Loesbanluechai, D. et al. (2019) Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine. International Journal for Parasitology: Drugs and Drug Resistance, 9, pp. 16-22. (doi: 10.1016/j.ijpddr.2018.11.004) (PMID:30580023) (PMCID:PMC6304341)
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Abstract
Artemisinin derivatives and their partner drugs in artemisinin combination therapies (ACTs) have played a pivotal role in global malaria mortality reduction during the last two decades. The loss of artemisinin efficacy due to evolving drug-resistant parasites could become a serious global health threat. Dihydroartemisinin-piperaquine is a well tolerated and generally highly effective ACT. The implementation of a partner drug in ACTs is critical in the control of emerging artemisinin resistance. Even though artemisinin is highly effective in parasite clearance, it is labile in the human body. A partner drug is necessary for killing the remaining parasites when the pulses of artemisinin have ceased. A population of Plasmodium falciparum parasites in Cambodia and adjacent countries has become resistant to piperaquine. Increased copy number of the genes encoding the haemoglobinases Plasmepsin II and Plasmepsin III has been linked with piperaquine resistance by genome-wide association studies and in clinical trials, leading to the use of increased plasmepsin II/plasmepsin III copy number as a molecular marker for piperaquine resistance. Here we demonstrate that overexpression of plasmepsin II and plasmepsin III in the 3D7 genetic background failed to change the susceptibility of P. falciparum to artemisinin, chloroquine and piperaquine by both a standard dose-response analysis and a piperaquine survival assay. Whilst plasmepsin copy number polymorphism is currently implemented as a molecular surveillance resistance marker, further studies to discover the molecular basis of piperaquine resistance and potential epistatic interactions are needed.
| Item Type: | Articles |
|---|---|
| Additional Information: | The work was supported by the National Science and Technology Development Agency (NSTDA), the Tres Cantos Open Lab Foundation, The Thailand Research Fund-Mahidol University (RSA5880062), Newton Advanced Fellowship under The Thailand Research Fund-Royal Society (DBG5980010), the Faculty of Tropical Medicine, Mahidol University and the Royal Golden Jubilee Ph.D. Program (The Thailand Research Fund). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Loesbanluechai, Ms Duangkamon |
| Authors: | Loesbanluechai, D., Kotanan, N., de Cozar, C., Kochakarn, T., Ansbro, M. R., Chotivanich, K., White, N. J., Wilairat, P., Lee, M. C. S., Javier Gamo, F., Maria Sanz, L., Chookajorn, T., and Kümpornsin, K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | International Journal for Parasitology: Drugs and Drug Resistance |
| Publisher: | Elsevier |
| ISSN: | 2211-3207 |
| ISSN (Online): | 2211-3207 |
| Published Online: | 01 December 2018 |
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