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Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance
S Krishna1, D W Waller, F ter Kuile
1Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Insights
Sustained high blood lactate levels in children with severe malaria indicate a poor prognosis. This finding is crucial for understanding mortality in severe malaria cases.
Area of Science:
- Pediatrics
- Infectious Diseases
- Clinical Biochemistry
Background:
- Severe malaria is a significant cause of mortality in children.
- Metabolic derangements, including lactic acidosis, are common in severe malaria.
- Cytokines play a role in the pathogenesis of severe malaria.
Purpose of the Study:
- To monitor clinical and metabolic changes in Gambian children with severe malaria.
- To identify prognostic indicators for mortality in severe malaria.
- To investigate the relationship between lactate, cytokines, and clinical outcomes.
Main Methods:
- Serial clinical assessments and blood sample analysis in 115 children (1.5-12 years) with severe malaria.
- Measurement of venous blood lactate, glucose, and plasma cytokine levels (TNF-alpha, IL-1alpha).
- Correlation analysis between metabolic markers, cytokine levels, and patient outcomes (survival vs. death).
Main Results:
- Higher admission lactate and lower glucose levels were observed in fatal cases compared to survivors.
- Lactate concentrations correlated with tumor necrosis factor and interleukin-1alpha levels.
- Sustained hyperlactataemia (4 hours post-admission) was the strongest predictor of outcome.
- Quinine treatment was associated with more hypoglycaemia than artemether or chloroquine.
Conclusions:
- Lactic acidosis is a critical factor contributing to mortality in severe malaria.
- Sustained hyperlactataemia is a key prognostic indicator in severe malaria.
- Understanding metabolic profiles aids in predicting and managing severe malaria outcomes.
Abstract:
Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous blood lactate concentrations were almost twice as high in fatal cases as in survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001). Treatment with quinine was associated with significantly more episodes of post-admission hypoglycaemia when compared with artemether or chloroquine. After treatment, lactate concentrations fell rapidly in survivors but fell only slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after admission) proved to be the best overall prognostic indicator of outcome in this series. Lactic acidosis is an important cause of death in severe malaria.