Pathogenesis of Malarial Parasites-Saral
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The document discusses the pathogenesis and hematological changes caused by Plasmodium falciparum malaria. It notes that P. falciparum causes the most severe form of malaria and that release of merozoites and hemozoin during erythrocytic schizogony induces cytokines and inflammatory mediators, causing the systemic manifestations of disease seen in malaria. A major hematological change is anemia and thrombocytopenia. Cytoadherence of infected red blood cells in the deep microvasculature also contributes to virulence and can lead to complications like cerebral malaria.
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Pathogenesis of Malarial Parasites-Saral
- 1. Pathogenesis of Malarial parasites & Hematological changes by P. falciparum -SARAL LAMICHHANE Roll-61
- 2. Pathogenesis Classification of Malarial Parasites: Plasmodium vivax : Benign tertian malaria (most common) Plasmodium falciparum: Malignant tertian malaria (severe) Plasmodium malariae :Quartan malaria Plasmodium ovale :Tertian malaria Paroxysm occur cyclically every 48 hrs except Quartan in which it is 72 hrs. Mode of Transmission: - Bite of infected female anopheles mosquito injects along with saliva the infective stages of parasites- Sporozoites. -Blood transfusion of affected ones 2
- 3. 3
- 4. Manifestations of malarial illness are by infection of RBCs by the asexual forms of the malarial parasite and their circulation in blood makes malaria a multisystem disease. Sporozoites in blood Liver within 30 mins Pre-erythrocytic schizony (Merozoites ) Release in bloodstream (wrapping by host liver cell membrane) Erythrocytic Schizony (RBCs penetrated by Duffy Blood Group Ag Fya & b PvRBP-1,2 proteins) 4
- 5. Release of Merozoites(phanerozoites) + Merozoite Surface Proteins + Hemozoin in bloodstream Plasmodial DNA is internalized using MSP-1, MSP-2, MSP-4 are key parasite Apoptosis of developing hemozoin with Toll-like- receptor 9 toxins with GPI tail (Glycosylphosphatidylinositol) Erythroid cells in marrow Proinflammatory cytokines of Activate macrophages, endothelial cells COX-2 Prostaglandins Cytokinemia and Fever Cytokines, inflamm. Mediators TNF,IFN-,IL-1,6,8, Anemia in patients Lymphotoxin, Superoxide, NO Systemic manifestation of disease Headache, Nausea,Vomiting Fever ,Chills , Rigor Thrombocytopenia , Coagulopathy Tiredness, Joint/muscle ache Immunosupression 5
- 6. Severe Malaria: Severe anemia, cerebral malaria, hypoglycemia, metabolic acidosis, renal failure and respiratory distress Cytoadherence, Sequestration, and Rosetting -Structural changes increasing rigidity and adhesiveness of RBCs are major contributors to the virulence for P. falciparum malaria. -Due to PfEMP1 (P. falciparum erythrate membrane protein1) on red cells infected with late stages of P. falciparum , adhere to the capillary and postcapillary venular endothelium in the deep microvasculature (cytoadherence). 6
- 7. -The infected red cells also adhere to the uninfected red cells, resulting in the formation of red cell rosettes (rosetting). -Cytoadherence leads to sequestration of parasites in heart, lung, brain, liver, kidney, intestines, adipose tissue, placenta giving microaerophilic venous environment suited for maturation, adhesion to endothelium and escape clearance by the spleen+immunity. 7
- 8. Hematological changes Thrombocytopenia Anemia (decrease in Hb level) Jaundice Monocytosis and Lymphopenia Brain capillaries distended and occluded (cytoadherence) causing hemorrhages-----Cerebral malaria Peripheral vascular collapse leading to circulatory failure and shock-----Algid malaria Autoimmune response against RBCs causing hemolysis leading to hemoglobinuria----Black water fever 8
- 9. Summary Release of merozoites and hemozoin after erythrocytic schizogony contains GPI, key parasite toxin which induces cytokines, inflamm. mediators They cause the systemic manifestations of disease and their cyclic release causes paroxysm. Major hematological change is Anemia and Thrombocytopenia. 9
- 10. References Harrissons Principles of Internal Medicine www.malaria.com www.malariasite.com www.en.wikipedia.org Class Notes 10
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