Risk of resistance against artemisinin-based anti-malaria drugs, a new study

Malaria parasites in western Cambodia are opposed to therapies based on artemisinin, the first line treatment of malaria, according to a study in the New England Journal of Medicine today. Resistance against drugs, it is less effective and could make obsolete the millions of people in danger.

Signs of artemisinin resistance have already been in the region, but this new research is the first detailed study on the problem. The study was conducted by the Wellcome Trust, Li Ka Shing Foundation and the Global Malaria Program of the World Health Organization (in the form of grants from the Bill and Melinda Gates Foundation and the Western Pacific Regional Office) .

Malaria is a potentially fatal disease, kills more than one million people every year, especially young children and pregnant women. It is caused by malaria parasites, the injection in the blood of infected mosquitoes. The most fatal form, Plasmodium falciparum, is responsible for nine of the ten deaths from malaria.

The most effective anti-malarial drug artemisinin in Artemisia annua, also known as sweet vermouth, was used in Chinese medicine for centuries as Qinghaosu. He was still in the 1970s, ranked first in Southeast Asia, and finally as an essential element of drug treatment of malaria in recent years. The artemisinin derivatives have the advantage, compared with other anti-malaria drugs such as chloroquine and mefloquine, a few side effects, and - so far - of malaria parasites have not resistance against it.

Although the drug - most often in the form of artesunate products - could be used on their own as monotherapy, fears concerning the possibility of development of resistance means that, in general, in conjunction with a or more other drugs such as artemisinin combination therapies (ACTS), currently by WHO as first line treatment of falciparum malaria endemic simple in all countries.

After increasing reports that the effectiveness of combination therapies of artemisinin monotherapy and decreased in western Cambodia, researchers, the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Program, headquartered in Bangkok, studies of the vulnerability of P. falciparum parasite on drugs. The research program is a collaboration between Mahidol University, Bangkok, and the University of Oxford, supported by the Wellcome Trust.

The researchers studied forty patients in the Pailin, western Cambodia, and Wang Pha, north-western Thailand. Opened in two randomized studies, each summer with the dose, the weight of their bodies either artesunate or a combination of artesunate and mefloquine.

On average, patients in Thailand was free of parasites at 48 hours, west of Cambodia 84 hours - in other words, it took almost twice as long for the parasites in Cambodia as Thailand.

During treatment, as the number of parasites in the blood decreases, so that infection, it should be clear. Repetition may be a sign that the medication does not work effectively.

In this study, twenty patients with monotherapy in different countries, there was a recurrence of the infection in six patients in the west of Cambodia in relation to one person in Thailand. Of the twenty patients with the combination treatment, the infection in two patients in Cambodia compared to one in Thailand. These results suggest that artemisinin has been less effective on pests of Cambodia.

"Our study suggests that the malaria parasite in Cambodia are less susceptible to artemisinin as in Thailand," says Arjen Dondorp, lead-author of the study. "This means that it takes longer for the parasite. Artemisinin is clear parasites at an early stage, which further maturation and reproduction. If the action of drugs, it is increasingly difficult for parasites body.

"With artesunate lose their effectiveness, ACTS is much lower on the partners of drug, the risk that the resistance is also a partner of drugs. This has very important consequences for the life of ACTS. ACTES loss would be a disaster for the fight against malaria. "

Based drugs artemisinin have been on mission in western Cambodia near thirty years, and the country was one of the first acts for 2001. However, the majority of patients in the region obtain their drugs in the private sector, the least regulated. Patients in the private sector are often incomplete or monotherapy with courses of treatment. There is also the problem of under-or fake medicines with subclinical doses of artemisinin. This long period of sub-optimal drug artemisinin-based have contributed to the emergence of resistance.

If signs of artemisinin resistance, which in other areas of Cambodia and Thailand, said Dr. Dondorp for rapid action is necessary to ensure propagation.

"Preventing the spread of resistant parasites if it is of crucial importance," he says. "The use of combination therapy is very important for that. I hope that the prohibition of artesunate monotherapy, except for special cases."

Professor Nick White, co-author of the study and chairman of the Wellcome Trust South-East Asia program, said the impact of the results are potentially enormous.

"Artemisinin are weapons in our fight against malaria," he said. "If they were, we have no immediate replacement. The consequences could be devastating. Elimination of malaria will not be possible, and millions of lives could be lost. "