Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms |
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Authors: | Jessica T. Lin Jaymin C. Patel Oksana Kharabora Jetsumon Sattabongkot Sinuon Muth Ratawan Ubalee Anthony L. Schuster William O. Rogers Chansuda Wongsrichanalai Jonathan J. Juliano |
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Affiliation: | Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina; Department of Entomology, USAMC Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; National Malaria Center, Phnom Penh, Cambodia; Naval Medical Research Unit #2, Phnom Penh, Cambodia |
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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. |
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