Background: Enteroaggregative E. coli (EAEC) have been associated with mildly inflammatory diarrhea in outbreaks and in travelers and have been increasingly recognized as enteric pathogens in young children with and without overt diarrhea. We examined the risk factors for EAEC infections and their associations with environmental enteropathy biomarkers and growth outcomes over the first two years of life in eight low-resource settings of the MAL-ED study. Methods: EAEC infections were detected by PCR gene probes for aatA and aaiC virulence traits in 27,094 non-diarrheal surveillance stools and 7,692 diarrheal stools from 2,092 children in the MAL-ED birth cohort. We identified risk factors for EAEC and estimated the associations of EAEC with diarrhea, enteropathy biomarker concentrations, and both short-term (one to three months) and long-term growth (to two years of age). Results: Overall, 9,581 samples (27.5%) were positive for EAEC, and almost all children had at least one detection (94.8%) by two years of age. Exclusive breastfeeding, higher enrollment weight, and macrolide use within the preceding 15 days were protective. Although not associated with diarrhea, EAEC infections were weakly associated with biomarkers of intestinal inflammation and more strongly with reduced length at two years of age (LAZ difference associated with high frequency of EAEC detections: -0.30, 95% CI: -0.44, -0.16). Conclusions: Asymptomatic EAEC infections were common early in life and were associated with linear growth shortfalls. Associations with intestinal inflammation were small in magnitude, but suggest a pathway for the growth impact. Increasing the duration of exclusive breastfeeding may help prevent these potentially inflammatory infections and reduce the long-term impact of early exposure to EAEC.
Bibliographical noteFunding Information:
The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH and the National Institutes of Health/Fogarty International Center. This work was supported by the Fogarty International Center, National Institutes of Health (D43-TW009359 to ETR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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