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Intrahost Selection of Plasmodium falciparum pfmdr1 Alleles after Antimalarial Treatment on the Northwestern Border of Thailand
Anne-Catrin Uhlemann, Rose McGready, Elizabeth A. Ashley, Alan Brockman, Pratap Singhasivanon, Sanjeev Krishna, Nicholas J. White, François Nosten and Ric N. Price
The Journal of Infectious Diseases
Vol. 195, No. 1 (Jan. 1, 2007), pp. 134-141
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30087459
Page Count: 8
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Background. Increased pfmdr1 copy number is associated with reduced susceptibility to structurally unrelated antimalarial drugs. We assessed how administration of different antimalarial drugs altered pfmdr1 polymorphism in parasites from patients who experienced treatment failure. Methods. In studies conducted on the northwestern border of Thailand, amplifications and single-nucleotide polymorphisms in pfmdr1 were compared before and after antimalarial drug treatment. Results. Intrahost changes in pfmdr1 copy number were observed in 20% (26/132) of patients with recurrent infections. Among infections that recrudesced after mefloquine-containing regimens, increases in pfmdr1 copy number occurred in 68% (95% confidence interval [CI], 46%-85%), and decreases occurred in 2% (95% CI, 0.4%-11%) of isolates; corresponding proportions after artemether-lumefantrine were 25% (2/8) and 11% (2/19); after quinine, 50% (1/2) and 40% (4/10); and after artemisinins alone, 0% (0/10) and 19% (3/16) of isolates (overall P<.001). Conclusions. Intrahost selection based on pfmdr1 copy number occurs frequently in parasite populations within individual patients. Amplification confers multidrug resistance but probably imposes a significant fitness cost to the parasites.
The Journal of Infectious Diseases © 2007 Oxford University Press