After years of hesitation, world health agencies are racing to acquire 100 million doses of a Chinese herbal drug that has proved strikingly effective against malaria, one of the leading killers of the poor.
The drug, artemisinin (pronounced are-TEM-is-in-in), is a compound based on qinghaosu, or sweet wormwood. First isolated in 1965 by Chinese military researchers, it cut the death rate by 97 percent in a malaria epidemic in Vietnam in the early 1990's.
It is rapidly replacing quinine derivatives and later drugs against which the disease has evolved into resistant strains.
To protect artemisinin from the same fate, it will be given as part of multidrug cocktails.
Until recently, big donors like the United States and Britain had opposed its use on a wide scale, saying it was too expensive, had not been tested enough on children and was not needed in areas where other malaria drugs still worked.
Unicef, the United Nations Children's Fund, which procures drugs for the world's poorest countries, opposed its use during an Ethiopian epidemic last year, saying that there was too little supply and that switching drugs in mid-outbreak would cause confusion.
But now almost all donors, Unicef and the World Bank have embraced the drug. The new Global Fund for AIDS, Tuberculosis and Malaria has given 11 countries grants to buy artemisinin and has instructed 34 others to drop requests for two older drugs chloroquine and sulfadoxine-pyrimethamine and switch to the new one.
We want countries to move very rapidly to use it as a first-line treatment, said Dr. Vinand Nantulya, the fund's malaria adviser. The fund expects to spend 450 million on the drug over the next five years, he said.
The World Health Organization, a United Nations agency based in Geneva, estimates that 100 million doses will be needed by late 2005.
Malaria causes about 300 million illnesses a year, and at least 1 million deaths, 90 percent of them in Africa and most of them children under 5. Despite more than a century of eradication efforts, the disease is endemic from the Mekong Delta in Vietnam to the Amazon Basin in Brazil, and is particularly severe across central Africa, from the cane fields of Mozambique to the oases of Somalia to the rubber plantations of Liberia.
Like many tropical disease drugs, artemisinin is a fruit of military research. Chinese scientists first isolated it in 1965 while seeking a new antimalarial treatment for Vietnamese troops fighting American forces, said Dr. Nelson Tan, medical director of Holley Pharmaceuticals, which makes the drug in Chongqing, China.
Another antimalarial drug still in use, mefloquine, was isolated at the Walter Reed Army Institute of Research in 1963 for American troops in the same jungles. Under the name Lariam, it is still issued to troops and sold to travelers.
Artemisinin, which has no significant side effects, quickly reduces fevers and rapidly lowers blood-parasite levels, which can keep small outbreaks in mosquito-infested areas from becoming epidemics.
Two years ago, Dr. Dennis Carroll, a health adviser to the United States Agency for International Development, said artemisinin was not ready for prime time. But on April 30 at a malaria conference at the Columbia University School of Public Health, he led a session on ways to induce farmers to plant more wormwood.
Dr. Carroll said that more evidence had emerged that the drug was safe and that older drugs were not working. Also, the creation of the Global Fund expedited grants for it.
Dr. Stewart Tyson, a health expert with the British Department for International Development, said his agency changed its opinion about the drug after its experience in Uganda, where resistance to older drugs had climbed to 31 percent in some areas in 2003 from 6 percent in 2000.
The price of artemisinin cocktails has fallen from 2 per treatment to 90 cents or less as more companies in China, India and Vietnam have begun making them. (Older drugs cost only 20 cents.) Novartis, the Swiss drug giant, sells its artemisinin-lumefantrine mix, Coartem, to poor countries for 10 cents less than it costs to make, a company official said. The same drug, under the name Riamet, is sold to European travelers for about 20.
As a plant material, artemisinin cannot be patented, said Dr. Allan Schapira, a policy specialist for the Roll Back Malaria campaign of the World Health Organization. Nor can the simple extraction process. Some synthetics, he said, are old and off patent, which public health officials like but pharmaceutical companies do not, because they make a larger profit from drugs on which they have patent monopolies.
No company has registered artemisinin in the United States, said Dr. Nick White, a professor of tropical medicine at Mahidol University in Thailand, because sales would be too small to justify the cost of seeking approval from the Food and Drug Administration.
Now, with more purchases, fears of a shortage that would push prices up are developing. The W.H.O. estimates that 100 million doses will be needed by late 2005, and the world now has only about a third of that.
Though it grows wild even in the United States, wormwood is cultivated only in China, Vietnam and pilot projects in Tanzania and India. It is planted in December and needs eight months to mature. Drug companies want firm orders from donors before they try to triple production.
Dr. Tan said he had seed banks ready to plant 62,000 acres, but we need to pay farmers to give up other crops and arrange for fertilizer.
Time is against us, he said.
Even if enough artemisinin can be made, obstacles will arise, experts warned. For example, Dr. Kopano Mukelabai, a malaria specialist at Unicef, said shopkeepers would have to be trained not to sell one or two pills to patients who lacked the money for a full course of 12.
And what Richard Allan, director of the Mentor Initiative, a public health group that fights malaria epidemics, called the love of chloroquine will have to be broken. That quinine derivative, in use since the 1950's, is now almost useless against parasites, but poor people still buy it because it is cheap and lowers fever as aspirin does.
Also, counterfeiting will become a problem. In Kenya in 1997, Mr. Allan said, he found 120 versions of sulfadoxine-pyrimethamine for sale, ranging from very good drugs to talcum powder. A recent study of artemisinin drugs in Asia found that 38 percent were fakes, he said. We can expect the same thing to happen in Africa.
He favors giving artemisinin away to remove the counterfeiters' profit
motive. (Source: Donald G. McNeil Jr, NY Times, May 10, 2004)