A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax malaria

Abstract

Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.

Population genomics identifies a distinct Plasmodium vivax population on the China-Myanmar border of Southeast Asia

“…For consistency between F ST and PCA outputs during barcode evaluation, we also performed the PCA with the full set of high-quality samples, including those which may be polyclonal, and then confirmed overall topology with monoclonal samples. We also extracted SNPs from three global barcode publications and checked their variability within our dataset by quantifying called SNPs [30][31][32].…”

“…Only 9 SNPs from a 42 global barcode were called within our dataset [30]. For the more specific global barcode recently published by Benavente et al which included 72 SNPs, we had callable variants at 47 of the positions, and 41 of them were independent [31]. Finally, we tested the 28 and 51 SNP barcodes from Trimarsanto et al, which yielded 19 and 34 independent SNPs, respectively [32].…”

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes

“…Understanding P. vivax genome variation will advance our knowledge of parasite biology and host-parasite interactions, as well as identify potential drug resistance mechanisms [3,4]. Such data will also help identify molecular targets for vaccine development [5][6][7] and provide new means to track the transmission and spread of drug resistant parasites [8][9].…”

Population genomics reveals the expansion of highly inbred Plasmodium vivax lineages in the main malaria hotspot of Brazil

“…We reanalyzed raw paired-end whole-genome reads from P . vivax isolates from two sites in Acre State, Brazil: (a) CS, consisting of 16 samples [ 27 ] collected between 2013 and 2016 in the city of Cruzeiro do Sul (7°39′54″S, 72°39′01″W; population, 82,622), 35 km from ML, with an API of 253.5 cases per 1,000 inhabitants in 2017, and (b) AC, consisting of 8 samples [ 6 ] collected between 2011 and 2013 in the town of Acrelândia (9°49'31”S, 66°53'11”W; population, 14,366), 700 km southeast of ML, with an API of 6.4 cases per 1,000 inhabitants in 2017 ( Fig 1 ). Fastq files were downloaded from SRA and processed in the same way as our new sequences.…”