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New findings about severe malaria

Researchers from the University of Copenhagen have recently uncovered new knowledge about severe malaria that could lead to new interventions.

Red blood cells infected with the malaria parasite Plasmodium falciparum, which is the type most lethal to humans, bind to receptors on cells lining blood vessel walls. This helps the parasite avoid being discovered and killed by the spleen. Binding is mediated through one of several members of a family of proteins. One member of this family is known as PfEMP1, P. falciparum erythrocyte membrane protein 1. One single PfEMP1 can mediate placental malaria, the cause of malaria during a pregnancy, which strikes and kills thousands of women as well as leading to both low-birth weight babies and premature births each year. But other PfEMP variants that result in serious diseases in young children remain unidentified.

Assistant Professor Thomas Lavstsen and his team at University of Copenhagen have used molecular techniques to comp-are the levels of various PfEMP1 transcripts in blood samples, in order to target specific PfEMP1 types that are linked to severe malaria. The samples were acquired from children in the pediatric ward of the
Korogwe District Hospital in Tanzania.

According to the scientists, the research has revealed that transcripts 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.

The findings were published together with two other papers in an online edition of PNAS (Proceedings of the National Academy of Sciences) in May. The study also showed that these PfEMP1 cassettes can be recognized by natural acquired immunity in African children.

This could hopefully lead to the possibility of basing a vaccine on the detected PfEMP1 types. Domain cassettes 8 and 13 mediate the binding of infected blood cells to the cells that line the blood vessels in the brain, as reported in a related paper from the University of Edinburgh in the same PNAS issue. According to the authors, new molecules could be targeted to develop drugs for the treatment of the most deadly forms of malaria.

The discovery could possibly also lead to a laboratory tool to test vaccines and drugs that block the binding of the parasite to blood vessels in the brain.