title: Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 (pvmdr1) polymorphisms.
abstract: Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (HE = 0.86) but closely related (GST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants.
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Jessica_lin@med.unc.edu
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Lin
authors.forename: Jaymin C
authors.initials: JC
authors.lastname: Patel
authors.forename: Oksana
authors.initials: O
authors.lastname: Kharabora
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Sinuon
authors.initials: S
authors.lastname: Muth
authors.forename: Ratawan
authors.initials: R
authors.lastname: Ubalee
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Schuster
authors.forename: William O
authors.initials: WO
authors.lastname: Rogers
authors.forename: Chansuda
authors.initials: C
authors.lastname: Wongsrichanalai
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000627:therapeutic use; D044822:Biodiversity; D002160:Cambodia; D002738:Chloroquine / Q000627:therapeutic use; D004351:Drug Resistance; D018628:Gene Dosage; D005838:Genotype; D020180:Heteroduplex Analysis; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013785:Thailand
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C541684:Mdr1 protein, Plasmodium vivax