Abstract

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.

Highlights

  • Malaria is a hazardous disease caused by 1 of the 5 human Plasmodium species, which are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium knowlesi, and Plasmodium malariae

  • Severe malaria is a heterogenous disease with several complications that are the main cause of death and that include cerebral malaria (CM), severe malarial anemia (SMA), malaria-associated acute respiratory distress syndrome (MA-ARDS), placental malaria (PM), acute kidney injury (AKI), and metabolic disturbances

  • Significant amounts, related to high parasite biomass Caused by massive parasite sequestration, which is abundant in severe falciparum malaria Caused by host inflammatory mediators, impaired nitric oxide bioavailability, sequestering parasites, and products released by the parasite Mainly caused by the destruction of RBCs by the parasite and by shortened life span of RBCs

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Summary

Etiology of lactic acidosis in malaria

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. The possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. Multiple factors participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance. HP holds an aspirant PhD fellowship of the F.W.O. Vlaanderen, LV holds a junior Postdoc fellowship of the F.W.O.Vlaanderen and PEVdS is a Research Professor at the KU Leuven.

Introduction
The Cori cycle and lactic acidosis
Hypovolemia and hypotension
Negligible May be caused by microthrombi or by leukocytes
At least in a subset of patients
Parasitic synthesis of lactate
Parasite sequestration
Circulatory failure
Immune responses in malaria patients
Decreased lactate clearance by the liver
Impaired renal lactate clearance
Findings
Conclusions
Full Text
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