Mechanisms of complement activation in malaria

Activation of the classical pathway of complement, mediated by immune complexes, is very well-documented in malaria. In addition, several of the breakdown products that are produced upon rupture of malaria-infected erythrocytes, including hemin and the digestive vacuole, activate the alternative pathway of complement. Evidence for complement activation in malaria includes reduction in serum titers of total complement hemolytic activity and of individual complement components as well as increases in soluble complement activation products in the serum. In addition, C3 activation fragments have been demonstrated to be covalently bound to both infected and uninfected erythrocytes under a variety of conditions in malaria, thus leading to the extravascular clearance of erythrocytes to the spleen. This erythrocyte opsonization reaction, mediated by both the classical and alternative pathways of complement, may be additionally amplified in severe cases of malaria complicated by acidosis due to increased activation of the alternative pathway of complement.