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Sometimes a small twist of fate can change the direction of research in remarkable ways. For the Wellcome Trust team based in Mahidol University in Bangkok, this twist occurred in 1979. While studying severe malaria in Chantaburi, eastern Thailand, Professors David Warrell and Nick White received a dog-eared copy of a paper from the Chinese Medical Journal.
Contained in five quaintly written pages was the first English version of antimalarial trials using the extract of a traditional herb, qinghao. Professor White admits the article was so startling that it left him "gobsmacked" and convinced him that here was a powerful weapon to use in the fight against malaria.
The astonishing powers of qinghao had in fact been harnessed by a team of young scientists during Chairman Mao's Cultural Revolution in China. This group of researchers had been spared hard labour in the fields, the fate of many academics at that time, as long as they found a cure for malaria.
Dutifully they worked their way through a list of medicinal herbs until they came to the qinghao plant, whose dried leaves, infused in hot water, had been used as fever remedy for 2000 years. They extracted the compound qinghaosu (now termed artemisinin) from this and within eight years had tested it in vitro, on rodents and humans and pronounced it ready to hit the streets.
Two years after reading the article, Professors Warrell and White travelled to Guangzhou to meet Professor Li Guo Qiao, one of Chairman Mao's team, who worked in the Qinghaosu Anti-Malaria Coordinating Research Group. When they left they were handed the ultimate farewell present – a bottle of the powdered compound.
The Wellcome Trust team was prepared to begin tests immediately, but they were held in the starting blocks by some Western health officials who wanted to produce their own version of the drug.
By the late 1980s, with no sign of any real progress being made, Professor White began to obtain qinghaosu tablets and injections from China. Drug-resistant malaria was the major health problem affecting thousands of refugees from Burma who were camped along the border with Thailand. Based in the Wellcome Trust South-east Asia unit, Dr François Nosten and Professor Nick White had documented an alarming decline in the effectiveness of mefloquine in this population, and so turned to the artemisinin compounds in combination with the failing drug.
The 'two-punch' combination of drugs works beautifully because the artemisinin explodes into action, attacking the parasites ferociously before quickly evacuating the body, so allowing no time for resistance to build. The second wave of mefloquine wipes up any remaining parasitic stragglers.
Before these combination drugs were used in the camps, there was, on average, one case of malaria per person per year. Now this is down to one in ten per year and there are no signs of resistance from the parasite; indeed, the parasites isolated today are more sensitive than they were seven years ago.
With the backing of a US$4.7 million grant from the Bill and Melinda Gates Foundation, the Communicable Disease Control Department of the Thai Ministry of Public Health and the Faculty of Tropical Medicine, Mahidol University, are now extending this new control strategy throughout Tak province in north-western Thailand.
Before the project started Tak was the most malaria-affected province in the country; within two years it has already fallen to fifth. Professor White feels that inexpensive artesunate combination drugs should be introduced in sub-Saharan Africa as soon as possible. Chloroquine is still the front-line drug in most African countries, but it appears well beyond its sell-by date as parasite resistance to the drug is rife.
Cost may be the prohibitive factor in some cases where cash-starved governments might baulk at paying £1.25 for a combination drug when they have become accustomed to paying somewhere in the region of 5p for chloroquine.
But whatever the reason Professor White believes we must not pass up another opportunity to make significant inroads in the fight against malaria: "We haven't done well in this field for the past 30 years," he says. "There has been a culture of not succeeding and not changing. People don't realise that there is not an endless timescale for this.
"We're losing effective drugs very quickly. There will always be pressure on the parasite to evolve and resist the chemicals designed to fight them. We're never going to beat evolution – all we can do is slow the rate."
Professor Nick White is Director of the Wellcome Trust's South-east Asia Unit, which is based in the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Page of 2; 2/9/04
[WTD023861] Developing artemisinin.doc