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Title: Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax
Authors: R. Suwanarusk
M. Chavchich
B. Russell
A. Jaidee
F. Chalfein
M. Barends
B. Prasetyorini
E. Kenangalem
K. A. Piera
U. Lek-Uthai
N. M. Anstey
E. Tjitra
F. Nosten
Q. Cheng
R. N. Price
Menzies School of Health Research
Australian Army Malaria Institute
Shoklo Malaria Research Unit
Mahidol University
National Institutes of Health, Bethesda
District Health Authority
Badan Penelitian Dan Pengembangan Kesehatan, Kementerian Kesehatan Republik Indonesia
John Radcliffe Hospital
Keywords: Medicine
Issue Date: 15-Nov-2008
Citation: Journal of Infectious Diseases. Vol.198, No.10 (2008), 1558-1564
Abstract: Background. Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia. Methods. In vitro drug susceptibility and pvmdr1 genotype were determined in P. vivax field isolates from Indonesia and Thailand. Results. Increased pvmdr1 copy number was present in 21% of isolates from Thailand (15/71) and none from Indonesia (0/114; P < .001). Compared with Indonesian isolates, the median IC50of Thai isolates was lower for chloroquine (36 vs. 114 nmol/L; P < .001) but higher for amodiaquine (34 vs. 13.7 nmol/L; P < .032), artesunate (8.33 vs. 1.58 nmol/L; P < .001), and mefloquine (111 vs. 9.87 nmol/L; P < .001). In 11 cryopreserved Thai isolates, those with increased pvmdr1 copy number had a higher IC50for mefloquine (78.6 vs. 38 nmol/L for single-copy isolates; P = .006). Compared with isolates with the wild-type allele, the Y976F mutation of pvmdr1 was associated with reduced susceptibility to chloroquine (154 nmol/L [range, 4.6 -3505] vs. 34 nmol/L [range, 6.7-149]; P < .001) but greater susceptibility to artesunate (1.8 vs. 9.5 nmol/L; P < .009) and mefloquine (14 vs. 121 nmol/L; P = .001). Conclusions. Amplification of pvmdr1 and single-nucleotide polymorphisms are correlated with susceptibility of P. vivax to multiple antimalarial drugs. Chloroquine and mefloquine appear to exert competitive evolutionary pressure on pvmdr1, similar to that observed with pfmdr1 in Plasmodium falciparum. © 2008 by the Infectious Diseases Society of America. All rights reserved.
ISSN: 00221899
Appears in Collections:Scopus 2006-2010

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