Intestinal Injury in Ugandan Children Hospitalized With Malaria

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). I-FABP was above the normal range (≥400 pg/mL) in 415/523 patients (79%). I-FABP correlated with ZO-1 (ρ=0.11, p = 0.014), sCD14 (ρ=0.12, p = 0.0046), as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic blood pressure (ρ= -0.14, p = 0.0015), delayed capillary refill time (ρ= 0.17, p = 0.00011), higher lactate level (ρ= 0.40, p < 0.0001), increasing stage of acute kidney injury (ρ= 0.20, p = 0.0034), and coma (p < 0.0001). Admission I-FABP levels ≥5.6 ng/mL were associated with a 7.4-fold higher relative risk of in-hospital death (95%CI 1.4-11, p = 0.0016). Conclusion Intestinal injury occurs commonly in children hospitalized with malaria and is associated with microbial translocation, systemic inflammation, tissue hypoperfusion, MODS, and fatal outcome.

Biomarkers of Intestinal Injury and Dysfunction: Adding New Possibilities to Current Methods for Risk Stratification of Children with Malaria Disease

“…Remarkably, Ngai and colleagues ( 16 ) recently published a similar study that complements, validates, and further expands the findings of Sarangam et al The biomarkers I-FABP, LBP, and sCD14 (in addition to zonula occludens-1 [ZO-1], another marker of intestinal injury) were studied in a different cohort of 523 Ugandan children hospitalized with SM. That study showed that severe intestinal injury, defined slightly differently (i.e., I-FABP levels of ≥5.6 ng/mL), was present in 1 out of every 10 sick children.…”

The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study

“…In other studies, associations between IFABP and inflammatory biomarkers have been found in malaria, but not in sepsis and cardiac surgery. 15 , 17 , 18 , 19 , 38 Further, IFABP has been convincingly associated with mortality after cardiac arrest, while IL-6 are among the few inflammatory biomarkers which are associated with poor outcome after adjustment for confounding factors. 9 , 39 , 40 , 41 , 42 , 43 , 44 Importantly, IFABP and inflammatory biomarkers could merely increase in parallel with the degree of whole-body ischaemia.…”

“… 12 , 13 , 14 , 15 However, there are few reports investigating the associations between intestinal injury and systemic inflammatory biomarkers in general. 15 , 16 , 17 , 18 , 19 Previously, we have reported that both IFABP and some of the analysed inflammatory biomarkers, including interleukin (IL)-6 and the terminal complement complex (TCC), were associated with multiple organ dysfunction and mortality after out-of-hospital cardiac arrest (OHCA). 20 , 21 …”

Inflammation, the kynurenines, and mucosal injury during human experimental enterotoxigenic Escherichia coli infection

“…Regenerating islet-derived protein 3A (Reg3a) is a bactericidal, gut-specific protein that is often secreted in response to inflammation during the acute phase of infection to protect the gut epithelium [ 21 , 22 ]. Intestinal fatty acid-binding protein 2 (iFABP) is another small intestine-specific protein that is involved in the metabolism of long-chain fatty acids and can be used as a marker for gut injury [ 23 ].…”