Pathology and Pathogenesis of Malaria

Abstract

This chapter focuses on the pathogenesis of malaria caused by Plasmodium falciparum and Plasmodium vivax. It talks about two factors, parasite multiplication rate and cytoadherence of parasitized Red Blood Cells (RBCs), both of which enable parasites to achieve high densities and induce microvascular inflammation. The chapter considers several cytoadherence interactions between parasitized RBCs and host cells to better understand how parasites cause microvascular obstruction, inflammation, and dysfunction in vivo. Additional evidence for endothelial dysfunction in severe malaria has now been reported from a study of Indonesian adults. In this study, cell-free hemoglobin and arginase levels were elevated in patients with severe malaria, compared to those with moderately severe malaria or those who were healthy. The chapter presents the pathogenesis of vivax malaria, and discusses human genetic resistance to vivax malaria. It also describes working models of malaria pathogenesis which the authors believe provide useful frameworks for future studies. The authors propose that the levels of parasitemia and the strength of pathogen-host cell interactions are critically involved in the pathogenesis of malaria, and that host factors which interfere with parasite multiplication and sequestration are centrally important in ameliorating the severity of malaria. They suggest that RBC polymorphisms other than Duffy-negativity may reduce P. vivax infection of RBCs or impair cytoadherence interactions between P. vivax-infected RBCs and host cells. Like Duffy negativity, RBC polymorphisms that are found to protect against P. vivax may teach the important aspects of the pathogenesis of this fascinating and sometimes deadly parasite.