Breakthrough discovery on why the malaria parasite has become resistant to chloroquine

Scientists at the Liverpool School of Tropical Medicine have made a major breakthrough in discovering why the malaria parasite Plasmodium Falciparum, deposited in humans by the mosquito, has become resistant to chloroquine, one of the most successful drugs ever used to treat the disease.

Their discovery, described as "a big piece in the jigsaw puzzle" paves the way for the creation of new drugs to save the lives of millions of people still infected with malaria every year, many of them children under five in sub-Saharan Africa.

Once in the body, the malaria parasite multiplies and invades the red blood cells. A concentration of high levels of chloroquine can kill the parasites living in the cells. But the research of Professor Steve Ward and Dr Pat Bray, of the Liverpool School of Tropical Medicine, working with Dr David Fidock at the Albert Einstein College of Medicine in New York, has shown how a protein called PfCRT inside the parasite has enabled it to become resistant to important antimalarial drugs by creating a ‘back door’ and actually moving the drugs out of the parasite by leakage. They believe that PfCRT may be a ‘master’ gene that controls the parasite's resistance to a variety of antimalarial drugs.

Malaria death rates have been rising in recent years, partly due to the parasite's resistance to widely used drugs like chloroquine so insights into the resistance mechanism are urgently needed.

Said Professor Ward whose research paper is featured in the scientific journal Molecular Cell on Friday 24th September, 2004: “While other drugs are available, most are much more expensive than chloroquine, putting them out of the reach of health care workers in developing countries. This research will eventually help us to develop new drugs, based on a modified structure of chloroquine, that cannot be got rid of through this ‘back door’, thereby eliminating the parasites' resistance to existing drugs. Whatever drug we come up with will have to be cheap as well as effective. But this is a big piece in the jig saw puzzle.“

Dr Ward and his colleagues have recently been involved in a collaboration with Professor Peter Winstanley's team at the University of Liverpool to produce an exciting new antimalarial drug called Lapdap which has been found to be effective when other antimalarials have failed because of resistance.

http://www.liv.ac.uk

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