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.
New mutations
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."
Genetic clues
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.
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6 Comments
Add Comment600,000 thousand lives a year is over 1600 per people dying every day, almost 70 people per hour, averaging over 1 fatality a minute.
Reply | Report Abuse | Link to thisHoping something can be done to solve this problem once and for all.
You misinterpret him, and Ayn Rand. Paul asserts that charity should be private and voluntary, rather than public and coercive toward people who don't share you priorities. As you seem to feel strongly about the third world plight, I urge you to donate *your* money voluntarily toward the cause.
Reply | Report Abuse | Link to thisSomehow I doubt you will.
It is unseemly to hijack scientific article commentary to make political statements. Everyone, please hit the "Report Abuse" buttons when such occurs. I have.
Reply | Report Abuse | Link to thisThe malarial organism is clearly well evolved to quickly evolve in response to its environment. In part, this is a result of its large distribution and population. Large wild populations retain great variation. Epigenetic factors, such as a gene's variable capacity to acquire epigenetic modifications that matter, may also be key to engineering countermeasures.
Plasmodium species have only a single PDH compex occurring within the apicoplast, a cholorplast-like endosymbiotic structure; there much research in combating the organism is focused.
Artemisinin is from an ancient Chinese herb given for fevers, and its fast action gives quick relief (I'm not selling it!). Since its isolation about 40 years past, the WHO has kept strict control on its usage, hoping to prevent Plasmodium evolution of tolerance by only allowing it as part of combinations which help prevent adaptation.
20% is not a small percentage of resistance, and suggests that artemisinin's days as cure are over.
There is no once-and-for-all. Some remember the spray trucks of DDT driving through neighborhoods that did abate mosquitoes here; significant climate change may help create conditions more amenable to malaria vectors in the US.
Remember that it was reported as far north as Maryland, and perhaps further, before the warming trend began in the 1800s.
Please do not make these facts meat for political posturing. Take that elsewhere.
It might be worth it to tackle the other end of malaria: OUR resistance to IT. Much work has been done in other areas to discover why the human animal builds tolerance/resistance to medications and other stimuli. For example, my immunity to poison oak made me priceless during my search and rescue days. I am not talking about a vaccine, but possibly a genetic treatment similar to the ones being developed for blindness.
Reply | Report Abuse | Link to thisAloha, I lived in Thailand when I took multiple 6 month entrepreneurial work/vacations there as I worked 6 months a years, 7 days a week & 12 hours a day in the oil drilling industry & in shipping. I traveled to the Northern border areas in the early & mid 1980's & again in the early 90's. I ended-up in a Bangkok hospital with massive headaches, chills, fever & I could not move my neck without intense & excruciating pain. I do not recall how long it had been since I had been in Northern Thailand before I fell ill. The doctors did not speak English & originally I was diagnosed with Malaria. A day later I was diagnosed with spinal meningitis. I had blood tests done & was put on some unknown medications & may have received some injections. After a few days back in my hotel room the pain was slowly subsiding & took a week or two to feel better. As well my girlfriend of many years was from the N. Thailand & would visit her family & then come back to stay with me. I was young & very healthy at the time. In 95 I became ill almost overnight after working too hard too long & on a business trip. I experienced joint & muscle pain seemly spurred on by immediate & severe insomnia. In 97 I was flew to Mass General hospital from my home in Hawaii after suffering from a bout of shingles & then a host of dibialtating symptoms or hell: Encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome. I made the mistake of selling my franchise to take care of my health thinking I would regain my health & buy another franchise elsewhere in Hawaii. I have been severely sick every since & have never recovered. I have not researched this however, my guess is there are some genetically predisposed & those more vulnerable to viral illnesses. While others may not every develop illness even after exposer, again I don't know the science. What I do is for those who have an open mind & evolve with science we understand there is a lot we don't know & we should not believe we know with certainty many "medical facts". If anyone has any thoughts or knows of any information or references that I may investigate regarding post viral fatigue syndrome I would be very appreciative. I may be off topic here in this forum & I apologize to those who are focused on the specific topic in this article. However, I have learned share my story as one never knows what one might learn or light one might shed. Thank you for the conversation & your passion for science & medicine. I'm open to any info. 23
Reply | Report Abuse | Link to thisP.S. I forgot to mention I was released from the Bangkok hospital without a final diagnosis. 23
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