The importance of tissue-sequestration of malaria parasites for their growth

Malaria infected red blood cells can bind to the small blood vessels inside various organs. In humans, the malaria parasite Plasmodium falciparum causes severe disease because this sequestration can lead to malfunctioning of the affected organs and coma in case the brain is affected. Therapeutic interventions to avoid this sequestration are currently being investigated, but the consequences of disrupting sequestration are unknown, since this can not be studied in humans.

The rodent malaria parasite P. berghei can sequester in organs in an analogous way as the human parasite. To determine the significance of sequestration for parasite growth, researchers of LUMC and BPRC have generated a mutant P. berghei parasite that has lost the capacity to adhere to the blood vessels. It is thought that the sequestration of malaria parasites enables the parasites to avoid clearance by the spleen. The researchers have shown that the mutant parasite has a reduced growth even in the absence of the spleen. This indicates that sequestration is not only beneficial for the parasite to avoid parasite removal by the spleen, but also is important for parasite growth. This now offers the opportunity to create a new P. berghei mutant parasite by introducing proteins of P. falciparum that are known to bind to small blood vessels. Subsequently, vaccines/small molecules can be tested for the efficacy to interfere with sequestration.

To summarise, this work, published in the Journal of Experimental Medicine, now for the first time offers the opportunity to create an in vivo screening system for testing molecules that can disrupt P. falciparum sequestration and thereby decrease pathology.