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Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages

Author

Listed:
  • Mariana Kleinecke

    (Menzies School of Health Research and Charles Darwin University)

  • Edwin Sutanto

    (Exeins Health Initiative
    Menzies School of Health Research)

  • Angela Rumaseb

    (Menzies School of Health Research and Charles Darwin University)

  • Kian Soon Hoon

    (Menzies School of Health Research and Charles Darwin University)

  • Hidayat Trimarsanto

    (Menzies School of Health Research and Charles Darwin University
    National Research and Innovation Agency)

  • Ashley Osborne

    (Menzies School of Health Research and Charles Darwin University)

  • Paulo Manrique

    (Harvard T.H. Chan School of Public Health
    Broad Institute)

  • Trent Peters

    (Australian Genome Research Facility)

  • David Hawkes

    (Australian Genome Research Facility)

  • Ernest Diez Benavente

    (University Medical Center Utrecht)

  • Georgia Whitton

    (Wellcome Sanger Institute)

  • Sasha V. Siegel

    (Wellcome Sanger Institute)

  • Richard D. Pearson

    (Wellcome Sanger Institute)

  • Roberto Amato

    (Wellcome Sanger Institute)

  • Anjana Rai

    (Menzies School of Health Research and Charles Darwin University)

  • Nguyen Thanh Thuy Nhien

    (Hospital for Tropical Diseases)

  • Hoang Chau Nguyen

    (Hospital for Tropical Diseases)

  • Ashenafi Assefa

    (Ethiopian Public Health Institute)

  • Tamiru S. Degaga

    (Arba Minch University)

  • Dagimawie Tadesse Abate

    (Arba Minch University)

  • Awab Ghulam Rahim

    (Afghan International Islamic University)

  • Ayodhia Pitaloka Pasaribu

    (Universitas Sumatera Utara)

  • Inge Sutanto

    (University of Indonesia)

  • Mohammad Shafiul Alam
  • Zuleima Pava

    (Menzies School of Health Research and Charles Darwin University)

  • Tatiana Lopera-Mesa

    (Universidad de Antioquia)

  • Diego Echeverry

    (Universidad del Valle)

  • Tim William

    (Menzies School of Health Research and Charles Darwin University
    Queen Elizabeth Hospital)

  • Nicholas M. Anstey

    (Menzies School of Health Research and Charles Darwin University)

  • Matthew J. Grigg

    (Menzies School of Health Research and Charles Darwin University)

  • Nicholas P. Day

    (University of Oxford
    Mahidol University)

  • Nicholas J. White

    (University of Oxford
    Mahidol University)

  • Dominic P. Kwiatkowski

    (Wellcome Sanger Institute)

  • Aimee R. Taylor

    (Infectious Disease Epidemiology and Analytics Unit)

  • Rintis Noviyanti

    (National Research and Innovation Agency)

  • Daniel Neafsey

    (Harvard T.H. Chan School of Public Health
    Broad Institute)

  • Ric N. Price

    (Menzies School of Health Research and Charles Darwin University
    University of Oxford
    Mahidol University)

  • Sarah Auburn

    (Menzies School of Health Research and Charles Darwin University
    University of Oxford)

Abstract

Plasmodium vivax elimination is challenged by dormant liver stages (hypnozoites) that can reactivate months after initial infection resulting in relapses. Relapsing infections confound antimalarial clinical efficacy trials due to the inability to distinguish between recurrences arising from blood-stage treatment failure (recrudescence), reinfection or relapse. Genetic relatedness of paired parasite isolates, measured by identity-by-descent (IBD), can provide important information on whether individuals have had single or multiple mosquito inoculations, thus informing on recurrence origin. We developed a high-throughput amplicon sequencing assay comprising 93 multi-SNP (microhaplotype) markers to determine IBD between P. vivax clinical isolates. The assay was evaluated in 745 global infections, including 128 infection pairs from a randomized controlled trial (RCT) (ClinicalTrials.gov NCT01680406). Simulations demonstrate low error in pairwise IBD estimation at the panel (RMSE

Suggested Citation

  • Mariana Kleinecke & Edwin Sutanto & Angela Rumaseb & Kian Soon Hoon & Hidayat Trimarsanto & Ashley Osborne & Paulo Manrique & Trent Peters & David Hawkes & Ernest Diez Benavente & Georgia Whitton & Sa, 2025. "Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62357-x
    DOI: 10.1038/s41467-025-62357-x
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    References listed on IDEAS

    as
    1. Sasha V. Siegel & Hidayat Trimarsanto & Roberto Amato & Kathryn Murie & Aimee R. Taylor & Edwin Sutanto & Mariana Kleinecke & Georgia Whitton & James A. Watson & Mallika Imwong & Ashenafi Assefa & Awa, 2024. "Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Zachary R. Popkin-Hall & Karamoko Niaré & Rebecca Crudale & Alfred Simkin & Abebe A. Fola & Juan F. Sanchez & Danielle L. Pannebaker & David J. Giesbrecht & Isaac E. Kim & Özkan Aydemir & Jeffrey A. B, 2024. "High-throughput genotyping of Plasmodium vivax in the Peruvian Amazon via molecular inversion probes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Aimee R. Taylor & James A. Watson & Cindy S. Chu & Kanokpich Puaprasert & Jureeporn Duanguppama & Nicholas P. J. Day & Francois Nosten & Daniel E. Neafsey & Caroline O. Buckee & Mallika Imwong & Nicho, 2019. "Resolving the cause of recurrent Plasmodium vivax malaria probabilistically," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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