“Our findings suggest that these background mutations emerged with limited impact on artemisinin resistance — until mutations occurred in the kelch13 gene,” explains Roberto Amato, a first author. “It’s similar to what we see with pre-cancerous cells which accumulate genetic changes but only become malignant when they acquire critical driver mutations that kick-off growth.”
“We are at a pivotal point for malaria control. While malaria deaths have been halved, this progress is at risk if artemisinin ceases to be effective,” says Nick Day, Director of the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. “We need to use every tool at our disposal to protect this drug. Monitoring parasites for background mutations could provide an early warning system to identify areas at risk for artemisinin resistance.”
There remain many unanswered questions. “We don’t yet know the role of these background mutations,” says Olivo Miotto. “Some may not affect drug resistance directly, but rather provide an environment where drug resistance mutations are tolerated. Since kelch13 has hardly changed in 50 million years of Plasmodium evolution, we can assume that this gene is essential to parasite survival. Therefore, kelch13 mutations may severely handicap mutant parasites, compromising their survival unless some other change can counteract this negative effect.”
“These data serve as a reminder of how crucial surveillance and elimination programmes are,” says Dominic Kwiatkowski. “At present artemisinin resistance appears to be largely confined to Southeast Asia but the situation might change as the parasite population continues to evolve. By linking genomic data with clinical data we’re developing a better understanding of the multiple genetic factors involved in the emergence of resistance, and that is starting to provide vital clues about how to prevent its spread.”
Notes to Editors
Miotto et al. Genetic architecture of artemisinin resistant Plasmodium falciparum. Nat Genet. 2015 Mar;47(3):226-34. doi: 10.1038/ng.3189. Epub 2015 Jan 19.
The Wellcome Trust, the Medical Research Council, the National Institutes of Health and the Howard Hughes Medical Institute.
A full list can be found in the paper.
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Telephone: +44 (0)1223 492 368
Email: press.office [at] sanger.ac.uk