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Rubrik: Science Life

Monday was World Malaria Day: ETH researchers are focussing on this tropical disease
Sweet Hope

Published: 28.04.2005 06:00
Modified: 27.04.2005 21:28
Malaria, the most common tropical disease in the world, continues its relentless advance, reports a group of scientists in the magazine Nature. Researchers at the ETH Zurich have also taken up the fight against this scourge. Among other things, they are trying to combatthe disease’s transmitter, and to develop a new generation of vaccines against the virus responsible for the disease.

By Michael Breu

Malaria has become the biggest killer among tropical diseases. Over 300 million people worldwide fall victim to ‘marsh fever’, every third person becomes clinically infected, and two to three million are killed by it – every year. Infection with the deadliest of the malarial parasites, Plasmodium falciparum, is fatal in 30 percent of cases. Tropical malaria continues unremittingly to gain ground. This is the conclusion reached by Robert W. Snow and his research team at the Centre for Tropical Medicine at Oxford University in England. Snow and his colleagues have taken a close look at data from the World Health Organisation (WHO) for 2002 and demonstrated that the rate of infection lies between 50 and 200 per cent higher than WHO's own estimates. Their findings are published in Nature (1) .

Drugs too expensive

While drugs to treat malaria such as chloroquine, meflaquine, quinine and relatively recent artemisinin derivatives are available on the market, they are too expensive for the people of the affected regions in Africa. Moreover, drug resistant strains of malaria are rapidly increasing. This is why intense research efforts are underway to find vaccines: 18 of these are currently undergoing clinical trials. What they all have in common, however, is that they target the protein in the cell membrane of the plasmodes, and are therefore selective and only effective for a certain strain.

Sugar from the conveyer belt: Professor of chemistry Peter Seeberger and his team use this appliance to produce sugar molecules.

Three years ago, Louis Schofield and Peter H. Seeberger (2) decided on a different tack. Schofield, from the Royal Melbourne Hospital in Australia, and Seeberger, at that time chemistry professor at MIT and now at the ETH Zurich, published their first report on the synthetically produced malaria toxin GPI in Nature (3) . Glycolipids – sugar-fat compounds – occur on the cell membrane surface of the plasmodial cells and are responsible for the toxic effect. The principle idea: if this toxic effect could be blocked, an ideal malaria vaccine would have been discovered.

Bacillus thuringiensis: in the service of the battle against malaria.

Vectobac means hope: this medicine is being used in East Africa, in the highlands around Lake Victoria, to combat the larvae of the genus anopheles.

In the meantime Peter Seeberger and his team have moved a step nearer to achieving this goal. The first stage was reached in 2001 when the team successfully developed an apparatus capable of producing sugar molecules – quickly, simply and cheaply (4) . Recently they had a further success, reporting in the specialist journal Chemistry & Biology four months ago how communication between the virus and body cells can be observed (5) .

Bt-toxins vs malaria

Peter Lüthy, ETH Professor Emeritus, is working on a way to fight malaria in another field (6) . Since the early 1980s he has been investigating at the ETH Institute of Microbiology the effectiveness of Bt-toxins (or, properly speaking, cry-toxins) as biological pest controls. Starting in 1987 Lüthy used Bacillus thuringiensis israelensis (Bti) to effectively combat the larvae of the mosquito Aedes vexans in the plains of the Magadino region. The variety israelensis is named after the place where it was by chance discovered, in the arid Negev region of southern Israel.

All the fundamental research and animal experiments have shown that Bacillus thuringiensis products comply with safety regulations and do not affect the environment. Since autumn 2004, Lüthy has been investigating in the highlands above Lake Victoria in East Africa how, with the help of Bti products stagnant-water-breeding anopheles larvae – the transmitters of malaria – can be killed selectively and efficiently. Following successful trials the scientists have now extended their treatment to larger areas.

Swiss support for research

The project is co-ordinated with scientists at the International Center for Insect Physiology and Ecology (ICIPE) in Nairobi, Kenya. The Swiss Agency for Development and Co-operation (Deza) and the private foundation BioVision (7) provide financial support.

The use of Vectobac – as the commercially available product is called – is only one step in Lüthy's work. Equally important for him is the transfer of know-how and information to the local population concerning how and under what conditions larvae develop into mosquitoes. "In the area covered by the project hundreds of stagnant ponds offer ideal breeding grounds for anopheles larvae. These ponds are the result of loam cutting to make bricks," says Lüthy.

The microbiologist is fully aware that the use of Bacillus thuringiensis can only ever be a small – though important – part of our fight against malaria. "We can only achieve success if all available methods are taken into account and integrated. These range from environmental measures through bednets treated with insecticide all the way to drugs and vaccines," says Lüthy. "Education and information are a very important part of malaria programmes. Children must learn about malaria at school and take the information back home. The population must help in the reduction of breeding grounds. For actual combat measures, which will be supported by GPS and GIS positioning systems, people with a basic knowledge in natural sciences must be employed,“ says the specialist. "If the current Bti treatment continues to be successful, it is be a method that could be extended, with the necessary modifications, to other afflicted regions."

According to preliminary calculations, the cost of Bti treatment is low. A price of one Swiss franc per 1,000–2,000 square metres of treated water surface is modest when compared to the benefits that can be achieved. Nor should a vaccine cost a king's ransom: Peter Seeberger hopes that a dose will cost less than five dollars. Peter Lüthy, however, thinks that it is simply an integrated, functioning fight against malaria that should receive priority. Faced with the immense human suffering caused by this scourge, the cost of finding an effective way to combat it should take a back seat during the experimental phase.

Roll Back Malaria

(mib) "Roll back Malaria“ is an initiative launched in 1998 by two organs of the United Nations, the World Health Organisation and Unicef (8) . A number of events are currently taking place aimed at raising the awareness of people in wealthy countries to the problems of the tropics. The World Malaria Day, or African Malaria Day, on 25th April was an important marker.

(1 The global distribution of clinical episodes of Plasmodium falciparum malaria, Nature, 2005, 434: 214-217. Cf. also the World Health Organisation: (
(2 Peter H. Seeberger and his team: (
(3 Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria, Nature, 2002, 418: 785-789
(4 Automated Solid-Phase Synthesis of Oligosaccharides, Science, 2001, 291: 1523-1527. Cf. also "Vaccines By Automated Synthesis“, Chemical & Engineering News, 2002, 80(3): 43-44 and "Carbohydrate Vaccines“, Chemical & Engineering News, 2004, 82(32): 31-35
(5 The Use of Carbohydrate Microarrays to Study Carbohydrate-Cell Interactions and to Detect Pathogens, Chemistry & Biology, 2004, 11: 1701-1707. Also under the title of "Sweet hope" ETH Life reported on the research on 21st December 2004: (
(6 Peter Lüthy and his team: (
(7 BioVision Foundation: (
(8 Roll Back Malaria: (

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