HighlightsChildren living in these settings had a high prevalence of enteropathogens, high levels of intestinal inflammation, abnormal intestinal permeability, high markers of systemic inflammation, and postnatal acquired linear growth deficits when compared to children living in the US or EuropeThis study contributes empiric evidence to demonstrate that enteric infection alters both fecal markers of inflammation and permeabilityCurrent markers of enteropathy fail to account for a large portion of the observed shortfalls in linear growth in these populations, and markers of systemic inflammation appear as the most promising predictive biomarkers for identifying linear growth failure in childrenEnvironmental enteropathy (EE) is hypothesized as a mediator of growth faltering, but few prospective studies have evaluated pathways linking enteropathogen exposure, intestinal inflammation and permeability, and growth. The MAL-ED study represents a novel analytical framework and explicitly evaluates multiple putative EE pathways in combination and using an unprecedented quantity of data. Despite evidence that gut inflammation and altered gut permeability are frequently present and that associations between enteropathogen exposure and gut dysfunction exist, the observed attributable effects of EE on growth faltering in young children were small.

This longitudinal, multisite study reports a high prevalence of norovirus infection and norovirus-positive diarrhea and describes patterns of age acquisition, disease severity, genogroup-specific immunity, and relationships between norovirus and undernutrition in the first 2 years of life.

Astrovirus is an overlooked cause of diarrhea among vulnerable children worldwide. With the evidence presented here, we highlight the need for future research as well as the potential for astrovirus to be a target for vaccine development.

Background Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru. Methods Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition were investigated using multiple linear regression adjusting for within-child correlations, age, and breastfeeding. Indicator species analyses identified taxa specifically associated with Campylobacter burden. Results Ninety-three percent (251) of children had Campylobacter present in asymptomatic fecal samples during the follow-up period. A 10% increase in the proportion of stools infected was associated with mean reductions of 0.02 length-for-age z scores (LAZ) at 3, 6, and 9 months thereafter (P < .01). We identified 13 bacterial taxa indicative of cumulative Campylobacter burden and 14 taxa significantly associated with high or low burden of enteroaggregative Escherichia coli, norovirus, or Giardia. Conclusions Campylobacter infection is common in this cohort and associated with changes in microbial community composition. These results support the notion that disruptions to the fecal microbiota may help explain the observed effects of asymptomatic infections on growth in early life.

BackgroundCampylobacter is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species, C. coli and C. jejuni. Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other Campylobacter species, i.e. non-C. coli/jejuni. We performed a nested case-control study to compare the prevalence of C. coli/jejuni and other Campylobacter in children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with Campylobacter species other than C. coli/jejuni.Methodology/Principal findingsOur nested case-control study of 439 stool samples included dysenteric stools, stools collected during severe diarrhea episodes, and asymptomatic stools which were systematically selected to be representative of clinical phenotypes from 9,160 stools collected during a birth cohort study of 201 children followed until two years of age. Other Campylobacter accounted for 76.4% of the 216 Campylobacter detections by qPCR and were more prevalent than C. coli/jejuni across all clinical groups. Other Campylobacter were also more prevalent than C. coli/jejuni across all age groups, with older children bearing a higher burden of other Campylobacter. Biomarkers of intestinal inflammation and injury (methylene blue, fecal occult test, myeloperoxidase or MPO) showed a strong association with dysentery, but mixed results with infection. MPO levels were generally higher among children infected with C. coli/jejuni, but Shigella-infected children suffering from dysentery recorded the highest levels (26,224 ng/mL); the lowest levels (10,625 ng/mL) were among asymptomatic children infected with other Campylobacter. Adjusting for age, sex, and Shigella infection, dysentery was significantly associated with C. coli/jejuni but not with other Campylobacter, whereas severe diarrhea was significantly associated with both C. coli/jejuni and other Campylobacter. Compared to asymptomatic children, children suffering from dysentery had a 14.6 odds of C. coli/jejuni infection (p-value < 0.001, 95% CI 5.5–38.7) but were equally likely to have other Campylobacter infections–odds ratio of 1.3 (0.434, 0.7–2.4). Children suffering from severe diarrhea were more likely than asymptomatic children to test positive for both C. coli/jejuni and other Campylobacter–OR of 2.8 (0.034, 1.1–7.1) and 1.9 (0.018, 1.1–3.1), respectively. Compared to the Campylobacter-free group, the odds of all diarrhea given C. coli/jejuni infection and other Campylobacter infection were 8.8 (<0.001, 3.0–25.7) and 2.4 (0.002, 1.4–4.2), respectively. Eliminating other Campylobacter in this population would eliminate 24.9% of the diarrhea cases, which is almost twice the population attributable fraction of 15.1% due to C. coli/jejuni.Conclusions/SignificanceEighty-seven percent of the dysentery and 59.5% of the severe diarrhea samples were po...