Pathophysiology, clinical presentation, and treatment of coma and acute kidney injury complicating falciparum malaria

Abstract

Purpose of reviewCerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research.Recent findingsCerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria.SummaryThe direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue.

Genome-Wide Analysis of the Malaria Parasite Plasmodium falciparum Isolates From Togo Reveals Selective Signals in Immune Selection-Related Antigen Genes

“…Malaria clinical presentation ensues when Plasmodium parasites invade and destroy red blood cells (RBCs). Fever and chills occur at the time of rupture of infected RBCs (iRBCs) containing merozoites that are freed to invade uninfected RBCs (1,2). Failure to receive prompt treatment may lead to dyserythropoietic anaemia or severe malaria.…”

Prognostic models for the clinical management of malaria and its complications: a systematic review

“…Similarly, in adults, all the models predicting mortality also had neurological dysfuction as a predictor. Microvascular obstruction in capillaries of the brain due to direct sequestration of red blood cells infected with the malaria parasite could lead to tissue hypoxia 46. The effects of this sequestration and its sequelae in the brain can be directly visualised in both adults and children as retinopathy 16 46–48.…”

“…Microvascular obstruction in capillaries of the brain due to direct sequestration of red blood cells infected with the malaria parasite could lead to tissue hypoxia 46. The effects of this sequestration and its sequelae in the brain can be directly visualised in both adults and children as retinopathy 16 46–48. This leads to varied results with increased intracranial pressure more pronounced in children than in adults 46.…”

“…The effects of this sequestration and its sequelae in the brain can be directly visualised in both adults and children as retinopathy 16 46–48. This leads to varied results with increased intracranial pressure more pronounced in children than in adults 46. With the increased oxygen demand associated with brain hypoxia and raised intracranial pressure, coma and brain dysfunction could therefore become an important predictor of mortality.…”

Hematological parameters of malaria infected adult patients in Raya Alamata Hospital, Northeast Ethiopia.

“…including parasite proteins on the surface of infected RBCs. Proteins of the plasmodium falciparum (PF) RBC membrane protein 1 (RBCMP1) family attaches to the endothelium and mediate the adhesion of parasite through specific binding to multiple cell receptors (10,11). Intercellular adhesion molecule-1 (ICAM-1), CD36, E-selectin, neural cell adhesion molecule are the major adhesion molecules for the attachment of malaria parasites.…”