Program in Bioinformatics and Integrative Biology; Division of Transfusion Medicine, Department of Medicine
Computational Biology | Immunology and Infectious Disease | Parasitic Diseases | Population Biology
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.
Antimicrobial resistance, Antiparasitic agents, Malaria, Parasite genetics
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DOI of Published Version
Nat Commun. 2019 Sep 20;10(1):4300. doi: 10.1038/s41467-019-12256-9. Link to article on publisher's site
Sa JM, DeConti DK, Bailey JA, Wellems TE. (2019). Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross. Open Access Articles. https://doi.org/10.1038/s41467-019-12256-9. Retrieved from https://escholarship.umassmed.edu/oapubs/3997
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.