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Increasing Parasite Resistance Hinders Malaria Treatment - 2003-08-23


Malaria was largely eliminated in the industrialized nations half a century ago. But in the developing world this quickly evolving menace still kills millions each year and sickens hundreds of millions more. In this third report in our series, Mike Osborne looks at the parasite's growing resistance to every known anti-malarial medication.

Wes Van Voorhis, a veteran medical researcher at the University of Washington, specializing in the study of malaria, is also the founder of a Seattle medical clinic that treats tropical diseases exclusively. But Dr. Voorhis's experience and skill were put to the test by a patient recently back from a family trip to Thailand.

"We had a young nine-year-old boy who we treated for malaria seven times until we were finally able to get a cure," he recalled. "We were really kind of riding by the seat of our pants because he had an incredibly resistant malaria strain from the northern Thailand area. He was getting sicker and sicker and finally by combining a whole bunch of drugs in sort of an experimental manner we were able to cure him."

Sadly, that young patient's narrow escape is becoming the rule, not the exception. several strains of the malaria parasite are resistant if not immune to every known medication. According to National Institutes of Health researcher Thomas Wellems, chloroquin, the oldest synthetic anti-malarial drug, provides a telling example.

"For fifteen years after its discovery and its implementation there was really no resistance against chloroquin," he explained. "And then in the late 1950s and early 1960s some chloroquin resistance started to emerge in Southeast Asia and South America. And then spread gradually, village by village, and country by country in a slow and steady march and by the late 1970s began to enter Africa. So you see what was once a very effective drug, about fifty years later had become much less effective."

The trend seems to be accelerating. More recently created drugs have lost effectiveness in half the time it took for chloroquin resistance to develop. The most common reason for this is drug misuse. Poor patients can't always afford a full course of medication and so will buy just a few pills on the black market. The hardiest malaria parasites survive this partial treatment and are then transmitted to new victims. But Dyann Wirth, director of the Harvard University Malaria Initiative, explains that new technology and recent advances in genetics offer some hope this trend can be reversed.

"One of the very exciting things that's happened over the past couple of years is that the genome of the plasmodium valcipirum parasite has been completely sequenced," she said. "In addition the genome of the mosquito vector the insect that carries the parasite has also been sequenced. And of course as many of you know, the human genome is now available."

Just as importantly, the technology used to read these genetic blueprints has gotten cheaper and faster, allowing researchers like Dr. Wirth to quickly detect even the smallest genetic adaptations.

"So through this technology we are actually able to search out among the entire 24 million base pairs of the parasite those changes which are specifically associated with acquisition of resistance to drug, and in this way one very rapidly is able to determine, using this genetic approach whether or not a parasite is sensitive or resistant to drug," she said.

This timely and detailed information allows researchers to design new drugs that target vulnerable points in the malaria parasite's genetic structure. The same approach may also be used to breathe new life into existing medications. Dr. Thomas Wellem's team at NIH has discovered a genetic adaptation that allows the malaria parasite to recognize chloroquin and literally excrete it back out again, preventing enough of the drug from accumulating in the parasite to kill it.

"With that fundamental information we're now beginning to see that there are new ways in which the chloroquin molecule can be changed or altered so that it can once again be effective against the resistant forms of malaria," he said.

Happily, for patients like the Seattle boy who contracted a nasty strain of malaria in Thailand, several new anti-malarial drugs and modified older medications are on the horizon. In the fourth report of our series on malaria we'll look at several of the more promising treatments.