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Gene found that makes malaria resist quinine

WASHINGTON (Reuters) -- A single gene makes the malaria parasite resistant to the preferred drug used to treat it, researchers said Thursday -- a finding that could make it easier to develop drugs to treat the infection.

The discovery could also make it possible to bring back chloroquine -- a cheap and effective drug that has eventually become useless in many regions around the world because of the mutated parasite.

Malaria infects between 300 million and 500 million people worldwide each year and more than a million people -- most of them young children -- die from it each year.

It is caused by a parasite carried by mosquitoes.

The drug chloroquine, based on the same tree-bark compound that is used in quinine, was developed as part of a crash treatment program in the 1940s.

But the parasite gradually developed resistance, and the mutant form has spread to all continents affected by malaria.

"Chloroquine resistance didn't arise until the 1950s," Dr. Thomas Wellems, chief of the malaria genetics section at the National Institute of Allergies and Infectious Disease (NIAID), said in a telephone interview.

"It took a long time. That long time means it was a complicated genetic process." Chloroquine-resistant malaria did not reach Africa until the 1970s, he said.

Scientists thought that must mean that many different genes must be involved, and that chloroquine resistance would be a tough nut to crack.

But Wellems and colleagues found that instead, between four and eight small mutations in a gene known as pfcrt seem to account for chloroquine resistance in parasites from Asia, Africa and South America.

Writing in the Oct. 20 issue of the journal Molecular Cell, Wellems' team said their finding meant it might be possible to rework chloroquine's formula a bit so that it will work against the mutant parasite.

"We know there are certain reversal agents out there that can be administered with chloroquine to give it a new lease on life," Wellems said.

"A good working hypothesis is we can eventually move ahead and alter the drug chloroquine in specific ways and those may be active against specific strains."

The knowledge might make it easier for doctors and researchers to pick out resistant strains in the field, as well, Wellems said.

"The Department of Defense has these hand-held polymerase chain reaction or PCR devices, these fantastic devices that can detect anthrax in the field and so on," Wellems said.

The devices use PCR to quickly grow and identify DNA -- the best way of identifying a strain of bacteria, virus or parasite.

"The same method can be used in drug resistance," Wellems added. "Now with this knowledge and knowing that mutations in this one gene are the core player, we can devise methods to detect chloroquine-resistant strains in the field."

In place of chloroquine, doctors recommend mefloquine, sold in the United States under the brand name Lariam, by Swiss drug maker Roche. But complaints are mounting that Lariam can cause strange psychiatric side-effects such as bizarre dreams and sleep disturbances.

Copyright 2000 Reuters. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

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NIAID-Supported Malaria Activities
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