Genetic screen for P. vivax CQR

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DESCRIPTION (provided by applicant): Plasmodium vivax resistant to chloroquine (CQ) is widely reported, seriously hampering the case management and malaria control/elimination effort. The molecular determinant and mechanism of resistance is unclear. As homologs of P. falciparum chloroquine resistance (CQR) determinant and other key molecules have been found not implicated in P. vivax CQR, it is clear that P. vivax has developed CQR using a mechanism different to P. falciparum. Therefore, we propose to use a whole genome recombineering type of approach, whereby the entire cDNA of a CQR P. vivax genome is cloned into piggyBac vector and transfected into a chloroquine sensitive (CQS) cultured line of P. falciparum. The transfected P. falciparum parasites will be cultured under CQ pressure and cloned by limiting dilution. cDNA-containing plasmids will be rescued from clones with growing parasites to identify candidate gene(s) that plays significant roles in P. vivax CQR. The outcome will enable large-scale monitor and surveillance of the spread of CQR P. vivax, provide predictive value for treatment outcome and provide information for policy changes.