Drug abuse

Can render ineffective the only antimalarial medicine against Plasmodium falci

By Vibha Varshney
Published: Sunday 15 January 2006

P falciarum   is watching keen artemisinin is the only drug available right now against Plasmodium falciparum, one of the malaria-causing pathogens. But its indiscriminate use may make the drug ineffectual, warns a study published in The Lancet (Vol 366, No 9501, December 3, 2005).

Though the World Health Organization (who) recommends that artemisinin should be used in combination with other antimalarial drugs, it is being used as a monotherapy in many parts of the world. This could make P falciparum, which affects the brain, acquire drug resistance. A combination therapy ensures that all pathogens in the body are killed during treatment.

The study was conducted by researchers from units of Paris-based Institut Pasteur in different countries. They investigated the in vitro susceptibility of 530 P falciparum samples taken from malaria patients in Cambodia, French Guiana and Senegal.

These countries were chosen because they have different patterns of artemisinin use. In Cambodia, mefloquine, an antimalarial drug, is used in combination with artemisinin; in French Guiana, halofantrine, another antimalarial, is the first-line treatment and artemisinin is used although not registered; and, in Senegal, the recommended first-line treatment is chloroquine but artemisinin monotherapy is also registered.

The scientists found that all drug-resistant cases came from areas with uncontrolled use of artemisinin. The pathogen from Cambodia, where artemisinin combination therapy is used, was sensitive but the samples from Senegal and French Guiana showed drug resistance. In French Guiana, two resistant samples originated from Cacao, a small town where artemisinin derivatives illegally imported from Southeast Asia were being used. The other resistant samples came from the gold mining region along the Maroni river, where self-medication is common. In Senegal, monotherapy is common in the private sector. The researchers also found that the loss of sensitivity was linked to mutations in the gene, serca -type pfatp ase6, which is thought to be targeted by artemisinin.

The researchers feel the pathogen's reduced susceptibility to drugs could be the first indication of a probable resistance. "This rise in resistance indicates the need for increased vigilance and a coordinated and rapid deployment of drug combinations," write the researchers led by Ronan Jambou from Institut Pasteur, Senegal.

The study is significant for India, which recently decided to change its policy and adopt a combination therapy, at least in areas where falciparum malaria has been seen. Studies by the National Institute of Malaria Research have shown high treatment failure for chloroquine in 44 districts of 18 states, where a revised drug policy would be followed as per the National Vector Borne Disease Control Programme. The drugs used will be sulfadoxine pyremethamine (sp) and artemisinin.

A survey carried out in Assam in 2001 by Mdicins sans Frontires (msf), an international non-profit organisation, showed that more than 70 per cent of malaria cases were resistant to chloroquine. who recommends that when 17 per cent of malaria cases show resistance to chloroquine, artemisinin should be used. When msf used artemisinin together with mefloquine or sp, the cure rate increased to more than 90 per cent. Assam reports about 180,000 cases of malaria every year. "If the prescription of artemisinin is unregulated, then monotherapy is likely. We have already observed that in Assam. This will accelerate the development of resistance in India, threatening access of future generations to malaria treatment," says Neeti Ghanekar from msf, Delhi.

The key to effective use of artemisinin lies in quick diagnosis of drug-resistant malaria. The standard practice is that health workers give chloroquine to all patients at the time of collecting blood samples. While this does take care of initial symptoms, a relapse occurs if the pathogen does not respond.

To get around the problem of monotherapy, the Drugs for Neglected Diseases Initiative, an international ngo, is developing fixed-dose, artemisinin-based combination drugs. This approach would also cut treatment costs by half.

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