EpidemicsScientists "domesticate" -- and disarm -- malaria parasite

Published 1 September 2011

Malaria is one of the Earth’s most notorious scourges, accounting for more than 250 million new cases — and one million deaths — each year, researchers have developed a novel technique to “tame” the malaria parasite by forcing it to depend on an external supply of a vital chemical; this could help to speed up drug development and provide the basis for the first effective vaccine against malaria

A novel technique to “tame” the malaria parasite by forcing it to depend on an external supply of a vital chemical has been developed by researchers at the Stanford University School of Medicine and the University of California-San Francisco. The scientists have, in effect, created a domesticated strain of Plasmodium — the one-celled parasite that causes malaria — which would no longer cause this dreaded disease.

Their findings not only make it possible to grow large volumes of this modified parasite, but also reveal how the parasite’s very survival turns on the production of one chemical — isopentenyl pyrophosphate, or IPP. These developments could help to speed up drug development and provide the basis for the first effective vaccine against malaria.

The study, published online 30 August in PLoS Biology, was conducted by Ellen Yeh, M.D., Ph.D., an instructor in Stanford’s Department of Pathology, and UCSF professor of biochemistry and biophysics and Howard Hughes Medical Institute investigator Joseph DeRisi, Ph.D.

A Stanford university release reports that at the heart of the paper is a discovery by Yeh and DeRisi: The scientists identified IPP as absolutely essential to the malaria parasite’s viability during the stage when it invades blood cells. Normally, Plasmodium’s IPP supply is manufactured in a unique structure within the parasite, called the apicoplast. IPP is pivotal to Plasmodium’s survival, but the researchers showed that during its blood-infecting stage, the parasite can live without its apicoplast — as long it continues to get IPP from another source.

Malaria is one of the Earth’s most notorious scourges, accounting for more than 250 million new cases each year, mostly in Africa but also in Southeast Asia, India, and Latin America. It is transferred to humans via a mosquito bite, during which one-celled parasites of the genus Plasmodium are injected into the bloodstream. The resulting infection causes some one million deaths annually, largely among children under the age of 5.

At present, no effective malaria vaccines exist. What is more, Plasmodium strains usually develop resistance to drugs that have been approved to combat the disease. The World Health Organization (WHO), for instance, currently recommends artemesinin in combination with other, older anti-malarials for combating Plasmodium falciparum, the deadliest and most widespread form of the malaria parasite. But while that drug is still believed to be effective, reports of resistance are starting to emerge, said Yeh.

“If resistance becomes widespread, we’re in big trouble, because