Trapping Malaria in Liver May Lead to New Drug, Vaccine

December 23, 2004
By Erik Wasson

Researchers working separately in Germany and Australia published papers this month that claim significant progress in understanding how malaria parasites progress from the liver into red blood cells.

Worldwide, anti-malaria drugs are losing their effectiveness as resistant mutations of the Plasmodium falciparum parasite gain currency. The Germany-led team says that their research makes a whole-organism vaccine for malaria possible, while the Australian scholar sees new possibilities for more effective drugs coming out of his research.

After a person is bitten by a malaria-carrying mosquito, malaria parasites lodge themselves in the liver. Once malaria has moved from the liver and invaded red blood cells, it is harder to treat and, in the case of more than one million persons per year, proves fatal.

Alan Cowman, working at the Howard Hughes Medical Institute in Melbourne published a paper in the journal Science which, the author says, identifies the protein mechanism by which malaria can remain inside red blood cells, evading immune response and damaging health.

The protein, labeled PfEMP1, allows the parasite to remodel the erythrocyte membrane wall of the blood cell into a knob-like structure that it can adhere to and obtain nutrients from.

"If the parasite didn't stick to the host erythrocyte, it would be dislodged in the blood stream and eliminated rapidly by organs such as the spleen," Cowman explained in a Howard Hughes news release. Cowman's team said it had identified 400 proteins that the parasite injects into the red blood cell membrane, but finding the PfEMP1 protein allows focused research for a knockout drug that will prevent the parasite from lodging in the cell. "Identification of an export mechanism unique to Plasmodium [the malaria parasite] raises the possibility of developing completely novel strategies to interfere with multiple aspects of parasite development through a single target," Cowman said.

Trapping the malaria parasite in the liver may be possible by removing one of its genes, the German-led team writes in the journal Nature. Heidelberg University's Ann-Kristin Mueller, working in conjunction with scholars at the US-based Seattle Biomedical Research Institute and the University of Washington, claims it has been successful in removing the uis3 gene that allows liver-stage malaria in rodents to progress to a fatal blood infection.

A version of the parasite that is unable to jump from the liver could be controlled, allowing time for a vaccine immunity response to develop in test subjects.
Tests on the human form of the disease are years away, but the team writes: "Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible." But National Malaria Center Director Duong Socheat said, when asked about vaccine development: "It's not available now, we don't when it will be available.

"Until it is, we must continue with our bed net programs," Doung Socheat said.