Abstract
Malaria is a leading cause of morbidity and mortality in the world. In general, malaria is easily treated but in a subset of cases it develops to severe disease. Severe malaria has a high rate of mortality even with the best available care. This creates the need for intensive research to fully characterise the pathogenesis of the disease in order to create future novel therapies. One of the hallmarks of malaria infections is its ability to adhere to specific sites in the body leading to severe disease syndromes such as cerebral malaria and pregnancy associated malaria. In this review, the platelet-mediated clumping adhesion phenotypes of malaria-infected erythrocytes were discussed in the context of infected erythrocyte adhesion phenotypes such as cytoadhesion and rosetting. Platelet-mediated clumping refers to a phenomenon of P. falciparum-infected erythrocytes whereby they agglutinate to form large aggregates held together by activated platelets. This unique phenotype is important because it has been associated with severe malaria in both children and adults in diverse geographical and transmission settings. The precise mechanisms by which platelet-mediated clumping occurs are yet to be precisely described. The platelet receptors implicated in this phenotype include CD36, P-Selectin and gC1qR. The parasite derived ligands that mediate this phenotype are yet to be described. Key words: Malaria, platelets, platelet-mediated clumping, infections.
Highlights
According to the World Health Organization (WHO), 212 million people contracted malaria in 2015 whereby 90% of them happened in Africa (WHO, 2016)
There are several perceived contradictions on what is known about platelet-mediated clumping
An interesting paradox exists in the relationship of the platelet-mediated clumping phenotype and severe disease
Summary
According to the World Health Organization (WHO), 212 million people contracted malaria in 2015 whereby 90% of them happened in Africa (WHO, 2016). This intra-erythrocytic parasite stage coincides with the symptomatic phase of malaria infections. The adhesive properties of mature IEs are thought to contribute to the pathogenesis of severe malaria by causing disturbed blood flow, leading to localized host inflammatory responses and deprived oxygen concentrations. Binding to chondroitin sulfate A (CSA) in synctiotrophoblasts has been associated with pregnancy associated malaria whereas resetting has been associated with severe malaria anaemia These examples illustrate why there is a compelling need to precisely study and describe the mechanisms that lead to the development of these adhesion phenotypes. For laboratory experiments on clumping, it is important that the limitations of the assay
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