Article

Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax.

International Health Division, Menzies School of Health Research, Darwin, Australia.
The Journal of Infectious Diseases (impact factor: 6.41). 10/2008; 198(10):1558-64. DOI:10.1086/592451 pp.1558-64
Source: PubMed

ABSTRACT Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia.
In vitro drug susceptibility and pvmdr1 genotype were determined in P. vivax field isolates from Indonesia and Thailand.
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 IC(50) of 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 IC(50) for 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).
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.

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Keywords

11 cryopreserved Thai
 
Chloroquine
 
competitive evolutionary pressure
 
greater susceptibility
 
Increased pvmdr1 copy number
 
Indonesia
 
Multidrug-resistant strains
 
multiple antimalarial drugs
 
P. vivax
 
P. vivax field
 
Plasmodium falciparum
 
Plasmodium vivax
 
pvmdr1
 
pvmdr1 copy number
 
pvmdr1 genotype
 
single-copy
 
Thailand
 
vitro drug susceptibility
 
wild-type allele
 
Y976F mutation