A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria

Author:

Trimarsanto Hidayat,Amato Roberto,Pearson Richard D.ORCID,Sutanto EdwinORCID,Noviyanti Rintis,Trianty Leily,Marfurt JuttaORCID,Pava Zuleima,Echeverry Diego F.ORCID,Lopera-Mesa Tatiana M.,Montenegro Lidia M.,Tobón-Castaño AlbertoORCID,Grigg Matthew J.ORCID,Barber Bridget,William Timothy,Anstey Nicholas M.,Getachew Sisay,Petros Beyene,Aseffa Abraham,Assefa Ashenafi,Rahim Awab G.,Chau Nguyen H.,Hien Tran T.,Alam Mohammad S.ORCID,Khan Wasif A.ORCID,Ley BenediktORCID,Thriemer Kamala,Wangchuck Sonam,Hamedi Yaghoob,Adam Ishag,Liu Yaobao,Gao Qi,Sriprawat Kanlaya,Ferreira Marcelo U.,Laman Moses,Barry Alyssa,Mueller IvoORCID,Lacerda Marcus V. G.ORCID,Llanos-Cuentas Alejandro,Krudsood Srivicha,Lon Chanthap,Mohammed Rezika,Yilma Daniel,Pereira Dhelio B.ORCID,Espino Fe E. J.ORCID,Chu Cindy S.,Vélez Iván D.,Namaik-larp Chayadol,Villegas Maria F.,Green Justin A.,Koh GavinORCID,Rayner Julian C.ORCID,Drury EleanorORCID,Gonçalves Sónia,Simpson Victoria,Miotto OlivoORCID,Miles Alistair,White Nicholas J.,Nosten FrancoisORCID,Kwiatkowski Dominic P.ORCID,Price Ric N.ORCID,Auburn SarahORCID

Abstract

AbstractTraditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection’s country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.

Funder

HT was supported by a Charles Darwin University International PhD Scholarship

Department of Health | National Health and Medical Research Council

Malaysian Ministry of Health

Wellcome Trust

RCUK | Medical Research Council

Department of Foreign Affairs and Trade, Australian Government

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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