The malaria parasite is a wily organism, shifting its life stages as it flits from human to mosquito and back again. It still kills some 600,000 people each year and has outwitted eradication efforts, having developed resistance to previously popular drugs and, thus far, eluded vaccine-induced immunity.

The arrival of a powerful drug in the late-20th century gave researchers new hope. Called artemisinin and based on a traditional Chinese herbal remedy, it cleared the parasite faster and more thoroughly than any other current antimalarial. Researchers are still somewhat uncertain about exactly how it works, but they know that it targets the parasite as it infects red blood cells.

But the hope that artemisinin would serve as a final, exterminanting blow against malaria has begun to fade. Since 2008 patients in Southeast Asia have been slower to lose the malaria parasite Plasmodium falciparum than they once were. And this precursor to resistance seems to be spreading, despite efforts to carefully use artemisinin (by giving it in combination with other drugs) to avoid the emergence of resistance.

Researchers have been tracking that spread—and looking into the genetic basis of the trait—to try to develop more effective ways of keeping the disease in check. The findings, described in two related papers published online April 5 in Science and The Lancet, were called "a tour de force" by David Sullivan, an associate professor at Johns Hopkins Malaria Research Institute, who was not involved in the new research.

Loci of resistance
The confirmation of additional resistance will likely be a blow to malaria battlers. "Artemisinin-based compounds have really been the key to success in pushing back malaria in recent years," says Timothy Anderson, of the Texas Biomedical Research Institute and a co-author on both new studies. "But there's been a cloud on the horizon: patients in western Cambodia have been showing very, very slow parasite clearance." As a result, such patients have a greater chance of having the parasite return. They also provide a wider window for mosquitoes to bite them and then transmit their (more resistant) infection to other people.

For their Lancet study, Anderson and his colleagues (from the U.S. and Southeast Asia) studied the infections of 3,202 malaria patients on the western border of Thailand over the course of a decade. They found that the time it took the artemisinin-based combination therapy to clear the parasites steadily increased, from a mean of 2.6 hours in 2001 to 3.7 hours in 2010. They also found that the infections that persisted with a half-life of more than 6.2 hours jumped from 0.6 percent at the beginning of the study to 20 percent at the end.

These numbers might look small, but they are quickly creeping toward those figures already present in the resistance epicenter of western Cambodia, about 800 kilometers away, where the mean clearance time in 119 different patients was 5.5 hours, and 42 percent of the infections had a half-life of more than 6.2 hours. The researchers predict that the Thailand border area, which has used the artemisinin-based therapy since the mid-1990s, will see these levels of resistance within the next two to six years.

"Slow-clearing, resistant parasites are not restricted to western Cambodia as everyone had hoped," Anderson says. "Our approach to containment really has to be rethought."

6 Comments

1. 1. sparcboy 02:37 PM 4/5/12

   600,000 thousand lives a year is over 1600 per people dying every day, almost 70 people per hour, averaging over 1 fatality a minute.
   
   Hoping something can be done to solve this problem once and for all.
   

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2. 2. laughtrack in reply to Vendicar Decarian 12:10 PM 4/6/12

   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.
   
   Somehow I doubt you will.

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3. 3. Michael M 07:30 PM 4/10/12

   It is unseemly to hijack scientific article commentary to make political statements. Everyone, please hit the "Report Abuse" buttons when such occurs. I have.
   
   The 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.

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4. 4. sfwendie 07:50 PM 4/10/12

   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.

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5. 5. herenow23 12:18 AM 4/11/12

   Aloha, 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

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6. 6. herenow23 12:27 AM 4/11/12

   P.S. I forgot to mention I was released from the Bangkok hospital without a final diagnosis. 23

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