ArticleNature communications2019
Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross.
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Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
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32 citing papers in PubMed, 54 citations in OpenAlex.
- PvGTSeq and PvCRiSP: Two amplicon-based targeted sequencing panels for Plasmodium vivax.PLoS neglected tropical diseases · 2026Article
- A common DNA deletion altering the 3'UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients.Nature communications · 2026Article
- A common DNA deletion altering the 3'UTR ofResearch square · 2025Article
- High-throughput genotyping of Plasmodium vivax in the Peruvian Amazon via molecular inversion probes.Nature communications · 2024Article
- Optimization of loop mediated isothermal amplification assay (LAMP) for detection of chloroquine resistance in P. vivax malaria.Scientific reports · 2024Article
- Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission.Nature communications · 2024Article
- Single-cell analyses of polyclonalResearch square · 2024Article
- Quest for malaria management using natural remedies.Frontiers in pharmacology · 2024Review
- Analytic Approaches in Genomic Epidemiological Studies of Parasitic Protozoa.Transboundary and emerging diseases · 2024Review
- No Association between the Plasmodium vivaxAntimicrobial agents and chemotherapy · 2023Article
- Bulk segregant linkage mapping for rodent and human malaria parasites.Parasitology international · 2022Review
- Genome-wide functional screening of drug-resistance genes in Plasmodium falciparum.Nature communications · 2022Article
- Population genomics in neglected malaria parasites.Frontiers in microbiology · 2022Review
- Novel highly-multiplexed AmpliSeq targeted assay forFrontiers in cellular and infection microbiology · 2022Article
- High Proportion of Genome-Wide Homology and Increased PretreatmentAntimicrobial agents and chemotherapy · 2021Article
- Activity of Plasmodium vivax promoter elements in Plasmodium knowlesi, and a centromere-containing plasmid that expresses NanoLuc throughout the parasite life cycle.Malaria journal · 2021Article
- An Ecologically Framed Comparison of The Potential for Zoonotic Transmission of Non-Human and Human-Infecting Species of Malaria Parasite.The Yale journal of biology and medicine · 2021Review
- Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.International journal for parasitology. Drugs and drug resistance · 2021Review
- The changing epidemiology of Plasmodium vivax: Insights from conventional and novel surveillance tools.PLoS medicine · 2021Review
- Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.Molecules (Basel, Switzerland) · 2021Article
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Authors and funding
36 authors at 7 institutions in 1 country.
Juliana M SáLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Sarah R KaslowLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-2179-6787
Roberto R Moraes BarrosLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nicholas F BrazeauDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
Christian M ParobekCurriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Dingyin TaoW Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0001-6531-2740
Rebecca E SalzmanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Tyler J GibsonLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-2796-2176
Soundarapandian VelmuruganSanaria Inc., Rockville, MD, 20850, USA.
Michael A KrauseLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Viviana Melendez-MunizLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Whitney A KiteLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Paul K HanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Richard T EastmanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0003-3580-380X
Adam KimInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Evan G KesslerLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Yonas AbebeSanaria Inc., Rockville, MD, 20850, USA.
Eric R JamesSanaria Inc., Rockville, MD, 20850, USA.
Sumana ChakravartySanaria Inc., Rockville, MD, 20850, USA.
Sachy Orr-GonzalezLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Lynn E LambertLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Theresa EngelsDivision of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD, 20892, USA.
Marvin L ThomasDivision of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD, 20892, USA.
Pius S FasinuDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, 27506, USA.
David SerreInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0002-2446-9095
Robert W GwadzLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Larry WalkerDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, 27506, USA.ORCID http://orcid.org/0000-0002-0683-2209
Derrick K DeContiProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Jianbing MuLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Jeffrey A BaileyDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC, 27506, USA.ORCID http://orcid.org/0000-0002-6899-8204
B Kim Lee SimSanaria Inc., Rockville, MD, 20850, USA.
Stephen L HoffmanSanaria Inc., Rockville, MD, 20850, USA.
Michael P FayBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.ORCID http://orcid.org/0000-0002-8643-9625
Rhoel R DinglasanW Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Jonathan J JulianoDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
Thomas E WellemsLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. twellems@niaid.nih.gov.ORCID http://orcid.org/0000-0003-3899-8454
National Institutes of Health · USSanaria · USCampbell University · USUniversity of North Carolina at Chapel Hill · USJohns Hopkins University · USUniversity of Maryland, Baltimore · USUniversity of Massachusetts Chan Medical School · US
Funding
Malaria Drug Resistance and Disease VirulenceZIAAI000483 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WELLEMS, THOMAS E · 2009 to 2025
$24.5MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008719 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DARVILLE, TONI, DESHMUKH, MOHANISH P · 1999 to 2023
$15.1MNRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9MDissecting Chloroquine Resistance in the Plasmodium vivax CrossR21AI111108 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JULIANO, JONATHAN J · 2014 to 2015
$442kIdentifying the Distribution, Origin, and Threat of Plasmodium vivax in the DRCF30AI143172 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRAZEAU, NICHOLAS FORD · 2019 to 2022
$171kIntramural NIH HHS ZIA AI000483NIAID NIH HHS F30 AI143172NIAID NIH HHS R21 AI111108NIGMS NIH HHS T32 GM007092NIGMS NIH HHS T32 GM008719
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.
Indexed as
Crosses, GeneticAnimalsAnophelesAntimalarialsChloroquineCulicidaeDrug DiscoveryDrug ResistanceFemaleGene ExpressionGenes, ProtozoanMalariaMalaria, VivaxMaleMembrane Transport ProteinsPlasmodium falciparumAntimalarialsChloroquineCrt-o protein, Plasmodium vivaxMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan Proteins
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