Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites
Issued Date
2024-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85200853671
Journal Title
Nature Communications
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.15 No.1 (2024)
Suggested Citation
Siegel S.V., Trimarsanto H., Amato R., Murie K., Taylor A.R., Sutanto E., Kleinecke M., Whitton G., Watson J.A., Imwong M., Assefa A., Rahim A.G., Nguyen H.C., Tran T.H., Green J.A., Koh G.C.K.W., White N.J., Day N., Kwiatkowski D.P., Rayner J.C., Price R.N., Auburn S. Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites. Nature Communications Vol.15 No.1 (2024). doi:10.1038/s41467-024-51015-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/100499
Title
Lineage-informative microhaplotypes for recurrence classification and spatio-temporal surveillance of Plasmodium vivax malaria parasites
Author's Affiliation
Badan Riset dan Inovasi Nasional
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Ethiopian Public Health Institute
Oxford University Clinical Research Unit
Université Paris Cité
Cambridge Institute for Medical Research
Northwick Park Hospital
Menzies School of Health Research
UNC School of Medicine
Nuffield Department of Medicine
Wellcome Sanger Institute
Formerly GlaxoSmithKline
Afghan International Islamic University (AIIU)
Exeins Health Initiative
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Ethiopian Public Health Institute
Oxford University Clinical Research Unit
Université Paris Cité
Cambridge Institute for Medical Research
Northwick Park Hospital
Menzies School of Health Research
UNC School of Medicine
Nuffield Department of Medicine
Wellcome Sanger Institute
Formerly GlaxoSmithKline
Afghan International Islamic University (AIIU)
Exeins Health Initiative
Corresponding Author(s)
Other Contributor(s)
Abstract
Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences. As whole genome sequencing of P. vivax remains challenging, targeted genotyping methods are needed for scalability. We describe a P. vivax marker discovery framework to identify and select panels of microhaplotypes (multi-allelic markers within small, amplifiable segments of the genome) that can accurately capture IBD. We evaluate panels of 50–250 microhaplotypes discovered in a global set of 615 P. vivax genomes. A candidate global 100-microhaplotype panel exhibits high marker diversity in the Asia-Pacific, Latin America and horn of Africa (median HE = 0.70–0.81) and identifies 89% of the polyclonal infections detected with genome-wide datasets. Data simulations reveal lower error in estimating pairwise IBD using microhaplotypes relative to traditional biallelic SNP barcodes. The candidate global panel also exhibits high accuracy in predicting geographic origin and captures local infection outbreak and bottlenecking events. Our framework is open-source enabling customised microhaplotype discovery and selection, with potential for porting to other species or data resources.