Chloroquine resistance mechanisms of P. vivax: a transcriptomic/transgenic approach (PvRESIST)

Plasmodium vivax is the predominant malaria-causing species outside Africa. Countries moving toward malaria elimination by 2030 are seeing an increase in P. vivax resistance to chloroquine, complicating these efforts. Molecular markers and the mechanism of chloroquine resistance (CQR) remain unknown, making surveillance and accurate diagnosis of CQR difficult. The hypothesis, based on studies by the Brazilian and Belgian groups participating in this project. Results from a clinical study in Vietnam, published data from non-human primate models, and observations from samples from the Brazilian Amazon suggest that alterations in gene expression of transporter genes play an important role in PvCQR. This project will use clinical samples of P. vivax from Brazil and characterize their response to CQ. These samples will be used for DNA and RNA sequencing using cutting-edge technology, such as single-cell RNA sequencing (scRNAseq). This project will unravel the transcriptional network of PvCQR-associated genes and the impact of infection complexity (different parasite life stages and clones present in natural infections) on treatment outcome. Transgenic P. knowlesi lines, differentially expressing P. vivax genes, will be generated in PvRESIST using advanced genome editing strategies such as CRISPR-Cas9 in order to determine resistance mechanisms. The results of PvRESIST strengthen research efforts and push the boundaries of previous results, for example by directly benefiting P. vivax patients and drug resistance surveillance, while advancing research with new tools, datasets and transgenic lines to investigate P. vivax biology.

Project Details

Drug Resistance
Genetics and Genomics
P. vivax

Jan 2025 — Dec 2027

Brazil