Researchers have identified a region on a chromosome in Plasmodium falciparum—a major malaria parasite—that helps to explain how the parasite developed resistance to the best known anti-malarial treatments in Southeast Asia.
Currently, artemisinin-based combination therapies represent the first-line treatment in nearly all countries where malaria has become endemic. But emerging resistance to the therapies has recently been confirmed in western Cambodia and western Thailand. This growing resistance, or “treatment delay,” means that artemisinin-based therapies aren’t clearing parasites from people as quickly in that region of the world compared to others.
“Approximately 700,000 people a year are killed by this parasite,” said Ian Cheeseman from the Texas Biomedical Research Institute in San Antonio, Texas, who led the Science study. “However, this represents about a 30% drop in mortality over the last decade, and one of the major contributors to this decline has been the use of highly efficacious artemisinin-based combination therapies.”
Cheeseman, along with colleagues from Europe and Asia, sequenced the genomes of nearly 100 P. falciparum parasites from Cambodia and Thailand as well as from Laos, where resistance to the latest artemisinin-based drugs has not yet emerged. Their results appear in the 6 April issue of Science.
“We compared the genomes of parasites from three different Southeast Asian countries, which have very different levels of resistance,” explained Cheeseman. “Laos, where infections are rapidly cured, generally within about 48 hours; Cambodia, where treatment can last a week or longer; and Thailand, which is a mix of these two extremes.”
Poring over their results, the researchers identified 33 regions on the P. falciparum genome that appear to be under strong selection for artemisinin drug resistance. And after taking a closer look at the genomes of parasites in Thailand, the researchers were able to narrow this genetic hotspot down to just seven genes on chromosome 13.
According to Cheeseman and his colleagues, changes to this particular section of chromosome 13 can explain up to 35% of the slower P. falciparum clearance rates that have been observed in Southeast Asia.
Most researchers believe that parasite resistance to chloroquine and antifolate—two drugs that were once used to treat malaria—also arose in western Cambodia and then spread throughout Southeast Asia into Africa, rapidly reducing the ability of those drugs to treat infections.
“And for this reason,” said Cheeseman, “it’s been suggested that western Cambodia is the crucible of drug resistance for malaria.
“However, one major difference is that artemisinin resistance has been detected very early on in this stage, and this raises hope that its spread can be prevented.”
Read the abstract, “A Major Genome Region Underlying Artemisinin Resistance in Malaria,” by Ian Cheeseman and colleagues.
Listen to a Science Podcast interview with Ian Cheeseman.