Antimalarial Drug Resistance in Plasmodium Falciparum

Plasmodium falciparum has evolved resistance to virtually every antimalarial introduced for widespread use, posing a major challenge to malaria control and elimination. Resistance emerged first against chloroquine and later against sulfadoxine-pyrimethamine, before threatening the efficacy of artemisinin-based combination therapies (ACTs). Key molecular determinants include mutations in the pfcrt gene, which alter the digestive vacuole transporter to reduce chloroquine accumulation, and in the pfmdr1 gene, where both single-nucleotide polymorphisms and gene amplification modulate susceptibility to multiple partner drugs such as mefloquine and lumefantrine. More recently, mutations in the propeller domain of the pfk13 gene have been linked to delayed clearance after artemisinin exposure. These genetic adaptations have arisen and spread across Africa, Southeast Asia and beyond, driven by drug pressure, parasite population dynamics and human mobility. Continuous molecular surveillance and innovative diagnostic approaches are essential to detect emerging resistance, guide treatment policy and sustain the gains achieved by ACTs and future combination regimens.

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Antimalarial Drug Resistance in Plasmodium Falciparum publication trend

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

Technical terms

Pfcrt: The gene encoding the chloroquine resistance transporter protein in the parasite’s digestive vacuole; key mutations (e.g. K76T) reduce drug accumulation and efficacy.

Pfmdr1: The gene for P. falciparum multidrug resistance protein 1; polymorphisms and copy number changes influence susceptibility to several antimalarials.

Pfk13: The gene coding for a kelch-propeller domain protein; specific propeller-region mutations are markers of delayed artemisinin clearance.

Artemisinin-based Combination Therapy (ACT): A treatment combining a fast-acting artemisinin derivative with a partner drug to achieve rapid parasite clearance and slow resistance development.

Haplotype: A set of linked genetic variants at adjacent loci, used to characterise combinations of resistance-associated mutations on a single chromosome.

References

1. Distribution patterns of molecular markers of antimalarial drug resistance in Plasmodium falciparum isolates on the Thai-Myanmar border during the periods of 1993–1998 and 2002–2008. BMC Genomics (2024).
2. Setting Up an NGS Sequencing Platform and Monitoring Molecular Markers of Anti-Malarial Drug Resistance in Djibouti. Biology (2024).
3. Rapid and supersensitive allele detection of Plasmodium falciparum chloroquine resistance via a Pyrococcus furiosus argonaute-triggered dual-signal biosensing platform. Parasites & Vectors (2024).