Discovering Keys to Controlling Malaria

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“These analyses will provide valuable knowledge regarding genes potentially involved in the mechanisms underlying drug resistance and the biological mechanisms of red blood cell invasion.”

Serre investigates genetic diversity as key to drug resistance of Plasmodium vivax

Malaria affected 219 million people around the globe in 2010, according to the World Health Organization. This life-threatening disease, caused by plasmodium parasites that are transmitted to people through the bites of infected mosquitoes, killed about 660,000 people in 2010 – mostly African children under the age of five.

David Serre, assistant staff, Genomic Medical Institute, Cleveland Clinic, is doing his part to understand how the genetic diversity of one particular parasite species, Plasmodium vivax, enables the species to develop resistance to treatment drugs. P. vivax is the most frequent cause of recurring malaria and can lead to severe disease and sometimes death.

“We know that the parasites’ genetic diversity affects their ability to resist eradication and acquire and develop new strategies for invasion,” Serre said. “However, little research has been done to understand the genetic diversity of P. vivax, in part because it cannot be propagated in continuous in vitro culture. This limits our understanding of the parasite’s biology.”

As an alternative to studying P. vivax in vitro, Serre and his colleagues used high-throughput sequencing to analyze the entire genomes of five P. vivax isolates. They were collected from the monkey-adapted Belem strain and from blood samples of infected patients in Madagascar, where P. vivax has invaded a population previously thought to be protected against this parasite, and Cambodia, where drug resistance is a growing problem. 

Their results identified more than 80,000 Single Nucleotide Polymorphisms, or DNA sequence variations, distributed throughout the genome, and revealed that each patient was infected with multiple P. vivax strains. 

With these enormous data sets in hand, Serre and his colleagues now are using the Ohio Supercomputer Center to conduct rigorous population genetic analyses to better understand the history and organization of the P. vivax population. These studies notably include searching the genome for patterns of genetic diversity consistent with the effects of natural selection and identifying the genetic basis of disease-related traits by association.

“These analyses will provide valuable knowledge regarding genes potentially involved in the mechanisms underlying drug resistance and the biological mechanisms of red blood cell invasion,” Serre said. “Ultimately, the results from this effort will provide crucial information for understanding the spread of drug resistance phenotypes and help design more efficient malaria control programs.”

Project Lead: David Serre, Assistant Staff, Genomic Medical Institute, Cleveland Clinic

Research Title: Investigation of the diversity, population and evolutionary history of Plasmodium vivax

Funding Source: National Institute for Allergy and Infectious Diseases (NIAID – NIH)

Website: http://bit.ly/GSq61Y