Pathophysiology of severe malaria
Cerebral malaria
Malarial anaemia
Acute kidney injury (AKI)
Acute respiratory distress syndrome (ARDS)
Impaired conscious associated with malaria
Parasites within infected red blood cells (iRBC) transport plasmodium falciparum erythrocyte membrane protein 1 (pfEMP1) to red blood cells (RBC) membrane as key ligand to cytoadherence
Key endothelial receptor for brain is intercellular adhesion molecule-1 consist of protein C binds to pfEMP1
Cytoadhesion result in sequestration of parasitized RBC in capillary and postcapillary venules
Leads to blockage of microcirculation and tissue hypoxia
Increase rigidity of iRBC and uninfected red blood cells (uRBC)
Clumping of iRBC (agglutination) and adherence of uRBC to iRBC (rosetting)
Activation of endothelial and astroglial with variable inflammatory response and mild functional changes to blood-brain barrier
Imbalance of anti-flammatory and proinflammatory cytokines
Early parasite stages infection causes mild modification of adhesion and deformability of RBC
Late parasite stages infection causes substantial alteration of adhesion and deformability of RBC
Sequestration of late parasite stages induced by their adherence to endothelial cells, blood cells, platelets and uRBC
Sequestration leads to iRBC escape destruction by spleen
iRBC will be ruptured upon merozoite released
uRBC will also be deformed in parasitized blood
uRBC susceptible to be destroyed by the spleen due to being slightly altered by parasite during invasion
Exacerbate loss of RBC
One other cause is ineffective erythropoiesis
Cause black water fever as RBC destroyed and hemoglobin excreted in the urine
Caused by acute tubular necrosis associated with severe falciparum malaria
Up to 40% adults compared to 10% children develop AKI
Plasmodium falciparum histidine rich protein shown to contribute to AKI in adults with severe malaria
Sequestration of parasitized RBC in renal glomerular and peritubular capillaries
Reduces renal cortical blood flow, increased kidney size and endothelial changes in glomerular and peritubular capillaries
Develop after treatment and clearance of parasitemia
Increase permeability of pulmonary capillaries
RBC sequestration clogs the pulmonary microcirculation
Leads to fluid overload