General Parasitology and Protozoa
Cerebral malaria is caused by plamodium:
a. Cerebral malaria is a complication of P falciparum.
b. Cerebral malaria collectively involves the clinical manifestations of Plasmodium falciparum malaria that induce changes in mental status and coma. It is an acute, widespread disease of the brain which is accompanied by fever.
c. If a person is not treated, it is fatal in 24-72 hours. The histopathological hallmark of this encephalopathy is the sequestration of cerebral capillaries and venules with parasitized red blood cells and non-prbcs.
d. Pathogenesis- P.falciparum is the only species that induces cytoadherence to vascular endothelium of erythrocytes containing the mature forms of the parasite.
e. As the parasite matures, parasite proteins are transported and inserted into the erythrocyte membrane. The high molecular transmembrane protein P. Falciparum erythrocyte membrane protein 1 or pfemp1 is the most important ligand for cytoadherence.
f. It is seen on the surface of RBC’s as knobs. The vascular epithelium has receptors that bind to pfemp1. The
g. Intercellular adhesion molecule 1 (ICAM-1) is the most important receptor on brain endothelium. Cytoadherence causes sequestration of parasitized erythrocytes in the microcirculation of vital organs and is prominent in cerebrum, cerebellum as well as the medulla oblongata.
h. Sequestration of parasitized erythrocytes compromises the microcirculation.
i. In addition formation of erythrocyte clumps through rosetting and auto-agglutination could further compromise flow.
j. Rosette formationis the in vitro phenomenon in which uninfected red blood cells adhere to erythrocytes containing the mature forms of the parasite.
k. Also, in severe malaria the RBC’s have reduced deformability. Rigid RBC’s further reduce blood circulation contributing to hypoxia leading to lactic acidosis, organ dysfunction and death.