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08 October 2008
Scientists Find New Insight into Genome of Neglected Malaria Parasite
As international health authorities step up efforts to fight malaria, leading scientists say the stealthy and increasingly debilitating Plasmodium vivax parasite deserves more attention.

The complete sequence of the P. vivax genome, reported in the Oct.9, 2008 journal Nature, could help scientists unlock its secrets.

Electron micrograph of a schizont form of the Plasmodium vivax parasite. At maturity, each of the round merozoite forms will burst out of the cell and infect other young red blood cells. Image used by permission.
P. vivax is responsible for at least 25 percent of the roughly 500 million cases of malaria worldwide and is the major cause of malaria outside Africa, mainly afflicting Asia and the Americas.

While P. vivax infection is usually non-lethal and doctors once considered it "benign," an increasing number of reports show the parasite can kill, says Mary Galinski, PhD, co-author of the Nature article and a researcher at Yerkes National Primate Research Center and Emory Vaccine Center of the Emory University School of Medicine.

Galinski, a professor of infectious diseases at Emory University School of Medicine, and her colleague at Yerkes, co-author and research associate Esmeralda Meyer, MD, played a critical role in assembling P. vivax's genetic information because the parasite cannot be cultured in the laboratory and can only be grown in living monkeys.

The full sequence and its analysis were a collaboration involving scientists from a dozen institutions and coordinated by the Institute of Genomic Research, part of the J. Craig Venter Institute in Rockville, Md. The first author is microbiologist Jane Carlton, PhD, now associate professor of parasitology at New York University School of Medicine.

Galinski says the complete genetic sequence of P. vivax has revealed unique genes that appear to be important for invading the host's cells and in evading the host's immune system. Unlike other malaria parasites such as P. falciparum, P. vivax can only invade reticulocytes, immature red blood cells.

Both P. vivax and P. falciparum are carried by mosquitoes and can cause fever, chills, headache, nausea and vomiting. P. falciparum's genomic sequence was published in 2002.

Compared with P. falciparum, P. vivax's ability to come back from dormancy in the liver, its faster development in the mosquito and the outdoor biting behavior of mosquitoes it prefers may make P. vivax more resilient to common control methods such as insecticide-treated nets, Galinski says.

She says knowing P. vivax's full set of genes could help scientists better understand the distinctive "hypnozoite" phase of its life cycle, when the parasite lays dormant in liver cells for months or years after initial infection.

"That's one of the areas we hope to crack, but it will only be possible by combining the new genetic information with experiments in living animals," she says.

The complete sequence of the P. vivax genome could help scientists look for new drugs and design vaccines. In the Nature paper, the authors analyzed P. vivax enzymes by computer to examine how easily resistance could develop against the antimalarial compounds artemisinin and atovaquone.

Despite the threat posed by P. vivax, Galinski notes that only two candidate vaccines and one drug against P. vivax are now in clinical trials, compared with 23 vaccine candidates and 13 drugs for P. falciparum.

She and Alberto Moreno, MD, professor of infectious diseases at Emory and an resear chers at Ye rkes and Emory Vaccine Center, recently published studies of a P. vivax vaccine candidate. They showed that the vaccine effectively stimulated monkeys' immune systems to produce antibodies, which in laboratory tests could block proteins the parasites use to invade blood cells.

Galinski is also a co-author on a companion paper in the same issue of Nature describing the genome of the malaria parasite Plasmodium knowlesi, whose natural host is the Kra monkey but can also infect humans. Because a laboratory culture system for P. vivax is lacking, this related parasite will be important for future malaria research, she says.

Galinski's research is funded by the National Institutes of Health and the Burroughs Welcome Fund.

References: Carlton, J.M. et al Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature Vol 455. Oct. 9, 2008.

Pain, A et al. The genome of the simian and human malaria parasite Plasmodium knowlesi. Nature Vol 455. Oct. 9, 2008.

Moreno, A. et al. Preclinical assessment of the receptor-binding domain of Plasmodium vivax Duffy-binding protein as a vaccine candidate in rhesus macaques Vaccine Vol 26, p. 4338-4344, Aug, 12, 2008.

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