Trapping Malaria in Liver May Lead to New Drug, Vaccine

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.