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Largest synthetic gene ever built offers insights into anti-malarial drug resistance

and divides there, and then ruptures liver cells, spewing many new parasites into the blood. A fever results from the infection, and this is followed by repeated cycles of mounting parasitic reproduction within red blood cells and accompanying fever. During red blood cell infection, P. falciparum degrades the hemoglobin in the red cell, producing a toxic byproduct known as heme, which the parasite then crystallizes so that it won't be poisoned by it. Eventually, however, an infected person can die from cerebral hemorrhages or anemia that are consequences of red cell infection.

Natural products such as quinine, extracted from the cinchona tree, and leaves from the artemisinin shrub were the only options available to treat the infection until World War II, when both Germany and the United States started massive drug discovery programs based on the toll the parasite was having on soldiers − more U.S. soldiers died from malaria in the Pacific than from all enemy fire, Roepe said. The Germans first invented chloroquine (CQ), a synthetic version of quinine, which quickly became the treatment of choice because it was inexpensive − now seven cents a dose − and needs no refrigeration. The drug works by preventing heme crystallization, which destroys the parasite by building up toxic levels of non crystalline heme.

But because of the overuse of chloroquine, isolates of P. falciparum from around the globe have developed genetic mutations that make them resistant to that drug as well as other similar agents. Not all mutations found in all resistant isolates are the same, however. Parasites in different geographic regions have developed unique patterns of mutations in the three genes mentioned above. Now, researchers can tell where a drug resistant parasite comes from depending on the varied mutations in the three different resistance genes, Roepe said. "There are patterns of mutations in these genes that can tell you if the parasite came from Africa
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Source:Georgetown University Medical Center


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