Solving an antimalarial resistance puzzle

The Proceedings of the National Academy of Sciences (PNAS) recently published an article on the ‘Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt.’ This study addresses the evolutionary dynamics in place in the malaria parasite that causes resistance to occur after changes in drug use.

In regions with high malaria endemicity, the withdrawal of chloroquine (CQ) as first-line treatment of Plasmodium falciparum infections has typically led to the restoration of CQ susceptibility. This team discovered a single mutation on the pfcrt gene in the malaria parasite genome that is associated with the restoration of CQ susceptibility. The study also demonstrated that the same allele is also associated with a significant decrease in piperaquine susceptibility in the lab, suggesting that piperaquine pressure, in addition to potential fitness costs, may have selected for this mutation. 

Coinciding with this publication, WWARN Scientific Director, Prof Carol Sibley and Prof Kristin Lane from the National Insitute’s of Health wrote a commentary article on the study, also published in PNAS.

The commentary article describes the study as finding ‘an unexpected mechanism by which Plasmodium falciparum malaria parasites responded to the pressure of antimalarial medicines in French Guiana’. The article goes describes the historical use of chloroquine and the emergence and spread of resistance to this former frontline drug in the Plasmodium falciparum malaria parasite.The analysis of the Pelleau et al. study combines long-term surveillance of the parasites in the field with genomic analysis and precise editing of the gene involved to demonstrate interesting twists that organisms use to evade existential threats. 

In addition, the commentary article highlights that this study was largely built on the power of strong collaborations and robust storage of archived samples and data, a key requirement to understand the pace and trajectory of genetic changes underpinning the current situation of antimalarial drug resistance.

Publication details:

Stéphane Pelleau, Eli L. Mossb, Satish K. Dhingrac et al. 'Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt' Proceedings of the National Academy of Sciences (2015). DOI: 10.1073/pnas.1507142112

Carol Hopkins Sibley and Kristin D. Lane. 'Fusion of field studies and the laboratory solves a puzzle in antimalarial resistance' Proceedings of the National Academy of Sciences (2015). DOI: 10.1073/pnas.1514403112