A team at LSTM with their collaborators in Malawi and Denmark have
provided, for the first time, evidence which links the ability of red
blood cells infected with the malaria parasite to bind to the cells
lining the blood vessels of the brain, with the clinical syndrome
cerebral malaria.

Cerebral
malaria is a life-threatening complication of infection with the
parasite Plasmodium falciparum. This complication is characterised by
the parasite infected red blood cells accumulating in the brain and
occurs in 1 to 2 percent of the over 200 million reported cases of
malaria.

First author on the paper, published recently in the journal EMBO Molecular Medicine,
Dr. Janet Storm, explained: “Very little is known about why this
serious complication occurs in some children but not others. However, it
is understood that infected red blood cells, presenting with a protein
called P. falciparum erythrocyte membrane protein 1 (PfEMP1) on its
surface bind to host cells lining the blood vessels in many organs, including the brain.”

A property of the PfEMP1protein is its variability, which results in
changes in the ability of infected red blood cells to bind to host cells
in the brain. This has been suggested as the reason we only see
cerebral malaria in some infected individuals, and if the infected red
blood cells do not bind in the brain cerebral malaria cannot occur.

In their lab in at MLW in Malawi, the team utilised a flow-based
adhesion assays to study the binding of infected red blood cells from
children with cerebral or uncomplicated malaria to cells derived from
human brain blood vessels. The team also used molecular techniques to study the PfEMP1 expressed by the infected red blood cells.

Results showed that binding of infected red blood cells from patients
with cerebral malaria to the brain-derived cells was higher than that
seen from patients with uncomplicated malaria. This suggests that in
most cases P. falciparum avoids targeting the brain and that cerebral
malaria only occurs when red blood cells express a subset of PfEMP1
proteins with particular adhesion phenotypes which allow for efficient
binding to the cerebral blood vessels. Knowing that binding in the brain
is a key feature of celebral malaria
allows researchers to focus their attention on developing new
interventions for severe disease based on the interaction between
infected red blood cells and the host cells lining the blood vessels in the brain.

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