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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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  • 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

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.

Author Notes

* Address correspondence to Jessica T. Lin, Division of Infectious Diseases, University of North Carolina School of Medicine, 130 Mason Farm Road, Suite 2115 CB 7030, Chapel Hill, NC 27599. E-mail: Jessica_lin@med.unc.edu

Financial support: This work was supported by the U.S. Department of Defense Global Emerging Infections Surveillance and Response System Program and the National Institutes of Health [grant number AI089819 to J.J.J.]. J.T.L. was supported by an NIH Infectious Disease Pathogenesis Research Training Grant [grant number 5T32AI0715132] and the North Carolina Clinical and Translational Science Award [grant number UL1RR025747].

Authors' addresses: Jessica T. Lin, Oksana Kharabora, and Jonathan J. Juliano, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mails: jessica_lin@med.unc.edu, kharabor@email.unc.edu, and jonthan_juliano@med.unc.edu. Jaymin C. Patel, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, E-mail: jaymin86@email.unc.edu. Jetsumon Sattabongkot, Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: jetsumon.pra@mahidol.ac.th. Sinuon Muth, National Malaria Center, Phnom Penh, Cambodia, E-mail: sinuonm@cnm.gov.kh. Ratawan Ubalee and Anthony L. Schuster, Department of Entomology, USAMC Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: RatawanU@afrims.org and Schuster.Anthony@afrims.org. William O. Rogers, E-mail: mrogers70@yahoo.com. Chansuda Wongsrichanalai, Bangkok, Thailand, E-mail: dr.chansuda@gmail.com.

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