Plasmodium vivax Drug Resistance Mechanisms

Plasmodium vivax poses a persistent challenge to malaria control due to its ability to develop resistance against key antimalarial agents. Resistance to chloroquine has been documented across multiple endemic regions, prompting shifts towards artemisinin‐based combination therapies. At the molecular level, the parasite exploits point mutations, copy number variations and altered gene expression in transporter proteins and metabolic enzymes to reduce drug susceptibility. Central to these adaptations are polymorphisms in the chloroquine resistance transporter gene (pvcrt‐o) and the multidrug resistance gene (pvmdr1), together with selection in loci affecting folate metabolism. Genome‐wide analyses have further revealed selective sweeps and regional population structures, indicating that drug pressure drives local emergence and spread of resistance alleles. Continued surveillance of these genetic changes and the identification of novel markers are essential to guide treatment policies and sustain the efficacy of existing therapies.

Research from Nature Portfolio

Recent genomic investigations have leveraged large collections of global isolates to map the evolutionary dynamics of drug resistance in P. vivax. A comprehensive study of over 1,500 isolates spanning multiple continents identified strong signatures of selection around the pvmdr1 locus in regions with established chloroquine resistance. In Indonesian Papua, where treatment failure is most pronounced, researchers observed a rising prevalence of novel single‐nucleotide variants in the pvmrp1 gene following the adoption of dihydroartemisinin–piperaquine. These variants co‐occur with transcriptional regulators implicated in drug response, suggesting a multifactorial basis for reduced drug sensitivity. The work delivers an expanded panel of genetic markers for surveillance and underscores the importance of integrating temporal sampling to detect emerging resistance trends.

Plasmodium vivax Drug Resistance Mechanisms publication trend

The graph below shows the total number of articles in plasmodium vivax drug resistance mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Single‐nucleotide polymorphism (SNP): A variation at a single base‐pair position in the DNA sequence among individuals.

Copy number variation (CNV): A change in the number of copies of a particular gene segment in the genome, which can affect gene dosage.

Selective sweep: A process by which a beneficial genetic variant increases in frequency, reducing genetic diversity around that locus.

pvcrt-o: The Plasmodium vivax chloroquine resistance transporter gene, implicated in reduced drug accumulation within the parasite.

pvmdr1: The Plasmodium vivax multidrug resistance transporter gene, encoding a protein associated with efflux of antimalarial compounds.

References

1. Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance. Nature Communications (2024).
2. No Association between the Plasmodium vivax crt-o MS334 or In9pvcrt Polymorphisms and Chloroquine Failure in a Pre-Elimination Clinical Cohort from Malaysia with a Large Clonal Expansion. Antimicrobial Agents and Chemotherapy (2023).
3. Investigation of Mutations in the crt-o and mdr1 Genes of Plasmodium vivax for the Molecular Surveillance of Chloroquine Resistance in Parasites from Gold Mining Areas in Roraima, Brazil. Microorganisms (2024).