Alfred Mavondo-Nyajena Mukuwa Greanious

By Greanious Alfred Mavondo and Mayibongwe Louis Mzingwane

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.

Part of the book: Current Topics in Anemia

By Greanious Alfred Mavondo, Joy Mavondo, Wisdom Peresuh, Mary Dlodlo and Obadiah Moyo

Severe malaria presents with varied pathophysiological manifestations to include derangement in glucose homeostasis. The changes in glucose management by the infected human host emanate from both Plasmodium parasitic and host factors and/or influences which are aimed at creating a proliferative advantage to the parasite. This also includes morphological changes that that take place to both infected and uninfected cells as structural alterations occur on the cell membranes to allow for increased nutrients (glucose) transportation into the cells. Without the availability, effective and efficient intervention there is a high cost incurred by the human host. Hyperglycaemia, hypoglycaemia and hyperinsulinemia are critical aspects displayed in severe malaria. Conventional treatment to malaria renders itself hostile to the host with negative glucose metabolism changes experiences in the young, pregnant women and malaria naïve individuals. In malaria, therefore, host effects, parasite imperatives and treatment regimens play a pivotal role in the return to wellness of the patient. Phytotherapeutics are emerging as treatment alternatives that ameliorate glucose homeostasis alternations as well as combat malaria parasitaemia. The phytochemicals e.g. triterpenes, have been shown to alleviate the “disease” and “parasitic” aspects of malaria pointing at key aspects in ameliorating malaria glucose homeostasis fallings-out that are experienced in malaria.

Part of the book: Parasites and Parasitic Diseases

By Greanious Alfred Mavondo, Blessing Nkazimulo Mkhwanazi, Joy Mavondo, Wisdom Peresuh and Obadiah Moyo

Malarial systemic pathophysiology refers to physiological changes or abnormalities that are experienced by individuals infected with the Plasmodium parasite not be presenting in the absence of active, chronic or previous infection. The pathologies are derived, in part, from OS induced insults whose mediators are readily available in malaria. The malaria disease is equivalent to the pathophysiology as shown by the abnormal syndromic expressions ranging from ailments that affect homeostatic mechanisms and processes to tissues and organ specific damages and derangements. Phytotherapeutic remedies refer to the natural phytochemicals or plant medicinal compounds and their derivatives with known antiparasitic and antimalarial disease effects in both experimental and clinical situations. The chapter explores how Plasmodium infection generates or cause to be generated oxidative stress, how oxidative stress drives systemic disease process and how phytotherapeutics treatment (artemisinins) and administration (asiatic acid) in malaria resolves the various pathologies as a current situational analysis.

Part of the book: Malaria

By Greanious Alfred Mavondo, Blessing Nkazimulo Mkhwanazi, Mayibongwe Louis Mzingwane, Rachael Dangarembizi, Blessing Zambuko, Obadiah Moyo, Patience Musiwaro, Francis Farai Chikuse, Colline Rakabopa, Tariroyashe Mpofu and Joy Mavondo

Malaria driven pathophysiology inimically conjoined to systemic inflammation response cascade in a vicious feed-forward cycle destined to a terrible debilitation or demise of the host. The Plasmodium parasite initiates physiological changes when it is transmitted into the human host by intermediate host and vector. Sporozoites injection elicits immunological and inflammatory response suppression facilitating movement into the blood stream undetected, destined to hepatocyte. Subsequently, hepatocyte invasion culminates in intracellular growth and conversion of the parasites rapturing hepatocytes releasing merozoites into the extrahepatic circulation. Inflammatory and immunological response initiation results in overt malarial disease symptoms. Initially, inflammatory response alleviates and curtails infection. Activation of leukocytes, lymphocytes, monocytes, and phagocytes secretes inflammatory mediators, chemokines, cytokines cytoadhering molecules which accelerate infection patency. Hormonal processes influence disease tolerance without necessarily interfering with parasitemia. Current treatment is anti-parasitic. Phytotherapeutic intervention in malaria is anti-parasitic and anti-disease effects that terminate the vicious cycle and alleviating disease. The phytochemicals, in malarial experimental and clinical work, include asiatic acid, maslinic acid, oleanolic acid, and inflammatory and immunological aberrations evolving in malaria and the effects of phytochemical therapeutics in the alleviation of the disease to enable leverage of future treatment regimens through harnessing existing plants materials is explored.

Part of the book: Parasitology and Microbiology Research

By Alfred Mavondo-Nyajena Mukuwa Greanious , Nesisa Ncube, Alfred Sibanda, Delton Dube, Francis Chikuse Farai and Paul Makoni

Lipid peroxidation is an end process of cellular injury driven by oxidative stress (OS) and inflammation through several molecular changes. Metabolism-generated reactive oxygen species avidly attack the polyunsaturated fatty acids in lipid cell membranes, initiating a self-propagating chain-reaction. Cell membrane destruction, lipids and the end-products of lipid peroxidation reactions are hostile to the viability of cells, even tissues causing and exacerbating Diabetes Mellitus (DM), neurodegenerative disorders (NDDs), cardiovascular diseases (CVDs) and Rheumatoid Arthritis (RA). Current treatment regimens have untoward side effects in the long-term necessitating phytochemical use as these are part of natural food sources. Enzymatic and non-enzymatic antioxidant defense mechanisms may be over run causing lipid peroxidation to take place. In disease states, oxidative stress may increase with subsequent production of increased free radicals which may over run the antioxidant capacity of the body with resultant oxidative damage on polyunsaturated fatty acids in the cell fluid membranes with cellular and tissue damage. Phytochemicals, have been shown to ameliorate diseases through attenuation of oxidative stress, inflammation, lipid peroxidation, causing tissue regeneration by regulating signaling systems and neuroprotective processes. Involvement of polyphenolic and non-phenolic phytochemical in the attenuation of OS, inflammation and lipid peroxidation remain areas of critical importance in combating DM, CVDA, NDD and RA.

Part of the book: Accenting Lipid Peroxidation