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Adhesive Interactions in Malaria: New Targets for Intervention
Framework programme:
Project number:
EC contribution:
€ 1 300 000
36 months
Starting date:
1 September 2000

Keywords: Malaria; cytoadhesion; drug design


The pathophysiology of malaria is, in the main, associated with the ability of erythrocytes infected with malarial parasites to sequester in the deep vascular bed and cause damage to vital organs. The aim of the project is to investigate the molecular mechanisms underpinning sequestration in an effort to identify targets for the development of drugs that prevent and/or reverse cytoadhesion of infected erythrocytes. The consortium has identified novel adhesive interactions, studied the structure, function and evolution of the parasite genes mediating adhesive phenotypes, and developed the first lead compounds capable of inhibiting adhesive interactions.


Malaria remains one of the major infectious diseases worldwide. The disease burden is borne mainly by developing countries where the vast majority of the 300-500 million cases and 1.7-3 million deaths occur, imposing a huge burden on under-resourced health systems and limiting the prospects for economic growth and development. The emergence and spread of drug-resistant strains of the human malaria parasite Plasmodium falciparum has made the discovery and production of new therapeutic interventions a priority.  The morbidity and mortality associated with malaria has been attributed, mainly, to the unique ability of Plasmodium falciparum infected erythrocytes to adhere to small vascular endothelial cells and to uninfected erythrocytes. Adhesion to host cells is essential for parasite survival, as it prevents destruction of the parasitised erythrocytes in the spleen. However, sequestration of parasitised erythrocytes in the deep vascular bed of inner organs, such as the brain, lung and kidney, is a major pathogenic factor in severe malarial disease, resulting in localised hypoxia and inflammatory reactions.

To control the progressive development of the life-threatening complications brought about by adhesive events is a major challenge in the therapy of acute severe malaria. Chemotherapeutics that disrupt and/or prevent sequestration of infected erythrocytes in the deep vascular bed will be of immense clinical value, as such an adjuvant treatment would substantially improve microcirculation, reverse tissue hypoxia, remove the pro-inflammatory stimulus from endothelial cells and bring the parasitised erythrocytes back into circulation where they are more accessible to drug killing.

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