In a recently published article in the journal Nature Communications, researchers at Karolinska Institutet present results indicating that repeated treatment with piperaquine, an antimalarial drug, can lead to parasites developing decreased sensitivity to this drug. These findings may impact the use of piperaquine in the future.
Piperaquine is an important antimalarial drug characterized by a long half-life, meaning it remains in the body for several weeks and protects against new infections. This is a key asset of this drug However, the researchers behind the study have discovered that this advantage can disappear with repeated treatment in areas with high malaria transmission.
"The study shows that repeated treatment with dihydroartemisinin-piperaquine can lead to parasites developing drug tolerance by duplicating the plasmepsin 3 (pm3) gene. This allows them to reinfect patients earlier than expected during the expected protective period, reducing piperaquine's effectiveness as a prophylactic medicine," says Pedro Gil , senior author and associate professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.
Next steps in research
"Dihydroartemisinin has a very short half-life, leaving piperaquine alone only a couple of hours after treatment completion. We suggest that future combinations of antimalarial drugs should have similar pharmacokinetics to delay the development of resistance. Additionally, we recommend caution and active surveillance upon the use of piperaquine for large scale protective strategies, such as intermittent preventive treatment for pregnant women (IPTp) or seasonal malaria chemoprevention (SMC), as this are likely to select pm3 duplications, and as such swiftly decrease piperaquine usefulness for these purposes," says Pedro Gil.
Accordingly, the researchers behind the study plan to conduct a clinical trial to compare piperaquine with the current standard medication for IPTp, sulfadoxine-pyrimethamine, in treating pregnant women. The goal is to investigate whether repeated treatment with piperaquine leads to the same patterns of pm3 selection and decreased protection, and if this can be reduced by alternating between the two medications.
Publication
Pernaute-Lau L, Recker M, Tékété M, de Sousa TN, Traore A, Fofana B, Sanogo K, Morris U, Inoue J, Ferreira PE, Diallo N, Burhenne J, Sagara I, Dicko A, Veiga MI, Haefeli W, Björkman A, Djimde AA, Borrmann S, Gil JP
Nat Commun 2025 Mar;16(1):2680
