Severe Malarial Anemia (SMA) Pathophysiology and the Use of Phytotherapeutics as Treatment Options

Hemolytic anemia results when red blood cells (RBCs) are destroyed prematurely by a number of agents. Obligate intracellular parasites like the Plasmodium species proliferate by infecting RBCs, growing through different stages of their life cycles, expanding their population to unsustainable numbers and eventually rupturing the cell membranes in order to transmit and infect new RBCs. In this manner, more RBCs are infected by the parasites and destroyed together with some nonparasitized cells. Membranes of RBCs are altered and deformed by parasite antigens expressed on the surfaces of both parasitized and nonparasitized cells, which lead to their premature phagocytosis and destruction by the reticuloendothelial system. Parasites and the hemoglobin waste products produced by them are released when the RBCs burst. Activated leukocytes take up the hemoglobin waste (hemozoin which is a polymerized heme), which stimulates the innate immune system leading to the synthesis and secretion of pro- and anti-inflammatory cytokines, chemokines, growth factors and mediators. Together with the destruction of RBCs in malaria, imbalance between pro- and anti-inflammatory events results in the modification of erythroid cell proliferation leading to severe malarial anemia (SMA) and other pathophysiologies of malaria. While current malarial management is targeted at the destruction of the parasite, it is the malaria-related pathophysiology (disease aspect of malaria) like severe malarial anemia that results in the high malaria morbidity and mortality. Antidisease approaches promise to be more effective at malarial management. Triterpenes with antioxidant, pro-oxidant, anti-inflammatory and antiparasitic effect show effects at retarding and abrogating severe malarial anemia. Asiatic acid, amongst other triterpenes like oleanolic acid, masilinic acid administered through oral or transdermal route improves severe malaria anaemia providing promise in the management of malaria pathophysiology