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Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross

Author

Listed:
  • Juliana M. Sá

    (National Institutes of Health)

  • Sarah R. Kaslow

    (National Institutes of Health)

  • Roberto R. Moraes Barros

    (National Institutes of Health)

  • Nicholas F. Brazeau

    (University of North Carolina)

  • Christian M. Parobek

    (University of North Carolina at Chapel Hill)

  • Dingyin Tao

    (Johns Hopkins Bloomberg School of Public Health)

  • Rebecca E. Salzman

    (National Institutes of Health)

  • Tyler J. Gibson

    (National Institutes of Health)

  • Soundarapandian Velmurugan

    (Sanaria Inc.)

  • Michael A. Krause

    (National Institutes of Health)

  • Viviana Melendez-Muniz

    (National Institutes of Health)

  • Whitney A. Kite

    (National Institutes of Health)

  • Paul K. Han

    (National Institutes of Health)

  • Richard T. Eastman

    (National Institutes of Health)

  • Adam Kim

    (University of Maryland School of Medicine)

  • Evan G. Kessler

    (National Institutes of Health)

  • Yonas Abebe

    (Sanaria Inc.)

  • Eric R. James

    (Sanaria Inc.)

  • Sumana Chakravarty

    (Sanaria Inc.)

  • Sachy Orr-Gonzalez

    (National Institutes of Health)

  • Lynn E. Lambert

    (National Institutes of Health)

  • Theresa Engels

    (National Institutes of Health)

  • Marvin L. Thomas

    (National Institutes of Health)

  • Pius S. Fasinu

    (Campbell University)

  • David Serre

    (University of Maryland School of Medicine)

  • Robert W. Gwadz

    (National Institutes of Health)

  • Larry Walker

    (Campbell University)

  • Derrick K. DeConti

    (University of Massachusetts Medical School)

  • Jianbing Mu

    (National Institutes of Health)

  • Jeffrey A. Bailey

    (Campbell University
    University of Massachusetts Medical School)

  • B. Kim Lee Sim

    (Sanaria Inc.)

  • Stephen L. Hoffman

    (Sanaria Inc.)

  • Michael P. Fay

    (National Institutes of Health)

  • Rhoel R. Dinglasan

    (Johns Hopkins Bloomberg School of Public Health
    University of Florida)

  • Jonathan J. Juliano

    (University of North Carolina
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Thomas E. Wellems

    (National Institutes of Health)

Abstract

Mainstay treatment for Plasmodium vivax malaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis of P. vivax chloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics of P. vivax CQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods for P. vivax cloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving >15 mg/kg CQ identifies a 76 kb region in chromosome 1 including pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene. Transcriptional analysis supports upregulated pvcrt expression as a mechanism of CQR.

Suggested Citation

  • Juliana M. Sá & Sarah R. Kaslow & Roberto R. Moraes Barros & Nicholas F. Brazeau & Christian M. Parobek & Dingyin Tao & Rebecca E. Salzman & Tyler J. Gibson & Soundarapandian Velmurugan & Michael A. K, 2019. "Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12256-9
    DOI: 10.1038/s41467-019-12256-9
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    Cited by:

    1. Brittany Hazzard & Juliana M. Sá & Haikel N. Bogale & Tales V. Pascini & Angela C. Ellis & Shuchi Amin & Jennifer S. Armistead & John H. Adams & Thomas E. Wellems & David Serre, 2024. "Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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