Fecal Markers of Intestinal Inflammation and Permeability Associated with the Subsequent Acquisition of Linear Growth Deficits in Infants

Abstract

Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood.

The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants

“…15,25 However, faecal neopterin -a marker of activated cell-mediated immunity -was unaffected and remained high relative to normal values observed in healthy children in high-income countries. 15 Plasma biomarkers of microbial translocation from the intestine to systemic sites (EndoCAb, sCD14) and of damage to the intestinal epithelium (I-FABP) were also unaffected and remained high relative to values observed in high-income countries. 26,27 This may reflect an inherent limitation in the effectiveness of azithromycin against EE or the relatively short course of treatment (3 days).…”

“…Additionally EE was examined when defined by a) a binary variable equal to one if ≥1 biomarker was in the top quartile for measurements on stool or plasma and zero otherwise, and b) an EE score based on faecal biomarkers as defined by Kosek et al 2013. 15 The association between biomarkers of EE and the number of intestinal pathogens by group (bacteria, viruses, eukaryotes) was assessed using log-linear regression.…”

“…15 The association between biomarkers of EE and the number of intestinal pathogens by group (bacteria, viruses, eukaryotes) was assessed using log-linear regression.…”

“…Faecal biomarkers of intestinal inflammation, protein-losing enteropathy and immune activation (myeloperoxidase, calprotectin, α1-antitrypsin, neopterin) and plasma biomarkers of microbial translocation (soluble CD14 and endotoxin-core IgG (EndoCAb)) and epithelial damage (intestinal fatty acid binding protein (I-FABP)) were measured using enzyme-linked immunosorbent assays. 14, 15 Shedding of poliovirus in stool samples was assessed using quantitative real-time PCR. Further details are provided in the appendix.…”

“…[11][12][13][14] Faecal and blood biomarkers of EE have been used to determine its extent and role in growth faltering and malnutrition. 15 Some of these biomarkers have also been found to correlate with the outcome of immunisation with oral rotavirus and poliovirus vaccines. 16 We investigated the association between infection with intestinal pathogens, EE and the immune response to oral vaccination in a randomised placebo-controlled trial of the effect of a 3-day course of oral azithromycin on the immunogenicity of a subsequent dose of serotype-3 monovalent OPV given to Indian infants who lacked immunity to this serotype.…”