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Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective
Daniel B Blatt1, Benjamin Hanisch2, Katrina Co3
1Department of Pediatrics, Division of Infectious Diseases, University of Louisville, Louisville, Kentucky, USA.
Insights
Oxidative stress is linked to higher mortality in Ugandan children with cerebral malaria, but not severe malarial anemia. Biomarkers like HO-1 and SOD indicate this association, impacting clinical outcomes.
Area of Science:
- Malaria pathogenesis
- Pediatric infectious diseases
- Oxidative stress research
Background:
- Severe malaria in children is a significant health concern in regions like Uganda.
- Oxidative stress is implicated in various disease states, but its specific role in severe malaria outcomes requires further elucidation.
- Understanding the relationship between oxidative stress and mortality in pediatric malaria is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the association between oxidative stress biomarkers and mortality in Ugandan children diagnosed with severe malaria.
- To compare oxidative stress levels in children with cerebral malaria (CM) and severe malarial anemia (SMA) against healthy community children (CC).
- To determine if admission levels of oxidative stress biomarkers predict in-hospital death or 6-month readmission risk.
Main Methods:
- Biomarkers of oxidative stress, including heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) activity, were measured in children with CM (n=77) and SMA (n=79) upon admission.
- These measurements were compared to those of community children (CC, n=83).
- Statistical analyses were performed to correlate biomarker levels with the risk of death during hospitalization and readmission within six months.
Main Results:
- Children with CM or SMA exhibited elevated HO-1 levels and reduced SOD activity compared to CC, indicating increased oxidative stress.
- Higher HO-1 concentrations were significantly associated with an increased risk of death in children with CM (OR, 6.07).
- Conversely, higher SOD activity was linked to a decreased risk of death in children with CM (OR, 0.02).
- No significant associations were found between oxidative stress biomarkers and the risk of readmission within six months.
Conclusions:
- Severe malaria, specifically CM and SMA, induces oxidative stress in affected children.
- Oxidative stress is a significant predictor of mortality in children with cerebral malaria.
- The findings suggest that while oxidative stress is present in both CM and SMA, its direct link to mortality is specific to CM in this cohort.
Background:
We hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality.
Methods:
We evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n = 77) or severe malarial anemia (SMA, n = 79), who were enrolled in a randomized clinical trial of immediate vs delayed iron therapy, compared with community children (CC, n = 83). Associations between admission biomarkers and risk of death during hospitalization or risk of readmission within 6 months were analyzed.
Results:
Nine children with CM and none with SMA died during hospitalization. Children with CM or SMA had higher levels of heme oxygenase-1 (HO-1) (P < .001) and lower superoxide dismutase (SOD) activity than CC (P < .02). Children with CM had a higher risk of death with increasing HO-1 concentration (odds ratio [OR], 6.07 [95% confidence interval {CI}, 1.17-31.31]; P = .03) but a lower risk of death with increasing SOD activity (OR, 0.02 [95% CI, .001-.70]; P = .03). There were no associations between oxidative stress biomarkers on admission and risk of readmission within 6 months of enrollment.
Conclusions:
Children with CM or SMA develop oxidative stress in response to severe malaria. Oxidative stress is associated with higher mortality in children with CM but not with SMA.
Clinical Trials Registration:
NCT01093989.
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