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Local differentiation in Plasmodium falciparum drug resistance genes in Sudan

Published online by Cambridge University Press:  07 May 2003

A. A. ABDEL-MUHSIN ,
M. J. MACKINNON ,
P. AWADALLA ,
E. ALI ,
S. SULEIMAN ,
S. AHMED ,
D. WALLIKER  and
H. A. BABIKER
A. A. ABDEL-MUHSIN
Affiliation:
Tropical Medicine Research Institute, National Institute for Research, Khartoum, Sudan Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan
M. J. MACKINNON
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK
P. AWADALLA
Affiliation:
Section of Evolution and Ecology, University of California Davis, Davis, CA USA 95616
E. ALI
Affiliation:
Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan
S. SULEIMAN
Affiliation:
Tropical Medicine Research Institute, National Institute for Research, Khartoum, Sudan
S. AHMED
Affiliation:
Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan
D. WALLIKER
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK
H. A. BABIKER
Affiliation:
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK
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Abstract

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 (polyα, 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 FST 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.

Keywords

malariaPlasmodium falciparumantimalarialsselectiondrug resistance genes
Type
Research Article
Information
Parasitology , Volume 126 , Issue 5 , May 2003 , pp. 391 - 400
Copyright
2003 Cambridge University Press

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