Intestinal Injury in Ugandan Children Hospitalized With Malaria
Michelle Ngai1, Michael T Hawkes2,3,4, Clara Erice1
1Sandra Rotman Centre for Global Health, Department of Medicine, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Insights
Severe malaria commonly causes intestinal injury in children, linked to microbial translocation and organ dysfunction. High intestinal fatty-acid binding protein (I-FABP) levels predict a significantly increased risk of death.
Area of Science:
- Pediatric Infectious Diseases
- Gastroenterology
- Critical Care Medicine
Background:
- Severe malaria can lead to multiple organ dysfunction syndrome (MODS), frequently affecting the gastrointestinal tract.
- Understanding the role of intestinal injury in severe malaria is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the prevalence and clinical significance of intestinal injury in children with severe malaria.
- To examine the association between markers of intestinal injury and microbial translocation with inflammation, endothelial activation, hypoperfusion, organ injury, and mortality.
Main Methods:
- A prospective cohort study was conducted in Uganda involving 523 children admitted with malaria.
- Markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP], zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP], soluble complement of differentiation 14 [sCD14]) were measured.
- Associations with clinical parameters and biomarkers were analyzed.
Main Results:
- Intestinal injury, indicated by elevated I-FABP, was present in 79% of children.
- I-FABP levels correlated with microbial translocation markers, inflammation, and endothelial activation.
- Higher I-FABP levels were significantly associated with hypoperfusion, acute kidney injury, coma, and a 7.4-fold increased risk of in-hospital death.
Conclusions:
- Intestinal injury is a common complication in children hospitalized with severe malaria.
- This injury is linked to microbial translocation, systemic inflammation, hypoperfusion, and MODS.
- Elevated I-FABP levels are a strong predictor of mortality in pediatric malaria.
Background:
Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which may involve the gastrointestinal tract.
Methods:
In a prospective cohort study in Uganda, we measured markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP] and zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP] and soluble complement of differentiation 14 [sCD14]) among children admitted with malaria. We examined their association with biomarkers of inflammation, endothelial activation, clinical signs of hypoperfusion, organ injury, and mortality.
Results:
We enrolled 523 children (median age 1.5 years, 46% female, 7.5% mortality). Intestinal FABP was above the normal range (≥400 pg/mL) in 415 of 523 patients (79%). Intestinal FABP correlated with ZO-1 (ρ = 0.11, P = .014), sCD14 (ρ = 0.12, P = .0046) as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic blood pressure (ρ = -0.14, P = .0015), delayed capillary refill time (ρ = 0.17, P = .00011), higher lactate level (ρ = 0.40, P < .0001), increasing stage of acute kidney injury (ρ = 0.20, P = .0034), and coma (P < .0001). Admission I-FABP levels ≥5.6 ng/mL were associated with a 7.4-fold higher relative risk of in-hospital death (95% confidence interval, 1.4-11, P = .0016).
Conclusions:
Intestinal injury occurs commonly in children hospitalized with malaria and is associated with microbial translocation, systemic inflammation, tissue hypoperfusion, MODS, and fatal outcome.
