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.

Author summary

Plasmodium vivax is the most widespread parasite causing human malaria, with more than one-third of the world’s population being at risk of infection. P. vivax is resilient due to its dormant liver phase, and there are increasing reports of drug-resistance and life-threatening infections. Despite this, P. vivax malaria is not always prioritised by elimination programmes. New molecular tools are needed to inform elimination efforts, including through better understanding the geographical source and outbreaks of P. vivax, thereby leading to the halting of transmission and the targeting of reservoirs of infection. Our work describes a 71 genetic marker barcode for P. vivax that has high predictive ability to identify the geographic origin, and has the potential to distinguish local transmission networks. If the 71 genetic marker barcode is implemented within new portable molecular platforms, it is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.