Observing the evolution of artemisinin resistance: The story so far

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Published in BMC Medicine, Prof Carol Sibley’s commentary piece explores the rare opportunity to observe the early stages of drug resistance in malaria parasites.

Advances in genomic analysis have allowed us to see more clearly the changes in pathogen genomes that contribute to resistance to modern medicines. In the past, this genetic detective work has occurred long after the pathogen has evolved resistance.

Current genetic surveillance of artemisinin drug resistance provides a rare opportunity to observe the early stages in the evolution of antimalarial drug resistance. This privileged view  may allow design of strategies to mitigate the threat of antimalarial resistance and protect key medicines. Prof Carol Sibley has published a commentary article in BMC Medicine highlighting some of the recent insights on the current evolution of resistance to artemisinins, a key component of all current antimalarials.

In 2014, results published in Nature found that a genetic signature on the Kelch 13 gene was strongly associated in Southeast Asia with slow clearing of the malaria parasite from the patient’s body, a clear indicator artemisinins were losing their potency. Since then, more than 50 different mutations on the K13 gene have been identified, most of which are associated in Southeast Asia with slow parasite clearance.

An article in Nature Genetics by Miotto and colleagues utilized parasites from the Mekong region of Southeast Asia to analyse the population structure of highly resistant parasites.  They verified the strong association between specific K13 mutations and slow parasite clearance.  Moreover, they identified a set of additional genetic changes that appear to permit the emergence of K13 mutant genes in different parasite populations. These studies also highlight the rapid pace at which malaria parasites are evolving to become resistant to artemisinin-based treatments.

Artemisinin combination therapies are still highly effective in treating malaria patients in most parts of the world. However, it is essential that we continue international collaborative efforts to transform these insights into tools and resources that can support policies and strategies to reduce the pace, and potentially curb the spread of antimalarial drug resistance.

Publication details:

Sibley CH. Observing in real time the evolution of artemisinin resistance in Plasmodium falciparum. BMC Medicine 2015, 13:67.  doi: 10.1186/s12916-015-0316-5