Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages
2
Issued Date
2025-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-105012629758
Journal Title
Nature Communications
Volume
16
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.16 No.1 (2025)
Suggested Citation
Kleinecke M., Sutanto E., Rumaseb A., Hoon K.S., Trimarsanto H., Osborne A., Manrique P., Peters T., Hawkes D., Benavente E.D., Whitton G., Siegel S.V., Pearson R.D., Amato R., Rai A., Nhien N.T.T., Nguyen H.C., Assefa A., Degaga T.S., Abate D.T., Rahim A.G., Pasaribu A.P., Sutanto I., Alam M.S., Pava Z., Lopera-Mesa T., Echeverry D., William T., Anstey N.M., Grigg M.J., Day N.P., White N.J., Kwiatkowski D.P., Taylor A.R., Noviyanti R., Neafsey D., Price R.N., Auburn S. Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages. Nature Communications Vol.16 No.1 (2025). doi:10.1038/s41467-025-62357-x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111611
Title
Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages
Author(s)
Kleinecke M.
Sutanto E.
Rumaseb A.
Hoon K.S.
Trimarsanto H.
Osborne A.
Manrique P.
Peters T.
Hawkes D.
Benavente E.D.
Whitton G.
Siegel S.V.
Pearson R.D.
Amato R.
Rai A.
Nhien N.T.T.
Nguyen H.C.
Assefa A.
Degaga T.S.
Abate D.T.
Rahim A.G.
Pasaribu A.P.
Sutanto I.
Alam M.S.
Pava Z.
Lopera-Mesa T.
Echeverry D.
William T.
Anstey N.M.
Grigg M.J.
Day N.P.
White N.J.
Kwiatkowski D.P.
Taylor A.R.
Noviyanti R.
Neafsey D.
Price R.N.
Auburn S.
Sutanto E.
Rumaseb A.
Hoon K.S.
Trimarsanto H.
Osborne A.
Manrique P.
Peters T.
Hawkes D.
Benavente E.D.
Whitton G.
Siegel S.V.
Pearson R.D.
Amato R.
Rai A.
Nhien N.T.T.
Nguyen H.C.
Assefa A.
Degaga T.S.
Abate D.T.
Rahim A.G.
Pasaribu A.P.
Sutanto I.
Alam M.S.
Pava Z.
Lopera-Mesa T.
Echeverry D.
William T.
Anstey N.M.
Grigg M.J.
Day N.P.
White N.J.
Kwiatkowski D.P.
Taylor A.R.
Noviyanti R.
Neafsey D.
Price R.N.
Auburn S.
Author's Affiliation
Université Paris Cité
Harvard T.H. Chan School of Public Health
University Medical Center Utrecht
Universitas Indonesia
Universidad de Antioquia
Broad Institute
Nuffield Department of Medicine
Badan Riset dan Inovasi Nasional
Universitas Sumatera Utara
Wellcome Sanger Institute
Universidad del Valle, Cali
International Centre for Diarrhoeal Disease Research Bangladesh
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
Arba Minch University
Oxford University Clinical Research Unit
Ethiopian Public Health Institute
Australian Genome Research Facility Ltd
Queen Elizabeth Hospital
Afghan International Islamic University
Exeins Health Initiative
Harvard T.H. Chan School of Public Health
University Medical Center Utrecht
Universitas Indonesia
Universidad de Antioquia
Broad Institute
Nuffield Department of Medicine
Badan Riset dan Inovasi Nasional
Universitas Sumatera Utara
Wellcome Sanger Institute
Universidad del Valle, Cali
International Centre for Diarrhoeal Disease Research Bangladesh
Menzies School of Health Research
Mahidol Oxford Tropical Medicine Research Unit
Arba Minch University
Oxford University Clinical Research Unit
Ethiopian Public Health Institute
Australian Genome Research Facility Ltd
Queen Elizabeth Hospital
Afghan International Islamic University
Exeins Health Initiative
Corresponding Author(s)
Other Contributor(s)
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 < 0.12) and IBD-based networks illustrate strong clustering by geography. IBD analysis in the RCT demonstrates a lower frequency of suspected relapses or recrudescence in patients treated with primaquine compared to those without primaquine; the impact is greater when paired with chloroquine than with artemether-lumefantrine. Our results demonstrate the potential to derive new information on P. vivax treatment and transmission using IBD generated by amplicon sequencing data that can be further improved with time-to-event models.