Presentation on Pathogenesis of Malarial Parasites

1. Pathogenesis of Malarial parasites
&
Hematological changes by P. falciparum
-SARAL LAMICHHANE
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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
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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-ϒ,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
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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).
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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.
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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
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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.
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10. References
Harrisson’s Principles of Internal Medicine
www.malaria.com
www.malariasite.com
www.en.wikipedia.org
Class Notes
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