Pathophysiology of Malaria

This week’s learning goal was the pathophysiology of our selected disease. Instead of focusing on the life cycle of malaria which includes the vector stages, I chose an article that concentrated on the two broad categories of severe malaria manifestations: metabolic and neurological complications.

While anemia (due to RBC destruction and reduced RBC production as a result of cytokine-mediated suppression of erythrogenesis), hypoglycemia, and renal failure (more common in adults) require urgent treatment, Planche and Krishna found that cerebral malaria and lactic acidosis were independent predictors of poor outcomes.

The (interrelated) metabolic changes that are important in severe malaria are acidosis, hyperlactatemia (serum levels >5mM), and respiratory distress. The biggest culprit appears to be increased anaerobic glycolysis due to microvascular obstruction. Interestingly, serum lactate levels were found to be higher in malaria than in sepsis, indicating impaired oxygen delivery. Dichloroacetate has been shown to safely lower blood lactate concentration, but more research is needed to assess its capacity to reduce mortality in cases of severe malaria.

In addition to the hypoglycemia induced by patients who are administered quinine (due to increased insulin secretion), hypoglycemia can also be a result of the demands of anaerobic glycolysis. Every patient should be assessed for hypoglycemia on admission, and inpatient care must include regular monitoring of blood glucose levels.

Cerebral malaria is defined as “an unrousable coma with asexual P. falciparum infection at least 30 minutes after a convulsion, when hypoglycemia has been excluded and without interference by sedative drugs or other confounding variables.” However, the authors cited studies that suggest that impaired consciousness, rather than coma, may be a more accurate predictor of death. Originally, it was believed that cerebral edema resulting from increased capillary permeability, was the cause of cerebral malaria. Post-mortem studies now suggest that sequestration of the parasites in the cerebral vasculature, and the simple mechanical obstruction that ensues, is responsible for the symptoms of cerebral malaria.


Planche T, Krishna S. The relevance of malaria pathophysiology to strategies of clinical management. Current Opinion in Infectious Diseases. 2005;18(5):369-375.