Genomic warfare to counter malaria drug resistance

Scientists battling malaria have earned a major victory. According to a Nature Genetics study, an international group of researchers has used genomics to decode the blueprint of Plasmodium falciparum – a strain of malaria most resistant to drugs that causes the most deaths around the world. The discovery may lead to advanced pharmaceuticals to fight the disease and prevent drug resistance among the 250 million people infected by malaria each year.

“Combating malaria resistance is nothing short of an arms race,” says lead author Dr. Philip Awadalla, a pediatrics professor at the Université de Montréal, a scientist at the Sainte-Justine University Hospital Research Center and scientific director of CARTaGENE. “As the malaria pathogen evolves, researchers must evolve with it to find ways to counter the disease.”

The team decoded 200 malaria samples from Asia, Africa, Central America, South America and Papua New Guinea. Their goal was to identify how Plasmodium falciparum strains were becoming resistant to the eight anti-malaria drugs currently available.

“There are substantial genetic differences in malaria around the world,” stresses Dr. Awadalla, noting African strains differ from Asia strains. “What has occurred is a combination of genetic drift, where genes segregated over space and time from differential environments, immune pressures and exposures to drugs.”

As part of their genomic mapping, the research team found that Plasmodium falciparum recombined fastest in Africa. Dr. Awadalla compares malaria genomes to human genomes. In malaria, however, variation among some genetic material is so high and evolves so rapidly that the parasite can develop drug resistance.

New clues garnered by this study, he says, “will allow pharmaceutical companies to create treatments that target the evolving malaria genome.”

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Study collaborators included researchers from the University of Calgary in Canada, the National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories and Pennsylvania State University in the United States, the University of Oxford in England, Mahidol University in Thailand, the Guangzhou University of Chinese Medicine in China and the National Centre for Parasitology, Entomology and Malaria Control in Cambodia.

About malaria:
Malaria is transmitted when people are bitten by infected mosquitoes. According to the World Health Organization, malaria symptoms include fever, headaches, vomiting and appear within 10 to 15 days after an infected mosquito bite. Left untreated, malaria can be life-threatening and kills an estimated five million people yearly.

About the study:
The article “Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs,” published in the journal Nature, was coauthored by Philip Awadalla and Rachel A. Myers, of the Université de Montréal and its affiliated Sainte-Justine University Hospital Research Center (Canada); May Ho of the University of Calgary (Canada); Jianbing Mu, Hongying Jiang, Thomas E. Wellems, Rick M. Fairhurst, Xin-zhuan Su, Michael Waisberg and Shengfa Liu of the National Institute of Allergy and Infectious Diseases (U.S.A.); Stacy Ricklefs, Daniel E. Sturdevant, Stephen F. Porcella of Rocky Mountain Laboratories, (U.S.A.); Liwang Cui of Pennsylvania State University (U.S.A.); Nicholas J. White of the University of Oxford (United Kingdom); Kesinee Chotivanich, Polrat Wilairatana, Srivicha Krudsood and Rachanee Udomsangpetch of Mahidol University (Thailand); Fengzhen Ou, Haibo Li, Jianping Song, Guoqiao Li, Xinhua Wang, Guangzhou University of Chinese Medicine (China); Suon Seila, Sreng Sokunthea and Duong Socheat of the National Centre for Parasitology, Entomology and Malaria Control (Cambodia).

Partners in Research:
This study was funded by the National Institute of Allergy and Infectious Diseases (U.S.A.), the Canadian Institutes of Health Research (Canada), the National Academies Keck Futures Initiative (U.S.A.), the Human Frontiers in Science Program (France), the Wellcome Trust (U.K.) and the National Basic Research Program of China.

Contact: Sylvain-Jacques Desjardins
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514-343-7593
University of Montreal