Healthcare Blog

The Genetics Behind Malaria's Drug Evasion

July 28, 2017

Several genes have been identified that may be implicated in the malaria parasite's notorious ability to rapidly evade drug treatments. The researchers from the Harvard School of Public Health and the Broad Institute then discovered that one of the genes, when inserted into drug-sensitive parasites, rendered them less susceptible to the effects of three antimalarial drugs. The study appears in the open-access journal PLoS Genetics on April 21, in time for World Malaria Day on April 25.

Malaria kills nearly a million people a year, mainly young children in Sub-Saharan Africa, although diverse populations of the parasite are endemic in Africa, Asia and South America. However, reducing mortality due to Plasmodium falciparum is a major challenge because of the parasite's talent for swiftly developing resistance to multiple drugs by generating resistant clone.

For the study, the scientists analyzed the DNA of 57 parasites from the three continents and also measured the parasites' responses to 13 antimalarial drugs. They identified 20 rapidly-evolving loci in the genome and then carried out a genome-wide association study to identify the variants that are associated with the drug-resistance trait. The investigation pinpointed 11 genes implicated in drug resistance, of which one was previously known. Follow-up testing revealed that one of the novel genes, PF10_0355, caused a drug-sensitive parasite to become more resistant to three standard antimalarial agents.

Sarah Volkman, co-author, said "Understanding how the parasite is changing before clinical drug resistance is apparent offers some hope that we might be able to extend the useful life of available drugs and identify new effective antimalarials."

Financial Disclosure: The study is supported by the Bill and Melinda Gates Foundation, Ellison Medical Foundation, ExxonMobil Foundation, NIH Fogarty, and NIAID. Pardis C Sabeti is also supported by fellowships from the Burroughs Wellcome and Packard Foundations. Daniel J Park is supported by an NSF Graduate Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation:
"Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium falciparum."
Van Tyne D, Park DJ, Schaffner SF, Neafsey DE, Angelino E, et al. (2011)
PLoS Genet 7(4): e1001383. doi:10.1371/journal.pgen.1001383