Infections: New Discoveries About Severe Malaria

Photo: Mosquito

Malaria is a mosquito-borne
infectious disease of humans and
other animals; © Gregor Buir/

International researchers have uncovered new knowledge related to host-parasite interaction in severe malaria, concerning how malaria parasites are able to bind to cells in the brain and cause cerebral malaria – the most lethal form of the disease.

"Identifying the molecules that allow malaria parasites to 'stick' to the brain takes us one step closer to new treatments," said Doctor Joseph Smith of Seattle Biomedical Research Institute.

Red blood cells infected with the malaria parasite Plasmodium falciparum, the type most lethal to humans, bind to receptors on cells lining blood vessel walls, which helps the parasite avoid being detected and killed by the spleen. The binding is mediated by one of several members of a family of parasite proteins called P. falciparum erythrocyte membrane protein 1, or PfEMP1. A single PfEMP1 mediates placental malaria – the cause of malaria during pregnancy, which kills thousands of women and causes premature births and low-birth weight babies each year – but other PfEMP1 types causing life-threatening disease in young children are unknown.

To hone in on specific PfEMP1 types associated with severe malaria, Doctor Thomas Lavstsen and his team from the University of Denmark used molecular techniques to compare the levels of different PfEMP1 transcripts in blood samples from children hospitalised in the paediatric ward of the Korogwe District Hospital in Tanzania. "Our research revealed that genes encoding two distinct types of PfEMP1 - named domain cassettes 8 and 13 - were tied to cases of severe malaria, suggesting that those proteins might be suitable targets in efforts aimed at curbing the disease," explained Lavstsen. Co-author Louise Turner adds "Another important aspect of our study is that we show these PfEMP1 domain cassettes are recognised by natural acquired immunity in young African children, which gives us hope that we can base a vaccine on the discovered PfEMP1 types."

Alexandra Rowe of the University of Edinburgh said: "This provides us with new molecules that could be targeted to develop drugs to treat the most deadly forms of malaria. In addition, because animal models for cerebral malaria are currently unavailable, we believe our findings might lead to a laboratory tool for testing drugs and vaccines that block the binding of the parasite to blood vessels in the brain."; Source: Seattle Biomedical Research Institute