Cerebral malaria: clinical features, pathophysiology and treatment

Area of Science:

• Tropical Medicine
• Infectious Diseases
• Clinical Research

Background:

• Cerebral malaria remains a significant cause of mortality and morbidity, particularly in African children.
• The pathophysiology of cerebral malaria is complex, with ongoing debate between mechanical and toxin-cytokine hypotheses.
• Antimalarial drug resistance poses a continuous challenge to effective chemotherapy.

Purpose of the Study:

• To review the historical context and evolution of cerebral malaria research.
• To discuss the current understanding of cerebral malaria pathophysiology.
• To evaluate the efficacy and safety of existing and potential treatments for cerebral malaria.

Main Methods:

• Review of historical randomized controlled trials, including the 1980 dexamethasone trial.
• Analysis of clinical and histopathological studies on cerebral malaria.
• Examination of laboratory studies investigating cyto-adherence, malaria toxin, and cytokine production.
• Evaluation of recent large-scale antimalarial drug trials.

Main Results:

• The 1980 dexamethasone trial led to the abandonment of corticosteroid therapy in cerebral malaria.
• Evidence supports both mechanical and toxin-cytokine hypotheses for cerebral malaria pathophysiology.
• Artemether and quinine show similar case fatality rates (11%-21%) but have distinct advantages and disadvantages.
• Clinical manifestations in non-immune adults and African children require further detailed description.

Conclusions:

• Ancillary corticosteroid therapy is not recommended for cerebral malaria.
• Further research is crucial to define the role of prophylactic anticonvulsants and exchange transfusion.
• Optimizing chemotherapy and understanding pathophysiology are essential to reduce cerebral malaria mortality and morbidity.