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.

Public Health Relevance

Plasmodium vivax is the major cause of malaria outside of Africa and is has developing resistance to chloroquine (CQR), which is the first line treatment, thereby impeding effective case management and control. Genetic traits underlying P. vivax CQR are different from P. falciparum and cannot be identified by a simple 'copy cat'approach. We propose a novel whole genome genetic screening approach to identify P. vivax CQR resistance genes by transgene complementation and phenotype selection of P falciparum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI098098-02
Application #
8446957
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Joy, Deirdre A
Project Start
2012-03-20
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$180,146
Indirect Cost
$21,644
Name
University of South Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
069687242
City
Tampa
State
FL
Country
United States
Zip Code
33612