Scientists at the Max Planck Institute and the Free University in Berlin have found a way to extract artemisinin, one of the most effective anti-malaria drugs, from by-product material that was formerly discarded. The international edition of the journal Angewandte Chemie published their findings this past January. The new process is significant in light of research by the Institute for Health Metrics and Evaluation (IHME) in the US, which estimates that malaria kills 1.2 million people each year. This is double the number of deaths previously estimated, according to a study published in The Lancet at the beginning of February. Malaria is endemic in more than 100 countries, with 200 to 500 million cases worldwide each year. The most effective treatment is the use of insecticide-treated bed nets and artemisinin combination therapies, or ACTs. But 150 tons of the drug are needed to treat those sickened by the disease, and right now there just isn't enough to go around. Persistent difficulties in distribution channels add to the problem. Ancient knowledge, modern method Artemisinin comes from a plant called Artemisia annua, also known as sweet wormwood. Chinese herbalists used it in ancient times to treat fever. In the 1970s, scientists started isolating it for prevention and treatment of malaria. But until now, yield of artemisinin from the plant has been low - generation of the by-product artemisinic acid has outstripped useful yield 10-to-1. The scientists in Berlin have developed a way to convert this by-product, which is currently thrown away, into the molecule needed for the drug. For this, drug companies typically use what's called a batch process, which in layman's terms means mixing chemicals together in a large pot. Peter Seeberger, a professor of chemistry at the Free University Berlin, instead uses a process called continuous flow chemistry. With this more efficient method, chemicals are passed continuously through a tube, where the materials react with one another. It's a method being used in manufacturing and oil refining but is relatively new in the lab environment. Seeberger described how the starting material moves from a flask via a pump through thin tubing. "The key piece of our reaction process is a reactor, which consists of a very strong lamp generating heat," Seeberger told DW. The tubing is wrapped around a quartz-glass cooling device covering the lamp, which "ensures that the entire solution is completely irradiated at all times," Seeberger added. Fulfilling global need Seeberger hopes that flow chemistry will streamline the production of artemisinin for use in combination therapies against malaria. Seeberger's team estimates that it would take about 400 to 500 of these very small reactors to produce up to 150 tons of artemisinin per year. Those 150 tons would be around 65 tons more than the amount of artemisinin currently produced through conventional means. "Although it's a formidable amount of material, you can actually use very small instruments to make it," Seeberger said. The original reactor cost about 50,000 euros ($65,000), but Seeberger and his team say they've been able to simplify the process, which could bring the cost down significantly. Seeberger is hoping to work with companies like Amyris or Sanofi, which are isolating artemisinin from plants and have plenty of waste product for conversion. Frank Mockenhaupt, head of the Malaria Research Group at the Institute for Tropical Medicine at the Charite Hospital in Berlin, says that Seeberger's findings are important, but pointed out that there are still other factors to consider. The new method could reduce costs for the drug considerably while increasing production, which is a good starting point, Mockenhaupt said. "But we still need to have the distribution channels, and we need to have the drugs in stock. We need to consider shelf life and a lot of logistical issues," Mockenhaupt told DW. Aside from poor distribution channels, bad governance and inefficient health systems in poor countries often prevent anti-malaria drugs from actually getting to the people who need them. Increasing drug resistance in some parts of the world, most notably along the border between Thailand and Cambodia, is also a growing concern. Prevention versus treatment Seeberger has been working for the past 12 years on a malaria vaccine which he believes is the ultimate way forward. "Vaccines are the least expensive way for societies to protect themselves against infectious disease," Seeberger said, pointing to their effectiveness against polio and smallpox in developed countries. But many researchers and public health officials caution against pinning all their hopes on simply vaccinating everyone. Mockenhaupt made clear that even if there were a malaria vaccine, it would probably only be effective in 50 percent of all cases. So theoretically, half of those who were vaccinated could still contract the disease and need treatment. He believes that drugs for treatment would still be necessary, as well as other forms of prevention. Seeberger and Mockenhaupt both agree that malaria needs to be fought on many different fronts with all possible methods. Over the past 10 years, public health experts have shown that the most effective way to control malaria in East and West Africa is to use insecticide-treated bed nets. Mockenhaupt attributed a 50 percent reduction of malaria cases, including those that are fatal, to "efficient distribution of insecticide treated bed nets and also of the available good and working ACT treatments." Seeberger said that the first commercial prototypes of the artemisinin production reactors should be ready to go by the end of 2012, and may be deployed early in 2013. From: DW
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