Intestinal Injury in Ugandan Children Hospitalized With Malaria

J Infect Dis. 2022 Nov 28;226(11):2010-2020. doi: 10.1093/infdis/jiac340.

Abstract

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.

Keywords: Uganda; inflammation; intestinal injury; malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Child
  • Fatty Acid-Binding Proteins
  • Female
  • Hospital Mortality
  • Humans
  • Infant
  • Inflammation
  • Intestinal Diseases*
  • Lipopolysaccharide Receptors
  • Malaria* / complications
  • Male
  • Multiple Organ Failure
  • Prospective Studies
  • Uganda / epidemiology

Substances

  • Lipopolysaccharide Receptors
  • Fatty Acid-Binding Proteins
  • Biomarkers