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Scientists Seek Genes Responsible for Drug Resistance To Aid Development of Better Malaria Drugs

Image of malaria parasite.
Pictured is an artist’s rendering of different life-cycle stages of the Plasmodium falciparum malaria parasite (middle and left columns). A ‘heatmap’ (right column) shows the results of a protein microarray experiment in which antibodies in the serum of P. falciparum-exposed individuals bind to hundreds of P. falciparum proteins.
Credit: NIAID

To determine how malaria parasites evolved resistance to chloroquine and other major antimalarial drugs, Thomas E. Wellems, M.D., Ph.D., Chief, Laboratory Malaria and Vector Research (LMVR), and his colleagues use genetic strategies to find the important factors that are involved. Data from their studies help scientists identify which parasites carry drug-resistance genes, how new diagnostic methods might be devised to locate regions in which malaria-resistant strains are emerging, and how existing drugs might be modified or new drugs developed against these resistant strains.

Recently, a team led by Dr. Wellems identified a new pathway used by malaria parasites to invade red blood cells. In examining why only some Plasmodium falciparum strains infected Aotus monkeys—an important animal model of malaria for vaccine and drug development—the team found variations in a previously uncharacterized parasite protein called PfRH5, which also binds to human red blood cells. In Aotus monkey infections, changes in the amino acids in PfRH5 rendered virulent malaria infections non-virulent, and vice versa. Future studies will compare in detail the differences in infection of human and Aotus cells.

In other work, an NIAID team studies the most drug-resistant form of malaria, which exists along the border of Cambodia and Thailand. Prolonged parasite clearance times after treatment with artemisinin have recently been documented in the region. Generally, when it takes longer than 48 to 72 hours after artemisinin treatment to clear the parasite, it is likely that the parasite is developing resistance to the drug.

Researchers do not yet know why clearance times have become prolonged there. That is why LMVR scientists want to determine whether resistance has developed and focus their research on the genetic reasons for the parasite’s resistance. Once they understand whether and how the parasite has developed drug resistance, scientists might then be able to design a new generation of drugs or new drug combinations to get rid of the parasite.

Dr. Wellems' Lab

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Last Updated April 23, 2009