Emergence of chloroquine resistance in Cambodian Plasmodium vivax threatens the entire malaria control strategy in the region. In collaboration with the Pasteur Institute in Cambodia, we will collect blood samples from 280 individuals infected with P. vivax and use next generation sequencing to investigate the patterns of genetic diversity across the entire P. vivax genome. First, we will conduct population genomic analyses to characterize the structure of the parasite population and better understand how and how fast drug resistance alleles can spread across the country. We will also use these data to identify loci under positive selection which could be responsible for drug resistance. Second, we will determine drug susceptibility of the P. vivax strains present in 100 vivax malaria patients using a combination of in vivo and ex vivo approaches. We will then conduct a genome-wide association study to identify genetic polymorphisms statistically associated with drug resistance in P. vivax. Our findings will improve our understanding of drug resistance in this neglected human malaria parasite and have the potential to significantly advance vivax malaria control.

Public Health Relevance

Extensive use of antimalarial drugs in the past decades has led to the emergence of resistant Plasmodium vivax parasites which greatly complicates malaria elimination. We will combine modern fieldwork with state-of- the-art genomic analyses to understand how drug resistance can spread in a population and identify the genetic bases of this resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI103228-01A1
Application #
8576980
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Joy, Deirdre A
Project Start
2013-05-13
Project End
2018-04-30
Budget Start
2013-05-13
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$339,971
Indirect Cost
$97,571
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195