FRIDAY, SEPTEMBER 30, 2016

Malaria cases down, but remain global health concern

Researchers find key to drug-resistant malaria | Courtesy of wikipedia.org
The World Health Organization’s (WHO) 2014 World Malaria Report released recently identified approximately 198 million malaria cases around the world and said an additional 3.3 billion people are at risk for malaria infections.

Despite these statistics, the figures also show that malaria has been significantly reduced around the world. Since 2010, malaria transmissions have decreased 30 percent and malaria mortality has decreased almost 50 percent.

The most effective malaria treatment is artemisinin, a drug rapidly that rapidly treats Plasmodium falciparum, which causes the most dangerous malaria cases. Artemisinin combination therapies (ACTs) are standard treatment for P. falciparum malaria infections around the world.

Unfortunately, malaria has grown resistant to these treatments within five Southeast Asian countries. The treatments are no longer effective against malaria by the Cambodia-Thailand border, news which is a major threat to worldwide health care.

"There are two phases of blood stage malaria infection,” Kasturi Haldar, director of the Boler-Parseghian Center for Rare and Neglected Diseases, said. “In the first phase, the 'ring' parasite stage circulates in the bloodstream, and in the second phase, the 'mature' parasite stage sequesters in the tissues of the body. Artemisinins are highly effective in treating malaria quickly because they target the first ring stage. When patients take the medication, their fevers reduce quickly, and the parasite is eliminated rapidly."

Alassane Mbengue, a postdoctoral associate in biological sciences and co-first author on the study, said levels of a lipid called phosphatidylinositol-3-phosphate (PI3P) were higher in artemisinin-resistant P. falciparum than artemisinin-sensitive strains.

"This lipid is produced by an enzyme called PfPI3K," she said. "We found that artemisinins block this kinase from producing PI3P lipids. We also discovered that the amount of the kinase present in the parasite is controlled by the gene PfKelch13. Mutation in the gene increases the kinase levels, which in turn increases PI3P lipid levels. The higher the level of PI3P lipids present in the parasite, the greater the level of artemisinin resistance. We also studied the lipid levels in parasites without the gene mutation and observed that when PI3P lipid levels were increased artificially, the parasites still became proportionately resistant."

The researchers' results were especially significant because they studied clinical parasites from Cambodia, where artemisinin resistance is highly prevalent.

The collaborative study included researchers and clinicians in Asia, Europe and the U.S., including members the Boler-Parseghian Center's Department of Chemistry and Biochemistry, Computer Assisted Molecular Design Core, Department of Biological Sciences, and Genomics and Bioinformatics Core.

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Boler-Parseghian Center for Rare and Neglected Diseases Galvin Life Science Building Notre Dame, IN 46556 ,

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