyped for 3 putatively neutral microsatellite loci (polya, TA81 and pfg377), and for 2 antigenic loci that are either under balancing selection or neutral, merozoite surface protein 1 and 2, (MSP-1 and MSP-2). Cross-sectional surveys were carried out during the peak transmission (wet) season and in the ensuing dry season. No significant variation in frequencies of MSP-1 and MSP-2 alleles was seen among villages in the eastern region and between the villages and Khartoum, nor between the wet and dry season. However, the drug resistance genes, pfmdr-1, pfcrt and dhfr and to a lesser extent the microsatellite loci showed high F-ST values when comparing villages with Khartoum, indicating strong geographical differentiation at these loci. Moreover, variation in frequencies of the drug resistance genes, pfmdr-1, pfcrt and dhfr, was observed between the wet and dry season. These differences most probably reflect the variation in drug pressure between each region, and in drug usage between the wet and dry season in a given region.
引用
收藏
页码:391 / 400
页数:10
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