Scientists Decode Genome of Parasite that Causes Relapsing Malaria

Advance May Speed Development of Malaria Drugs and Vaccines

Scientists have deciphered the complete genetic sequence of the parasite Plasmodium vivax, the leading cause of relapsing malaria, and compared it with the genomes of other species of malaria parasites. The findings shed light on distinctive genetic features of P. vivax, and may lead to new tools to prevent and treat P. vivax malaria. Results of the study, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), appear in the Oct. 9 issue of Nature.

More than 2.6 billion people are at risk of developing vivax malaria, with a heavy concentration of cases in Asia and Latin America. Although infection is rarely fatal, it causes severe clinical symptoms that include repeated episodes of high fever followed by headache, chills and profuse sweating, often accompanied by vomiting, diarrhea and enlargement of the spleen. Patients treated for the primary blood stage infection but not specifically for dormant disease in the liver are at substantial risk of relapse.

According to coauthors at The Institute for Genomic Research/J. Craig Venter Institute in Rockville, Md., and their colleagues, the P. vivax gene sequence will drive research in three key areas: study of the genetic diversity of P. vivax, the problem of drug resistance and the phenomenon of P. vivax relapse.

“Plasmodium vivax relapse presents serious challenges to scientists and doctors alike,” says NIAID Director Anthony S. Fauci, M.D. “Completion of the P. vivax genome promises to provide new insights into the biology of vivax malaria and new leads for therapies and vaccines.”

One obstacle for researchers has been that P. vivax cannot be grown in the laboratory, making it a relatively neglected area of study. “With the publication of the first genome sequence, we hope to reverse this trend and provide a resource for scientists to pursue studies on this important parasite,” says lead investigator Jane M. Carlton, Ph.D., of the NYU Langone Medical Center.

Four species of Plasmodium parasite commonly cause malaria in humans: P. falciparum, P. malariae, P. ovale and P. vivax. Although P. vivax resembles the other three species of human malaria parasites, it has novel gene families that encode for potential alternative pathways into red blood cells not recognized previously, according to study authors. Importantly, Dr. Carlton’s team identified some P. vivax genes with similarities to genes in other organisms, such as yeast, that are responsible for dormancy. These genes may allow scientists to study the mechanisms of the dormant liver stage P. vivax — and perhaps find ways to disrupt it.

Research resources generated by this work are available for use by the malaria research community and are deposited in the NIAID funded Malaria Research and Reference Reagent Resource Center (MR4) http://www.mr4.org and the Pathogen Functional Genomics Resource Center (PFGRC) http://pfgrc.jcvi.org/index.php/microarray/array_description/plasmodium_vivax/version1.html.

The NIH National Institute of General Medical Sciences also provided funding for this study.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference:
JM Carlton et al. Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature DOI:10.1038/nature 07327 (2008).