Feature

Traditional remedy from Madagascar intrigues malaria scientists

Hawk Jia and Christina Scott

Swing that axe: Dr Dina Rakotondramanitra is not chopping down a tree for firewood. He specialises in phytochemistry, and is trying to save lives by decoding the unusual properties of this Malagasy tree, long used to ward off malaria and since found to attack the mosquito-born parasite early on, in your liver. Trekking through the eastern rain forests of Madagascar are team members Armand Rakotozafy, an expert in plant classification, with malaria researcher Dr David Ramanitrahasimbola.

Researchers are excited about a compound they have derived from a rare tree bark in the Madagascar rain forests, according to a study published online in the journal Medicine by the Public Library of Science.

The compound has passed some laboratory tests and is being tested in animals because it shows potential as a  preventative treatment for malaria, which kills millions of people and handicaps the economic growth of many nations.

The treatment is unusual because it targets the early stages of malaria infection, after being bitten by a parasite-carrying mosquito but before the parasite has re-emerged and infected an enormous number of red blood cells.

Targeting this stage, in the liver when parasites are few and relatively vulnerable, would make it more difficult for the parasite to develop the kind of drug resistance that hampers conventional malaria treatment
programmes.

Next step: In the middle of the rainforest in Andasibe National Park, Madagascar botanist Rova Razafindrazaka and French biochemistry laboratory researcher Dr Maelle Carraz, one of the authors of the new online malaria parasite research, hunker down to carefully peel off the precious bark containing an active ingredient which fights malaria in the disease's earlier stages, long before it invades your red blood cells.

A team of scientists funded by France's National Institute of Health and Medical Research (INSERM) isolated a new molecule from bark collected in
Madagascar's eastern rain forest and tested it in the laboratory.

They found that a less-toxic compound, a variant of the molecule, was effective against early, liver-stage malaria parasites in mice.

The newly-discovered molecule, tazopsine comes from the stem bark of the plant Strychnopsis thouarsii. Named for the Malagasy word for malaria, tazopsine comes from the sole ingredient in a traditional tea used to treat
malaria infection. The authors of the study hope that variants of tazopsine-related molecules can be tested to find one of low toxicity, suitable for clinical trials.

A resurgence of malaria since the 1980s, combined with a shortage of conventional drugs, has forced many Madagascans to rely on medicines from more than 200 plants to fight the disease. This has triggered scientific interest, as Madagascar's long isolation from neighbouring countries has resulted in a unique mix of plants and animals.

There is currently a shortage of treatments which target the malaria
parasite after it migrates to the liver and before it reproduces into the
bloodstream and infects red blood cells.

Plants have evolved complex chemicals to ward off insects and other life-threatening attacks. The research confirms what ordinary people of Madagascar have known for decades. This plant contains an ingredient which makes life very hard for the malaria parasite. A wealth of new research is underway: testing for side effects, commercial production of the plant, animal and then human tests for effectiveness, and hopefully, largescale production of a new malaria medication on the island of Madagascar. Photo credit: Philippe Rasoanaivo/Malagasy Institute of Applied Research (IMRA).

The lead author of the study, Dominique Mazier of the Pierre and Marie Curie
University in Paris, France, said if a drug is eventually developed to specifically target the parasite in the liver, this could prove significant in combating drug resistance. "The chances for a resistant parasite to appear are minimal," said Professor Mazier, who also works at the Faculty of Medicine at the University of Pitié-Salpêtrière in France.

A member of the research team, Philippe Rasoanaivo of the Malagasy Institute of Applied Research (IMRA) in Antananarivo, Madagascar, told SciDev.Net that negotiations were underway to conduct the legally-required tests on chimpanzees this year in Gabon, while tests on rhesus monkeys will hopefully be done in Thailand before the end of 2007. Animal tests have to be done before permission can be obtained for tests on human beings. 

Rasoanaivo also has a graduate student investigating two tempting
possibilities: the commercial cultivation of the plant, and creating the
infrastructure to produce the compound on the island itself, rather than
shipping large quantities through the difficult Indian Ocean currents to
become value-added products in the developed world. www.SciDev.Net 

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  Article © and courtesy Scidev.net

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