Wednesday, January 20, 2010

Artemisia annua and Malaria

Malaria is a major problem for public health and development. More than 40% of the world's population is exposed to this parasitic disease, which kills around 1.5 million human beings every year, largely in Africa.

Malaria had been successfully contained in many countries by use of measures to promote hygiene (the draining of marshlands, where the mosquito larvae hatch out, the use of high-remanence insecticides such as DDT) and through the development of cheap but effective drugs such as Chloroquin.

However, malaria has been spreading rapidly once again since the early 1980s. It has reappeared in countries where it had been eradicated and is today responsible for three or four times more deaths than in 1970. This resurgence is linked to the parasite's resistance to Chloroquin and the other conventional anti-malarial drugs (Sulfadoxine-Pyrimethamine in Africa, Mefloquin in Asia). Development of an effective malaria vaccine continues to be problematic.

Global supply of a key, plant-based, anti-malaria drug called artemisinin (a sesquiterpene lactone) is set to be boosted by a genetic study, scientists say. Researchers have mapped the genes of the sweet wormwood plant Artemisia annua to allow selection of high-yield varieties.

The study, published in the journal Science, aims to make growing the plant more profitable for farmers. "It's a major milestone for the development of this crop," Professor Ian Graham from the University of York in the UK told BBC News.

Artemisinin combination therapies, or ACTs, are used widely to treat malaria and are seen as the best solution to the parasite's increasing resistance to anti-malarial drugs.

"Our aim is to have hybrid seeds that can be released to farmers in the developing world by 2011 or 2012. With a year lag for planting, this would have an impact on supply in 2012 or 2013."

"We have to wait six to eight months from putting the seed in the ground to harvesting the crop and seeing how it has performed."

To identify the best plants for hybrid seed production, researchers measured characteristics of individual plants, for example, the number of artemisinin-producing glands on the leaf. They also performed tests to find the plants with the best genetic make-up.

The resulting seeds are being planted in field trials in China, East Africa, India and Madagascar. "We are expecting to end up with not just one hybrid. Ideally we would like good hybrids for east Africa and good hybrids for India etc.," explained Professor Graham. "We're also working with seed producers so they can produce the seeds as cheaply as possible for the developing world."

A team from the University of California, Berkeley, succeeded two years ago in engineering bacteria to make a chemical precursor of artemisinin.

They have now gone one step further by developing a strain of yeast that can churn out large quantities of artemisinic acid - a chemical just one tiny change away from the drug itself.

They did this by adding two genes from A. annua to the yeast, Saccharomyces cerevisiae.

The Berkeley team now hope eventually to drive down costs still further by using a similar process to stimulate bacteria to produce artemisinic acid. Bacteria grow much more quickly than yeast, and so could potentially offer a much more productive source of the chemical.

The researchers say it could still be several years before a microbe-produced version of artemisinin will be widely available. Artemisinin is currently expensive to manufacture, and so is denied to many in the developing world. Writing in Nature, they say their work may eventually help slash the cost of artemisinin, and improve access.

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