Last Updated: 16/06/2015
Genetic determinants of Plasmodium vivax relapse
Objectives
This proposal will use new genomic technologies to achieve a better understanding of the genetic determinants of vivax relapse, with the ultimate goal of identifying targets for therapeutic intervention.
Specifically, in light of limited experimental models of vivax, next-generation sequencing techniques to clinical samples from vivax-infected Cambodian patients to provide the first detailed look at the genetic signatures of relapsing parasites.
The specific aims are:
- to use amplicon deep sequencing to characterize the in-host diversity of initial and recurrent vivax infections in this cohort. Results will be combined with microsatellite genotyping, population genetic analysis, and statistical modeling to distinguish relapses from re-infections and identify genetic variants predisposed to relapse.
- to whole genome sequence parasites causing relapsing vs. non-relapsing infection to search for genetic polymorphisms associated with relapse.
The overall hypothesis is that frequently relapsing parasites contain polymorphisms in sporozoite (pre-hypnozoite) specific genes that increase hypnozoite formation and confer increased relapse potential.
In recent years, there has been an increased appreciation that global malaria elimination efforts cannot succeed without a better understanding of Plasmodium vivax, the most prevalent malaria species outside Africa. In particular, our poor understanding of P. vivax‘s ability to establish dormant hypnozoite stages that reactivate to cause periodic relapse is a major barrier to malaria elimination due to the lack of deployable anti-relapse therapy.
Feb 2014 — Jan 2019
$869,147
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