On island off Africa, China tries to wipe out malaria

David Lague | 05 Jun 2007
International Herald Tribune
After decades of fighting malaria in a grinding war of attrition, Li Guoqiao and a team of Chinese medical researchers are confident that the world has the weapons to defeat the disease.

But they are convinced that the tactics are flawed.

The veteran physician and researcher, who first treated malaria in the 1960s in rural China, said he believed that potent antimalarial drugs developed in China have the capacity to deliver a decisive blow against the mosquito-borne disease that the World Health Organization estimates kills more than one million people each year, the majority of them young children in Africa.

But, he argues that these drugs, which have been used in China for more than two decades, are not being exploited to their full potential.

"We need to do more than control this disease," Li said in an interview. "My goal is to eliminate it because if you simply try and control it, as soon as you relax your efforts, it will get away again."

To make his point, Li and his team from the Tropical Medicine Institute at the Guangzhou University of Traditional Chinese Medicine propose to take the medical world's last line of defense against malaria, the drug artemisinin, and dispense it in combination with another drug as a mass treatment to the 40,000 people living on Moheli Island, a small island off the east coast of Africa where the disease in endemic.

In the eyes of some scientists and public health experts it is a risky plan. They fear that mass treatments with artemisinin, particularly without associated measures to control the mosquitoes that carry the disease, could hasten the onset of resistance to the world's most effective antimalarial drug.

To lose a medicine that is 95 percent effective in curing malaria would be a terrible blow at a time when the World Health Organization estimates that there are at least 300 million acute cases of malaria each year, the vast majority in sub-Saharan Africa.

"Using artemisinin the way Li wants to use it could increase the prospect of resistance," said Tu Youyou, director of the Artemisinin Research Center at the China Academy of Chinese Medical Sciences in Beijing, and the scientist credited with first extracting the drug from the sweet wormwood bush years ago. "We went through all the trouble to invent this medicine so we should protect it. We should not abuse it."

But Li said that the current practice of repeatedly administering doses of the drug risks making the drug ineffective as well. He argues that the probability of resistance developing is higher in the current situation, where millions of people in areas where the disease is endemic are repeatedly treated with artemisinin-based drugs, some times two or three times each year.

"The current method of treating malaria is not ideal, not efficient or effective," he said. "I want to prove that my method can work very quickly."

If successful, the experiment could become a blueprint for the global eradication of a parasite that has afflicted humans with bouts of violent fever, aches and chills since ancient times.

"It is a new approach that needs to be looked at as a large operational research project," said Andrea Bosman, a medical officer with the World Health Organization's Global Malaria Program. "We are ready to collaborate on the scientific side and other ongoing activity."

In a sign of the increasing Chinese influence in international public health and the Chinese expertise in treating malaria, the World Health Organization has offered to support the Chinese government-funded project. Bosman said the health agency would advise the Chinese team on measures to control mosquitoes and prevent a "bounce back" of malaria once the mass treatments were completed.

As part of growing Chinese aid and investment in Africa, Beijing would pay the estimated $320,000 for the drugs used in the Moheli treatments and would also meet the cost of additional drugs used to clear up remaining infections over a five-year period, according to World Health Organization officials.

Moheli, the smallest of the three major islands that make up the Union of the Comoros, was selected by Li's team for the experiment because of its size, isolation and small population.

People will not be compelled to participate in the program, which is expected to begin in as little as a few months, but with backing from the government and the health agency, plus free treatments, Li's team expects a high percentage of them to take part.

For the authorities in the Comoros, Chinese assistance holds out the hope of a sharp improvement in public health.

"Of course we welcome it because we want to eradicate malaria," Moussa Mohamed, director general of health for Comoros, said in an interview by telephone. "Malaria is a top priority for our health system because it is the major cause of sickness and death."

Mohamed said figures collected last year from the 17 health centers on the islands showed that about 60 people died from the disease in 2006, but mortality was almost certainly much higher because only about 10 percent of the population of 800,000 visited these clinics.

In some areas of Moheli, more than 60 percent of the people were infected with Malaria each year, according to Chinese researchers.

Mohamed said Comoros and the Guangzhou University of Traditional Chinese Medicine had yet to sign a formal agreement, but he hoped the trial would start within three months.

Li, 71, is widely respected for his decades of work with other Chinese scientists in developing and introducing artemisinin-based medicines. The theory behind his proposal is simple.

The human malaria parasite infects only people and female anopheles mosquitoes, which transmit the disease.

If a population is simultaneously treated with artemisinin in combination with piperaquine, another antimalarial drug, and then the treatment is repeated about 40 days later, the parasite would be cleared from their blood for an extended period. This drug combination, which has been proposed for the trial in Moheli, is a new treatment that Li and his colleagues developed.

Because the mosquitoes have a life span of 30 days, Li and his team argue that the incidence of transmission would be dramatically reduced. Any isolated infections that occur after the mass treatments would then be quickly mopped up with additional courses of drugs.

Eventually, they argue, the presence of malaria parasites in the blood of the population could be maintained at a very low level.

The Chinese researchers argue it is the potency of artemisinin-based drugs against all stages of parasite's life cycle in humans that makes their idea workable. "Artemisinin is amazing because it kills all different stages of the parasite, unlike other medicines which only kill the mature stage," said Song Jianping, one of Li's collaborators. "And, it cleans the parasite out very quickly."

Li said the idea for mass treatment drew on decades of experience in China, where earlier antimalarial drugs and then artemisinin had been used in a similar way to effectively eliminate the disease in all but a few isolated areas.

A chief challenge for all health authorities in the battle against malaria is the speed with which the parasite that causes the disease - a single-celled protozoan - can adapt to new drugs.

Since 1945, a series of antimalarial drugs including chloroquine, proguanil, sulfadoxine-pyrimethamine, mefloquine and atovaquone have been introduced only to be followed by the rapid onset of resistance, in some cases within a year of a drug's first use.

Artemisinin has been in use in China for more than two decades and more widely since 2001, when the WHO recommended its use in countries where resistance was undermining the effectiveness of other drugs.

"So far, there is no sign of resistance, but if the drug is used in the wrong way, it could happen very quickly," said Tu, the scientist who first worked with artemisinin.

In an effort to head off resistance and prolong the life of the drug, the World Health Organization last year called on drug makers to end the marketing and sale of medicines containing only artemisinin or derivative compounds. Instead, it recommends that drug makers produce treatments combining artemisinin-type compounds with other antimalarials in what are called artemisinin combination therapies.

"It is the last generation of malaria medicines we have," Bosman said. "Without it, we would have huge morbidity and mortality. For us it is a very precious compound."

Novartis, the Swiss pharmaceutical company, markets the most widely used combination drug, Coartem, which it sells on a nonprofit bases for public-sector use in developing countries. Coartem is approved for sale in Europe but not in the United States because the cost of winning regulatory approval there for the drug outweighs potential revenue from the drug.

Bosman said the treatment that the Chinese team was planning to try on Moheli was one that had the potential to be cheaper and more effective than other combination therapies.

In earlier experimental work in Cambodia, Li and his fellow researchers said, mass treatments with artemisinin yielded very encouraging results in areas with persistently high infection rates.

After two mass treatments in early 2004 of more than 20,000 people in a region of Kompong Speu Province, about 50 kilometers, or 30 miles, from Phnom Penh, the occurrence of disease parasites in the blood of local people had dropped from 57 percent to almost zero within six months, according to data collected by Li and his fellow researchers.

If successful on Moheli, Li said he believed this technique could be systematically extended to other regions where malaria is endemic, particularly in Africa and parts of Southeast Asia, with the ultimate goal of eradication.

"The emphasis is on eliminating the parasite from all of the people at the same time," Li said. "It not only treats the infection. It also blocks transmission."

Li acknowledged that working on a small, isolated island is dramatically different than treating a bigger area on the African mainland where the movement of people, national borders, political instability and conflict could complicate efforts to coordinate a mass treatment campaign.

But, he insisted it can be done. "It is not a technical challenge," he said. "The difficult part is to get people involved down to the lowest level in a village. Good organization is very important."

Lionel Derimais contributed reporting from Beijing.

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