The new locus of resistance is also of concern because the western border of Thailand abuts Burma (Myanmar), where malaria is much more common and the public health infrastructure is even less equipped to handle stubborn infections.
The researchers also found that the slow-clearing parasites harvested from Thailand were not all that closely related to those in Cambodia, which suggests that rather than having spread geographically, resistance has sprung forth anew.
This observation has researchers even more worried, because it suggests resistance could then emerge elsewhere, such as Africa. "We know from historical examples—from the emergence of other drug resistances—that when resistance does hit Africa, it can spread incredibly rapidly," says Ian Cheeseman, a postdoctoral researcher at Texas Biomed and co-author on the Science study.
History has already shown what this sort of resistance pattern looks like. Former mainstay drugs (chloroquine and sulfadoxine–pyrimethamine) also experienced their first resistance challenges in western Cambodia before spreading to other parts of Asia and on to Africa, where the parasites killed millions. Anderson describes this as a sort of resistance déjà vu.
Researchers also currently lack any quick lab tests to tell if a patient is infected with an artemisinin-resistant parasite. For now, they must simply try the standard treatment and watch and wait to see if it clears in a timely manner.
Nevertheless, Anderson notes, "We've shown that the slow clearance is definitely due to parasite genetic factors—not caused by low-quality drugs, poor nutrition or some other aspect of the patients."
With new genetic screening technology, researchers have been looking into the DNA of the parasites to see from whence their resistance might be springing.
As Anderson, Cheeseman and their colleagues describe in their Science paper, they analyzed 6,969 spots on the genome of 91 parasites (collected from Cambodia and Thailand as well as Laos, where resistance has not yet been reported). From that data, they found 33 locations on the genome that seem to be under strong selection pressure for resistance, with a hot spot located on chromosome 13. "We've narrowed down the search to a small area of the genome" that confers resistance, Anderson notes.
"This is a huge leap, but it doesn't really nail the mechanism of resistance," Sullivan says. "They've identified several novel areas," he continues, noting, "they still have a handful of genes to look at and really pin down."
Anderson, Cheeseman and their fellow researchers are planning to drill down further into the genetics to root out more specific regions of resistance. "The next step is going to be some fine mapping to define that mutation," Cheeseman says. "By finding out these mutations, we will hopefully be able to know more about this resistance and how this drug works. We don't have a great handle on that yet," he adds.
That more detailed picture should also allow them to better pinpoint just how many individual times artemisinin resistance has emerged already, "and that will allow us to predict the number of times resistance might emerge in the future," he notes.
A list of mutations might also help to point the way to new similar compounds that would still lay the parasite low.
Sullivan notes that although there is a grim history of resistance spreading from this region, unlike previous cases, which have taken more than a decade to characterize, this one has been spotted and described relatively quickly. "If we can identify the gene, then we might be able to circumvent the resistance in some way," he says.